#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:P05952	intact:EBI-7333987|intact:MINT-138666	intact:EBI-7167957|intact:MINT-118741	psi-mi:tat_hv112(display_long)|uniprotkb:tat(gene name)|psi-mi:tat(display_short)|uniprotkb:Transactivating regulatory protein(gene name synonym)	psi-mi:vpr_hv1a2(display_long)|uniprotkb:vpr(gene name)|psi-mi:vpr(display_short)|uniprotkb:Viral protein R(gene name synonym)|uniprotkb:R ORF protein(gene name synonym)	psi-mi:"MI:0096"(pull down)	Sawaya et al. (2000)	pubmed:10931842|mint:MINT-5212870	taxid:11679(hv112)|taxid:11679("Human immunodeficiency virus type 1 group M subtype B (isolate PCV12)")	taxid:11685(hv1a2)|taxid:11685("Human immunodeficiency virus type 1 group M subtype B (isolate ARV2/SF2)")	psi-mi:"MI:0407"(direct interaction)	psi-mi:"MI:0471"(MINT)	intact:EBI-7362739|mint:MINT-17238	-	-	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-429376(identity)	go:"GO:0006351"(transcription, DNA-templated)|go:"GO:0006355"(regulation of transcription, DNA-templated)|go:"GO:0006811"(ion transport)|go:"GO:0007049"(cell cycle)|go:"GO:0019051"(induction by virus of host apoptotic process)|go:"GO:0039592"(suppression by virus of G2/M transition of host mitotic cell cycle)|go:"GO:0042025"(host cell nucleus)|go:"GO:0043655"(host extracellular space)|go:"GO:0046718"(viral entry into host cell)|go:"GO:0051260"(protein homooligomerization)|go:"GO:0075732"(viral penetration into host nucleus)|interpro:IPR000012(Retroviral VpR/VpX protein)|mint:MINT-429373(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:mint|function:"Involved in the transport of the viral pre-integration (PIC) complex to the nucleus during the early stages of the infection. This function is crucial for viral infection of non-dividing macrophages. May interact with karyopherin alpha/KPNA1 and KPNA2 to increase their affinity for proteins containing basic-type nuclear localization signal, including the viral matrix protein MA, thus facilitating the translocation of the viral genome into the nucleus. May also act directly at the nuclear pore complex, by binding nucleoporins phenylalanine-glycine (FG)-repeat regions. Has an anti-apoptotic effect, whereas high level of expression induces apoptosis. Interacts with mitochondrial permeability transition pore complex (PTPC), presumably through the binding of ANT proteins. This induces a rapid dissipation of the mitochondrial transmembrane potential, and mitochondrial release of apoptogenic proteins such as cytochrome C or apoptosis inducing factors. Prevents infected cells from undergoing mitosis and proliferating, by inducing arrest or delay in the G2 phase of the cell cycle. The arrest in G2 is characterized by low levels of CCNB1-CDC2 complex and corresponding inhibitory phosphorylation of CDC2. Cell cycle arrest creates a favourable environment for maximizing viral expression and production. This may be mediated by interacting with and inhibiting human CDC25C, which normally activates the CCNB1-CDC2 complex, or by binding SF3B2/SAP145. This function is independent of nuclear localization. Cell cycle arrest reportedly occurs within hours of infection and is not blocked by antiviral agents, suggesting that it is initiated by the Vpr carried into the virion. Stimulates gene expression driven by the HIV-1 LTR by interacting with human SP1, TFIIB and TFIID. Moreover, the G2/M cell cycle arrest creates a cellular environment where the HIV-1 LTR is transcriptionally more active. Essential for unintegrated viral DNA expression. Detected in the serum and cerebrospinal fluid of AIDS patient, where it may induce cell death to bystander cells. This necrotic or apoptotic effect might function by entering target cell plasma membrane to form ion channel"|comment:"Stoichiometry: 1.0"	comment:homomint|comment:mint|dataset:Virus - Publications including interactions involving viral proteins	taxid:-1(in vitro)|taxid:-1(In vitro)	-	2001/02/28	2014/10/16	rogid:6IQLP0otFnozphvozdUWNnLP/cU11679	rogid:yc57WbpL9M1ZJjWRV6npPUqhJX011685	intact-crc:1B384477708D2514|rigid:0TwoPPw1kJfanXEgDRyQuKkSuwU	false	binding-associated region:50-67(MINT-429377)	-	-	-	psi-mi:"MI:0396"(predetermined participant)	psi-mi:"MI:0396"(predetermined participant)