TAT_HV1BR
ID TAT_HV1BR Reviewed; 86 AA.
AC P04610;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 13-AUG-1987, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Protein Tat {ECO:0000255|HAMAP-Rule:MF_04079};
DE AltName: Full=Transactivating regulatory protein {ECO:0000255|HAMAP-Rule:MF_04079};
GN Name=tat {ECO:0000255|HAMAP-Rule:MF_04079};
OS Human immunodeficiency virus type 1 group M subtype B (isolate BRU/LAI)
OS (HIV-1).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX NCBI_TaxID=11686;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=2981635; DOI=10.1016/0092-8674(85)90303-4;
RA Wain-Hobson S., Sonigo P., Danos O., Cole S., Alizon M.;
RT "Nucleotide sequence of the AIDS virus, LAV.";
RL Cell 40:9-17(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Clone pNL4-3;
RA Buckler C.E., Buckler-White A.J., Willey R.L., McCoy J.;
RL Submitted (JUN-1988) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP INTERACTION WITH HUMAN PSMC3.
RX PubMed=2194290; DOI=10.1126/science.2194290;
RA Nelbock P., Dillion P.J., Perkins A., Rosen C.A.;
RT "A cDNA for a protein that interacts with the human immunodeficiency virus
RT Tat transactivator.";
RL Science 248:1650-1653(1990).
RN [4]
RP INTERACTION WITH HUMAN TBP.
RX PubMed=8121496; DOI=10.1038/367295a0;
RA Kashanchi F., Piras G., Radonovich M.F., Duvall J.F., Fattaey A.,
RA Chiang C.M., Roeder R.G., Brady J.N.;
RT "Direct interaction of human TFIID with the HIV-1 transactivator tat.";
RL Nature 367:295-299(1994).
RN [5]
RP INTERACTION WITH HUMAN DPP4.
RX PubMed=7912830; DOI=10.1073/pnas.91.14.6594;
RA Gutheil W.G., Subramanyam M., Flentke G.R., Sanford D.G., Munoz E.,
RA Huber B.T., Bachovchin W.W.;
RT "Human immunodeficiency virus 1 Tat binds to dipeptidyl aminopeptidase IV
RT (CD26): a possible mechanism for Tat's immunosuppressive activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:6594-6598(1994).
RN [6]
RP FUNCTION.
RX PubMed=7638159; DOI=10.1073/pnas.92.16.7153;
RA Wu-Baer F., Sigman D., Gaynor R.B.;
RT "Specific binding of RNA polymerase II to the human immunodeficiency virus
RT trans-activating region RNA is regulated by cellular cofactors and Tat.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:7153-7157(1995).
RN [7]
RP INTERACTION WITH HUMAN TBP.
RX PubMed=7608968; DOI=10.1006/jmbi.1995.0368;
RA Veschambre P., Simard P., Jalinot P.;
RT "Evidence for functional interaction between the HIV-1 Tat transactivator
RT and the TATA box binding protein in vivo.";
RL J. Mol. Biol. 250:169-180(1995).
RN [8]
RP FUNCTION.
RX PubMed=8934526; DOI=10.1038/384375a0;
RA Parada C.A., Roeder R.G.;
RT "Enhanced processivity of RNA polymerase II triggered by Tat-induced
RT phosphorylation of its carboxy-terminal domain.";
RL Nature 384:375-378(1996).
RN [9]
RP INTERACTION WITH HUMAN KAT5.
RX PubMed=8607265; DOI=10.1006/viro.1996.0071;
RA Kamine J., Elangovan B., Subramanian T., Coleman D., Chinnadurai G.;
RT "Identification of a cellular protein that specifically interacts with the
RT essential cysteine region of the HIV-1 Tat transactivator.";
RL Virology 216:357-366(1996).
RN [10]
RP CYS-RICH REGION, ZINC-BINDING, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=8878561; DOI=10.1006/bbrc.1996.1554;
RA Huang H.-W., Wang K.-T.;
RT "Structural characterization of the metal binding site in the cysteine-rich
RT region of HIV-1 Tat protein.";
RL Biochem. Biophys. Res. Commun. 227:615-621(1996).
RN [11]
RP FUNCTION.
RX PubMed=8676466; DOI=10.1128/jvi.70.7.4427-4437.1996;
RA Demarchi F., d'Adda di Fagagna F., Falaschi A., Giacca M.;
RT "Activation of transcription factor NF-kappaB by the Tat protein of human
RT immunodeficiency virus type 1.";
RL J. Virol. 70:4427-4437(1996).
RN [12]
RP IDENTIFICATION IN A COMPLEX WITH P-TEFB; TAR RNA AND RNA POL II.
RX PubMed=9649438; DOI=10.1093/emboj/17.13.3681;
RA Zhou Q., Chen D., Pierstorff E., Luo K.;
RT "Transcription elongation factor P-TEFb mediates Tat activation of HIV-1
RT transcription at multiple stages.";
RL EMBO J. 17:3681-3691(1998).
