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Protein Tat (Transactivating regulatory protein)

 TAT_HV1BR               Reviewed;          86 AA.
P04610;
13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
13-AUG-1987, sequence version 1.
25-OCT-2017, entry version 133.
RecName: Full=Protein Tat {ECO:0000255|HAMAP-Rule:MF_04079};
AltName: Full=Transactivating regulatory protein {ECO:0000255|HAMAP-Rule:MF_04079};
Name=tat {ECO:0000255|HAMAP-Rule:MF_04079};
Human immunodeficiency virus type 1 group M subtype B (isolate
BRU/LAI) (HIV-1).
Viruses; Retro-transcribing viruses; Retroviridae; Orthoretrovirinae;
Lentivirus; Primate lentivirus group.
NCBI_TaxID=11686;
NCBI_TaxID=9606; Homo sapiens (Human).
[1]
NUCLEOTIDE SEQUENCE [GENOMIC RNA].
PubMed=2981635; DOI=10.1016/0092-8674(85)90303-4;
Wain-Hobson S., Sonigo P., Danos O., Cole S., Alizon M.;
"Nucleotide sequence of the AIDS virus, LAV.";
Cell 40:9-17(1985).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC RNA].
STRAIN=Clone pNL4-3;
Buckler C.E., Buckler-White A.J., Willey R.L., McCoy J.;
Submitted (JUN-1988) to the EMBL/GenBank/DDBJ databases.
[3]
INTERACTION WITH HUMAN PSMC3.
PubMed=2194290; DOI=10.1126/science.2194290;
Nelbock P., Dillion P.J., Perkins A., Rosen C.A.;
"A cDNA for a protein that interacts with the human immunodeficiency
virus Tat transactivator.";
Science 248:1650-1653(1990).
[4]
INTERACTION WITH HUMAN TBP.
PubMed=8121496; DOI=10.1038/367295a0;
Kashanchi F., Piras G., Radonovich M.F., Duvall J.F., Fattaey A.,
Chiang C.M., Roeder R.G., Brady J.N.;
"Direct interaction of human TFIID with the HIV-1 transactivator
tat.";
Nature 367:295-299(1994).
[5]
INTERACTION WITH HUMAN DPP4.
PubMed=7912830; DOI=10.1073/pnas.91.14.6594;
Gutheil W.G., Subramanyam M., Flentke G.R., Sanford D.G., Munoz E.,
Huber B.T., Bachovchin W.W.;
"Human immunodeficiency virus 1 Tat binds to dipeptidyl aminopeptidase
IV (CD26): a possible mechanism for Tat's immunosuppressive
activity.";
Proc. Natl. Acad. Sci. U.S.A. 91:6594-6598(1994).
[6]
FUNCTION.
PubMed=7638159; DOI=10.1073/pnas.92.16.7153;
Wu-Baer F., Sigman D., Gaynor R.B.;
"Specific binding of RNA polymerase II to the human immunodeficiency
virus trans-activating region RNA is regulated by cellular cofactors
and Tat.";
Proc. Natl. Acad. Sci. U.S.A. 92:7153-7157(1995).
[7]
INTERACTION WITH HUMAN TBP.
PubMed=7608968; DOI=10.1006/jmbi.1995.0368;
Veschambre P., Simard P., Jalinot P.;
"Evidence for functional interaction between the HIV-1 Tat
transactivator and the TATA box binding protein in vivo.";
J. Mol. Biol. 250:169-180(1995).
[8]
FUNCTION.
PubMed=8934526; DOI=10.1038/384375a0;
Parada C.A., Roeder R.G.;
"Enhanced processivity of RNA polymerase II triggered by Tat-induced
phosphorylation of its carboxy-terminal domain.";
Nature 384:375-378(1996).
[9]
INTERACTION WITH HUMAN KAT5.
PubMed=8607265; DOI=10.1006/viro.1996.0071;
Kamine J., Elangovan B., Subramanian T., Coleman D., Chinnadurai G.;
"Identification of a cellular protein that specifically interacts with
the essential cysteine region of the HIV-1 Tat transactivator.";
Virology 216:357-366(1996).
[10]
CYS-RICH REGION, ZINC-BINDING, AND IDENTIFICATION BY MASS
SPECTROMETRY.
PubMed=8878561; DOI=10.1006/bbrc.1996.1554;
Huang H.-W., Wang K.-T.;
"Structural characterization of the metal binding site in the
cysteine-rich region of HIV-1 Tat protein.";
Biochem. Biophys. Res. Commun. 227:615-621(1996).
[11]
FUNCTION.
PubMed=8676466;
Demarchi F., d'Adda di Fagagna F., Falaschi A., Giacca M.;
"Activation of transcription factor NF-kappaB by the Tat protein of
human immunodeficiency virus type 1.";
J. Virol. 70:4427-4437(1996).
[12]
IDENTIFICATION IN A COMPLEX WITH P-TEFB; TAR RNA AND RNA POL II.
