#ID(s) interactor A	ID(s) interactor B	Alt. ID(s) interactor A	Alt. ID(s) interactor B	Alias(es) interactor A	Alias(es) interactor B	Interaction detection method(s)	Publication 1st author(s)	Publication Identifier(s)	Taxid interactor A	Taxid interactor B	Interaction type(s)	Source database(s)	Interaction identifier(s)	Confidence value(s)	Expansion method(s)	Biological role(s) interactor A	Biological role(s) interactor B	Experimental role(s) interactor A	Experimental role(s) interactor B	Type(s) interactor A	Type(s) interactor B	Xref(s) interactor A	Xref(s) interactor B	Interaction Xref(s)	Annotation(s) interactor A	Annotation(s) interactor B	Interaction annotation(s)	Host organism(s)	Interaction parameter(s)	Creation date	Update date	Checksum(s) interactor A	Checksum(s) interactor B	Interaction Checksum(s)	Negative	Feature(s) interactor A	Feature(s) interactor B	Stoichiometry(s) interactor A	Stoichiometry(s) interactor B	Identification method participant A	Identification method participant B
uniprotkb:P04326	uniprotkb:O60563	intact:EBI-7333987|intact:MINT-138666	intact:EBI-2479671|ensembl:ENSP00000261900|uniprotkb:O60581|uniprotkb:A9XU13|uniprotkb:E7EX76	psi-mi:tat_hv112(display_long)|uniprotkb:tat(gene name)|psi-mi:tat(display_short)|uniprotkb:Transactivating regulatory protein(gene name synonym)	psi-mi:ccnt1_human(display_long)|uniprotkb:CCNT1(gene name)|psi-mi:CCNT1(display_short)	psi-mi:"MI:0007"(anti tag coimmunoprecipitation)	Tréand et al. (2006)	pubmed:16601680|imex:IM-11387|mint:MINT-5218478	taxid:11679(hv112)|taxid:11679("Human immunodeficiency virus type 1 group M subtype B (isolate PCV12)")	taxid:9606(human)|taxid:9606(Homo sapiens)	psi-mi:"MI:0915"(physical association)	psi-mi:"MI:0471"(MINT)	intact:EBI-8296643|mint:MINT-1898599|imex:IM-11387-13	-	-	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0496"(bait)	psi-mi:"MI:0498"(prey)	psi-mi:"MI:0326"(protein)	psi-mi:"MI:0326"(protein)	rcsb pdb:5SVZ|go:"GO:0001070"(RNA-binding transcription regulator activity)|go:"GO:0005576"(extracellular region)|go:"GO:0006351"(transcription, DNA-templated)|go:"GO:0010801"(negative regulation of peptidyl-threonine phosphorylation)|go:"GO:0019904"(protein domain specific binding)|go:"GO:0030332"(cyclin binding)|go:"GO:0030430"(host cell cytoplasm)|go:"GO:0032968"(positive regulation of transcription elongation from RNA polymerase II promoter)|go:"GO:0039502"(suppression by virus of host type I interferon-mediated signaling pathway)|go:"GO:0039525"(modulation by virus of host chromatin organization)|go:"GO:0039586"(modulation by virus of host PP1 activity)|go:"GO:0042805"(actinin binding)|go:"GO:0044196"(host cell nucleolus)|go:"GO:0046872"(metal ion binding)|go:"GO:0050434"(positive regulation of viral transcription)|go:"GO:1990970"(trans-activation response element binding)|interpro:IPR001831("Immunodeficiency virus transactivating regulatory protein (Tat)")|interpro:IPR036963|mint:MINT-1898600(identity)	go:"GO:0097322"(7SK snRNA binding)|go:"GO:1900364"(negative regulation of mRNA polyadenylation)|interpro:IPR006671(Cyclin, N-terminal)|go:"GO:0070691"(P-TEFb complex)|interpro:IPR013763(Cyclin-related)|interpro:IPR028863|interpro:IPR036915|interpro:IPR043198|mint:O60563|rcsb pdb:2PK2|rcsb pdb:3BLH|rcsb pdb:3BLQ|rcsb pdb:3BLR|rcsb pdb:3LQ5|rcsb pdb:3MI9|rcsb pdb:3MIA|rcsb pdb:3MY1|rcsb pdb:3TN8|rcsb pdb:3TNH|rcsb pdb:3TNI|rcsb pdb:4BCF|rcsb pdb:4BCG|rcsb pdb:4BCH|rcsb pdb:4BCI|rcsb pdb:4BCJ|rcsb pdb:4EC8|rcsb pdb:4EC9|rcsb pdb:4IMY|rcsb pdb:4OGR|rcsb pdb:4OR5|rcsb pdb:5L1Z|rcsb pdb:6CYT|rcsb pdb:6GZH|rcsb pdb:6Z45|reactome:R-HSA-112382|reactome:R-HSA-167152|reactome:R-HSA-167200|reactome:R-HSA-167238|reactome:R-HSA-167243|reactome:R-HSA-167246|reactome:R-HSA-167287|reactome:R-HSA-167290|reactome:R-HSA-176034|reactome:R-HSA-2173796|reactome:R-HSA-674695|reactome:R-HSA-6796648|reactome:R-HSA-6807505|reactome:R-HSA-75955|reactome:R-HSA-9018519|ensembl:ENSG00000129315(gene)|ensembl:ENST00000261900(transcript)|go:"GO:0000079"(regulation of cyclin-dependent protein serine/threonine kinase activity)|go:"GO:0000976"(transcription cis-regulatory region binding)|go:"GO:0003677"(DNA binding)|go:"GO:0003682"(chromatin binding)|go:"GO:0005634"(nucleus)|go:"GO:0005654"(nucleoplasm)|go:"GO:0005829"(cytosol)|go:"GO:0006357"(regulation of transcription by RNA polymerase II)|go:"GO:0006366"(transcription by RNA polymerase II)|go:"GO:0006468"(protein phosphorylation)|go:"GO:0007049"(cell cycle)|go:"GO:0008024"(cyclin/CDK positive transcription elongation factor complex)|go:"GO:0008134"(transcription factor binding)|go:"GO:0016538"(cyclin-dependent protein serine/threonine kinase regulator activity)|go:"GO:0019901"(protein kinase binding)|go:"GO:0032786"(positive regulation of DNA-templated transcription, elongation)|go:"GO:0043923"(positive regulation by host of viral transcription)|go:"GO:0045944"(positive regulation of transcription by RNA polymerase II)|go:"GO:0051301"(cell division)|go:"GO:0061575"(cyclin-dependent protein serine/threonine kinase activator activity)|go:"GO:0070063"(RNA polymerase binding)|refseq:NP_001231.2|refseq:NP_001264771.1|dip:DIP-29891N|mint:MINT-1898601(identity)	-	comment:mint|function:"Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. In the absence of Tat, the RNA Pol II generates short or non-processive transcripts that terminate at approximately 60 bp from the initiation site. Tat associates with the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. This binding increases Tat's affinity for a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) and allows Tat/P-TEFb complex to bind cooperatively to TAR RNA. The CDK9 component of P-TEFb hyperphosphorylates the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B. In this purpose, it activates EIF2AK2/PKR which, in turns, may phosphorylate and target to degradation the inhibitor IkappaB-alpha which normally retains NF-kappa-B in the cytoplasm of unstimulated cells. Through its interaction with TBP, Tat may be involved in transcription initiation as well. Interacts with the cellular capping enzyme RNGTT to mediate co-transcriptional capping of viral mRNAs. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter"|function:"Alters the cellular functions through the binding to various nuclear and cytoplasmic factors, and cell surface receptors. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines (such as IL10) or cytokine receptors. Tat plays a role in T-cell and neurons apoptosis. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Tat seems to inhibit the HAT activity of HTATIP/Tip60 and TAF1, and consequently modify the expression of specific cellular genes. Mediates the activation of cyclin-dependent kinases and dysregulation of microtubule network. Extracellular Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Endocytosed Tat translocate into the nucleus, and induces apoptosis by oxidative stress associated with mitochondrial dysfunction and perturbation of calcium-regulated channels and glutamate receptor (NMDAR). Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Host extracellular matrix metalloproteinase MMP1 cleaves Tat and decreases Tat's mediated neurotoxicity. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. Binds to KDR/VEGFR-2. All these Tat-mediated effects enhance angiogenesis in Kaposi's sarcoma lesions"|comment:"Stoichiometry: 1.0"	comment:"Stoichiometry: 1.0"	figure legend:F1A|comment:homomint|comment:mint|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation	taxid:9606(human-hela)|taxid:9606(Homo sapiens epitheloid cervix carcinoma cells)	-	2006/05/10	2014/10/16	rogid:6IQLP0otFnozphvozdUWNnLP/cU11679	rogid:y80GILqwBbb5hMtl/4U1Y/vNx909606	intact-crc:0474439DA597E839|rigid:wS3qDUzFetxktkiLmHf9qUEY9uU	false	flag tag:?-?(MINT-1898613)	-	1	1	psi-mi:"MI:0078"(nucleotide sequence identification)	psi-mi:"MI:0086"(polyclonal antibody western blot)
uniprotkb:P04326	uniprotkb:P50750	intact:EBI-7333987|intact:MINT-138666	intact:EBI-1383449|uniprotkb:Q5JU24|uniprotkb:Q5JU25|uniprotkb:Q5U006|uniprotkb:Q96TF1|ensembl:ENSP00000362361	psi-mi:tat_hv112(display_long)|uniprotkb:tat(gene name)|psi-mi:tat(display_short)|uniprotkb:Transactivating regulatory protein(gene name synonym)	psi-mi:cdk9_human(display_long)|uniprotkb:CDK9(gene name)|psi-mi:CDK9(display_short)|uniprotkb:CDC2L4(gene name synonym)|uniprotkb:Cell division protein kinase 9(gene name synonym)|uniprotkb:Serine/threonine-protein kinase PITALRE(gene name synonym)|uniprotkb:Cell division cycle 2-like protein kinase 4(gene name synonym)|uniprotkb:C-2K(gene name synonym)|uniprotkb:TAK(gene name synonym)|uniprotkb:Tat-associated kinase complex catalytic subunit(gene name synonym)	psi-mi:"MI:0007"(anti tag coimmunoprecipitation)	Tréand et al. (2006)	pubmed:16601680|imex:IM-11387|mint:MINT-5218478	taxid:11679(hv112)|taxid:11679("Human immunodeficiency virus type 1 group M subtype B (isolate PCV12)")	taxid:9606(human)|taxid:9606(Homo sapiens)	psi-mi:"MI:0915"(physical association)	psi-mi:"MI:0471"(MINT)	intact:EBI-8296682|mint:MINT-1898621|imex:IM-11387-14	-	-	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0496"(bait)	psi-mi:"MI:0498"(prey)	psi-mi:"MI:0326"(protein)	psi-mi:"MI:0326"(protein)	rcsb pdb:5SVZ|go:"GO:0001070"(RNA-binding transcription regulator activity)|go:"GO:0005576"(extracellular region)|go:"GO:0006351"(transcription, DNA-templated)|go:"GO:0010801"(negative regulation of peptidyl-threonine phosphorylation)|go:"GO:0019904"(protein domain specific binding)|go:"GO:0030332"(cyclin binding)|go:"GO:0030430"(host cell cytoplasm)|go:"GO:0032968"(positive regulation of transcription elongation from RNA polymerase II promoter)|go:"GO:0039502"(suppression by virus of host type I interferon-mediated signaling pathway)|go:"GO:0039525"(modulation by virus of host chromatin organization)|go:"GO:0039586"(modulation by virus of host PP1 activity)|go:"GO:0042805"(actinin binding)|go:"GO:0044196"(host cell nucleolus)|go:"GO:0046872"(metal ion binding)|go:"GO:0050434"(positive regulation of viral transcription)|go:"GO:1990970"(trans-activation response element binding)|interpro:IPR001831("Immunodeficiency virus transactivating regulatory protein (Tat)")|interpro:IPR036963|mint:MINT-1898622(identity)	refseq:NP_001252.1|dip:DIP-29016N|rcsb pdb:4BCI|rcsb pdb:4BCJ|rcsb pdb:4EC8|rcsb pdb:4EC9|rcsb pdb:4IMY|rcsb pdb:4OGR|rcsb pdb:4OR5|rcsb pdb:5L1Z|rcsb pdb:6CYT|rcsb pdb:6GZH|rcsb pdb:6Z45|reactome:R-HSA-112382|reactome:R-HSA-167152|reactome:R-HSA-167200|reactome:R-HSA-167238|reactome:R-HSA-167243|reactome:R-HSA-167246|reactome:R-HSA-167287|reactome:R-HSA-167290|reactome:R-HSA-176034|reactome:R-HSA-2173796|rcsb pdb:3MY1|rcsb pdb:3TN8|rcsb pdb:3TNH|rcsb pdb:3TNI|rcsb pdb:4BCF|rcsb pdb:4BCG|rcsb pdb:4BCH|reactome:R-HSA-674695|reactome:R-HSA-6796648|reactome:R-HSA-6807505|reactome:R-HSA-75955|reactome:R-HSA-9018519|ensembl:ENSG00000136807(gene)|ensembl:ENST00000373264(transcript)|go:"GO:0000978"(RNA polymerase II cis-regulatory region sequence-specific DNA binding)|go:"GO:0001223"(transcription coactivator binding)|go:"GO:0003677"(DNA binding)|go:"GO:0003682"(chromatin binding)|go:"GO:0004672"(protein kinase activity)|go:"GO:0004674"(protein serine/threonine kinase activity)|go:"GO:0004693"(cyclin-dependent protein serine/threonine kinase activity)|go:"GO:0005524"(ATP binding)|go:"GO:0005634"(nucleus)|go:"GO:0005654"(nucleoplasm)|go:"GO:0006281"(DNA repair)|go:"GO:0006282"(regulation of DNA repair)|go:"GO:0006367"(transcription initiation from RNA polymerase II promoter)|go:"GO:0006368"(transcription elongation from RNA polymerase II promoter)|go:"GO:0006468"(protein phosphorylation)|go:"GO:0008023"(transcription elongation factor complex)|go:"GO:0008024"(cyclin/CDK positive transcription elongation factor complex)|go:"GO:0008283"(cell population proliferation)|go:"GO:0008353"(RNA polymerase II CTD heptapeptide repeat kinase activity)|go:"GO:0010613"(positive regulation of cardiac muscle hypertrophy)|go:"GO:0016020"(membrane)|go:"GO:0016592"(mediator complex)|go:"GO:0016605"(PML body)|go:"GO:0019901"(protein kinase binding)|go:"GO:0031056"(regulation of histone modification)|go:"GO:0031297"(replication fork processing)|go:"GO:0033129"(positive regulation of histone phosphorylation)|go:"GO:0036464"(cytoplasmic ribonucleoprotein granule)|go:"GO:0042493"|go:"GO:0045944"(positive regulation of transcription by RNA polymerase II)|go:"GO:0051147"(regulation of muscle cell differentiation)|go:"GO:0051726"(regulation of cell cycle)|go:"GO:0070691"(P-TEFb complex)|go:"GO:0070816"(phosphorylation of RNA polymerase II C-terminal domain)|go:"GO:0071345"(cellular response to cytokine stimulus)|go:"GO:0097322"(7SK snRNA binding)|go:"GO:0106310"(protein serine kinase activity)|go:"GO:0106311"|go:"GO:1900364"(negative regulation of mRNA polyadenylation)|go:"GO:1903839"(positive regulation of mRNA 3'-UTR binding)|go:"GO:2001168"(positive regulation of histone H2B ubiquitination)|interpro:IPR000719(Protein kinase, core)|interpro:IPR008271(Serine/threonine protein kinase, active site)|interpro:IPR011009(Protein kinase-like)|interpro:IPR017441(Protein kinase ATP binding, conserved site)|mint:P50750|rcsb pdb:1PF6|rcsb pdb:3BLH|rcsb pdb:3BLQ|rcsb pdb:3BLR|rcsb pdb:3LQ5|rcsb pdb:3MI9|rcsb pdb:3MIA|mint:MINT-1898630(identity)	-	comment:mint|function:"Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. In the absence of Tat, the RNA Pol II generates short or non-processive transcripts that terminate at approximately 60 bp from the initiation site. Tat associates with the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. This binding increases Tat's affinity for a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) and allows Tat/P-TEFb complex to bind cooperatively to TAR RNA. The CDK9 component of P-TEFb hyperphosphorylates the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B. In this purpose, it activates EIF2AK2/PKR which, in turns, may phosphorylate and target to degradation the inhibitor IkappaB-alpha which normally retains NF-kappa-B in the cytoplasm of unstimulated cells. Through its interaction with TBP, Tat may be involved in transcription initiation as well. Interacts with the cellular capping enzyme RNGTT to mediate co-transcriptional capping of viral mRNAs. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter"|function:"Alters the cellular functions through the binding to various nuclear and cytoplasmic factors, and cell surface receptors. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines (such as IL10) or cytokine receptors. Tat plays a role in T-cell and neurons apoptosis. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Tat seems to inhibit the HAT activity of HTATIP/Tip60 and TAF1, and consequently modify the expression of specific cellular genes. Mediates the activation of cyclin-dependent kinases and dysregulation of microtubule network. Extracellular Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Endocytosed Tat translocate into the nucleus, and induces apoptosis by oxidative stress associated with mitochondrial dysfunction and perturbation of calcium-regulated channels and glutamate receptor (NMDAR). Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Host extracellular matrix metalloproteinase MMP1 cleaves Tat and decreases Tat's mediated neurotoxicity. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. Binds to KDR/VEGFR-2. All these Tat-mediated effects enhance angiogenesis in Kaposi's sarcoma lesions"|comment:"Stoichiometry: 1.0"	comment:"Stoichiometry: 1.0"	figure legend:F1A|comment:homomint|comment:mint|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation	taxid:9606(human-hela)|taxid:9606(Homo sapiens epitheloid cervix carcinoma cells)	-	2006/05/10	2014/10/16	rogid:6IQLP0otFnozphvozdUWNnLP/cU11679	rogid:XSEmM4b5tp/WCJCJxnQYyP0stvM9606	intact-crc:6DDE6A485652C21A|rigid:RgJQDIs8XtUPRyWLkeY3dVS5pdk	false	flag tag:?-?(MINT-1898628)	-	1	1	psi-mi:"MI:0078"(nucleotide sequence identification)	psi-mi:"MI:0086"(polyclonal antibody western blot)