RN [13]
RP INTERACTION WITH HUMAN CCR2 AND CCR3.
RX PubMed=9789057; DOI=10.1073/pnas.95.22.13153;
RA Albini A., Ferrini S., Benelli R., Sforzini S., Giunciuglio D.,
RA Aluigi M.G., Proudfoot A.E.I., Alouani S., Wells T.N.C., Mariani G.,
RA Rabin R.L., Farber J.M., Noonan D.M.;
RT "HIV-1 Tat protein mimicry of chemokines.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:13153-13158(1998).
RN [14]
RP INTERACTION WITH HUMAN HTATIP2.
RX PubMed=9482853; DOI=10.1073/pnas.95.5.2146;
RA Xiao H., Tao Y., Greenblatt J., Roeder R.G.;
RT "A cofactor, TIP30, specifically enhances HIV-1 Tat-activated
RT transcription.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:2146-2151(1998).
RN [15]
RP FUNCTION, INTERACTION WITH HUMAN CCNT1, AND IDENTIFICATION IN A COMPLEX
RP WITH CCNT1; CDK9 AND TAR RNA.
RX PubMed=10329125; DOI=10.1006/jmbi.1999.2663;
RA Ivanov D., Kwak Y.T., Nee E., Guo J., Garcia-Martinez L.F., Gaynor R.B.;
RT "Cyclin T1 domains involved in complex formation with Tat and TAR RNA are
RT critical for tat-activation.";
RL J. Mol. Biol. 288:41-56(1999).
RN [16]
RP NUCLEAR LOCALIZATION SIGNAL, AND INTERACTION WITH KPNB1.
RX PubMed=9891055; DOI=10.1128/mcb.19.2.1210;
RA Truant R., Cullen B.R.;
RT "The arginine-rich domains present in human immunodeficiency virus type 1
RT Tat and Rev function as direct importin beta-dependent nuclear localization
RT signals.";
RL Mol. Cell. Biol. 19:1210-1217(1999).
RN [17]
RP FUNCTION.
RX PubMed=10400814; DOI=10.1128/jvi.73.8.7080-7086.1999;
RA Demarchi F., Gutierrez M.I., Giacca M.;
RT "Human immunodeficiency virus type 1 tat protein activates transcription
RT factor NF-kappaB through the cellular interferon-inducible, double-stranded
RT RNA-dependent protein kinase, PKR.";
RL J. Virol. 73:7080-7086(1999).
RN [18]
RP INTERACTION WITH HUMAN ITGAV/ITGB3 AND ITGA5/ITGB1 INTEGRINS.
RX PubMed=10397733;
RA Barillari G., Sgadari C., Fiorelli V., Samaniego F., Colombini S.,
RA Manzari V., Modesti A., Nair B.C., Cafaro A., Stuerzl M., Ensoli B.;
RT "The Tat protein of human immunodeficiency virus type-1 promotes vascular
RT cell growth and locomotion by engaging the alpha5beta1 and alphavbeta3
RT integrins and by mobilizing sequestered basic fibroblast growth factor.";
RL Blood 94:663-672(1999).
RN [19]
RP INTERACTION WITH HUMAN CCNT1.
RX PubMed=10364329; DOI=10.1128/jvi.73.7.5777-5786.1999;
RA Bieniasz P.D., Grdina T.A., Bogerd H.P., Cullen B.R.;
RT "Analysis of the effect of natural sequence variation in Tat and in cyclin
RT T on the formation and RNA binding properties of Tat-cyclin T complexes.";
RL J. Virol. 73:5777-5786(1999).
RN [20]
RP ACETYLATION AT LYS-50 BY EP300, ACETYLATION AT LYS-28 BY PCAF, AND
RP MUTAGENESIS OF LYS-28 AND LYS-50.
RX PubMed=10545121; DOI=10.1093/emboj/18.21.6106;
RA Kiernan R.E., Vanhulle C., Schiltz L., Adam E., Xiao H., Maudoux F.,
RA Calomme C., Burny A., Nakatani Y., Jeang K.-T., Benkirane M., Van Lint C.;
RT "HIV-1 tat transcriptional activity is regulated by acetylation.";
RL EMBO J. 18:6106-6118(1999).
RN [21]
RP INTERACTION WITH HUMAN CXCR4.
RC STRAIN=Clone pNL4-3;
RX PubMed=11027346; DOI=10.1073/pnas.97.21.11466;
RA Xiao H., Neuveut C., Tiffany H.L., Benkirane M., Rich E.A., Murphy P.M.,
RA Jeang K.-T.;
RT "Selective CXCR4 antagonism by Tat: implications for in vivo expansion of
RT coreceptor use by HIV-1.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:11466-11471(2000).
RN [22]
RP INTERACTION WITH HUMAN KDR; ITGAV AND ITGB1.