PubMed=9649438; DOI=10.1093/emboj/17.13.3681;
Zhou Q., Chen D., Pierstorff E., Luo K.;
"Transcription elongation factor P-TEFb mediates Tat activation of
HIV-1 transcription at multiple stages.";
EMBO J. 17:3681-3691(1998).
[13]
INTERACTION WITH HUMAN CCR2 AND CCR3.
PubMed=9789057; DOI=10.1073/pnas.95.22.13153;
Albini A., Ferrini S., Benelli R., Sforzini S., Giunciuglio D.,
Aluigi M.G., Proudfoot A.E.I., Alouani S., Wells T.N.C., Mariani G.,
Rabin R.L., Farber J.M., Noonan D.M.;
"HIV-1 Tat protein mimicry of chemokines.";
Proc. Natl. Acad. Sci. U.S.A. 95:13153-13158(1998).
[14]
INTERACTION WITH HUMAN HTATIP2.
PubMed=9482853; DOI=10.1073/pnas.95.5.2146;
Xiao H., Tao Y., Greenblatt J., Roeder R.G.;
"A cofactor, TIP30, specifically enhances HIV-1 Tat-activated
transcription.";
Proc. Natl. Acad. Sci. U.S.A. 95:2146-2151(1998).
[15]
FUNCTION, INTERACTION WITH HUMAN CCNT1, AND IDENTIFICATION IN A
COMPLEX WITH CCNT1; CDK9 AND TAR RNA.
PubMed=10329125; DOI=10.1006/jmbi.1999.2663;
Ivanov D., Kwak Y.T., Nee E., Guo J., Garcia-Martinez L.F.,
Gaynor R.B.;
"Cyclin T1 domains involved in complex formation with Tat and TAR RNA
are critical for tat-activation.";
J. Mol. Biol. 288:41-56(1999).
[16]
NUCLEAR LOCALIZATION SIGNAL, AND INTERACTION WITH KPNB1.
PubMed=9891055; DOI=10.1128/MCB.19.2.1210;
Truant R., Cullen B.R.;
"The arginine-rich domains present in human immunodeficiency virus
type 1 Tat and Rev function as direct importin beta-dependent nuclear
localization signals.";
Mol. Cell. Biol. 19:1210-1217(1999).
[17]
FUNCTION.
PubMed=10400814;
Demarchi F., Gutierrez M.I., Giacca M.;
"Human immunodeficiency virus type 1 tat protein activates
transcription factor NF-kappaB through the cellular interferon-
inducible, double-stranded RNA-dependent protein kinase, PKR.";
J. Virol. 73:7080-7086(1999).
[18]
INTERACTION WITH HUMAN ITGAV/ITGB3 AND ITGA5/ITGB1 INTEGRINS.
PubMed=10397733;
Barillari G., Sgadari C., Fiorelli V., Samaniego F., Colombini S.,
Manzari V., Modesti A., Nair B.C., Cafaro A., Stuerzl M., Ensoli B.;
"The Tat protein of human immunodeficiency virus type-1 promotes
vascular cell growth and locomotion by engaging the alpha5beta1 and
alphavbeta3 integrins and by mobilizing sequestered basic fibroblast
growth factor.";
Blood 94:663-672(1999).
[19]
INTERACTION WITH HUMAN CCNT1.
PubMed=10364329;
Bieniasz P.D., Grdina T.A., Bogerd H.P., Cullen B.R.;
"Analysis of the effect of natural sequence variation in Tat and in
cyclin T on the formation and RNA binding properties of Tat-cyclin T
complexes.";
J. Virol. 73:5777-5786(1999).
[20]
ACETYLATION AT LYS-50 BY EP300, ACETYLATION AT LYS-28 BY PCAF, AND
MUTAGENESIS OF LYS-28 AND LYS-50.
PubMed=10545121; DOI=10.1093/emboj/18.21.6106;
Kiernan R.E., Vanhulle C., Schiltz L., Adam E., Xiao H., Maudoux F.,
Calomme C., Burny A., Nakatani Y., Jeang K.-T., Benkirane M.,
Van Lint C.;
"HIV-1 tat transcriptional activity is regulated by acetylation.";
EMBO J. 18:6106-6118(1999).
[21]
INTERACTION WITH HUMAN CXCR4.
STRAIN=Clone pNL4-3;
PubMed=11027346; DOI=10.1073/pnas.97.21.11466;
Xiao H., Neuveut C., Tiffany H.L., Benkirane M., Rich E.A.,
Murphy P.M., Jeang K.-T.;
"Selective CXCR4 antagonism by Tat: implications for in vivo expansion
of coreceptor use by HIV-1.";
Proc. Natl. Acad. Sci. U.S.A. 97:11466-11471(2000).
