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 http://mint.bio.uniroma2.it/mint kamine-1996-1 Identification of a cellular protein that specifically interacts with the essential cysteine region of the HIV-1 Tat transactivator. in vivo in vivo 2 hybrid two hybrid 2H 2h Gal4 transcription regeneration two-hybrid yeast two hybrid 2-hybrid classical two hybrid classical two hybrid 2H two-hybrid 2-hybrid Gal4 transcription regeneration 2h yeast two hybrid Y2H Y-2H 2 hybrid predetermined predetermined participant predetermined Kamine J., Elangovan B., Subramanian T., Coleman D., Chinnadurai G. Virus - Publications including interactions involving viral proteins Virology (0042-6822) 1996 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 kat5_human Histone acetyltransferase KAT5 KAT5 TIP60 HTATIP Lysine acetyltransferase 5 cPLA(2)-interacting protein Histone acetyltransferase HTATIP 60 kDa Tat-interactive protein protein protein human Homo sapiens Human MAEVGEIIEGCRLPVLRRNQDNEDEWPLAEILSVKDISGRKLFYVHYIDFNKRLDEWVTHERLDLKKIQFPKKEAKTPTKNGLPGSRPGSPEREVPASAQASGKTLPIPVQITLRFNLPKEREAIPGGEPDQPLSSSSCLQPNHRSTKRKVEVVSPATPVPSETAPASVFPQNGAARRAVAAQPGRKRKSNCLGTDEDSQDSSDGIPSAPRMTGSLVSDRSHDDIVTRMKNIECIELGRHRLKPWYFSPYPQELTTLPVLYLCEFCLKYGRSLKCLQRHLTKCDLRHPPGNEIYRKGTISFFEIDGRKNKSYSQNLCLLAKCFLDHKTLYYDTDPFLFYVMTEYDCKGFHIVGYFSKEKESTEDYNVACILTLPPYQRRGYGKLLIEFSYELSKVEGKTGTPEKPLSDLGLLSYRSYWSQTILEILMGLKSESGERPQITINEISEITSIKKEDVISTLQYLNLINYYKGQYILTLSEDIVDGHERAMLKRLLRIDSKCLHFTPKDWSKRGKW kat5-tat 4520 tat_hv112 4521 nucleotide sequence nucleotide sequence identification sequence cloning sequence cloning nucleotide sequence unspecified role unspecified role prey prey over-expressed over expressed level over-expressed tagged molecule tag tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false Stoichiometry: 1.0 kat5_human 4522 nucleotide sequence nucleotide sequence identification sequence cloning sequence cloning nucleotide sequence unspecified role unspecified role bait bait over-expressed over expressed level over-expressed tagged molecule tag tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false Stoichiometry: 1.0 physical association physical association false false false homomint mint