uniprotkb:P51531	uniprotkb:P04326	intact:EBI-679562|uniprotkb:B1ALG3|uniprotkb:B1ALG4|uniprotkb:D3DRH4|uniprotkb:D3DRH5|ensembl:ENSP00000265773|ensembl:ENSP00000371638	intact:EBI-7333987|intact:MINT-138666	psi-mi:smca2_human(display_long)|uniprotkb:ATP-dependent helicase SMARCA2(gene name synonym)|uniprotkb:SNF2-alpha(gene name synonym)|uniprotkb:SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2(gene name synonym)|uniprotkb:SMARCA2(gene name)|psi-mi:SMARCA2(display_short)|uniprotkb:BRM(gene name synonym)|uniprotkb:SNF2A(gene name synonym)|uniprotkb:SNF2L2(gene name synonym)|uniprotkb:BAF190B(gene name synonym)|uniprotkb:Protein brahma homolog(gene name synonym)|uniprotkb:BRG1-associated factor 190B(gene name synonym)	psi-mi:tat_hv112(display_long)|uniprotkb:tat(gene name)|psi-mi:tat(display_short)|uniprotkb:Transactivating regulatory protein(gene name synonym)	psi-mi:"MI:0007"(anti tag coimmunoprecipitation)	Tréand et al. (2006)	pubmed:16601680|imex:IM-11387|mint:MINT-5218478	taxid:9606(human)|taxid:9606(Homo sapiens)	taxid:11679(hv112)|taxid:11679("Human immunodeficiency virus type 1 group M subtype B (isolate PCV12)")	psi-mi:"MI:0915"(physical association)	psi-mi:"MI:0471"(MINT)	intact:EBI-8296718|mint:MINT-1898659|imex:IM-11387-16	-	-	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0498"(prey)	psi-mi:"MI:0496"(bait)	psi-mi:"MI:0326"(protein)	psi-mi:"MI:0326"(protein)	refseq:NP_003061.3|refseq:NP_620614.2|refseq:NP_001276325.1|refseq:NP_001276326.1|dip:DIP-29005N|ensembl:ENSG00000080503(gene)|ensembl:ENST00000349721(transcript)|ensembl:ENST00000382203(transcript)|go:"GO:0000122"(negative regulation of transcription by RNA polymerase II)|go:"GO:0000785"(chromatin)|go:"GO:0000976"(transcription cis-regulatory region binding)|go:"GO:0003677"(DNA binding)|go:"GO:0003682"(chromatin binding)|go:"GO:0003713"(transcription coactivator activity)|go:"GO:0004386"(helicase activity)|go:"GO:0005524"(ATP binding)|go:"GO:0005634"(nucleus)|go:"GO:0005654"(nucleoplasm)|go:"GO:0006338"(chromatin remodeling)|go:"GO:0006355"(regulation of transcription, DNA-templated)|go:"GO:0006357"(regulation of transcription by RNA polymerase II)|go:"GO:0007286"(spermatid development)|go:"GO:0007399"(nervous system development)|go:"GO:0008094"(ATP-dependent activity, acting on DNA)|go:"GO:0008285"(negative regulation of cell population proliferation)|go:"GO:0016514"(SWI/SNF complex)|go:"GO:0016787"(hydrolase activity)|go:"GO:0030308"(negative regulation of cell growth)|go:"GO:0042393"(histone binding)|go:"GO:0043044"|go:"GO:0043231"(intracellular membrane-bounded organelle)|go:"GO:0045111"(intermediate filament cytoskeleton)|go:"GO:0045892"(negative regulation of transcription, DNA-templated)|go:"GO:0045893"(positive regulation of transcription, DNA-templated)|go:"GO:0045944"(positive regulation of transcription by RNA polymerase II)|go:"GO:0070615"|go:"GO:0071564"(npBAF complex)|go:"GO:0071565"(nBAF complex)|interpro:IPR000330(SNF2-related)|interpro:IPR001487(Bromodomain)|interpro:IPR001650(DNA/RNA helicase, C-terminal)|interpro:IPR006576(BRK)|interpro:IPR014001(DEAD-like helicase, N-terminal)|interpro:IPR014012(Helicase/SANT-associated, DNA binding)|interpro:IPR014978(QLQ)|interpro:IPR018359|interpro:IPR027417|interpro:IPR029295|interpro:IPR030088|interpro:IPR036427|interpro:IPR037259|interpro:IPR038718|mint:P51531|rcsb pdb:2DAT|rcsb pdb:4QY4|rcsb pdb:5DKC|rcsb pdb:5DKH|rcsb pdb:6EG2|rcsb pdb:6EG3|rcsb pdb:6HAX|rcsb pdb:6HAY|rcsb pdb:6HAZ|reactome:R-HSA-3214858|reactome:R-HSA-8939243|mint:MINT-1898660(identity)	rcsb pdb:5SVZ|go:"GO:0001070"(RNA-binding transcription regulator activity)|go:"GO:0005576"(extracellular region)|go:"GO:0006351"(transcription, DNA-templated)|go:"GO:0010801"(negative regulation of peptidyl-threonine phosphorylation)|go:"GO:0019904"(protein domain specific binding)|go:"GO:0030332"(cyclin binding)|go:"GO:0030430"(host cell cytoplasm)|go:"GO:0032968"(positive regulation of transcription elongation from RNA polymerase II promoter)|go:"GO:0039502"(suppression by virus of host type I interferon-mediated signaling pathway)|go:"GO:0039525"(modulation by virus of host chromatin organization)|go:"GO:0039586"(modulation by virus of host PP1 activity)|go:"GO:0042805"(actinin binding)|go:"GO:0044196"(host cell nucleolus)|go:"GO:0046872"(metal ion binding)|go:"GO:0050434"(positive regulation of viral transcription)|go:"GO:1990970"(trans-activation response element binding)|interpro:IPR001831("Immunodeficiency virus transactivating regulatory protein (Tat)")|interpro:IPR036963|mint:MINT-1898666(identity)	-	comment:"Stoichiometry: 1.0"	comment:mint|function:"Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. In the absence of Tat, the RNA Pol II generates short or non-processive transcripts that terminate at approximately 60 bp from the initiation site. Tat associates with the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. This binding increases Tat's affinity for a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) and allows Tat/P-TEFb complex to bind cooperatively to TAR RNA. The CDK9 component of P-TEFb hyperphosphorylates the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B. In this purpose, it activates EIF2AK2/PKR which, in turns, may phosphorylate and target to degradation the inhibitor IkappaB-alpha which normally retains NF-kappa-B in the cytoplasm of unstimulated cells. Through its interaction with TBP, Tat may be involved in transcription initiation as well. Interacts with the cellular capping enzyme RNGTT to mediate co-transcriptional capping of viral mRNAs. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter"|function:"Alters the cellular functions through the binding to various nuclear and cytoplasmic factors, and cell surface receptors. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines (such as IL10) or cytokine receptors. Tat plays a role in T-cell and neurons apoptosis. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Tat seems to inhibit the HAT activity of HTATIP/Tip60 and TAF1, and consequently modify the expression of specific cellular genes. Mediates the activation of cyclin-dependent kinases and dysregulation of microtubule network. Extracellular Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Endocytosed Tat translocate into the nucleus, and induces apoptosis by oxidative stress associated with mitochondrial dysfunction and perturbation of calcium-regulated channels and glutamate receptor (NMDAR). Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Host extracellular matrix metalloproteinase MMP1 cleaves Tat and decreases Tat's mediated neurotoxicity. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. Binds to KDR/VEGFR-2. All these Tat-mediated effects enhance angiogenesis in Kaposi's sarcoma lesions"|comment:"Stoichiometry: 1.0"	figure legend:F1A|comment:homomint|comment:mint|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation	taxid:9606(human-hela)|taxid:9606(Homo sapiens epitheloid cervix carcinoma cells)	-	2006/05/10	2014/10/16	rogid:DmQot4h4SmtqmUGBgF5ictTah289606	rogid:6IQLP0otFnozphvozdUWNnLP/cU11679	intact-crc:348BA4AD8411F701|rigid:My0sWeTtD+phXNKqopXMDfgxTJg	false	-	flag tag:?-?(MINT-1898672)	1	1	psi-mi:"MI:0086"(polyclonal antibody western blot)	psi-mi:"MI:0078"(nucleotide sequence identification)
uniprotkb:P04326	uniprotkb:Q09472	intact:EBI-7333987|intact:MINT-138666	intact:EBI-447295|intact:EBI-3908041|uniprotkb:B1AKC2|intact:EBI-28987257|ensembl:ENSP00000263253	psi-mi:tat_hv112(display_long)|uniprotkb:tat(gene name)|psi-mi:tat(display_short)|uniprotkb:Transactivating regulatory protein(gene name synonym)	psi-mi:ep300_human(display_long)|uniprotkb:Histone butyryltransferase p300(gene name synonym)|uniprotkb:Histone crotonyltransferase p300(gene name synonym)|uniprotkb:Protein propionyltransferase p300(gene name synonym)|uniprotkb:EP300(gene name)|psi-mi:EP300(display_short)|uniprotkb:P300(gene name synonym)|uniprotkb:E1A-associated protein p300(gene name synonym)|uniprotkb:Protein 2-hydroxyisobutyryltransferase p300(gene name synonym)|uniprotkb:Protein lactyltransferas p300(gene name synonym)	psi-mi:"MI:0007"(anti tag coimmunoprecipitation)	Tréand et al. (2006)	pubmed:16601680|imex:IM-11387|mint:MINT-5218478	taxid:11679(hv112)|taxid:11679("Human immunodeficiency virus type 1 group M subtype B (isolate PCV12)")	taxid:9606(human)|taxid:9606(Homo sapiens)	psi-mi:"MI:0915"(physical association)	psi-mi:"MI:0471"(MINT)	intact:EBI-8296700|mint:MINT-1898638|imex:IM-11387-15	-	-	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0496"(bait)	psi-mi:"MI:0498"(prey)	psi-mi:"MI:0326"(protein)	psi-mi:"MI:0326"(protein)	rcsb pdb:5SVZ|go:"GO:0001070"(RNA-binding transcription regulator activity)|go:"GO:0005576"(extracellular region)|go:"GO:0006351"(transcription, DNA-templated)|go:"GO:0010801"(negative regulation of peptidyl-threonine phosphorylation)|go:"GO:0019904"(protein domain specific binding)|go:"GO:0030332"(cyclin binding)|go:"GO:0030430"(host cell cytoplasm)|go:"GO:0032968"(positive regulation of transcription elongation from RNA polymerase II promoter)|go:"GO:0039502"(suppression by virus of host type I interferon-mediated signaling pathway)|go:"GO:0039525"(modulation by virus of host chromatin organization)|go:"GO:0039586"(modulation by virus of host PP1 activity)|go:"GO:0042805"(actinin binding)|go:"GO:0044196"(host cell nucleolus)|go:"GO:0046872"(metal ion binding)|go:"GO:0050434"(positive regulation of viral transcription)|go:"GO:1990970"(trans-activation response element binding)|interpro:IPR001831("Immunodeficiency virus transactivating regulatory protein (Tat)")|interpro:IPR036963|mint:MINT-1898645(identity)	refseq:NP_001420.2|ensembl:ENSP00000263253|dip:DIP-257N|go:"GO:0140068"(histone crotonyltransferase activity)|go:"GO:0140069"(histone butyryltransferase activity)|go:"GO:0140297"(DNA-binding transcription factor binding)|go:"GO:1900034"(regulation of cellular response to heat)|go:"GO:1901224"(positive regulation of NIK/NF-kappaB signaling)|go:"GO:1901796"(regulation of signal transduction by p53 class mediator)|go:"GO:1905636"(positive regulation of RNA polymerase II regulatory region sequence-specific DNA binding)|interpro:IPR000197(Zinc finger, TAZ-type)|interpro:IPR000433(Zinc finger, ZZ-type)|interpro:IPR001487(Bromodomain)|interpro:IPR003101(Coactivator CBP, KIX)|interpro:IPR009110(Nuclear receptor coactivator, interlocking)|interpro:IPR010303(Protein of unknown function DUF902, CREBbp)|interpro:IPR013083(Zinc finger, RING/FYVE/PHD-type)|interpro:IPR013178(H3K56 histone acetylation protein, RTT109)|interpro:IPR014744(Nuclear receptor coactivator, CREB-bp-like, interlocking)|interpro:IPR018359|interpro:IPR031162|interpro:IPR035898|interpro:IPR036427|interpro:IPR036529|interpro:IPR037073|interpro:IPR038547|interpro:IPR043145|mint:Q09472|rcsb pdb:1L3E|rcsb pdb:1P4Q|rcsb pdb:2K8F|rcsb pdb:2MH0|rcsb pdb:2MZD|rcsb pdb:3BIY|rcsb pdb:3I3J|rcsb pdb:3IO2|go:"GO:0140067"(peptidyl-lysine butyrylation)|rcsb pdb:3P57|rcsb pdb:3T92|rcsb pdb:4PZR|rcsb pdb:4PZS|rcsb pdb:4PZT|rcsb pdb:5BT3|rcsb pdb:5KJ2|rcsb pdb:5LKT|rcsb pdb:5LKU|rcsb pdb:5LKX|rcsb pdb:5LKZ|rcsb pdb:5LPK|rcsb pdb:5LPM|rcsb pdb:5NU5|rcsb pdb:5XZC|rcsb pdb:6DS6|rcsb pdb:6FGN|rcsb pdb:6FGS|rcsb pdb:6GYR|rcsb pdb:6GYT|rcsb pdb:6K4N|rcsb pdb:6PF1|rcsb pdb:6PGU|rcsb pdb:6V8B|rcsb pdb:6V8K|rcsb pdb:6V8N|rcsb pdb:6V90|rcsb pdb:7LJE|reactome:R-HSA-1234158|reactome:R-HSA-1368082|reactome:R-HSA-156711|reactome:R-HSA-1912408|reactome:R-HSA-1989781|reactome:R-HSA-201722|reactome:R-HSA-210744|reactome:R-HSA-2122947|reactome:R-HSA-2197563|reactome:R-HSA-2644606|reactome:R-HSA-2894862|reactome:R-HSA-3134973|reactome:R-HSA-3214847|reactome:R-HSA-3371568|reactome:R-HSA-381340|reactome:R-HSA-3899300|reactome:R-HSA-400253|reactome:R-HSA-5250924|reactome:R-HSA-5617472|reactome:R-HSA-5621575|reactome:R-HSA-5689901|reactome:R-HSA-6781823|reactome:R-HSA-6781827|reactome:R-HSA-6782135|reactome:R-HSA-6782210|reactome:R-HSA-6804114|reactome:R-HSA-6804758|reactome:R-HSA-6804760|reactome:R-HSA-6811555|reactome:R-HSA-8866907|reactome:R-HSA-8936459|reactome:R-HSA-8939243|reactome:R-HSA-8941856|reactome:R-HSA-8941858|reactome:R-HSA-8951936|reactome:R-HSA-9013508|reactome:R-HSA-9013695|reactome:R-HSA-9018519|reactome:R-HSA-9029569|reactome:R-HSA-9031628|reactome:R-HSA-918233|reactome:R-HSA-933541|reactome:R-HSA-9614657|reactome:R-HSA-9616222|reactome:R-HSA-9617629|reactome:R-HSA-9707616|rcsb pdb:4BHW|go:"GO:0000122"(negative regulation of transcription by RNA polymerase II)|ensembl:ENSG00000100393(gene)|ensembl:ENST00000263253(transcript)|go:"GO:0000123"(histone acetyltransferase complex)|go:"GO:0001216"(DNA-binding transcription activator activity)|go:"GO:0001221"(transcription coregulator binding)|go:"GO:0001223"(transcription coactivator binding)|go:"GO:0001666"(response to hypoxia)|go:"GO:0001756"(somitogenesis)|go:"GO:0001966"(thigmotaxis)|go:"GO:0002039"(p53 binding)|go:"GO:0002209"(behavioral defense response)|go:"GO:0002223"(stimulatory C-type lectin receptor signaling pathway)|go:"GO:0003677"(DNA binding)|go:"GO:0003682"(chromatin binding)|go:"GO:0003684"(damaged DNA binding)|go:"GO:0003713"(transcription coactivator activity)|go:"GO:0004402"(histone acetyltransferase activity)|go:"GO:0004468"(lysine N-acetyltransferase activity, acting on acetyl phosphate as donor)|go:"GO:0005634"(nucleus)|go:"GO:0005654"(nucleoplasm)|go:"GO:0005667"(transcription regulator complex)|go:"GO:0005694"(chromosome)|go:"GO:0005829"(cytosol)|go:"GO:0006110"(regulation of glycolytic process)|go:"GO:0007049"(cell cycle)|go:"GO:0007399"(nervous system development)|go:"GO:0007507"(heart development)|go:"GO:0007519"(skeletal muscle tissue development)|go:"GO:0007611"(learning or memory)|go:"GO:0007623"(circadian rhythm)|go:"GO:0008013"(beta-catenin binding)|go:"GO:0008022"(protein C-terminus binding)|go:"GO:0008134"(transcription factor binding)|go:"GO:0008270"(zinc ion binding)|go:"GO:0009887"(animal organ morphogenesis)|go:"GO:0010484"(H3 histone acetyltransferase activity)|go:"GO:0010485"(H4 histone acetyltransferase activity)|go:"GO:0010506"(regulation of autophagy)|go:"GO:0010742"(macrophage derived foam cell differentiation)|go:"GO:0010821"(regulation of mitochondrion organization)|go:"GO:0010976"(positive regulation of neuron projection development)|go:"GO:0016407"(acetyltransferase activity)|go:"GO:0016573"(histone acetylation)|go:"GO:0016746"(acyltransferase activity)|go:"GO:0016922"(nuclear receptor binding)|go:"GO:0018076"(N-terminal peptidyl-lysine