[22]
INTERACTION WITH HUMAN KDR; ITGAV AND ITGB1.
PubMed=10590123; DOI=10.1128/JVI.74.1.344-353.2000;
Mitola S., Soldi R., Zanon I., Barra L., Gutierrez M.I., Berkhout B.,
Giacca M., Bussolino F.;
"Identification of specific molecular structures of human
immunodeficiency virus type 1 Tat relevant for its biological effects
on vascular endothelial cells.";
J. Virol. 74:344-353(2000).
[23]
ACETYLATION AT LYS-50 AND LYS-51 BY EP300, AND MUTAGENESIS OF LYS-50
AND LYS-51.
PubMed=11080476; DOI=10.1006/viro.2000.0593;
Deng L., de la Fuente C., Fu P., Wang L., Donnelly R., Wade J.D.,
Lambert P., Li H., Lee C.-G., Kashanchi F.;
"Acetylation of HIV-1 Tat by CBP/P300 increases transcription of
integrated HIV-1 genome and enhances binding to core histones.";
Virology 277:278-295(2000).
[24]
FUNCTION.
PubMed=10958691; DOI=10.1128/MCB.20.18.6958-6969.2000;
Garber M.E., Mayall T.P., Suess E.M., Meisenhelder J., Thompson N.E.,
Jones K.A.;
"CDK9 autophosphorylation regulates high-affinity binding of the human
immunodeficiency virus type 1 tat-P-TEFb complex to TAR RNA.";
Mol. Cell. Biol. 20:6958-6969(2000).
[25]
INTERACTION WITH HOST RNGTT.
PubMed=11278368; DOI=10.1074/jbc.M007901200;
Chiu Y.-L., Coronel E., Ho C.K., Shuman S., Rana T.M.;
"HIV-1 Tat protein interacts with mammalian capping enzyme and
stimulates capping of TAR RNA.";
J. Biol. Chem. 276:12959-12966(2001).
[26]
INTERACTION WITH HEPARAN SULFATE PROTEOGLYCANS.
PubMed=11024024; DOI=10.1074/jbc.M006701200;
Tyagi M., Rusnati M., Presta M., Giacca M.;
"Internalization of HIV-1 tat requires cell surface heparan sulfate
proteoglycans.";
J. Biol. Chem. 276:3254-3261(2001).
[27]
INTERACTION WITH HUMAN GCN5L2, AND ACETYLATION AT LYS-50 AND LYS-51 BY
HUMAN GCN5L2.
PubMed=11384967; DOI=10.1074/jbc.M101385200;
Col E., Caron C., Seigneurin-Berny D., Gracia J., Favier A.,
Khochbin S.;
"The histone acetyltransferase, hGCN5, interacts with and acetylates
the HIV transactivator, Tat.";
J. Biol. Chem. 276:28179-28184(2001).
[28]
FUNCTION.
PubMed=12052871; DOI=10.1128/MCB.22.13.4622-4637.2002;
Kim Y.K., Bourgeois C.F., Isel C., Churcher M.J., Karn J.;
"Phosphorylation of the RNA polymerase II carboxyl-terminal domain by
CDK9 is directly responsible for human immunodeficiency virus type 1
Tat-activated transcriptional elongation.";
Mol. Cell. Biol. 22:4622-4637(2002).
[29]
INTERACTION WITH HUMAN PCAF.
PubMed=12486002; DOI=10.1093/emboj/cdf669;
Bres V., Tagami H., Peloponese J.-M., Loret E., Jeang K.-T.,
Nakatani Y., Emiliani S., Benkirane M., Kiernan R.E.;
"Differential acetylation of Tat coordinates its interaction with the
co-activators cyclin T1 and PCAF.";
EMBO J. 21:6811-6819(2002).
[30]
FUNCTION.
PubMed=12154097; DOI=10.1074/jbc.M206694200;
Col E., Gilquin B., Caron C., Khochbin S.;
"Tat-controlled protein acetylation.";
J. Biol. Chem. 277:37955-37960(2002).
[31]
INTERACTION WITH HUMAN PCAF BROMODOMAIN.
PubMed=12032084; DOI=10.1093/emboj/21.11.2715;
Dorr A., Kiermer V., Pedal A., Rackwitz H.R., Henklein P.,
Schubert U., Zhou M.-M., Verdin E., Ott M.;
"Transcriptional synergy between Tat and PCAF is dependent on the
binding of acetylated Tat to the PCAF bromodomain.";
EMBO J. 21:2715-2723(2002).
[32]
UBIQUITINATION AT LYS-71 BY HUMAN MDM2, AND INTERACTION WITH HUMAN
MDM2.