RX PubMed=10590123; DOI=10.1128/jvi.74.1.344-353.2000;
RA Mitola S., Soldi R., Zanon I., Barra L., Gutierrez M.I., Berkhout B.,
RA Giacca M., Bussolino F.;
RT "Identification of specific molecular structures of human immunodeficiency
RT virus type 1 Tat relevant for its biological effects on vascular
RT endothelial cells.";
RL J. Virol. 74:344-353(2000).
RN [23]
RP ACETYLATION AT LYS-50 AND LYS-51 BY EP300, AND MUTAGENESIS OF LYS-50 AND
RP LYS-51.
RX PubMed=11080476; DOI=10.1006/viro.2000.0593;
RA Deng L., de la Fuente C., Fu P., Wang L., Donnelly R., Wade J.D.,
RA Lambert P., Li H., Lee C.-G., Kashanchi F.;
RT "Acetylation of HIV-1 Tat by CBP/P300 increases transcription of integrated
RT HIV-1 genome and enhances binding to core histones.";
RL Virology 277:278-295(2000).
RN [24]
RP FUNCTION.
RX PubMed=10958691; DOI=10.1128/mcb.20.18.6958-6969.2000;
RA Garber M.E., Mayall T.P., Suess E.M., Meisenhelder J., Thompson N.E.,
RA Jones K.A.;
RT "CDK9 autophosphorylation regulates high-affinity binding of the human
RT immunodeficiency virus type 1 tat-P-TEFb complex to TAR RNA.";
RL Mol. Cell. Biol. 20:6958-6969(2000).
RN [25]
RP INTERACTION WITH HOST RNGTT.
RX PubMed=11278368; DOI=10.1074/jbc.m007901200;
RA Chiu Y.-L., Coronel E., Ho C.K., Shuman S., Rana T.M.;
RT "HIV-1 Tat protein interacts with mammalian capping enzyme and stimulates
RT capping of TAR RNA.";
RL J. Biol. Chem. 276:12959-12966(2001).
RN [26]
RP INTERACTION WITH HEPARAN SULFATE PROTEOGLYCANS.
RX PubMed=11024024; DOI=10.1074/jbc.m006701200;
RA Tyagi M., Rusnati M., Presta M., Giacca M.;
RT "Internalization of HIV-1 tat requires cell surface heparan sulfate
RT proteoglycans.";
RL J. Biol. Chem. 276:3254-3261(2001).
RN [27]
RP INTERACTION WITH HUMAN GCN5L2, AND ACETYLATION AT LYS-50 AND LYS-51 BY
RP HUMAN GCN5L2.
RX PubMed=11384967; DOI=10.1074/jbc.m101385200;
RA Col E., Caron C., Seigneurin-Berny D., Gracia J., Favier A., Khochbin S.;
RT "The histone acetyltransferase, hGCN5, interacts with and acetylates the
RT HIV transactivator, Tat.";
RL J. Biol. Chem. 276:28179-28184(2001).
RN [28]
RP FUNCTION.
RX PubMed=12052871; DOI=10.1128/mcb.22.13.4622-4637.2002;
RA Kim Y.K., Bourgeois C.F., Isel C., Churcher M.J., Karn J.;
RT "Phosphorylation of the RNA polymerase II carboxyl-terminal domain by CDK9
RT is directly responsible for human immunodeficiency virus type 1 Tat-
RT activated transcriptional elongation.";
RL Mol. Cell. Biol. 22:4622-4637(2002).
RN [29]
RP INTERACTION WITH HUMAN PCAF.
RX PubMed=12486002; DOI=10.1093/emboj/cdf669;
RA Bres V., Tagami H., Peloponese J.-M., Loret E., Jeang K.-T., Nakatani Y.,
RA Emiliani S., Benkirane M., Kiernan R.E.;
RT "Differential acetylation of Tat coordinates its interaction with the co-
RT activators cyclin T1 and PCAF.";
RL EMBO J. 21:6811-6819(2002).
RN [30]
RP FUNCTION.
RX PubMed=12154097; DOI=10.1074/jbc.m206694200;
RA Col E., Gilquin B., Caron C., Khochbin S.;
RT "Tat-controlled protein acetylation.";
RL J. Biol. Chem. 277:37955-37960(2002).
RN [31]
RP INTERACTION WITH HUMAN PCAF BROMODOMAIN.
RX PubMed=12032084; DOI=10.1093/emboj/21.11.2715;
RA Dorr A., Kiermer V., Pedal A., Rackwitz H.R., Henklein P., Schubert U.,
RA Zhou M.-M., Verdin E., Ott M.;
RT "Transcriptional synergy between Tat and PCAF is dependent on the binding
RT of acetylated Tat to the PCAF bromodomain.";
RL EMBO J. 21:2715-2723(2002).
RN [32]
RP UBIQUITINATION AT LYS-71 BY HUMAN MDM2, AND INTERACTION WITH HUMAN MDM2.