acetylation)|go:"GO:0018393"(internal peptidyl-lysine acetylation)|go:"GO:0018394"(peptidyl-lysine acetylation)|go:"GO:0030183"(B cell differentiation)|go:"GO:0030220"(platelet formation)|go:"GO:0030324"(lung development)|go:"GO:0030511"(positive regulation of transforming growth factor beta receptor signaling pathway)|go:"GO:0031333"(negative regulation of protein-containing complex assembly)|go:"GO:0031490"(chromatin DNA binding)|go:"GO:0031648"(protein destabilization)|go:"GO:0032092"(positive regulation of protein binding)|go:"GO:0032993"(protein-DNA complex)|go:"GO:0034212"(peptide N-acetyltransferase activity)|go:"GO:0034644"(cellular response to UV)|go:"GO:0006473"(protein acetylation)|go:"GO:0006475"(internal protein amino acid acetylation)|go:"GO:0035264"(multicellular organism growth)|go:"GO:0035855"(megakaryocyte development)|go:"GO:0006915"(apoptotic process)|go:"GO:0036268"(swimming)|go:"GO:0042771"(intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator)|go:"GO:0043627"(response to estrogen)|go:"GO:0043923"(positive regulation by host of viral transcription)|go:"GO:0043967"(histone H4 acetylation)|go:"GO:0043969"(histone H2B acetylation)|go:"GO:0045444"(fat cell differentiation)|go:"GO:0045721"(negative regulation of gluconeogenesis)|go:"GO:0045815"(epigenetic maintenance of chromatin in transcription-competent conformation)|go:"GO:0045893"(positive regulation of transcription, DNA-templated)|go:"GO:0045944"(positive regulation of transcription by RNA polymerase II)|go:"GO:0048156"(tau protein binding)|go:"GO:0050681"(androgen receptor binding)|go:"GO:0050821"(protein stabilization)|go:"GO:0051059"(NF-kappaB binding)|go:"GO:0051091"(positive regulation of DNA-binding transcription factor activity)|go:"GO:0051092"(positive regulation of NF-kappaB transcription factor activity)|go:"GO:0060325"(face morphogenesis)|go:"GO:0060765"(regulation of androgen receptor signaling pathway)|go:"GO:0061629"(RNA polymerase II-specific DNA-binding transcription factor binding)|go:"GO:0061733"(peptide-lysine-N-acetyltransferase activity)|go:"GO:0061920"(protein propionyltransferase activity)|go:"GO:0061921"(peptidyl-lysine propionylation)|go:"GO:0090043"(regulation of tubulin deacetylation)|go:"GO:0097043"(histone H3-K56 acetylation)|go:"GO:0097157"(pre-mRNA intronic binding)|go:"GO:0097677"(STAT family protein binding)|go:"GO:0106226"(peptide 2-hydroxyisobutyryltransferase activity)|go:"GO:0120301"(histone lactyltransferase activity)|go:"GO:0140065"(peptide butyryltransferase activity)|go:"GO:0140066"(peptidyl-lysine crotonylation)|go:"GO:0006990"(positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response)|mint:MINT-1898639(identity)	-	comment:mint|function:"Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. In the absence of Tat, the RNA Pol II generates short or non-processive transcripts that terminate at approximately 60 bp from the initiation site. Tat associates with the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. This binding increases Tat's affinity for a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) and allows Tat/P-TEFb complex to bind cooperatively to TAR RNA. The CDK9 component of P-TEFb hyperphosphorylates the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B. In this purpose, it activates EIF2AK2/PKR which, in turns, may phosphorylate and target to degradation the inhibitor IkappaB-alpha which normally retains NF-kappa-B in the cytoplasm of unstimulated cells. Through its interaction with TBP, Tat may be involved in transcription initiation as well. Interacts with the cellular capping enzyme RNGTT to mediate co-transcriptional capping of viral mRNAs. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter"|function:"Alters the cellular functions through the binding to various nuclear and cytoplasmic factors, and cell surface receptors. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines (such as IL10) or cytokine receptors. Tat plays a role in T-cell and neurons apoptosis. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Tat seems to inhibit the HAT activity of HTATIP/Tip60 and TAF1, and consequently modify the expression of specific cellular genes. Mediates the activation of cyclin-dependent kinases and dysregulation of microtubule network. Extracellular Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Endocytosed Tat translocate into the nucleus, and induces apoptosis by oxidative stress associated with mitochondrial dysfunction and perturbation of calcium-regulated channels and glutamate receptor (NMDAR). Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Host extracellular matrix metalloproteinase MMP1 cleaves Tat and decreases Tat's mediated neurotoxicity. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. Binds to KDR/VEGFR-2. All these Tat-mediated effects enhance angiogenesis in Kaposi's sarcoma lesions"|comment:"Stoichiometry: 1.0"	comment:"Stoichiometry: 1.0"	figure legend:F1A|comment:homomint|comment:mint|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation	taxid:9606(human-hela)|taxid:9606(Homo sapiens epitheloid cervix carcinoma cells)	-	2006/05/10	2014/10/16	rogid:6IQLP0otFnozphvozdUWNnLP/cU11679	rogid:7XzMU6kWdFN0GiLox7RamD9pZeM9606	intact-crc:F3C4F429B7DD9A9C|rigid:UCYs/3+/gRf+csLTP48dewetxVc	false	flag tag:?-?(MINT-1898646)	-	1	1	psi-mi:"MI:0078"(nucleotide sequence identification)	psi-mi:"MI:0086"(polyclonal antibody western blot)
uniprotkb:P04326	uniprotkb:Q8TAQ2	intact:EBI-7333987|intact:MINT-138666	intact:EBI-357418|ensembl:ENSP00000267064|uniprotkb:Q92923|uniprotkb:Q96E12|uniprotkb:Q96GY4|intact:EBI-1759986|intact:EBI-1965079|uniprotkb:F8VTJ5|uniprotkb:Q59GV3	psi-mi:tat_hv112(display_long)|uniprotkb:tat(gene name)|psi-mi:tat(display_short)|uniprotkb:Transactivating regulatory protein(gene name synonym)	psi-mi:smrc2_human(display_long)|uniprotkb:SMARCC2(gene name)|psi-mi:SMARCC2(display_short)|uniprotkb:BAF170(gene name synonym)|uniprotkb:SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily C member 2(gene name synonym)|uniprotkb:SWI/SNF complex 170 kDa subunit(gene name synonym)|uniprotkb:BRG1-associated factor 170(gene name synonym)	psi-mi:"MI:0096"(pull down)	Tréand et al. (2006)	pubmed:16601680|imex:IM-11387|mint:MINT-5218478	taxid:11679(hv112)|taxid:11679("Human immunodeficiency virus type 1 group M subtype B (isolate PCV12)")	taxid:9606(human)|taxid:9606(Homo sapiens)	psi-mi:"MI:0407"(direct interaction)	psi-mi:"MI:0471"(MINT)	intact:EBI-8296764|mint:MINT-1898819|imex:IM-11387-7	-	-	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0496"(bait)	psi-mi:"MI:0498"(prey)	psi-mi:"MI:0326"(protein)	psi-mi:"MI:0326"(protein)	rcsb pdb:5SVZ|go:"GO:0001070"(RNA-binding transcription regulator activity)|go:"GO:0005576"(extracellular region)|go:"GO:0006351"(transcription, DNA-templated)|go:"GO:0010801"(negative regulation of peptidyl-threonine phosphorylation)|go:"GO:0019904"(protein domain specific binding)|go:"GO:0030332"(cyclin binding)|go:"GO:0030430"(host cell cytoplasm)|go:"GO:0032968"(positive regulation of transcription elongation from RNA polymerase II promoter)|go:"GO:0039502"(suppression by virus of host type I interferon-mediated signaling pathway)|go:"GO:0039525"(modulation by virus of host chromatin organization)|go:"GO:0039586"(modulation by virus of host PP1 activity)|go:"GO:0042805"(actinin binding)|go:"GO:0044196"(host cell nucleolus)|go:"GO:0046872"(metal ion binding)|go:"GO:0050434"(positive regulation of viral transcription)|go:"GO:1990970"(trans-activation response element binding)|interpro:IPR001831("Immunodeficiency virus transactivating regulatory protein (Tat)")|interpro:IPR036963|mint:MINT-1898820(identity)	ensembl:ENSG00000139613(gene)|ensembl:ENST00000267064(transcript)|go:"GO:0000785"(chromatin)|go:"GO:0003713"(transcription coactivator activity)|go:"GO:0005654"(nucleoplasm)|go:"GO:0006337"(nucleosome disassembly)|go:"GO:0006338"(chromatin remodeling)|go:"GO:0006357"(regulation of transcription by RNA polymerase II)|go:"GO:0007399"(nervous system development)|go:"GO:0016514"(SWI/SNF complex)|go:"GO:0032991"(protein-containing complex)|go:"GO:0042393"(histone binding)|go:"GO:0043044"|go:"GO:0045892"(negative regulation of transcription, DNA-templated)|go:"GO:0045893"(positive regulation of transcription, DNA-templated)|go:"GO:0071564"(npBAF complex)|go:"GO:0071565"(nBAF complex)|interpro:IPR000953(Chromo domain)|interpro:IPR001005(SANT, DNA-binding)|interpro:IPR007526(SWIRM)|interpro:IPR009057(Homeodomain-like)|interpro:IPR017884|interpro:IPR017930|interpro:IPR032448|interpro:IPR032450|interpro:IPR032451|interpro:IPR036388|interpro:IPR036420|interpro:IPR038044|mint:Q8TAQ2|rcsb pdb:6KAG|rcsb pdb:6LTH|rcsb pdb:6LTJ|reactome:R-HSA-3214858|reactome:R-HSA-8939243|refseq:NP_003066.2|refseq:NP_001123892.1|refseq:NP_620706.1|refseq:NP_001317217.1|dip:DIP-27611N|mint:MINT-1898827(identity)	-	comment:mint|function:"Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. In the absence of Tat, the RNA Pol II generates short or non-processive transcripts that terminate at approximately 60 bp from the initiation site. Tat associates with the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. This binding increases Tat's affinity for a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) and allows Tat/P-TEFb complex to bind cooperatively to TAR RNA. The CDK9 component of P-TEFb hyperphosphorylates the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B. In this purpose, it activates EIF2AK2/PKR which, in turns, may phosphorylate and target to degradation the inhibitor IkappaB-alpha which normally retains NF-kappa-B in the cytoplasm of unstimulated cells. Through its interaction with TBP, Tat may be involved in transcription initiation as well. Interacts with the cellular capping enzyme RNGTT to mediate co-transcriptional capping of viral mRNAs. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter"|function:"Alters the cellular functions through the binding to various nuclear and cytoplasmic factors, and cell surface receptors. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines (such as IL10) or cytokine receptors. Tat plays a role in T-cell and neurons apoptosis. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Tat seems to inhibit the HAT activity of HTATIP/Tip60 and TAF1, and consequently modify the expression of specific cellular genes. Mediates the activation of cyclin-dependent kinases and dysregulation of microtubule network. Extracellular Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Endocytosed Tat translocate into the nucleus, and induces apoptosis by oxidative stress associated with mitochondrial dysfunction and perturbation of calcium-regulated channels and glutamate receptor (NMDAR). Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Host extracellular matrix metalloproteinase MMP1 cleaves Tat and decreases Tat's mediated neurotoxicity. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. Binds to KDR/VEGFR-2. All these Tat-mediated effects enhance angiogenesis in Kaposi's sarcoma lesions"|comment:"Stoichiometry: 1.0"	comment:"Stoichiometry: 1.0"	figure legend:F2A|comment:homomint|comment:mint|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation	taxid:-1(in vitro)|taxid:-1(In vitro)	-	2006/05/10	2014/10/16	rogid:6IQLP0otFnozphvozdUWNnLP/cU11679	rogid:60gIB3J1YI/FzqVCzdoSg1Oj3ME9606	intact-crc:5C766EBCD1D592F2|rigid:tSNtOnJExNJ9l1q06zBCFXRYZWQ	false	glutathione s tranferase tag:?-?(MINT-1898825)	-	1	1	psi-mi:"MI:0078"(nucleotide sequence identification)	psi-mi:"MI:0086"(polyclonal antibody western blot)
uniprotkb:P04326	uniprotkb:Q92922	intact:EBI-7333987|intact:MINT-138666	intact:EBI-355653|uniprotkb:Q6P172|uniprotkb:Q8IWH2|uniprotkb:Q17RS0|ensembl:ENSP00000254480	psi-mi:tat_hv112(display_long)|uniprotkb:tat(gene name)|psi-mi:tat(display_short)|uniprotkb:Transactivating regulatory protein(gene name synonym)	psi-mi:smrc1_human(display_long)|uniprotkb:SMARCC1(gene name)|psi-mi:SMARCC1(display_short)|uniprotkb:BAF155(gene name synonym)|uniprotkb:SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily C member 1(gene name synonym)|uniprotkb:SWI/SNF complex 155 kDa subunit(gene name synonym)|uniprotkb:BRG1-associated factor 155(gene name synonym)	psi-mi:"MI:0096"(pull down)	Tréand et al. (2006)	pubmed:16601680|imex:IM-11387|mint:MINT-5218478	taxid:11679(hv112)|taxid:11679("Human immunodeficiency virus type 1 group M subtype B (isolate PCV12)")	taxid:9606(human)|taxid:9606(Homo sapiens)	psi-mi:"MI:0407"(direct interaction)	psi-mi:"MI:0471"(MINT)	intact:EBI-8296803|mint:MINT-1898834|imex:IM-11387-8	-	-	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0496"(bait)	psi-mi:"MI:0498"(prey)	psi-mi:"MI:0326"(protein)	psi-mi:"MI:0326"(protein)	rcsb pdb:5SVZ|go:"GO:0001070"(RNA-binding transcription regulator activity)|go:"GO:0005576"(extracellular region)|go:"GO:0006351"(transcription, DNA-templated)|go:"GO:0010801"(negative regulation of peptidyl-threonine phosphorylation)|go:"GO:0019904"(protein domain specific binding)|go:"GO:0030332"(cyclin binding)|go:"GO:0030430"(host cell cytoplasm)|go:"GO:0032968"(positive regulation of transcription elongation from RNA polymerase II promoter)|go:"GO:0039502"(suppression by virus of host type I interferon-mediated signaling pathway)|go:"GO:0039525"(modulation by virus of host chromatin organization)|go:"GO:0039586"(modulation by virus of host PP1 activity)|go:"GO:0042805"(actinin binding)|go:"GO:0044196"(host cell nucleolus)|go:"GO:0046872"(metal ion binding)|go:"GO:0050434"(positive regulation of viral transcription)|go:"GO:1990970"(trans-activation response element binding)|interpro:IPR001831("Immunodeficiency virus transactivating regulatory protein (Tat)")|interpro:IPR036963|mint:MINT-1898840(identity)	refseq:NP_003065.3|go:"GO:0045944"(positive regulation of transcription by RNA polymerase II)|go:"GO:0047485"(protein N-terminus binding)|go:"GO:0071564"(npBAF complex)|go:"GO:0071565"(nBAF complex)|interpro:IPR000953(Chromo domain)|interpro:IPR001005(SANT, DNA-binding)|interpro:IPR007526(SWIRM)|interpro:IPR009057(Homeodomain-like)|interpro:IPR017884|interpro:IPR017930|interpro:IPR030087|interpro:IPR032448|interpro:IPR032450|interpro:IPR032451|interpro:IPR036388|interpro:IPR036420|mint:Q92922|rcsb pdb:2YUS|rcsb pdb:5GJK|rcsb pdb:6KZ7|rcsb pdb:6YXO|rcsb pdb:6YXP|reactome:R-HSA-3214858|reactome:R-HSA-8939243|go:"GO:0045893"(positive regulation of transcription, DNA-templated)|ensembl:ENSG00000173473(gene)|ensembl:ENST00000254480(transcript)|go:"GO:0000785"(chromatin)|go:"GO:0001741"(XY body)|go:"GO:0003682"(chromatin binding)|go:"GO:0003713"(transcription coactivator activity)|go:"GO:0005634"(nucleus)|go:"GO:0005654"(nucleoplasm)|go:"GO:0005737"(cytoplasm)|go:"GO:0006337"(nucleosome disassembly)|go:"GO:0006338"(chromatin remodeling)|go:"GO:0006357"(regulation of transcription by RNA polymerase II)|go:"GO:0007399"(nervous system development)|go:"GO:0008286"(insulin receptor signaling pathway)|go:"GO:0009887"(animal organ morphogenesis)|go:"GO:0016514"(SWI/SNF complex)|go:"GO:0030850"(prostate gland development)|go:"GO:0032435"(negative regulation of proteasomal ubiquitin-dependent protein catabolic process)|go:"GO:0032991"(protein-containing complex)|go:"GO:0042393"(histone binding)|go:"GO:0043044"|ensembl:ENSP00000254480|dip:DIP-27545N|dip:DIP-33044N|mint:MINT-1898835(identity)	-	comment:mint|function:"Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. In the absence of Tat, the RNA Pol II generates short or non-processive transcripts that terminate at approximately 60 bp from the initiation site. Tat associates with the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. This binding increases Tat's affinity for a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) and allows Tat/P-TEFb complex to bind cooperatively to TAR RNA. The CDK9 component of P-TEFb hyperphosphorylates the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B. In this purpose, it activates EIF2AK2/PKR which, in turns, may phosphorylate and target to degradation the inhibitor IkappaB-alpha which normally retains NF-kappa-B in the cytoplasm of unstimulated cells. Through its interaction with TBP, Tat may be involved in transcription initiation as well. Interacts with the cellular capping enzyme RNGTT to mediate co-transcriptional capping of viral mRNAs. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter"|function:"Alters the cellular functions through the binding to various nuclear and cytoplasmic factors, and cell surface receptors. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines (such as IL10) or cytokine receptors. Tat plays a role in T-cell and neurons apoptosis. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Tat seems to inhibit the HAT activity of HTATIP/Tip60 and TAF1, and consequently modify the expression of specific cellular genes. Mediates the activation of cyclin-dependent kinases and dysregulation of microtubule network. Extracellular Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Endocytosed Tat translocate into the nucleus, and induces apoptosis by oxidative stress associated with mitochondrial dysfunction and perturbation of calcium-regulated channels and glutamate receptor (NMDAR). Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Host extracellular matrix metalloproteinase MMP1 cleaves Tat and decreases Tat's mediated neurotoxicity. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. Binds to KDR/VEGFR-2. All these Tat-mediated effects enhance angiogenesis in Kaposi's sarcoma lesions"|comment:"Stoichiometry: 1.0"	comment:"Stoichiometry: 1.0"	figure legend:F2A|comment:homomint|comment:mint|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation	taxid:-1(in vitro)|taxid:-1(In vitro)	-	2006/05/10	2014/10/16	rogid:6IQLP0otFnozphvozdUWNnLP/cU11679	rogid:Uv0bjPkUICLtOXJcETUXDTLIQhY9606	intact-crc:C25951A41E71CEFA|rigid:R7H2biJGSdkKlMHSS9LCtAEfmas	false	glutathione s tranferase tag:?-?(MINT-1898841)	-	1	1	psi-mi:"MI:0078"(nucleotide sequence identification)	psi-mi:"MI:0086"(polyclonal antibody western blot)
uniprotkb:P04326	uniprotkb:Q12824	intact:EBI-7333987|intact:MINT-138666	intact:EBI-358419|uniprotkb:O75784|uniprotkb:O95474|uniprotkb:Q38GA1|uniprotkb:Q76N08|uniprotkb:Q9UBH2|ensembl:ENSP00000479330|ensembl:ENSP00000494049|uniprotkb:Q17S11	psi-mi:tat_hv112(display_long)|uniprotkb:tat(gene name)|psi-mi:tat(display_short)|uniprotkb:Transactivating regulatory protein(gene name synonym)	psi-mi:snf5_human(display_long)|uniprotkb:SMARCB1(gene name)|psi-mi:SMARCB1(display_short)|uniprotkb:INI1(gene name synonym)|uniprotkb:SNF5L1(gene name synonym)|uniprotkb:Integrase interactor 1 protein(gene name synonym)|uniprotkb:BAF47(gene name synonym)|uniprotkb:SNF5 homolog(gene name synonym)|uniprotkb:BRG1-associated factor 47(gene name synonym)	psi-mi:"MI:0096"(pull down)	Tréand et al. (2006)	pubmed:16601680|imex:IM-11387|mint:MINT-5218478	taxid:11679(hv112)|taxid:11679("Human immunodeficiency virus type 1 group M subtype B (isolate PCV12)")	taxid:9606(human)|taxid:9606(Homo sapiens)	psi-mi:"MI:0407"(direct interaction)	psi-mi:"MI:0471"(MINT)	intact:EBI-8296746|mint:MINT-1898795|imex:IM-11387-6	-	-	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0496"(bait)	psi-mi:"MI:0498"(prey)	psi-mi:"MI:0326"(protein)	psi-mi:"MI:0326"(protein)	rcsb pdb:5SVZ|go:"GO:0001070"(RNA-binding transcription regulator activity)|go:"GO:0005576"(extracellular region)|go:"GO:0006351"(transcription, DNA-templated)|go:"GO:0010801"(negative regulation of peptidyl-threonine phosphorylation)|go:"GO:0019904"(protein domain specific binding)|go:"GO:0030332"(cyclin binding)|go:"GO:0030430"(host cell cytoplasm)|go:"GO:0032968"(positive regulation of transcription elongation from RNA polymerase II promoter)|go:"GO:0039502"(suppression by virus of host type I interferon-mediated signaling pathway)|go:"GO:0039525"(modulation by virus of host chromatin organization)|go:"GO:0039586"(modulation by virus of host PP1 activity)|go:"GO:0042805"(actinin binding)|go:"GO:0044196"(host cell nucleolus)|go:"GO:0046872"(metal ion binding)|go:"GO:0050434"(positive regulation of viral transcription)|go:"GO:1990970"(trans-activation response element binding)|interpro:IPR001831("Immunodeficiency virus transactivating regulatory protein (Tat)")|interpro:IPR036963|mint:MINT-1898796(identity)	mint:Q12824|go:"GO:0006357"(regulation of transcription by RNA polymerase II)|rcsb pdb:5AJ1|rcsb pdb:5GJK|rcsb pdb:5L7A|rcsb pdb:5L7B|go:"GO:0007049"(cell cycle)|rcsb pdb:6AX5|go:"GO:0007399"(nervous system development)|rcsb pdb:6KAG|rcsb pdb:6KZ7|rcsb pdb:6LTH|rcsb pdb:6LTJ|rcsb pdb:6UCH|reactome:R-HSA-3214858|go:"GO:0008285"(negative regulation of cell population proliferation)|reactome:R-HSA-8939243|go:"GO:0015074"(DNA integration)|go:"GO:0016514"(SWI/SNF complex)|go:"GO:0030154"(cell differentiation)|go:"GO:0030957"(Tat protein binding)|go:"GO:0032991"(protein-containing complex)|go:"GO:0035060"(brahma complex)|go:"GO:0039692"(single stranded viral RNA replication via double stranded DNA intermediate)|go:"GO:0043044"|go:"GO:0043231"(intracellular membrane-bounded organelle)|go:"GO:0043923"(positive regulation by host of viral transcription)|go:"GO:0045944"(positive regulation of transcription by RNA polymerase II)|go:"GO:0051091"(positive regulation of DNA-binding transcription factor activity)|go:"GO:0071564"(npBAF complex)|go:"GO:0071565"(nBAF complex)|go:"GO:0090240"(positive regulation of histone H4 acetylation)|go:"GO:1900110"(negative regulation of histone H3-K9 dimethylation)|go:"GO:1900113"(negative regulation of histone H3-K9 trimethylation)|go:"GO:1901838"(positive regulation of transcription of nucleolar large rRNA by RNA polymerase I)|go:"GO:1902661"(positive regulation of glucose mediated signaling pathway)|go:"GO:2000617"(positive regulation of histone H3-K9 acetylation)|interpro:IPR006939(SNF5/SMARCB1/INI1)|interpro:IPR017393(SWI/SNF chromatin-remodeling complex, component hSNF5/Ini1)|go:"GO:0005730"(nucleolus)|go:"GO:0006337"(nucleosome disassembly)|go:"GO:0006338"(chromatin remodeling)|refseq:NP_001007469.1|refseq:NP_003064.2|ensembl:ENSG00000099956(gene)|ensembl:ENSG00000275837(gene)|ensembl:ENST00000618915(transcript)|ensembl:ENST00000644036(transcript)|go:"GO:0000228"(nuclear chromosome)|go:"GO:0000785"(chromatin)|go:"GO:0001188"(RNA polymerase I preinitiation complex assembly)|go:"GO:0001650"(fibrillar center)|go:"GO:0001741"(XY body)|go:"GO:0001835"(blastocyst hatching)|go:"GO:0002039"(p53 binding)|go:"GO:0003677"(DNA binding)|go:"GO:0003712"(transcription coregulator activity)|go:"GO:0003713"(transcription coactivator activity)|go:"GO:0005634"(nucleus)|go:"GO:0005654"(nucleoplasm)|dip:DIP-27550N|mint:MINT-1898804(identity)	-	comment:mint|function:"Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. In the absence of Tat, the RNA Pol II generates short or non-processive transcripts that terminate at approximately 60 bp from the initiation site. Tat associates with the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. This binding increases Tat's affinity for a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) and allows Tat/P-TEFb complex to bind cooperatively to TAR RNA. The CDK9 component of P-TEFb hyperphosphorylates the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B. In this purpose, it activates EIF2AK2/PKR which, in turns, may phosphorylate and target to degradation the inhibitor IkappaB-alpha which normally retains NF-kappa-B in the cytoplasm of unstimulated cells. Through its interaction with TBP, Tat may be involved in transcription initiation as well. Interacts with the cellular capping enzyme RNGTT to mediate co-transcriptional capping of viral mRNAs. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter"|function:"Alters the cellular functions through the binding to various nuclear and cytoplasmic factors, and cell surface receptors. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines (such as IL10) or cytokine receptors. Tat plays a role in T-cell and neurons apoptosis. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Tat seems to inhibit the HAT activity of HTATIP/Tip60 and TAF1, and consequently modify the expression of specific cellular genes. Mediates the activation of cyclin-dependent kinases and dysregulation of microtubule network. Extracellular Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Endocytosed Tat translocate into the nucleus, and induces apoptosis by oxidative stress associated with mitochondrial dysfunction and perturbation of calcium-regulated channels and glutamate receptor (NMDAR). Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Host extracellular matrix metalloproteinase MMP1 cleaves Tat and decreases Tat's mediated neurotoxicity. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. Binds to KDR/VEGFR-2. All these Tat-mediated effects enhance angiogenesis in Kaposi's sarcoma lesions"|comment:"Stoichiometry: 1.0"	comment:"Stoichiometry: 1.0"	figure legend:F2A|comment:homomint|comment:mint|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation	taxid:-1(in vitro)|taxid:-1(In vitro)	-	2006/05/10	2014/10/16	rogid:6IQLP0otFnozphvozdUWNnLP/cU11679	rogid:GjUm1RYfDvtNuSNGI6iCWpl8L+I9606	intact-crc:0D2AAC37B4E36F85|rigid:gkAaX2uNIC8v6wu//AkF/zh1LYI	false	glutathione s tranferase tag:?-?(MINT-1898802)	-	1	1	psi-mi:"MI:0078"(nucleotide sequence identification)	psi-mi:"MI:0086"(polyclonal antibody western blot)
uniprotkb:P51531	uniprotkb:P04326	intact:EBI-679562|uniprotkb:B1ALG3|uniprotkb:B1ALG4|uniprotkb:D3DRH4|uniprotkb:D3DRH5|ensembl:ENSP00000265773|ensembl:ENSP00000371638	intact:EBI-7333987|intact:MINT-138666	psi-mi:smca2_human(display_long)|uniprotkb:ATP-dependent helicase SMARCA2(gene name synonym)|uniprotkb:SNF2-alpha(gene name synonym)|uniprotkb:SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2(gene name synonym)|uniprotkb:SMARCA2(gene name)|psi-mi:SMARCA2(display_short)|uniprotkb:BRM(gene name synonym)|uniprotkb:SNF2A(gene name synonym)|uniprotkb:SNF2L2(gene name synonym)|uniprotkb:BAF190B(gene name synonym)|uniprotkb:Protein brahma homolog(gene name synonym)|uniprotkb:BRG1-associated factor 190B(gene name synonym)	psi-mi:tat_hv112(display_long)|uniprotkb:tat(gene name)|psi-mi:tat(display_short)|uniprotkb:Transactivating regulatory protein(gene name synonym)	psi-mi:"MI:0096"(pull down)	Tréand et al. (2006)	pubmed:16601680|imex:IM-11387|mint:MINT-5218478	taxid:9606(human)|taxid:9606(Homo sapiens)	taxid:11679(hv112)|taxid:11679("Human immunodeficiency virus type 1 group M subtype B (isolate PCV12)")	psi-mi:"MI:0915"(physical association)	psi-mi:"MI:0471"(MINT)	intact:EBI-8296917|mint:MINT-1898872|imex:IM-11387-10	-	-	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0498"(prey)	psi-mi:"MI:0496"(bait)	psi-mi:"MI:0326"(protein)	psi-mi:"MI:0326"(protein)	refseq:NP_003061.3|refseq:NP_620614.2|refseq:NP_001276325.1|refseq:NP_001276326.1|dip:DIP-29005N|ensembl:ENSG00000080503(gene)|ensembl:ENST00000349721(transcript)|ensembl:ENST00000382203(transcript)|go:"GO:0000122"(negative regulation of transcription by RNA polymerase II)|go:"GO:0000785"(chromatin)|go:"GO:0000976"(transcription cis-regulatory region binding)|go:"GO:0003677"(DNA binding)|go:"GO:0003682"(chromatin binding)|go:"GO:0003713"(transcription coactivator activity)|go:"GO:0004386"(helicase activity)|go:"GO:0005524"(ATP binding)|go:"GO:0005634"(nucleus)|go:"GO:0005654"(nucleoplasm)|go:"GO:0006338"(chromatin remodeling)|go:"GO:0006355"(regulation of transcription, DNA-templated)|go:"GO:0006357"(regulation of transcription by RNA polymerase II)|go:"GO:0007286"(spermatid development)|go:"GO:0007399"(nervous system development)|go:"GO:0008094"(ATP-dependent activity, acting on DNA)|go:"GO:0008285"(negative regulation of cell population proliferation)|go:"GO:0016514"(SWI/SNF complex)|go:"GO:0016787"(hydrolase activity)|go:"GO:0030308"(negative regulation of cell growth)|go:"GO:0042393"(histone binding)|go:"GO:0043044"|go:"GO:0043231"(intracellular membrane-bounded organelle)|go:"GO:0045111"(intermediate filament cytoskeleton)|go:"GO:0045892"(negative regulation of transcription, DNA-templated)|go:"GO:0045893"(positive regulation of transcription, DNA-templated)|go:"GO:0045944"(positive regulation of transcription by RNA polymerase II)|go:"GO:0070615"|go:"GO:0071564"(npBAF complex)|go:"GO:0071565"(nBAF complex)|interpro:IPR000330(SNF2-related)|interpro:IPR001487(Bromodomain)|interpro:IPR001650(DNA/RNA helicase, C-terminal)|interpro:IPR006576(BRK)|interpro:IPR014001(DEAD-like helicase, N-terminal)|interpro:IPR014012(Helicase/SANT-associated, DNA binding)|interpro:IPR014978(QLQ)|interpro:IPR018359|interpro:IPR027417|interpro:IPR029295|interpro:IPR030088|interpro:IPR036427|interpro:IPR037259|interpro:IPR038718|mint:P51531|rcsb pdb:2DAT|rcsb pdb:4QY4|rcsb pdb:5DKC|rcsb pdb:5DKH|rcsb pdb:6EG2|rcsb pdb:6EG3|rcsb pdb:6HAX|rcsb pdb:6HAY|rcsb pdb:6HAZ|reactome:R-HSA-3214858|reactome:R-HSA-8939243|mint:MINT-1898882(identity)	rcsb pdb:5SVZ|go:"GO:0001070"(RNA-binding transcription regulator activity)|go:"GO:0005576"(extracellular region)|go:"GO:0006351"(transcription, DNA-templated)|go:"GO:0010801"(negative regulation of peptidyl-threonine phosphorylation)|go:"GO:0019904"(protein domain specific binding)|go:"GO:0030332"(cyclin binding)|go:"GO:0030430"(host cell cytoplasm)|go:"GO:0032968"(positive regulation of transcription elongation from RNA polymerase II promoter)|go:"GO:0039502"(suppression by virus of host type I interferon-mediated signaling pathway)|go:"GO:0039525"(modulation by virus of host chromatin organization)|go:"GO:0039586"(modulation by virus of host PP1 activity)|go:"GO:0042805"(actinin binding)|go:"GO:0044196"(host cell nucleolus)|go:"GO:0046872"(metal ion binding)|go:"GO:0050434"(positive regulation of viral transcription)|go:"GO:1990970"(trans-activation response element binding)|interpro:IPR001831("Immunodeficiency virus transactivating regulatory protein (Tat)")|interpro:IPR036963|mint:MINT-1898873(identity)	-	comment:"Stoichiometry: 1.0"	comment:mint|function:"Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. In the absence of Tat, the RNA Pol II generates short or non-processive transcripts that terminate at approximately 60 bp from the initiation site. Tat associates with the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. This binding increases Tat's affinity for a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) and allows Tat/P-TEFb complex to bind cooperatively to TAR RNA. The CDK9 component of P-TEFb hyperphosphorylates the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B. In this purpose, it activates EIF2AK2/PKR which, in turns, may phosphorylate and target to degradation the inhibitor IkappaB-alpha which normally retains NF-kappa-B in the cytoplasm of unstimulated cells. Through its interaction with TBP, Tat may be involved in transcription initiation as well. Interacts with the cellular capping enzyme RNGTT to mediate co-transcriptional capping of viral mRNAs. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter"|function:"Alters the cellular functions through the binding to various nuclear and cytoplasmic factors, and cell surface receptors. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines (such as IL10) or cytokine receptors. Tat plays a role in T-cell and neurons apoptosis. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Tat seems to inhibit the HAT activity of HTATIP/Tip60 and TAF1, and consequently modify the expression of specific cellular genes. Mediates the activation of cyclin-dependent kinases and dysregulation of microtubule network. Extracellular Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Endocytosed Tat translocate into the nucleus, and induces apoptosis by oxidative stress associated with mitochondrial dysfunction and perturbation of calcium-regulated channels and glutamate receptor (NMDAR). Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Host extracellular matrix metalloproteinase MMP1 cleaves Tat and decreases Tat's mediated neurotoxicity. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. Binds to KDR/VEGFR-2. All these Tat-mediated effects enhance angiogenesis in Kaposi's sarcoma lesions"|comment:"Stoichiometry: 1.0"	figure legend:F3B|comment:homomint|comment:mint|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation	taxid:-1(in vitro)|taxid:-1(In vitro)	-	2006/05/10	2014/10/16	rogid:DmQot4h4SmtqmUGBgF5ictTah289606	rogid:6IQLP0otFnozphvozdUWNnLP/cU11679	intact-crc:4D79748F039002E2|rigid:My0sWeTtD+phXNKqopXMDfgxTJg	false	binding-associated region:1-686(MINT-2778409)	glutathione s tranferase tag:?-?(MINT-1898880)|binding-associated region:1-86(MINT-2778405)	1	1	psi-mi:"MI:0078"(nucleotide sequence identification)	psi-mi:"MI:0078"(nucleotide sequence identification)
