MINT MINT, Dpt of Biology, University of Rome Tor Vergata MINT http://mint.bio.uniroma2.it/mint url>http://mint.bio.uniroma2.it/mint/ https://mint.bio.uniroma2.it MINT-[0-9]+ https://mint.bio.uniroma2.it/index.php/results-interactions/?id=${ac} The Molecular INTeraction database (MINT) is a relational database designed to store interactions between biological molecules. http://mint.bio.uniroma2.it Cooperative interaction between HIV-1 regulatory proteins Tat and Vpr modulates transcription of the viral genome. Cooperative interaction between HIV-1 regulatory proteins Tat and Vpr modulates transcription of the viral genome. J. Biol. Chem. (0021-9258) 2000 Sawaya BE., Khalili K., Gordon J., Taube R., Amini S. Virus - Publications including interactions involving viral proteins no in vitro In vitro pull down pull down predetermined predetermined participant predetermined Sawaya BE., Khalili K., Gordon J., Taube R., Amini S. Virus - Publications including interactions involving viral proteins no J. Biol. Chem. (0021-9258) 2000 vpr_hv1a2 Protein Vpr vpr Viral protein R R ORF protein protein protein hv1a2 Human immunodeficiency virus type 1 group M subtype B (isolate ARV2/SF2) MEQAPEDQGPQREPYNEWTLELLEELKREAVRHFPRPWLHSLGQYIYETYGDTWAGVEAIIRILQQLLFIHFRIGCQHSRIGIIQQRRARRNGASRS mint 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 48E048E62A932430 tat_hv112 Protein Tat tat Transactivating regulatory protein protein protein hv112 Human immunodeficiency virus type 1 group M subtype B (isolate PCV12) MEPVDPRLEPWKHPGSQPKTACTNCYCKKCCFHCQVCFITKALGISYGRKKRRQRRRAPQGSQTHQVSLSKQPTSQSRGDPTGPKE mint 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 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 4DD609414FBE9115 vpr-tat 1 3 unspecified role unspecified role prey prey purified purified binding site binding region binding-associated region binding region deletion analysis deletion analysis certain certain sequence position certain certain certain sequence position certain range MINT-429378: original sequence: 50-67 : KKRRQRRRAPQGSQTHQ Stoichiometry: 1.0 2 unspecified role unspecified role bait bait purified purified Stoichiometry: 1.0 direct interaction direct interaction homomint mint