RC STRAIN=Clone pNL4-3;
RX PubMed=12883554; DOI=10.1038/ncb1023;
RA Bres V., Kiernan R.E., Linares L.K., Chable-Bessia C., Plechakova O.,
RA Treand C., Emiliani S., Peloponese J.-M., Jeang K.-T., Coux O.,
RA Scheffner M., Benkirane M.;
RT "A non-proteolytic role for ubiquitin in Tat-mediated transactivation of
RT the HIV-1 promoter.";
RL Nat. Cell Biol. 5:754-761(2003).
RN [33]
RP CYS-RICH REGION, AND ZINC-BINDING.
RX PubMed=15117453; DOI=10.1089/088922204322996536;
RA Misumi S., Takamune N., Ohtsubo Y., Waniguchi K., Shoji S.;
RT "Zn2+ binding to cysteine-rich domain of extracellular human
RT immunodeficiency virus type 1 Tat protein is associated with Tat protein-
RT induced apoptosis.";
RL AIDS Res. Hum. Retroviruses 20:297-304(2004).
RN [34]
RP FUNCTION, AND INTERACTION WITH HUMAN SATB1.
RX PubMed=15713622; DOI=10.1128/mcb.25.5.1620-1633.2005;
RA Kumar P.P., Purbey P.K., Ravi D.S., Mitra D., Galande S.;
RT "Displacement of SATB1-bound histone deacetylase 1 corepressor by the human
RT immunodeficiency virus type 1 transactivator induces expression of
RT interleukin-2 and its receptor in T cells.";
RL Mol. Cell. Biol. 25:1620-1633(2005).
RN [35]
RP INTERACTION WITH HUMAN SIRT1, AND DEACETYLATION AT LYS-50 BY SIRT1.
RX PubMed=15719057; DOI=10.1371/journal.pbio.0030041;
RA Pagans S., Pedal A., North B.J., Kaehlcke K., Marshall B.L., Dorr A.,
RA Hetzer-Egger C., Henklein P., Frye R., McBurney M.W., Hruby H., Jung M.,
RA Verdin E., Ott M.;
RT "SIRT1 regulates HIV transcription via Tat deacetylation.";
RL PLoS Biol. 3:210-220(2005).
RN [36]
RP INTERACTION WITH HUMAN KAT5.
RC STRAIN=Clone pNL4-3;
RX PubMed=16001085; DOI=10.1038/sj.emboj.7600734;
RA Col E., Caron C., Chable-Bessia C., Legube G., Gazzeri S., Komatsu Y.,
RA Yoshida M., Benkirane M., Trouche D., Khochbin S.;
RT "HIV-1 Tat targets Tip60 to impair the apoptotic cell response to genotoxic
RT stresses.";
RL EMBO J. 24:2634-2645(2005).
RN [37]
RP FUNCTION, AND INTERACTION WITH HUMAN TBP.
RX PubMed=15719058; DOI=10.1371/journal.pbio.0030044;
RA Raha T., Cheng S.W.G., Green M.R.;
RT "HIV-1 Tat stimulates transcription complex assembly through recruitment of
RT TBP in the absence of TAFs.";
RL PLoS Biol. 3:221-230(2005).
RN [38]
RP INTERACTION WITH HUMAN MMP1.
RX PubMed=16807369; DOI=10.1096/fj.05-5619fje;
RA Rumbaugh J., Turchan-Cholewo J., Galey D., St Hillaire C., Anderson C.,
RA Conant K., Nath A.;
RT "Interaction of HIV Tat and matrix metalloproteinase in HIV
RT neuropathogenesis: a new host defense mechanism.";
RL FASEB J. 20:1736-1738(2006).
RN [39]
RP FUNCTION.
RX PubMed=16920714; DOI=10.1074/jbc.m512109200;
RA Gee K., Angel J.B., Ma W., Mishra S., Gajanayaka N., Parato K., Kumar A.;
RT "Intracellular HIV-Tat expression induces IL-10 synthesis by the CREB-1
RT transcription factor through Ser133 phosphorylation and its regulation by
RT the ERK1/2 MAPK in human monocytic cells.";
RL J. Biol. Chem. 281:31647-31658(2006).
RN [40]
RP REVIEW, AND ALTERNATIVE SPLICING.
RX PubMed=16046164; DOI=10.1016/j.micinf.2005.06.003;
RA Hetzer C., Dormeyer W., Schnolzer M., Ott M.;
RT "Decoding Tat: the biology of HIV Tat posttranslational modifications.";
RL Microbes Infect. 7:1364-1369(2005).
RN [41]
RP REVIEW.
RX PubMed=16146763; DOI=10.2741/1829;
RA Peruzzi F.;
RT "The multiple functions of HIV-1 Tat: proliferation versus apoptosis.";
RL Front. Biosci. 11:708-717(2006).
RN [42]
RP REVIEW.
RX PubMed=16697675; DOI=10.1016/j.micinf.2005.11.014;
RA King J.E., Eugenin E.A., Buckner C.M., Berman J.W.;
RT "HIV tat and neurotoxicity.";
RL Microbes Infect. 8:1347-1357(2006).
RN [43]
RP FUNCTION.