uniprotkb:P51531	uniprotkb:P04326	intact:EBI-679562|uniprotkb:B1ALG3|uniprotkb:B1ALG4|uniprotkb:D3DRH4|uniprotkb:D3DRH5|ensembl:ENSP00000265773|ensembl:ENSP00000371638	intact:EBI-7333987|intact:MINT-138666	psi-mi:smca2_human(display_long)|uniprotkb:ATP-dependent helicase SMARCA2(gene name synonym)|uniprotkb:SNF2-alpha(gene name synonym)|uniprotkb:SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2(gene name synonym)|uniprotkb:SMARCA2(gene name)|psi-mi:SMARCA2(display_short)|uniprotkb:BRM(gene name synonym)|uniprotkb:SNF2A(gene name synonym)|uniprotkb:SNF2L2(gene name synonym)|uniprotkb:BAF190B(gene name synonym)|uniprotkb:Protein brahma homolog(gene name synonym)|uniprotkb:BRG1-associated factor 190B(gene name synonym)	psi-mi:tat_hv112(display_long)|uniprotkb:tat(gene name)|psi-mi:tat(display_short)|uniprotkb:Transactivating regulatory protein(gene name synonym)	psi-mi:"MI:0096"(pull down)	Tréand et al. (2006)	pubmed:16601680|imex:IM-11387|mint:MINT-5218478	taxid:9606(human)|taxid:9606(Homo sapiens)	taxid:11679(hv112)|taxid:11679("Human immunodeficiency virus type 1 group M subtype B (isolate PCV12)")	psi-mi:"MI:0407"(direct interaction)	psi-mi:"MI:0471"(MINT)	intact:EBI-8296883|mint:MINT-1898849|imex:IM-11387-9	-	-	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0498"(prey)	psi-mi:"MI:0496"(bait)	psi-mi:"MI:0326"(protein)	psi-mi:"MI:0326"(protein)	refseq:NP_003061.3|refseq:NP_620614.2|refseq:NP_001276325.1|refseq:NP_001276326.1|dip:DIP-29005N|ensembl:ENSG00000080503(gene)|ensembl:ENST00000349721(transcript)|ensembl:ENST00000382203(transcript)|go:"GO:0000122"(negative regulation of transcription by RNA polymerase II)|go:"GO:0000785"(chromatin)|go:"GO:0000976"(transcription cis-regulatory region binding)|go:"GO:0003677"(DNA binding)|go:"GO:0003682"(chromatin binding)|go:"GO:0003713"(transcription coactivator activity)|go:"GO:0004386"(helicase activity)|go:"GO:0005524"(ATP binding)|go:"GO:0005634"(nucleus)|go:"GO:0005654"(nucleoplasm)|go:"GO:0006338"(chromatin remodeling)|go:"GO:0006355"(regulation of transcription, DNA-templated)|go:"GO:0006357"(regulation of transcription by RNA polymerase II)|go:"GO:0007286"(spermatid development)|go:"GO:0007399"(nervous system development)|go:"GO:0008094"(ATP-dependent activity, acting on DNA)|go:"GO:0008285"(negative regulation of cell population proliferation)|go:"GO:0016514"(SWI/SNF complex)|go:"GO:0016787"(hydrolase activity)|go:"GO:0030308"(negative regulation of cell growth)|go:"GO:0042393"(histone binding)|go:"GO:0043044"|go:"GO:0043231"(intracellular membrane-bounded organelle)|go:"GO:0045111"(intermediate filament cytoskeleton)|go:"GO:0045892"(negative regulation of transcription, DNA-templated)|go:"GO:0045893"(positive regulation of transcription, DNA-templated)|go:"GO:0045944"(positive regulation of transcription by RNA polymerase II)|go:"GO:0070615"|go:"GO:0071564"(npBAF complex)|go:"GO:0071565"(nBAF complex)|interpro:IPR000330(SNF2-related)|interpro:IPR001487(Bromodomain)|interpro:IPR001650(DNA/RNA helicase, C-terminal)|interpro:IPR006576(BRK)|interpro:IPR014001(DEAD-like helicase, N-terminal)|interpro:IPR014012(Helicase/SANT-associated, DNA binding)|interpro:IPR014978(QLQ)|interpro:IPR018359|interpro:IPR027417|interpro:IPR029295|interpro:IPR030088|interpro:IPR036427|interpro:IPR037259|interpro:IPR038718|mint:P51531|rcsb pdb:2DAT|rcsb pdb:4QY4|rcsb pdb:5DKC|rcsb pdb:5DKH|rcsb pdb:6EG2|rcsb pdb:6EG3|rcsb pdb:6HAX|rcsb pdb:6HAY|rcsb pdb:6HAZ|reactome:R-HSA-3214858|reactome:R-HSA-8939243|mint:MINT-1898850(identity)	rcsb pdb:5SVZ|go:"GO:0001070"(RNA-binding transcription regulator activity)|go:"GO:0005576"(extracellular region)|go:"GO:0006351"(transcription, DNA-templated)|go:"GO:0010801"(negative regulation of peptidyl-threonine phosphorylation)|go:"GO:0019904"(protein domain specific binding)|go:"GO:0030332"(cyclin binding)|go:"GO:0030430"(host cell cytoplasm)|go:"GO:0032968"(positive regulation of transcription elongation from RNA polymerase II promoter)|go:"GO:0039502"(suppression by virus of host type I interferon-mediated signaling pathway)|go:"GO:0039525"(modulation by virus of host chromatin organization)|go:"GO:0039586"(modulation by virus of host PP1 activity)|go:"GO:0042805"(actinin binding)|go:"GO:0044196"(host cell nucleolus)|go:"GO:0046872"(metal ion binding)|go:"GO:0050434"(positive regulation of viral transcription)|go:"GO:1990970"(trans-activation response element binding)|interpro:IPR001831("Immunodeficiency virus transactivating regulatory protein (Tat)")|interpro:IPR036963|mint:MINT-1898855(identity)	-	comment:"Stoichiometry: 1.0"	comment:mint|function:"Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. In the absence of Tat, the RNA Pol II generates short or non-processive transcripts that terminate at approximately 60 bp from the initiation site. Tat associates with the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. This binding increases Tat's affinity for a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) and allows Tat/P-TEFb complex to bind cooperatively to TAR RNA. The CDK9 component of P-TEFb hyperphosphorylates the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B. In this purpose, it activates EIF2AK2/PKR which, in turns, may phosphorylate and target to degradation the inhibitor IkappaB-alpha which normally retains NF-kappa-B in the cytoplasm of unstimulated cells. Through its interaction with TBP, Tat may be involved in transcription initiation as well. Interacts with the cellular capping enzyme RNGTT to mediate co-transcriptional capping of viral mRNAs. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter"|function:"Alters the cellular functions through the binding to various nuclear and cytoplasmic factors, and cell surface receptors. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines (such as IL10) or cytokine receptors. Tat plays a role in T-cell and neurons apoptosis. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Tat seems to inhibit the HAT activity of HTATIP/Tip60 and TAF1, and consequently modify the expression of specific cellular genes. Mediates the activation of cyclin-dependent kinases and dysregulation of microtubule network. Extracellular Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Endocytosed Tat translocate into the nucleus, and induces apoptosis by oxidative stress associated with mitochondrial dysfunction and perturbation of calcium-regulated channels and glutamate receptor (NMDAR). Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Host extracellular matrix metalloproteinase MMP1 cleaves Tat and decreases Tat's mediated neurotoxicity. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. Binds to KDR/VEGFR-2. All these Tat-mediated effects enhance angiogenesis in Kaposi's sarcoma lesions"|comment:"Stoichiometry: 1.0"	figure legend:F2A|figure legend:F2C|comment:homomint|comment:mint|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation	taxid:-1(in vitro)|taxid:-1(In vitro)	-	2006/05/10	2014/10/16	rogid:DmQot4h4SmtqmUGBgF5ictTah289606	rogid:6IQLP0otFnozphvozdUWNnLP/cU11679	intact-crc:008F77812D0B7D90|rigid:My0sWeTtD+phXNKqopXMDfgxTJg	false	-	glutathione s tranferase tag:?-?(MINT-1898860)|binding-associated region:40-72(MINT-1898864)	1	1	psi-mi:"MI:0086"(polyclonal antibody western blot)	psi-mi:"MI:0078"(nucleotide sequence identification)
uniprotkb:P51531	uniprotkb:P04326	intact:EBI-679562|uniprotkb:B1ALG3|uniprotkb:B1ALG4|uniprotkb:D3DRH4|uniprotkb:D3DRH5|ensembl:ENSP00000265773|ensembl:ENSP00000371638	intact:EBI-7333987|intact:MINT-138666	psi-mi:smca2_human(display_long)|uniprotkb:ATP-dependent helicase SMARCA2(gene name synonym)|uniprotkb:SNF2-alpha(gene name synonym)|uniprotkb:SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2(gene name synonym)|uniprotkb:SMARCA2(gene name)|psi-mi:SMARCA2(display_short)|uniprotkb:BRM(gene name synonym)|uniprotkb:SNF2A(gene name synonym)|uniprotkb:SNF2L2(gene name synonym)|uniprotkb:BAF190B(gene name synonym)|uniprotkb:Protein brahma homolog(gene name synonym)|uniprotkb:BRG1-associated factor 190B(gene name synonym)	psi-mi:tat_hv112(display_long)|uniprotkb:tat(gene name)|psi-mi:tat(display_short)|uniprotkb:Transactivating regulatory protein(gene name synonym)	psi-mi:"MI:0096"(pull down)	Tréand et al. (2006)	pubmed:16601680|imex:IM-11387|mint:MINT-5218478	taxid:9606(human)|taxid:9606(Homo sapiens)	taxid:11679(hv112)|taxid:11679("Human immunodeficiency virus type 1 group M subtype B (isolate PCV12)")	psi-mi:"MI:0915"(physical association)	psi-mi:"MI:0471"(MINT)	intact:EBI-8296993|mint:MINT-1898955|imex:IM-11387-5	-	-	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0496"(bait)	psi-mi:"MI:0498"(prey)	psi-mi:"MI:0326"(protein)	psi-mi:"MI:0326"(protein)	refseq:NP_003061.3|refseq:NP_620614.2|refseq:NP_001276325.1|refseq:NP_001276326.1|dip:DIP-29005N|ensembl:ENSG00000080503(gene)|ensembl:ENST00000349721(transcript)|ensembl:ENST00000382203(transcript)|go:"GO:0000122"(negative regulation of transcription by RNA polymerase II)|go:"GO:0000785"(chromatin)|go:"GO:0000976"(transcription cis-regulatory region binding)|go:"GO:0003677"(DNA binding)|go:"GO:0003682"(chromatin binding)|go:"GO:0003713"(transcription coactivator activity)|go:"GO:0004386"(helicase activity)|go:"GO:0005524"(ATP binding)|go:"GO:0005634"(nucleus)|go:"GO:0005654"(nucleoplasm)|go:"GO:0006338"(chromatin remodeling)|go:"GO:0006355"(regulation of transcription, DNA-templated)|go:"GO:0006357"(regulation of transcription by RNA polymerase II)|go:"GO:0007286"(spermatid development)|go:"GO:0007399"(nervous system development)|go:"GO:0008094"(ATP-dependent activity, acting on DNA)|go:"GO:0008285"(negative regulation of cell population proliferation)|go:"GO:0016514"(SWI/SNF complex)|go:"GO:0016787"(hydrolase activity)|go:"GO:0030308"(negative regulation of cell growth)|go:"GO:0042393"(histone binding)|go:"GO:0043044"|go:"GO:0043231"(intracellular membrane-bounded organelle)|go:"GO:0045111"(intermediate filament cytoskeleton)|go:"GO:0045892"(negative regulation of transcription, DNA-templated)|go:"GO:0045893"(positive regulation of transcription, DNA-templated)|go:"GO:0045944"(positive regulation of transcription by RNA polymerase II)|go:"GO:0070615"|go:"GO:0071564"(npBAF complex)|go:"GO:0071565"(nBAF complex)|interpro:IPR000330(SNF2-related)|interpro:IPR001487(Bromodomain)|interpro:IPR001650(DNA/RNA helicase, C-terminal)|interpro:IPR006576(BRK)|interpro:IPR014001(DEAD-like helicase, N-terminal)|interpro:IPR014012(Helicase/SANT-associated, DNA binding)|interpro:IPR014978(QLQ)|interpro:IPR018359|interpro:IPR027417|interpro:IPR029295|interpro:IPR030088|interpro:IPR036427|interpro:IPR037259|interpro:IPR038718|mint:P51531|rcsb pdb:2DAT|rcsb pdb:4QY4|rcsb pdb:5DKC|rcsb pdb:5DKH|rcsb pdb:6EG2|rcsb pdb:6EG3|rcsb pdb:6HAX|rcsb pdb:6HAY|rcsb pdb:6HAZ|reactome:R-HSA-3214858|reactome:R-HSA-8939243|mint:MINT-1898964(identity)	rcsb pdb:5SVZ|go:"GO:0001070"(RNA-binding transcription regulator activity)|go:"GO:0005576"(extracellular region)|go:"GO:0006351"(transcription, DNA-templated)|go:"GO:0010801"(negative regulation of peptidyl-threonine phosphorylation)|go:"GO:0019904"(protein domain specific binding)|go:"GO:0030332"(cyclin binding)|go:"GO:0030430"(host cell cytoplasm)|go:"GO:0032968"(positive regulation of transcription elongation from RNA polymerase II promoter)|go:"GO:0039502"(suppression by virus of host type I interferon-mediated signaling pathway)|go:"GO:0039525"(modulation by virus of host chromatin organization)|go:"GO:0039586"(modulation by virus of host PP1 activity)|go:"GO:0042805"(actinin binding)|go:"GO:0044196"(host cell nucleolus)|go:"GO:0046872"(metal ion binding)|go:"GO:0050434"(positive regulation of viral transcription)|go:"GO:1990970"(trans-activation response element binding)|interpro:IPR001831("Immunodeficiency virus transactivating regulatory protein (Tat)")|interpro:IPR036963|mint:MINT-1898956(identity)	-	comment:"Stoichiometry: 1.0"	comment:mint|function:"Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. In the absence of Tat, the RNA Pol II generates short or non-processive transcripts that terminate at approximately 60 bp from the initiation site. Tat associates with the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. This binding increases Tat's affinity for a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) and allows Tat/P-TEFb complex to bind cooperatively to TAR RNA. The CDK9 component of P-TEFb hyperphosphorylates the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B. In this purpose, it activates EIF2AK2/PKR which, in turns, may phosphorylate and target to degradation the inhibitor IkappaB-alpha which normally retains NF-kappa-B in the cytoplasm of unstimulated cells. Through its interaction with TBP, Tat may be involved in transcription initiation as well. Interacts with the cellular capping enzyme RNGTT to mediate co-transcriptional capping of viral mRNAs. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter"|function:"Alters the cellular functions through the binding to various nuclear and cytoplasmic factors, and cell surface receptors. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines (such as IL10) or cytokine receptors. Tat plays a role in T-cell and neurons apoptosis. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Tat seems to inhibit the HAT activity of HTATIP/Tip60 and TAF1, and consequently modify the expression of specific cellular genes. Mediates the activation of cyclin-dependent kinases and dysregulation of microtubule network. Extracellular Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Endocytosed Tat translocate into the nucleus, and induces apoptosis by oxidative stress associated with mitochondrial dysfunction and perturbation of calcium-regulated channels and glutamate receptor (NMDAR). Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Host extracellular matrix metalloproteinase MMP1 cleaves Tat and decreases Tat's mediated neurotoxicity. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. Binds to KDR/VEGFR-2. All these Tat-mediated effects enhance angiogenesis in Kaposi's sarcoma lesions"|comment:"Stoichiometry: 1.0"	figure legend:F3D|comment:homomint|comment:mint|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation	taxid:-1(in vitro)|taxid:-1(In vitro)	-	2006/05/10	2014/10/16	rogid:DmQot4h4SmtqmUGBgF5ictTah289606	rogid:6IQLP0otFnozphvozdUWNnLP/cU11679	intact-crc:CC6AA5B2AD8B6EF6|rigid:My0sWeTtD+phXNKqopXMDfgxTJg	false	binding-associated region:400-570(MINT-1898965)|glutathione s tranferase tag:?-?(MINT-1898971)	-	1	1	psi-mi:"MI:0078"(nucleotide sequence identification)	psi-mi:"MI:0072"(monoclonal antibody western blot)
