#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:0055"(fluorescent resonance energy transfer) Zhang et al. (2000) pubmed:10944537|mint:MINT-5212906 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:2364"(proximity) psi-mi:"MI:0471"(MINT) intact:EBI-7369242|mint:MINT-15543 - - psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0499"(unspecified role) 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-429682(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-429692(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" comment:homomint|comment:mint|dataset:Virus - Publications including interactions involving viral proteins taxid:-4(in vivo)|taxid:-4(in vivo) - 2001/02/06 2014/10/16 rogid:6IQLP0otFnozphvozdUWNnLP/cU11679 rogid:y80GILqwBbb5hMtl/4U1Y/vNx909606 intact-crc:CE7F2B5B06A953D4|rigid:wS3qDUzFetxktkiLmHf9qUEY9uU false tag:?-?(MINT-429686)|binding-associated region:1-48(MINT-429683) tag:?-?(MINT-429693) - - psi-mi:"MI:0078"(nucleotide sequence identification) psi-mi:"MI:0078"(nucleotide sequence identification)