RX PubMed=19671151; DOI=10.1186/1742-4690-6-74;
RA Charnay N., Ivanyi-Nagy R., Soto-Rifo R., Ohlmann T., Lopez-Lastra M.,
RA Darlix J.L.;
RT "Mechanism of HIV-1 Tat RNA translation and its activation by the Tat
RT protein.";
RL Retrovirology 6:74-74(2009).
RN [44]
RP STRUCTURE BY NMR OF 46-55 IN COMPLEX WITH PCAF BROMODOMAIN.
RX PubMed=11931765; DOI=10.1016/s1097-2765(02)00483-5;
RA Mujtaba S., He Y., Zeng L., Farooq A., Carlson J.E., Ott M., Verdin E.,
RA Zhou M.-M.;
RT "Structural basis of lysine-acetylated HIV-1 Tat recognition by PCAF
RT bromodomain.";
RL Mol. Cell 9:575-586(2002).
RN [45]
RP STRUCTURE BY NMR.
RX PubMed=11098404; DOI=10.1016/s0764-4469(00)01228-2;
RA Peloponese J.M. Jr., Gregoire C., Opi S., Esquieu D., Sturgis J.,
RA Lebrun E., Meurs E., Collette Y., Olive D., Aubertin A.M., Witvrow M.,
RA Pannecouque C., De Clercq E., Bailly C., Lebreton J., Loret E.P.;
RT "1H-13C nuclear magnetic resonance assignment and structural
RT characterization of HIV-1 Tat protein.";
RL C. R. Acad. Sci. III, Sci. Vie 323:883-894(2000).
CC -!- FUNCTION: Nuclear transcriptional activator of viral gene expression,
CC that is essential for viral transcription from the LTR promoter and
CC replication. Acts as a sequence-specific molecular adapter, directing
CC components of the cellular transcription machinery to the viral RNA to
CC promote processive transcription elongation by the RNA polymerase II
CC (RNA pol II) complex, thereby increasing the level of full-length
CC transcripts. In the absence of Tat, the RNA Pol II generates short or
CC non-processive transcripts that terminate at approximately 60 bp from
CC the initiation site. Tat associates with the CCNT1/cyclin-T1 component
CC of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain
CC elongation. This binding increases Tat's affinity for a hairpin
CC structure at the 5'-end of all nascent viral mRNAs referred to as the
CC transactivation responsive RNA element (TAR RNA) and allows Tat/P-TEFb
CC complex to bind cooperatively to TAR RNA. The CDK9 component of P-TEFb
CC and other Tat-activated kinases hyperphosphorylate the C-terminus of
CC RNA Pol II that becomes stabilized and much more processive. Other
CC factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also
CC important for Tat's function. Besides its effect on RNA Pol II
CC processivity, Tat induces chromatin remodeling of proviral genes by
CC recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF
CC to the chromatin. This also contributes to the increase in proviral
CC transcription rate, especially when the provirus integrates in
CC transcriptionally silent region of the host genome. To ensure maximal
CC activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B
CC by interacting with host RELA. Through its interaction with host TBP,
CC Tat may also modulate transcription initiation. Tat can reactivate a
CC latently infected cell by penetrating in it and transactivating its LTR
CC promoter. In the cytoplasm, Tat is thought to act as a translational
CC activator of HIV-1 mRNAs. {ECO:0000255|HAMAP-Rule:MF_04079}.
CC -!- FUNCTION: Extracellular circulating Tat can be endocytosed by
CC surrounding uninfected cells via the binding to several surface
CC receptors such as CD26, CXCR4, heparan sulfate proteoglycans (HSPG) or
CC LDLR. Neurons are rarely infected, but they internalize Tat via their
CC LDLR. Through its interaction with nuclear HATs, Tat is potentially
CC able to control the acetylation-dependent cellular gene expression.
CC Modulates the expression of many cellular genes involved in cell
CC survival, proliferation or in coding for cytokines or cytokine
CC receptors. Tat plays a role in T-cell and neurons apoptosis. Tat
CC induced neurotoxicity and apoptosis probably contribute to neuroAIDS.
CC Circulating Tat also acts as a chemokine-like and/or growth factor-like
CC molecule that binds to specific receptors on the surface of the cells,
CC affecting many cellular pathways. In the vascular system, Tat binds to
CC ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of
CC endothelial cells and competes with bFGF for heparin-binding sites,
CC leading to an excess of soluble bFGF. {ECO:0000255|HAMAP-
CC Rule:MF_04079}.
CC -!- SUBUNIT: Interacts with host CCNT1. Associates with the P-TEFb complex
CC composed at least of Tat, P-TEFb (CDK9 and CCNT1), TAR RNA, RNA Pol II.
CC Recruits the HATs CREBBP, TAF1/TFIID, EP300, PCAF and GCN5L2. Interacts
CC with host KAT5/Tip60; this interaction targets the latter to
CC degradation. Interacts with the host deacetylase SIRT1. Interacts with
CC host capping enzyme RNGTT; this interaction stimulates RNGTT. Binds to
CC host KDR, and to the host integrins ITGAV/ITGB3 and ITGA5/ITGB1.