uniprotkb:P51531	uniprotkb:P04326	intact:EBI-679562|uniprotkb:B1ALG3|uniprotkb:B1ALG4|uniprotkb:D3DRH4|uniprotkb:D3DRH5|ensembl:ENSP00000265773|ensembl:ENSP00000371638	intact:EBI-7333987|intact:MINT-138666	psi-mi:smca2_human(display_long)|uniprotkb:ATP-dependent helicase SMARCA2(gene name synonym)|uniprotkb:SNF2-alpha(gene name synonym)|uniprotkb:SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2(gene name synonym)|uniprotkb:SMARCA2(gene name)|psi-mi:SMARCA2(display_short)|uniprotkb:BRM(gene name synonym)|uniprotkb:SNF2A(gene name synonym)|uniprotkb:SNF2L2(gene name synonym)|uniprotkb:BAF190B(gene name synonym)|uniprotkb:Protein brahma homolog(gene name synonym)|uniprotkb:BRG1-associated factor 190B(gene name synonym)	psi-mi:tat_hv112(display_long)|uniprotkb:tat(gene name)|psi-mi:tat(display_short)|uniprotkb:Transactivating regulatory protein(gene name synonym)	psi-mi:"MI:0096"(pull down)	Tréand et al. (2006)	pubmed:16601680|imex:IM-11387|mint:MINT-5218478	taxid:9606(human)|taxid:9606(Homo sapiens)	taxid:11679(hv112)|taxid:11679("Human immunodeficiency virus type 1 group M subtype B (isolate PCV12)")	psi-mi:"MI:0915"(physical association)	psi-mi:"MI:0471"(MINT)	intact:EBI-8296955|mint:MINT-1898930|imex:IM-11387-11	-	-	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0496"(bait)	psi-mi:"MI:0498"(prey)	psi-mi:"MI:0326"(protein)	psi-mi:"MI:0326"(protein)	refseq:NP_003061.3|refseq:NP_620614.2|refseq:NP_001276325.1|refseq:NP_001276326.1|dip:DIP-29005N|ensembl:ENSG00000080503(gene)|ensembl:ENST00000349721(transcript)|ensembl:ENST00000382203(transcript)|go:"GO:0000122"(negative regulation of transcription by RNA polymerase II)|go:"GO:0000785"(chromatin)|go:"GO:0000976"(transcription cis-regulatory region binding)|go:"GO:0003677"(DNA binding)|go:"GO:0003682"(chromatin binding)|go:"GO:0003713"(transcription coactivator activity)|go:"GO:0004386"(helicase activity)|go:"GO:0005524"(ATP binding)|go:"GO:0005634"(nucleus)|go:"GO:0005654"(nucleoplasm)|go:"GO:0006338"(chromatin remodeling)|go:"GO:0006355"(regulation of transcription, DNA-templated)|go:"GO:0006357"(regulation of transcription by RNA polymerase II)|go:"GO:0007286"(spermatid development)|go:"GO:0007399"(nervous system development)|go:"GO:0008094"(ATP-dependent activity, acting on DNA)|go:"GO:0008285"(negative regulation of cell population proliferation)|go:"GO:0016514"(SWI/SNF complex)|go:"GO:0016787"(hydrolase activity)|go:"GO:0030308"(negative regulation of cell growth)|go:"GO:0042393"(histone binding)|go:"GO:0043044"|go:"GO:0043231"(intracellular membrane-bounded organelle)|go:"GO:0045111"(intermediate filament cytoskeleton)|go:"GO:0045892"(negative regulation of transcription, DNA-templated)|go:"GO:0045893"(positive regulation of transcription, DNA-templated)|go:"GO:0045944"(positive regulation of transcription by RNA polymerase II)|go:"GO:0070615"|go:"GO:0071564"(npBAF complex)|go:"GO:0071565"(nBAF complex)|interpro:IPR000330(SNF2-related)|interpro:IPR001487(Bromodomain)|interpro:IPR001650(DNA/RNA helicase, C-terminal)|interpro:IPR006576(BRK)|interpro:IPR014001(DEAD-like helicase, N-terminal)|interpro:IPR014012(Helicase/SANT-associated, DNA binding)|interpro:IPR014978(QLQ)|interpro:IPR018359|interpro:IPR027417|interpro:IPR029295|interpro:IPR030088|interpro:IPR036427|interpro:IPR037259|interpro:IPR038718|mint:P51531|rcsb pdb:2DAT|rcsb pdb:4QY4|rcsb pdb:5DKC|rcsb pdb:5DKH|rcsb pdb:6EG2|rcsb pdb:6EG3|rcsb pdb:6HAX|rcsb pdb:6HAY|rcsb pdb:6HAZ|reactome:R-HSA-3214858|reactome:R-HSA-8939243|mint:MINT-1898938(identity)	rcsb pdb:5SVZ|go:"GO:0001070"(RNA-binding transcription regulator activity)|go:"GO:0005576"(extracellular region)|go:"GO:0006351"(transcription, DNA-templated)|go:"GO:0010801"(negative regulation of peptidyl-threonine phosphorylation)|go:"GO:0019904"(protein domain specific binding)|go:"GO:0030332"(cyclin binding)|go:"GO:0030430"(host cell cytoplasm)|go:"GO:0032968"(positive regulation of transcription elongation from RNA polymerase II promoter)|go:"GO:0039502"(suppression by virus of host type I interferon-mediated signaling pathway)|go:"GO:0039525"(modulation by virus of host chromatin organization)|go:"GO:0039586"(modulation by virus of host PP1 activity)|go:"GO:0042805"(actinin binding)|go:"GO:0044196"(host cell nucleolus)|go:"GO:0046872"(metal ion binding)|go:"GO:0050434"(positive regulation of viral transcription)|go:"GO:1990970"(trans-activation response element binding)|interpro:IPR001831("Immunodeficiency virus transactivating regulatory protein (Tat)")|interpro:IPR036963|mint:MINT-1898931(identity)	-	comment:"Stoichiometry: 1.0"	comment:mint|function:"Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. In the absence of Tat, the RNA Pol II generates short or non-processive transcripts that terminate at approximately 60 bp from the initiation site. Tat associates with the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. This binding increases Tat's affinity for a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) and allows Tat/P-TEFb complex to bind cooperatively to TAR RNA. The CDK9 component of P-TEFb hyperphosphorylates the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B. In this purpose, it activates EIF2AK2/PKR which, in turns, may phosphorylate and target to degradation the inhibitor IkappaB-alpha which normally retains NF-kappa-B in the cytoplasm of unstimulated cells. Through its interaction with TBP, Tat may be involved in transcription initiation as well. Interacts with the cellular capping enzyme RNGTT to mediate co-transcriptional capping of viral mRNAs. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter"|function:"Alters the cellular functions through the binding to various nuclear and cytoplasmic factors, and cell surface receptors. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines (such as IL10) or cytokine receptors. Tat plays a role in T-cell and neurons apoptosis. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Tat seems to inhibit the HAT activity of HTATIP/Tip60 and TAF1, and consequently modify the expression of specific cellular genes. Mediates the activation of cyclin-dependent kinases and dysregulation of microtubule network. Extracellular Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Endocytosed Tat translocate into the nucleus, and induces apoptosis by oxidative stress associated with mitochondrial dysfunction and perturbation of calcium-regulated channels and glutamate receptor (NMDAR). Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Host extracellular matrix metalloproteinase MMP1 cleaves Tat and decreases Tat's mediated neurotoxicity. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. Binds to KDR/VEGFR-2. All these Tat-mediated effects enhance angiogenesis in Kaposi's sarcoma lesions"|comment:"Stoichiometry: 1.0"	figure legend:F3C|comment:homomint|comment:mint|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation	taxid:-1(in vitro)|taxid:-1(In vitro)	-	2006/05/10	2014/10/16	rogid:DmQot4h4SmtqmUGBgF5ictTah289606	rogid:6IQLP0otFnozphvozdUWNnLP/cU11679	intact-crc:CCC073EF71E05A81|rigid:My0sWeTtD+phXNKqopXMDfgxTJg	false	glutathione s tranferase tag:?-?(MINT-1898950)|binding-associated region:320-686(MINT-1898939)	flag tag:?-?(MINT-1898936)	1	1	psi-mi:"MI:0078"(nucleotide sequence identification)	psi-mi:"MI:0078"(nucleotide sequence identification)
uniprotkb:P51531	uniprotkb:P04326	intact:EBI-679562|uniprotkb:B1ALG3|uniprotkb:B1ALG4|uniprotkb:D3DRH4|uniprotkb:D3DRH5|ensembl:ENSP00000265773|ensembl:ENSP00000371638	intact:EBI-7333987|intact:MINT-138666	psi-mi:smca2_human(display_long)|uniprotkb:ATP-dependent helicase SMARCA2(gene name synonym)|uniprotkb:SNF2-alpha(gene name synonym)|uniprotkb:SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2(gene name synonym)|uniprotkb:SMARCA2(gene name)|psi-mi:SMARCA2(display_short)|uniprotkb:BRM(gene name synonym)|uniprotkb:SNF2A(gene name synonym)|uniprotkb:SNF2L2(gene name synonym)|uniprotkb:BAF190B(gene name synonym)|uniprotkb:Protein brahma homolog(gene name synonym)|uniprotkb:BRG1-associated factor 190B(gene name synonym)	psi-mi:tat_hv112(display_long)|uniprotkb:tat(gene name)|psi-mi:tat(display_short)|uniprotkb:Transactivating regulatory protein(gene name synonym)	psi-mi:"MI:0096"(pull down)	Tréand et al. (2006)	pubmed:16601680|imex:IM-11387|mint:MINT-5218478	taxid:9606(human)|taxid:9606(Homo sapiens)	taxid:11679(hv112)|taxid:11679("Human immunodeficiency virus type 1 group M subtype B (isolate PCV12)")	psi-mi:"MI:0915"(physical association)	psi-mi:"MI:0471"(MINT)	intact:EBI-8297070|mint:MINT-1898983|imex:IM-11387-12	-	-	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0496"(bait)	psi-mi:"MI:0498"(prey)	psi-mi:"MI:0326"(protein)	psi-mi:"MI:0326"(protein)	refseq:NP_003061.3|refseq:NP_620614.2|refseq:NP_001276325.1|refseq:NP_001276326.1|dip:DIP-29005N|ensembl:ENSG00000080503(gene)|ensembl:ENST00000349721(transcript)|ensembl:ENST00000382203(transcript)|go:"GO:0000122"(negative regulation of transcription by RNA polymerase II)|go:"GO:0000785"(chromatin)|go:"GO:0000976"(transcription cis-regulatory region binding)|go:"GO:0003677"(DNA binding)|go:"GO:0003682"(chromatin binding)|go:"GO:0003713"(transcription coactivator activity)|go:"GO:0004386"(helicase activity)|go:"GO:0005524"(ATP binding)|go:"GO:0005634"(nucleus)|go:"GO:0005654"(nucleoplasm)|go:"GO:0006338"(chromatin remodeling)|go:"GO:0006355"(regulation of transcription, DNA-templated)|go:"GO:0006357"(regulation of transcription by RNA polymerase II)|go:"GO:0007286"(spermatid development)|go:"GO:0007399"(nervous system development)|go:"GO:0008094"(ATP-dependent activity, acting on DNA)|go:"GO:0008285"(negative regulation of cell population proliferation)|go:"GO:0016514"(SWI/SNF complex)|go:"GO:0016787"(hydrolase activity)|go:"GO:0030308"(negative regulation of cell growth)|go:"GO:0042393"(histone binding)|go:"GO:0043044"|go:"GO:0043231"(intracellular membrane-bounded organelle)|go:"GO:0045111"(intermediate filament cytoskeleton)|go:"GO:0045892"(negative regulation of transcription, DNA-templated)|go:"GO:0045893"(positive regulation of transcription, DNA-templated)|go:"GO:0045944"(positive regulation of transcription by RNA polymerase II)|go:"GO:0070615"|go:"GO:0071564"(npBAF complex)|go:"GO:0071565"(nBAF complex)|interpro:IPR000330(SNF2-related)|interpro:IPR001487(Bromodomain)|interpro:IPR001650(DNA/RNA helicase, C-terminal)|interpro:IPR006576(BRK)|interpro:IPR014001(DEAD-like helicase, N-terminal)|interpro:IPR014012(Helicase/SANT-associated, DNA binding)|interpro:IPR014978(QLQ)|interpro:IPR018359|interpro:IPR027417|interpro:IPR029295|interpro:IPR030088|interpro:IPR036427|interpro:IPR037259|interpro:IPR038718|mint:P51531|rcsb pdb:2DAT|rcsb pdb:4QY4|rcsb pdb:5DKC|rcsb pdb:5DKH|rcsb pdb:6EG2|rcsb pdb:6EG3|rcsb pdb:6HAX|rcsb pdb:6HAY|rcsb pdb:6HAZ|reactome:R-HSA-3214858|reactome:R-HSA-8939243|mint:MINT-1898989(identity)	rcsb pdb:5SVZ|go:"GO:0001070"(RNA-binding transcription regulator activity)|go:"GO:0005576"(extracellular region)|go:"GO:0006351"(transcription, DNA-templated)|go:"GO:0010801"(negative regulation of peptidyl-threonine phosphorylation)|go:"GO:0019904"(protein domain specific binding)|go:"GO:0030332"(cyclin binding)|go:"GO:0030430"(host cell cytoplasm)|go:"GO:0032968"(positive regulation of transcription elongation from RNA polymerase II promoter)|go:"GO:0039502"(suppression by virus of host type I interferon-mediated signaling pathway)|go:"GO:0039525"(modulation by virus of host chromatin organization)|go:"GO:0039586"(modulation by virus of host PP1 activity)|go:"GO:0042805"(actinin binding)|go:"GO:0044196"(host cell nucleolus)|go:"GO:0046872"(metal ion binding)|go:"GO:0050434"(positive regulation of viral transcription)|go:"GO:1990970"(trans-activation response element binding)|interpro:IPR001831("Immunodeficiency virus transactivating regulatory protein (Tat)")|interpro:IPR036963|mint:MINT-1898984(identity)	-	comment:"Stoichiometry: 1.0"	comment:mint|function:"Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. In the absence of Tat, the RNA Pol II generates short or non-processive transcripts that terminate at approximately 60 bp from the initiation site. Tat associates with the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. This binding increases Tat's affinity for a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) and allows Tat/P-TEFb complex to bind cooperatively to TAR RNA. The CDK9 component of P-TEFb hyperphosphorylates the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B. In this purpose, it activates EIF2AK2/PKR which, in turns, may phosphorylate and target to degradation the inhibitor IkappaB-alpha which normally retains NF-kappa-B in the cytoplasm of unstimulated cells. Through its interaction with TBP, Tat may be involved in transcription initiation as well. Interacts with the cellular capping enzyme RNGTT to mediate co-transcriptional capping of viral mRNAs. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter"|function:"Alters the cellular functions through the binding to various nuclear and cytoplasmic factors, and cell surface receptors. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines (such as IL10) or cytokine receptors. Tat plays a role in T-cell and neurons apoptosis. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Tat seems to inhibit the HAT activity of HTATIP/Tip60 and TAF1, and consequently modify the expression of specific cellular genes. Mediates the activation of cyclin-dependent kinases and dysregulation of microtubule network. Extracellular Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Endocytosed Tat translocate into the nucleus, and induces apoptosis by oxidative stress associated with mitochondrial dysfunction and perturbation of calcium-regulated channels and glutamate receptor (NMDAR). Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Host extracellular matrix metalloproteinase MMP1 cleaves Tat and decreases Tat's mediated neurotoxicity. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. Binds to KDR/VEGFR-2. All these Tat-mediated effects enhance angiogenesis in Kaposi's sarcoma lesions"|comment:"Stoichiometry: 1.0"	figure legend:F8A|comment:homomint|comment:mint|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation	taxid:-1(in vitro)|taxid:-1(In vitro)	-	2006/05/10	2014/10/16	rogid:DmQot4h4SmtqmUGBgF5ictTah289606	rogid:6IQLP0otFnozphvozdUWNnLP/cU11679	intact-crc:59C9F8051DBF9051|rigid:My0sWeTtD+phXNKqopXMDfgxTJg	false	glutathione s tranferase tag:?-?(MINT-1898996)|binding-associated region:320-686(MINT-1898990)	flag tag:?-?(MINT-1899004)|mutation disrupting interaction:50-50(MINT-1899007)	1	1	psi-mi:"MI:0078"(nucleotide sequence identification)	psi-mi:"MI:0078"(nucleotide sequence identification)