CC Interacts with host KPNB1/importin beta-1 without previous binding to
CC KPNA1/importin alpha-1. Interacts with EIF2AK2. Interacts with host
CC nucleosome assembly protein NAP1L1; this interaction may be required
CC for the transport of Tat within the nucleus, since the two proteins
CC interact at the nuclear rim. Interacts with host C1QBP/SF2P32; this
CC interaction involves lysine-acetylated Tat. Interacts with the host
CC chemokine receptors CCR2, CCR3 and CXCR4. Interacts with host
CC DPP4/CD26; this interaction may trigger an anti-proliferative effect.
CC Interacts with host LDLR. Interacts with the host extracellular matrix
CC metalloproteinase MMP1. Interacts with host PRMT6; this interaction
CC mediates Tat's methylation. Interacts with, and is ubiquitinated by
CC MDM2/Hdm2. Interacts with host PSMC3 and HTATIP2. Interacts with STAB1;
CC this interaction may overcome SATB1-mediated repression of IL2 and
CC IL2RA (interleukin) in T cells by binding to the same domain than
CC HDAC1. Interacts (when acetylated) with human CDK13, thereby increasing
CC HIV-1 mRNA splicing and promoting the production of the doubly spliced
CC HIV-1 protein Nef.Interacts with host TBP; this interaction modulates
CC the activity of transcriptional pre-initiation complex. Interacts with
CC host RELA. {ECO:0000255|HAMAP-Rule:MF_04079,
CC ECO:0000269|PubMed:10329125, ECO:0000269|PubMed:10364329,
CC ECO:0000269|PubMed:10397733, ECO:0000269|PubMed:10590123,
CC ECO:0000269|PubMed:11024024, ECO:0000269|PubMed:11027346,
CC ECO:0000269|PubMed:11278368, ECO:0000269|PubMed:11384967,
CC ECO:0000269|PubMed:11931765, ECO:0000269|PubMed:12032084,
CC ECO:0000269|PubMed:12486002, ECO:0000269|PubMed:12883554,
CC ECO:0000269|PubMed:15713622, ECO:0000269|PubMed:15719057,
CC ECO:0000269|PubMed:15719058, ECO:0000269|PubMed:16001085,
CC ECO:0000269|PubMed:16807369, ECO:0000269|PubMed:2194290,
CC ECO:0000269|PubMed:7608968, ECO:0000269|PubMed:7912830,
CC ECO:0000269|PubMed:8121496, ECO:0000269|PubMed:8607265,
CC ECO:0000269|PubMed:9482853, ECO:0000269|PubMed:9649438,
CC ECO:0000269|PubMed:9789057, ECO:0000269|PubMed:9891055}.
CC -!- INTERACTION:
CC P04610; O60563: CCNT1; Xeno; NbExp=2; IntAct=EBI-7845069, EBI-2479671;
CC P04610; Q9UBN7: HDAC6; Xeno; NbExp=10; IntAct=EBI-7845069, EBI-301697;
CC -!- SUBCELLULAR LOCATION: Host nucleus, host nucleolus {ECO:0000255|HAMAP-
CC Rule:MF_04079}. Host cytoplasm {ECO:0000255|HAMAP-Rule:MF_04079}.
CC Secreted {ECO:0000255|HAMAP-Rule:MF_04079}. Note=Probably localizes to
CC both nuclear and nucleolar compartments. Nuclear localization is
CC mediated through the interaction of the nuclear localization signal
CC with importin KPNB1. Secretion occurs through a Golgi-independent
CC pathway. Tat is released from infected cells to the extracellular space
CC where it remains associated to the cell membrane, or is secreted into
CC the cerebrospinal fluid and sera. Extracellular Tat can be endocytosed
CC by surrounding uninfected cells via binding to several receptors
CC depending on the cell type. {ECO:0000255|HAMAP-Rule:MF_04079}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=P04610-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P04610-2; Sequence=VSP_022299;
CC -!- DOMAIN: The cell attachment site mediates the interaction with
CC ITGAV/ITGB3 and ITGA5/ITGB1 integrins, leading to vascular cell
CC migration and invasion. This interaction also provides endothelial
CC cells with the adhesion signal they require to grow in response to
CC mitogens. {ECO:0000255|HAMAP-Rule:MF_04079,
CC ECO:0000269|PubMed:10397733}.
CC -!- DOMAIN: The Cys-rich region may bind 2 zinc ions. This region is
CC involved in binding to KAT5. {ECO:0000255|HAMAP-Rule:MF_04079}.
CC -!- DOMAIN: The transactivation domain mediates the interaction with CCNT1,
CC GCN5L2, and MDM2. {ECO:0000255|HAMAP-Rule:MF_04079}.
CC -!- DOMAIN: The Arg-rich RNA-binding region binds the TAR RNA. This region
CC also mediates the nuclear localization through direct binding to KPNB1
CC and is involved in Tat's transfer across cell membranes (protein
CC transduction). The same region is required for the interaction with
CC EP300, PCAF, EIF2AK2 and KDR.
CC -!- PTM: Asymmetrical arginine methylation by host PRMT6 seems to diminish
CC the transactivation capacity of Tat and affects the interaction with
CC host CCNT1. {ECO:0000255|HAMAP-Rule:MF_04079}.
CC -!- PTM: Acetylation by EP300, CREBBP, GCN5L2/GCN5 and PCAF regulates the
CC transactivation activity of Tat. EP300-mediated acetylation of Lys-50
CC promotes dissociation of Tat from the TAR RNA through the competitive
CC binding to PCAF's bromodomain. In addition, the non-acetylated Tat's N-
CC terminus can also interact with PCAF. PCAF-mediated acetylation of Lys-
CC 28 enhances Tat's binding to CCNT1. Lys-50 is deacetylated by SIRT1.
CC {ECO:0000255|HAMAP-Rule:MF_04079}.
CC -!- PTM: Polyubiquitination by host MDM2 does not target Tat to
CC degradation, but activates its transactivation function and fosters
CC interaction with CCNT1 and TAR RNA. {ECO:0000255|HAMAP-Rule:MF_04079,
CC ECO:0000269|PubMed:12883554}.
CC -!- PTM: Phosphorylated by EIF2AK2 on serine and threonine residues
CC adjacent to the basic region important for TAR RNA binding and
CC function. Phosphorylation of Tat by EIF2AK2 is dependent on the prior
CC activation of EIF2AK2 by dsRNA. {ECO:0000255|HAMAP-Rule:MF_04079}.
CC -!- MISCELLANEOUS: The infectious clone pNL4-3 is a chimeric provirus that
CC consists of DNA from HIV isolates NY5 (5' half) and BRU (3' half).
CC -!- MISCELLANEOUS: This truncated variant has a premature stop codon. It
CC may have arose as a consequence of tissue culture passaging.
CC {ECO:0000255|HAMAP-Rule:MF_04079}.
CC -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC majority of strains found worldwide belong to the group M. Group O
CC seems to be endemic to and largely confined to Cameroon and neighboring
CC countries in West Central Africa, where these viruses represent a small
CC minority of HIV-1 strains. The group N is represented by a limited
CC number of isolates from Cameroonian persons. The group M is further
CC subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC {ECO:0000255|HAMAP-Rule:MF_04079}.
CC -!- MISCELLANEOUS: [Isoform Short]: Expressed in the late stage of the
CC infection cycle, when unspliced viral RNAs are exported to the
CC cytoplasm by the viral Rev protein. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the lentiviruses Tat family. {ECO:0000255|HAMAP-
CC Rule:MF_04079}.
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DR EMBL; K02013; AAB59745.1; -; Genomic_RNA.
DR EMBL; M19921; AAA44985.1; -; Genomic_RNA.
DR PIR; A25700; A25700.
DR PDB; 1JFW; NMR; -; A=1-86.
DR PDB; 1JM4; NMR; -; A=46-55.
DR PDBsum; 1JFW; -.
DR PDBsum; 1JM4; -.
DR SMR; P04610; -.
DR IntAct; P04610; 8.
DR MINT; P04610; -.
DR iPTMnet; P04610; -.
DR EvolutionaryTrace; P04610; -.
DR Proteomes; UP000007692; Genome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0044196; C:host cell nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0042805; F:actinin binding; IEA:UniProtKB-UniRule.
DR GO; GO:0030332; F:cyclin binding; IEA:UniProtKB-UniRule.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0019904; F:protein domain specific binding; IEA:UniProtKB-UniRule.
DR GO; GO:0001070; F:RNA-binding transcription regulator activity; IEA:UniProtKB-UniRule.
DR GO; GO:1990970; F:trans-activation response element binding; IEA:UniProtKB-UniRule.
DR GO; GO:0060081; P:membrane hyperpolarization; IDA:CACAO.
DR GO; GO:0039525; P:modulation by virus of host chromatin organization; IEA:UniProtKB-UniRule.
DR GO; GO:0039586; P:modulation by virus of host PP1 activity; IEA:UniProtKB-UniRule.
DR GO; GO:1901856; P:negative regulation of cellular respiration; IDA:CACAO.
DR GO; GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; IEA:UniProtKB-UniRule.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:CACAO.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IDA:CACAO.
DR GO; GO:0032968; P:positive regulation of transcription elongation from RNA polymerase II promoter; IEA:UniProtKB-UniRule.
DR GO; GO:0050434; P:positive regulation of viral transcription; IEA:UniProtKB-UniRule.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-UniRule.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-UniRule.
DR Gene3D; 4.10.20.10; -; 1.
DR HAMAP; MF_04079; HIV_TAT; 1.
DR InterPro; IPR001831; IV_Tat.