uniprotkb:P51531	uniprotkb:P04326	intact:EBI-679562|uniprotkb:B1ALG3|uniprotkb:B1ALG4|uniprotkb:D3DRH4|uniprotkb:D3DRH5|ensembl:ENSP00000265773|ensembl:ENSP00000371638	intact:EBI-7333987|intact:MINT-138666	psi-mi:smca2_human(display_long)|uniprotkb:ATP-dependent helicase SMARCA2(gene name synonym)|uniprotkb:SNF2-alpha(gene name synonym)|uniprotkb:SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2(gene name synonym)|uniprotkb:SMARCA2(gene name)|psi-mi:SMARCA2(display_short)|uniprotkb:BRM(gene name synonym)|uniprotkb:SNF2A(gene name synonym)|uniprotkb:SNF2L2(gene name synonym)|uniprotkb:BAF190B(gene name synonym)|uniprotkb:Protein brahma homolog(gene name synonym)|uniprotkb:BRG1-associated factor 190B(gene name synonym)	psi-mi:tat_hv112(display_long)|uniprotkb:tat(gene name)|psi-mi:tat(display_short)|uniprotkb:Transactivating regulatory protein(gene name synonym)	psi-mi:"MI:0007"(anti tag coimmunoprecipitation)	Tréand et al. (2006)	pubmed:16601680|imex:IM-11387|mint:MINT-5218478	taxid:9606(human)|taxid:9606(Homo sapiens)	taxid:11679(hv112)|taxid:11679("Human immunodeficiency virus type 1 group M subtype B (isolate PCV12)")	psi-mi:"MI:0915"(physical association)	psi-mi:"MI:0471"(MINT)	intact:EBI-8297132|mint:MINT-1898725|imex:IM-11387-2	-	-	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0496"(bait)	psi-mi:"MI:0498"(prey)	psi-mi:"MI:0326"(protein)	psi-mi:"MI:0326"(protein)	refseq:NP_003061.3|refseq:NP_620614.2|refseq:NP_001276325.1|refseq:NP_001276326.1|dip:DIP-29005N|ensembl:ENSG00000080503(gene)|ensembl:ENST00000349721(transcript)|ensembl:ENST00000382203(transcript)|go:"GO:0000122"(negative regulation of transcription by RNA polymerase II)|go:"GO:0000785"(chromatin)|go:"GO:0000976"(transcription cis-regulatory region binding)|go:"GO:0003677"(DNA binding)|go:"GO:0003682"(chromatin binding)|go:"GO:0003713"(transcription coactivator activity)|go:"GO:0004386"(helicase activity)|go:"GO:0005524"(ATP binding)|go:"GO:0005634"(nucleus)|go:"GO:0005654"(nucleoplasm)|go:"GO:0006338"(chromatin remodeling)|go:"GO:0006355"(regulation of transcription, DNA-templated)|go:"GO:0006357"(regulation of transcription by RNA polymerase II)|go:"GO:0007286"(spermatid development)|go:"GO:0007399"(nervous system development)|go:"GO:0008094"(ATP-dependent activity, acting on DNA)|go:"GO:0008285"(negative regulation of cell population proliferation)|go:"GO:0016514"(SWI/SNF complex)|go:"GO:0016787"(hydrolase activity)|go:"GO:0030308"(negative regulation of cell growth)|go:"GO:0042393"(histone binding)|go:"GO:0043044"|go:"GO:0043231"(intracellular membrane-bounded organelle)|go:"GO:0045111"(intermediate filament cytoskeleton)|go:"GO:0045892"(negative regulation of transcription, DNA-templated)|go:"GO:0045893"(positive regulation of transcription, DNA-templated)|go:"GO:0045944"(positive regulation of transcription by RNA polymerase II)|go:"GO:0070615"|go:"GO:0071564"(npBAF complex)|go:"GO:0071565"(nBAF complex)|interpro:IPR000330(SNF2-related)|interpro:IPR001487(Bromodomain)|interpro:IPR001650(DNA/RNA helicase, C-terminal)|interpro:IPR006576(BRK)|interpro:IPR014001(DEAD-like helicase, N-terminal)|interpro:IPR014012(Helicase/SANT-associated, DNA binding)|interpro:IPR014978(QLQ)|interpro:IPR018359|interpro:IPR027417|interpro:IPR029295|interpro:IPR030088|interpro:IPR036427|interpro:IPR037259|interpro:IPR038718|mint:P51531|rcsb pdb:2DAT|rcsb pdb:4QY4|rcsb pdb:5DKC|rcsb pdb:5DKH|rcsb pdb:6EG2|rcsb pdb:6EG3|rcsb pdb:6HAX|rcsb pdb:6HAY|rcsb pdb:6HAZ|reactome:R-HSA-3214858|reactome:R-HSA-8939243|mint:MINT-1898726(identity)	rcsb pdb:5SVZ|go:"GO:0001070"(RNA-binding transcription regulator activity)|go:"GO:0005576"(extracellular region)|go:"GO:0006351"(transcription, DNA-templated)|go:"GO:0010801"(negative regulation of peptidyl-threonine phosphorylation)|go:"GO:0019904"(protein domain specific binding)|go:"GO:0030332"(cyclin binding)|go:"GO:0030430"(host cell cytoplasm)|go:"GO:0032968"(positive regulation of transcription elongation from RNA polymerase II promoter)|go:"GO:0039502"(suppression by virus of host type I interferon-mediated signaling pathway)|go:"GO:0039525"(modulation by virus of host chromatin organization)|go:"GO:0039586"(modulation by virus of host PP1 activity)|go:"GO:0042805"(actinin binding)|go:"GO:0044196"(host cell nucleolus)|go:"GO:0046872"(metal ion binding)|go:"GO:0050434"(positive regulation of viral transcription)|go:"GO:1990970"(trans-activation response element binding)|interpro:IPR001831("Immunodeficiency virus transactivating regulatory protein (Tat)")|interpro:IPR036963|mint:MINT-1898734(identity)	-	comment:"Stoichiometry: 1.0"	comment:mint|function:"Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. In the absence of Tat, the RNA Pol II generates short or non-processive transcripts that terminate at approximately 60 bp from the initiation site. Tat associates with the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. This binding increases Tat's affinity for a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) and allows Tat/P-TEFb complex to bind cooperatively to TAR RNA. The CDK9 component of P-TEFb hyperphosphorylates the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B. In this purpose, it activates EIF2AK2/PKR which, in turns, may phosphorylate and target to degradation the inhibitor IkappaB-alpha which normally retains NF-kappa-B in the cytoplasm of unstimulated cells. Through its interaction with TBP, Tat may be involved in transcription initiation as well. Interacts with the cellular capping enzyme RNGTT to mediate co-transcriptional capping of viral mRNAs. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter"|function:"Alters the cellular functions through the binding to various nuclear and cytoplasmic factors, and cell surface receptors. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines (such as IL10) or cytokine receptors. Tat plays a role in T-cell and neurons apoptosis. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Tat seems to inhibit the HAT activity of HTATIP/Tip60 and TAF1, and consequently modify the expression of specific cellular genes. Mediates the activation of cyclin-dependent kinases and dysregulation of microtubule network. Extracellular Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Endocytosed Tat translocate into the nucleus, and induces apoptosis by oxidative stress associated with mitochondrial dysfunction and perturbation of calcium-regulated channels and glutamate receptor (NMDAR). Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Host extracellular matrix metalloproteinase MMP1 cleaves Tat and decreases Tat's mediated neurotoxicity. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. Binds to KDR/VEGFR-2. All these Tat-mediated effects enhance angiogenesis in Kaposi's sarcoma lesions"|comment:"Stoichiometry: 1.0"	figure legend:F1B|comment:homomint|comment:mint|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation	taxid:9606(human-293)|taxid:9606(Homo sapiens transformed primary embryonal kidney cells)	-	2006/05/10	2014/10/16	rogid:DmQot4h4SmtqmUGBgF5ictTah289606	rogid:6IQLP0otFnozphvozdUWNnLP/cU11679	intact-crc:92BDD7CBD4381BDD|rigid:My0sWeTtD+phXNKqopXMDfgxTJg	false	ha tag:?-?(MINT-1898732)	flag tag:?-?(MINT-1898740)	1	1	psi-mi:"MI:0078"(nucleotide sequence identification)	psi-mi:"MI:0078"(nucleotide sequence identification)
uniprotkb:P51531	uniprotkb:P04326	intact:EBI-679562|uniprotkb:B1ALG3|uniprotkb:B1ALG4|uniprotkb:D3DRH4|uniprotkb:D3DRH5|ensembl:ENSP00000265773|ensembl:ENSP00000371638	intact:EBI-7333987|intact:MINT-138666	psi-mi:smca2_human(display_long)|uniprotkb:ATP-dependent helicase SMARCA2(gene name synonym)|uniprotkb:SNF2-alpha(gene name synonym)|uniprotkb:SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2(gene name synonym)|uniprotkb:SMARCA2(gene name)|psi-mi:SMARCA2(display_short)|uniprotkb:BRM(gene name synonym)|uniprotkb:SNF2A(gene name synonym)|uniprotkb:SNF2L2(gene name synonym)|uniprotkb:BAF190B(gene name synonym)|uniprotkb:Protein brahma homolog(gene name synonym)|uniprotkb:BRG1-associated factor 190B(gene name synonym)	psi-mi:tat_hv112(display_long)|uniprotkb:tat(gene name)|psi-mi:tat(display_short)|uniprotkb:Transactivating regulatory protein(gene name synonym)	psi-mi:"MI:0007"(anti tag coimmunoprecipitation)	Tréand et al. (2006)	pubmed:16601680|imex:IM-11387|mint:MINT-5218478	taxid:9606(human)|taxid:9606(Homo sapiens)	taxid:11679(hv112)|taxid:11679("Human immunodeficiency virus type 1 group M subtype B (isolate PCV12)")	psi-mi:"MI:0915"(physical association)	psi-mi:"MI:0471"(MINT)	intact:EBI-8297111|mint:MINT-1898698|imex:IM-11387-1	-	-	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0498"(prey)	psi-mi:"MI:0496"(bait)	psi-mi:"MI:0326"(protein)	psi-mi:"MI:0326"(protein)	refseq:NP_003061.3|refseq:NP_620614.2|refseq:NP_001276325.1|refseq:NP_001276326.1|dip:DIP-29005N|ensembl:ENSG00000080503(gene)|ensembl:ENST00000349721(transcript)|ensembl:ENST00000382203(transcript)|go:"GO:0000122"(negative regulation of transcription by RNA polymerase II)|go:"GO:0000785"(chromatin)|go:"GO:0000976"(transcription cis-regulatory region binding)|go:"GO:0003677"(DNA binding)|go:"GO:0003682"(chromatin binding)|go:"GO:0003713"(transcription coactivator activity)|go:"GO:0004386"(helicase activity)|go:"GO:0005524"(ATP binding)|go:"GO:0005634"(nucleus)|go:"GO:0005654"(nucleoplasm)|go:"GO:0006338"(chromatin remodeling)|go:"GO:0006355"(regulation of transcription, DNA-templated)|go:"GO:0006357"(regulation of transcription by RNA polymerase II)|go:"GO:0007286"(spermatid development)|go:"GO:0007399"(nervous system development)|go:"GO:0008094"(ATP-dependent activity, acting on DNA)|go:"GO:0008285"(negative regulation of cell population proliferation)|go:"GO:0016514"(SWI/SNF complex)|go:"GO:0016787"(hydrolase activity)|go:"GO:0030308"(negative regulation of cell growth)|go:"GO:0042393"(histone binding)|go:"GO:0043044"|go:"GO:0043231"(intracellular membrane-bounded organelle)|go:"GO:0045111"(intermediate filament cytoskeleton)|go:"GO:0045892"(negative regulation of transcription, DNA-templated)|go:"GO:0045893"(positive regulation of transcription, DNA-templated)|go:"GO:0045944"(positive regulation of transcription by RNA polymerase II)|go:"GO:0070615"|go:"GO:0071564"(npBAF complex)|go:"GO:0071565"(nBAF complex)|interpro:IPR000330(SNF2-related)|interpro:IPR001487(Bromodomain)|interpro:IPR001650(DNA/RNA helicase, C-terminal)|interpro:IPR006576(BRK)|interpro:IPR014001(DEAD-like helicase, N-terminal)|interpro:IPR014012(Helicase/SANT-associated, DNA binding)|interpro:IPR014978(QLQ)|interpro:IPR018359|interpro:IPR027417|interpro:IPR029295|interpro:IPR030088|interpro:IPR036427|interpro:IPR037259|interpro:IPR038718|mint:P51531|rcsb pdb:2DAT|rcsb pdb:4QY4|rcsb pdb:5DKC|rcsb pdb:5DKH|rcsb pdb:6EG2|rcsb pdb:6EG3|rcsb pdb:6HAX|rcsb pdb:6HAY|rcsb pdb:6HAZ|reactome:R-HSA-3214858|reactome:R-HSA-8939243|mint:MINT-1898699(identity)	rcsb pdb:5SVZ|go:"GO:0001070"(RNA-binding transcription regulator activity)|go:"GO:0005576"(extracellular region)|go:"GO:0006351"(transcription, DNA-templated)|go:"GO:0010801"(negative regulation of peptidyl-threonine phosphorylation)|go:"GO:0019904"(protein domain specific binding)|go:"GO:0030332"(cyclin binding)|go:"GO:0030430"(host cell cytoplasm)|go:"GO:0032968"(positive regulation of transcription elongation from RNA polymerase II promoter)|go:"GO:0039502"(suppression by virus of host type I interferon-mediated signaling pathway)|go:"GO:0039525"(modulation by virus of host chromatin organization)|go:"GO:0039586"(modulation by virus of host PP1 activity)|go:"GO:0042805"(actinin binding)|go:"GO:0044196"(host cell nucleolus)|go:"GO:0046872"(metal ion binding)|go:"GO:0050434"(positive regulation of viral transcription)|go:"GO:1990970"(trans-activation response element binding)|interpro:IPR001831("Immunodeficiency virus transactivating regulatory protein (Tat)")|interpro:IPR036963|mint:MINT-1898705(identity)	-	comment:"Stoichiometry: 1.0"	comment:mint|function:"Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. In the absence of Tat, the RNA Pol II generates short or non-processive transcripts that terminate at approximately 60 bp from the initiation site. Tat associates with the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. This binding increases Tat's affinity for a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) and allows Tat/P-TEFb complex to bind cooperatively to TAR RNA. The CDK9 component of P-TEFb hyperphosphorylates the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B. In this purpose, it activates EIF2AK2/PKR which, in turns, may phosphorylate and target to degradation the inhibitor IkappaB-alpha which normally retains NF-kappa-B in the cytoplasm of unstimulated cells. Through its interaction with TBP, Tat may be involved in transcription initiation as well. Interacts with the cellular capping enzyme RNGTT to mediate co-transcriptional capping of viral mRNAs. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter"|function:"Alters the cellular functions through the binding to various nuclear and cytoplasmic factors, and cell surface receptors. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines (such as IL10) or cytokine receptors. Tat plays a role in T-cell and neurons apoptosis. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Tat seems to inhibit the HAT activity of HTATIP/Tip60 and TAF1, and consequently modify the expression of specific cellular genes. Mediates the activation of cyclin-dependent kinases and dysregulation of microtubule network. Extracellular Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Endocytosed Tat translocate into the nucleus, and induces apoptosis by oxidative stress associated with mitochondrial dysfunction and perturbation of calcium-regulated channels and glutamate receptor (NMDAR). Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Host extracellular matrix metalloproteinase MMP1 cleaves Tat and decreases Tat's mediated neurotoxicity. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. Binds to KDR/VEGFR-2. All these Tat-mediated effects enhance angiogenesis in Kaposi's sarcoma lesions"|comment:"Stoichiometry: 1.0"	figure legend:F1B|comment:homomint|comment:mint|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation	taxid:9606(human-293)|taxid:9606(Homo sapiens transformed primary embryonal kidney cells)	-	2006/05/10	2014/10/16	rogid:DmQot4h4SmtqmUGBgF5ictTah289606	rogid:6IQLP0otFnozphvozdUWNnLP/cU11679	intact-crc:B297B01E6FD7377D|rigid:My0sWeTtD+phXNKqopXMDfgxTJg	false	ha tag:?-?(MINT-1898719)	flag tag:?-?(MINT-1898706)	1	1	psi-mi:"MI:0078"(nucleotide sequence identification)	psi-mi:"MI:0078"(nucleotide sequence identification)