DR InterPro; IPR036963; Tat_dom_sf.
DR Pfam; PF00539; Tat; 1.
DR PRINTS; PR00055; HIVTATDOMAIN.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; AIDS; Alternative splicing;
KW Apoptosis; Host cytoplasm; Host nucleus; Host-virus interaction;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus; Isopeptide bond;
KW Metal-binding; Methylation; Modulation of host chromatin by virus;
KW Modulation of host PP1 activity by virus; Phosphoprotein;
KW Reference proteome; RNA-binding; Secreted; Transcription;
KW Transcription regulation; Ubl conjugation; Viral immunoevasion; Zinc.
FT CHAIN 1..86
FT /note="Protein Tat"
FT /id="PRO_0000085346"
FT REGION 1..48
FT /note="Transactivation"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04079"
FT REGION 1..24
FT /note="Interaction with human CREBBP"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04079"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 22..37
FT /note="Cysteine-rich"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04079"
FT REGION 38..48
FT /note="Core"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04079"
FT REGION 47..86
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 49..86
FT /note="Interaction with the host capping enzyme RNGTT"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04079"
FT MOTIF 49..57
FT /note="Nuclear localization signal, RNA-binding (TAR), and
FT protein transduction"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04079,
FT ECO:0000269|PubMed:9891055"
FT MOTIF 78..80
FT /note="Cell attachment site"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04079"
FT COMPBIAS 60..79
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 22
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04079"
FT BINDING 25
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04079"
FT BINDING 27
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04079"
FT BINDING 30
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04079"
FT BINDING 33
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04079"
FT BINDING 34
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04079"
FT BINDING 37
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04079"
FT SITE 11
FT /note="Essential for Tat translocation through the
FT endosomal membrane"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04079"
FT MOD_RES 28
FT /note="N6-acetyllysine; by host PCAF"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04079,
FT ECO:0000269|PubMed:10545121"
FT MOD_RES 50
FT /note="N6-acetyllysine; by host EP300 and GCN5L2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04079,
FT ECO:0000269|PubMed:10545121, ECO:0000269|PubMed:11080476,
FT ECO:0000269|PubMed:11384967"
FT MOD_RES 51
FT /note="N6-acetyllysine; by host EP300 and GCN5L2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04079,
FT ECO:0000269|PubMed:11080476, ECO:0000269|PubMed:11384967"
FT MOD_RES 52
FT /note="Asymmetric dimethylarginine; by host PRMT6"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04079"
FT MOD_RES 53
FT /note="Asymmetric dimethylarginine; by host PRMT6"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04079"
FT CROSSLNK 71
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04079,
FT ECO:0000269|PubMed:12883554"
FT VAR_SEQ 73..86
FT /note="Missing (in isoform Short)"
FT /id="VSP_022299"
FT VARIANT 24
FT /note="T -> N (in strain: Clone pNL4-3)"
FT VARIANT 39
FT /note="T -> M (in strain: Clone pNL4-3)"
FT VARIANT 58..61
FT /note="PPQG -> AHQN (in strain: Clone pNL4-3)"
FT VARIANT 67
FT /note="V -> A (in strain: Clone pNL4-3)"
FT VARIANT 77
FT /note="P -> S (in strain: Clone pNL4-3)"
FT MUTAGEN 28
FT /note="K->A: Strong decrease in Tat transactivation."
FT /evidence="ECO:0000269|PubMed:10545121"
FT MUTAGEN 50
FT /note="K->A: Strong decrease in Tat transactivation."
FT /evidence="ECO:0000269|PubMed:10545121,
FT ECO:0000269|PubMed:11080476"
FT MUTAGEN 51
FT /note="K->A: Strong decrease in Tat transactivation."
FT /evidence="ECO:0000269|PubMed:11080476"
FT STRAND 16..18
FT /evidence="ECO:0007829|PDB:1JFW"
FT STRAND 20..23
FT /evidence="ECO:0007829|PDB:1JFW"
FT TURN 26..29
FT /evidence="ECO:0007829|PDB:1JFW"
FT STRAND 32..35
FT /evidence="ECO:0007829|PDB:1JFW"
FT TURN 39..41
FT /evidence="ECO:0007829|PDB:1JFW"
FT STRAND 42..44
FT /evidence="ECO:0007829|PDB:1JFW"
FT STRAND 47..50
FT /evidence="ECO:0007829|PDB:1JFW"
FT STRAND 60..62
FT /evidence="ECO:0007829|PDB:1JFW"
FT STRAND 69..73
FT /evidence="ECO:0007829|PDB:1JFW"
FT STRAND 78..82
FT /evidence="ECO:0007829|PDB:1JFW"
SQ SEQUENCE 86 AA; 9769 MW; 9B1B4A915FAF8A14 CRC64;
MEPVDPRLEP WKHPGSQPKT ACTTCYCKKC CFHCQVCFTT KALGISYGRK KRRQRRRPPQ
GSQTHQVSLS KQPTSQPRGD PTGPKE