uniprotkb:P04326	uniprotkb:Q12824	intact:EBI-7333987|intact:MINT-138666	intact:EBI-358419|uniprotkb:O75784|uniprotkb:O95474|uniprotkb:Q38GA1|uniprotkb:Q76N08|uniprotkb:Q9UBH2|ensembl:ENSP00000479330|ensembl:ENSP00000494049|uniprotkb:Q17S11	psi-mi:tat_hv112(display_long)|uniprotkb:tat(gene name)|psi-mi:tat(display_short)|uniprotkb:Transactivating regulatory protein(gene name synonym)	psi-mi:snf5_human(display_long)|uniprotkb:SMARCB1(gene name)|psi-mi:SMARCB1(display_short)|uniprotkb:INI1(gene name synonym)|uniprotkb:SNF5L1(gene name synonym)|uniprotkb:Integrase interactor 1 protein(gene name synonym)|uniprotkb:BAF47(gene name synonym)|uniprotkb:SNF5 homolog(gene name synonym)|uniprotkb:BRG1-associated factor 47(gene name synonym)	psi-mi:"MI:0007"(anti tag coimmunoprecipitation)	Tréand et al. (2006)	pubmed:16601680|imex:IM-11387|mint:MINT-5218478	taxid:11679(hv112)|taxid:11679("Human immunodeficiency virus type 1 group M subtype B (isolate PCV12)")	taxid:9606(human)|taxid:9606(Homo sapiens)	psi-mi:"MI:0915"(physical association)	psi-mi:"MI:0471"(MINT)	intact:EBI-8297195|mint:MINT-1898775|imex:IM-11387-4	-	-	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0496"(bait)	psi-mi:"MI:0498"(prey)	psi-mi:"MI:0326"(protein)	psi-mi:"MI:0326"(protein)	rcsb pdb:5SVZ|go:"GO:0001070"(RNA-binding transcription regulator activity)|go:"GO:0005576"(extracellular region)|go:"GO:0006351"(transcription, DNA-templated)|go:"GO:0010801"(negative regulation of peptidyl-threonine phosphorylation)|go:"GO:0019904"(protein domain specific binding)|go:"GO:0030332"(cyclin binding)|go:"GO:0030430"(host cell cytoplasm)|go:"GO:0032968"(positive regulation of transcription elongation from RNA polymerase II promoter)|go:"GO:0039502"(suppression by virus of host type I interferon-mediated signaling pathway)|go:"GO:0039525"(modulation by virus of host chromatin organization)|go:"GO:0039586"(modulation by virus of host PP1 activity)|go:"GO:0042805"(actinin binding)|go:"GO:0044196"(host cell nucleolus)|go:"GO:0046872"(metal ion binding)|go:"GO:0050434"(positive regulation of viral transcription)|go:"GO:1990970"(trans-activation response element binding)|interpro:IPR001831("Immunodeficiency virus transactivating regulatory protein (Tat)")|interpro:IPR036963|mint:MINT-1898784(identity)	mint:Q12824|go:"GO:0006357"(regulation of transcription by RNA polymerase II)|rcsb pdb:5AJ1|rcsb pdb:5GJK|rcsb pdb:5L7A|rcsb pdb:5L7B|go:"GO:0007049"(cell cycle)|rcsb pdb:6AX5|go:"GO:0007399"(nervous system development)|rcsb pdb:6KAG|rcsb pdb:6KZ7|rcsb pdb:6LTH|rcsb pdb:6LTJ|rcsb pdb:6UCH|reactome:R-HSA-3214858|go:"GO:0008285"(negative regulation of cell population proliferation)|reactome:R-HSA-8939243|go:"GO:0015074"(DNA integration)|go:"GO:0016514"(SWI/SNF complex)|go:"GO:0030154"(cell differentiation)|go:"GO:0030957"(Tat protein binding)|go:"GO:0032991"(protein-containing complex)|go:"GO:0035060"(brahma complex)|go:"GO:0039692"(single stranded viral RNA replication via double stranded DNA intermediate)|go:"GO:0043044"|go:"GO:0043231"(intracellular membrane-bounded organelle)|go:"GO:0043923"(positive regulation by host of viral transcription)|go:"GO:0045944"(positive regulation of transcription by RNA polymerase II)|go:"GO:0051091"(positive regulation of DNA-binding transcription factor activity)|go:"GO:0071564"(npBAF complex)|go:"GO:0071565"(nBAF complex)|go:"GO:0090240"(positive regulation of histone H4 acetylation)|go:"GO:1900110"(negative regulation of histone H3-K9 dimethylation)|go:"GO:1900113"(negative regulation of histone H3-K9 trimethylation)|go:"GO:1901838"(positive regulation of transcription of nucleolar large rRNA by RNA polymerase I)|go:"GO:1902661"(positive regulation of glucose mediated signaling pathway)|go:"GO:2000617"(positive regulation of histone H3-K9 acetylation)|interpro:IPR006939(SNF5/SMARCB1/INI1)|interpro:IPR017393(SWI/SNF chromatin-remodeling complex, component hSNF5/Ini1)|go:"GO:0005730"(nucleolus)|go:"GO:0006337"(nucleosome disassembly)|go:"GO:0006338"(chromatin remodeling)|refseq:NP_001007469.1|refseq:NP_003064.2|ensembl:ENSG00000099956(gene)|ensembl:ENSG00000275837(gene)|ensembl:ENST00000618915(transcript)|ensembl:ENST00000644036(transcript)|go:"GO:0000228"(nuclear chromosome)|go:"GO:0000785"(chromatin)|go:"GO:0001188"(RNA polymerase I preinitiation complex assembly)|go:"GO:0001650"(fibrillar center)|go:"GO:0001741"(XY body)|go:"GO:0001835"(blastocyst hatching)|go:"GO:0002039"(p53 binding)|go:"GO:0003677"(DNA binding)|go:"GO:0003712"(transcription coregulator activity)|go:"GO:0003713"(transcription coactivator activity)|go:"GO:0005634"(nucleus)|go:"GO:0005654"(nucleoplasm)|dip:DIP-27550N|mint:MINT-1898776(identity)	-	comment:mint|function:"Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. In the absence of Tat, the RNA Pol II generates short or non-processive transcripts that terminate at approximately 60 bp from the initiation site. Tat associates with the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. This binding increases Tat's affinity for a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) and allows Tat/P-TEFb complex to bind cooperatively to TAR RNA. The CDK9 component of P-TEFb hyperphosphorylates the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B. In this purpose, it activates EIF2AK2/PKR which, in turns, may phosphorylate and target to degradation the inhibitor IkappaB-alpha which normally retains NF-kappa-B in the cytoplasm of unstimulated cells. Through its interaction with TBP, Tat may be involved in transcription initiation as well. Interacts with the cellular capping enzyme RNGTT to mediate co-transcriptional capping of viral mRNAs. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter"|function:"Alters the cellular functions through the binding to various nuclear and cytoplasmic factors, and cell surface receptors. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines (such as IL10) or cytokine receptors. Tat plays a role in T-cell and neurons apoptosis. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Tat seems to inhibit the HAT activity of HTATIP/Tip60 and TAF1, and consequently modify the expression of specific cellular genes. Mediates the activation of cyclin-dependent kinases and dysregulation of microtubule network. Extracellular Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Endocytosed Tat translocate into the nucleus, and induces apoptosis by oxidative stress associated with mitochondrial dysfunction and perturbation of calcium-regulated channels and glutamate receptor (NMDAR). Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Host extracellular matrix metalloproteinase MMP1 cleaves Tat and decreases Tat's mediated neurotoxicity. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. Binds to KDR/VEGFR-2. All these Tat-mediated effects enhance angiogenesis in Kaposi's sarcoma lesions"|comment:"Stoichiometry: 1.0"	comment:"Stoichiometry: 1.0"	figure legend:F1C|comment:homomint|comment:mint|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation	taxid:9606(human-293)|taxid:9606(Homo sapiens transformed primary embryonal kidney cells)	-	2006/05/10	2014/10/16	rogid:6IQLP0otFnozphvozdUWNnLP/cU11679	rogid:GjUm1RYfDvtNuSNGI6iCWpl8L+I9606	intact-crc:EEDD65A75C870BC2|rigid:gkAaX2uNIC8v6wu//AkF/zh1LYI	false	flag tag:?-?(MINT-1898785)	ha tag:?-?(MINT-1898782)	1	1	psi-mi:"MI:0078"(nucleotide sequence identification)	psi-mi:"MI:0078"(nucleotide sequence identification)
uniprotkb:P04326	uniprotkb:Q12824	intact:EBI-7333987|intact:MINT-138666	intact:EBI-358419|uniprotkb:O75784|uniprotkb:O95474|uniprotkb:Q38GA1|uniprotkb:Q76N08|uniprotkb:Q9UBH2|ensembl:ENSP00000479330|ensembl:ENSP00000494049|uniprotkb:Q17S11	psi-mi:tat_hv112(display_long)|uniprotkb:tat(gene name)|psi-mi:tat(display_short)|uniprotkb:Transactivating regulatory protein(gene name synonym)	psi-mi:snf5_human(display_long)|uniprotkb:SMARCB1(gene name)|psi-mi:SMARCB1(display_short)|uniprotkb:INI1(gene name synonym)|uniprotkb:SNF5L1(gene name synonym)|uniprotkb:Integrase interactor 1 protein(gene name synonym)|uniprotkb:BAF47(gene name synonym)|uniprotkb:SNF5 homolog(gene name synonym)|uniprotkb:BRG1-associated factor 47(gene name synonym)	psi-mi:"MI:0007"(anti tag coimmunoprecipitation)	Tréand et al. (2006)	pubmed:16601680|imex:IM-11387|mint:MINT-5218478	taxid:11679(hv112)|taxid:11679("Human immunodeficiency virus type 1 group M subtype B (isolate PCV12)")	taxid:9606(human)|taxid:9606(Homo sapiens)	psi-mi:"MI:0915"(physical association)	psi-mi:"MI:0471"(MINT)	intact:EBI-8297153|mint:MINT-1898749|imex:IM-11387-3	-	-	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0498"(prey)	psi-mi:"MI:0496"(bait)	psi-mi:"MI:0326"(protein)	psi-mi:"MI:0326"(protein)	rcsb pdb:5SVZ|go:"GO:0001070"(RNA-binding transcription regulator activity)|go:"GO:0005576"(extracellular region)|go:"GO:0006351"(transcription, DNA-templated)|go:"GO:0010801"(negative regulation of peptidyl-threonine phosphorylation)|go:"GO:0019904"(protein domain specific binding)|go:"GO:0030332"(cyclin binding)|go:"GO:0030430"(host cell cytoplasm)|go:"GO:0032968"(positive regulation of transcription elongation from RNA polymerase II promoter)|go:"GO:0039502"(suppression by virus of host type I interferon-mediated signaling pathway)|go:"GO:0039525"(modulation by virus of host chromatin organization)|go:"GO:0039586"(modulation by virus of host PP1 activity)|go:"GO:0042805"(actinin binding)|go:"GO:0044196"(host cell nucleolus)|go:"GO:0046872"(metal ion binding)|go:"GO:0050434"(positive regulation of viral transcription)|go:"GO:1990970"(trans-activation response element binding)|interpro:IPR001831("Immunodeficiency virus transactivating regulatory protein (Tat)")|interpro:IPR036963|mint:MINT-1898758(identity)	mint:Q12824|go:"GO:0006357"(regulation of transcription by RNA polymerase II)|rcsb pdb:5AJ1|rcsb pdb:5GJK|rcsb pdb:5L7A|rcsb pdb:5L7B|go:"GO:0007049"(cell cycle)|rcsb pdb:6AX5|go:"GO:0007399"(nervous system development)|rcsb pdb:6KAG|rcsb pdb:6KZ7|rcsb pdb:6LTH|rcsb pdb:6LTJ|rcsb pdb:6UCH|reactome:R-HSA-3214858|go:"GO:0008285"(negative regulation of cell population proliferation)|reactome:R-HSA-8939243|go:"GO:0015074"(DNA integration)|go:"GO:0016514"(SWI/SNF complex)|go:"GO:0030154"(cell differentiation)|go:"GO:0030957"(Tat protein binding)|go:"GO:0032991"(protein-containing complex)|go:"GO:0035060"(brahma complex)|go:"GO:0039692"(single stranded viral RNA replication via double stranded DNA intermediate)|go:"GO:0043044"|go:"GO:0043231"(intracellular membrane-bounded organelle)|go:"GO:0043923"(positive regulation by host of viral transcription)|go:"GO:0045944"(positive regulation of transcription by RNA polymerase II)|go:"GO:0051091"(positive regulation of DNA-binding transcription factor activity)|go:"GO:0071564"(npBAF complex)|go:"GO:0071565"(nBAF complex)|go:"GO:0090240"(positive regulation of histone H4 acetylation)|go:"GO:1900110"(negative regulation of histone H3-K9 dimethylation)|go:"GO:1900113"(negative regulation of histone H3-K9 trimethylation)|go:"GO:1901838"(positive regulation of transcription of nucleolar large rRNA by RNA polymerase I)|go:"GO:1902661"(positive regulation of glucose mediated signaling pathway)|go:"GO:2000617"(positive regulation of histone H3-K9 acetylation)|interpro:IPR006939(SNF5/SMARCB1/INI1)|interpro:IPR017393(SWI/SNF chromatin-remodeling complex, component hSNF5/Ini1)|go:"GO:0005730"(nucleolus)|go:"GO:0006337"(nucleosome disassembly)|go:"GO:0006338"(chromatin remodeling)|refseq:NP_001007469.1|refseq:NP_003064.2|ensembl:ENSG00000099956(gene)|ensembl:ENSG00000275837(gene)|ensembl:ENST00000618915(transcript)|ensembl:ENST00000644036(transcript)|go:"GO:0000228"(nuclear chromosome)|go:"GO:0000785"(chromatin)|go:"GO:0001188"(RNA polymerase I preinitiation complex assembly)|go:"GO:0001650"(fibrillar center)|go:"GO:0001741"(XY body)|go:"GO:0001835"(blastocyst hatching)|go:"GO:0002039"(p53 binding)|go:"GO:0003677"(DNA binding)|go:"GO:0003712"(transcription coregulator activity)|go:"GO:0003713"(transcription coactivator activity)|go:"GO:0005634"(nucleus)|go:"GO:0005654"(nucleoplasm)|dip:DIP-27550N|mint:MINT-1898750(identity)	-	comment:mint|function:"Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. In the absence of Tat, the RNA Pol II generates short or non-processive transcripts that terminate at approximately 60 bp from the initiation site. Tat associates with the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. This binding increases Tat's affinity for a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) and allows Tat/P-TEFb complex to bind cooperatively to TAR RNA. The CDK9 component of P-TEFb hyperphosphorylates the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B. In this purpose, it activates EIF2AK2/PKR which, in turns, may phosphorylate and target to degradation the inhibitor IkappaB-alpha which normally retains NF-kappa-B in the cytoplasm of unstimulated cells. Through its interaction with TBP, Tat may be involved in transcription initiation as well. Interacts with the cellular capping enzyme RNGTT to mediate co-transcriptional capping of viral mRNAs. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter"|function:"Alters the cellular functions through the binding to various nuclear and cytoplasmic factors, and cell surface receptors. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines (such as IL10) or cytokine receptors. Tat plays a role in T-cell and neurons apoptosis. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Tat seems to inhibit the HAT activity of HTATIP/Tip60 and TAF1, and consequently modify the expression of specific cellular genes. Mediates the activation of cyclin-dependent kinases and dysregulation of microtubule network. Extracellular Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Endocytosed Tat translocate into the nucleus, and induces apoptosis by oxidative stress associated with mitochondrial dysfunction and perturbation of calcium-regulated channels and glutamate receptor (NMDAR). Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Host extracellular matrix metalloproteinase MMP1 cleaves Tat and decreases Tat's mediated neurotoxicity. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. Binds to KDR/VEGFR-2. All these Tat-mediated effects enhance angiogenesis in Kaposi's sarcoma lesions"|comment:"Stoichiometry: 1.0"	comment:"Stoichiometry: 1.0"	figure legend:F1C|comment:homomint|comment:mint|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation	taxid:9606(human-293)|taxid:9606(Homo sapiens transformed primary embryonal kidney cells)	-	2006/05/10	2014/10/16	rogid:6IQLP0otFnozphvozdUWNnLP/cU11679	rogid:GjUm1RYfDvtNuSNGI6iCWpl8L+I9606	intact-crc:0FA35DE05DF96298|rigid:gkAaX2uNIC8v6wu//AkF/zh1LYI	false	flag tag:?-?(MINT-1898764)	ha tag:?-?(MINT-1898756)	1	1	psi-mi:"MI:0078"(nucleotide sequence identification)	psi-mi:"MI:0078"(nucleotide sequence identification)