STRAIN=Clone pNL4-3;
PubMed=12883554; DOI=10.1038/ncb1023;
Bres V., Kiernan R.E., Linares L.K., Chable-Bessia C., Plechakova O.,
Treand C., Emiliani S., Peloponese J.-M., Jeang K.-T., Coux O.,
Scheffner M., Benkirane M.;
"A non-proteolytic role for ubiquitin in Tat-mediated transactivation
of the HIV-1 promoter.";
Nat. Cell Biol. 5:754-761(2003).
[33]
CYS-RICH REGION, AND ZINC-BINDING.
PubMed=15117453; DOI=10.1089/088922204322996536;
Misumi S., Takamune N., Ohtsubo Y., Waniguchi K., Shoji S.;
"Zn2+ binding to cysteine-rich domain of extracellular human
immunodeficiency virus type 1 Tat protein is associated with Tat
protein-induced apoptosis.";
AIDS Res. Hum. Retroviruses 20:297-304(2004).
[34]
FUNCTION, AND INTERACTION WITH HUMAN SATB1.
PubMed=15713622; DOI=10.1128/MCB.25.5.1620-1633.2005;
Kumar P.P., Purbey P.K., Ravi D.S., Mitra D., Galande S.;
"Displacement of SATB1-bound histone deacetylase 1 corepressor by the
human immunodeficiency virus type 1 transactivator induces expression
of interleukin-2 and its receptor in T cells.";
Mol. Cell. Biol. 25:1620-1633(2005).
[35]
INTERACTION WITH HUMAN SIRT1, AND DEACETYLATION AT LYS-50 BY SIRT1.
PubMed=15719057; DOI=10.1371/journal.pbio.0030041;
Pagans S., Pedal A., North B.J., Kaehlcke K., Marshall B.L., Dorr A.,
Hetzer-Egger C., Henklein P., Frye R., McBurney M.W., Hruby H.,
Jung M., Verdin E., Ott M.;
"SIRT1 regulates HIV transcription via Tat deacetylation.";
PLoS Biol. 3:210-220(2005).
[36]
INTERACTION WITH HUMAN KAT5.
STRAIN=Clone pNL4-3;
PubMed=16001085; DOI=10.1038/sj.emboj.7600734;
Col E., Caron C., Chable-Bessia C., Legube G., Gazzeri S., Komatsu Y.,
Yoshida M., Benkirane M., Trouche D., Khochbin S.;
"HIV-1 Tat targets Tip60 to impair the apoptotic cell response to
genotoxic stresses.";
EMBO J. 24:2634-2645(2005).
[37]
FUNCTION, AND INTERACTION WITH HUMAN TBP.
PubMed=15719058; DOI=10.1371/journal.pbio.0030044;
Raha T., Cheng S.W.G., Green M.R.;
"HIV-1 Tat stimulates transcription complex assembly through
recruitment of TBP in the absence of TAFs.";
PLoS Biol. 3:221-230(2005).
[38]
INTERACTION WITH HUMAN MMP1.
PubMed=16807369; DOI=10.1096/fj.05-5619fje;
Rumbaugh J., Turchan-Cholewo J., Galey D., St Hillaire C.,
Anderson C., Conant K., Nath A.;
"Interaction of HIV Tat and matrix metalloproteinase in HIV
neuropathogenesis: a new host defense mechanism.";
FASEB J. 20:1736-1738(2006).
[39]
FUNCTION.
PubMed=16920714; DOI=10.1074/jbc.M512109200;
Gee K., Angel J.B., Ma W., Mishra S., Gajanayaka N., Parato K.,
Kumar A.;
"Intracellular HIV-Tat expression induces IL-10 synthesis by the CREB-
1 transcription factor through Ser133 phosphorylation and its
regulation by the ERK1/2 MAPK in human monocytic cells.";
J. Biol. Chem. 281:31647-31658(2006).
[40]
REVIEW, AND ALTERNATIVE SPLICING.
PubMed=16046164; DOI=10.1016/j.micinf.2005.06.003;
Hetzer C., Dormeyer W., Schnolzer M., Ott M.;
"Decoding Tat: the biology of HIV Tat posttranslational
modifications.";
Microbes Infect. 7:1364-1369(2005).
[41]
REVIEW.
PubMed=16146763; DOI=10.2741/1829;
Peruzzi F.;
"The multiple functions of HIV-1 Tat: proliferation versus
apoptosis.";
Front. Biosci. 11:708-717(2006).
[42]
REVIEW.
PubMed=16697675; DOI=10.1016/j.micinf.2005.11.014;
King J.E., Eugenin E.A., Buckner C.M., Berman J.W.;
"HIV tat and neurotoxicity.";
Microbes Infect. 8:1347-1357(2006).
[43]
FUNCTION.
PubMed=19671151; DOI=10.1186/1742-4690-6-74;
Charnay N., Ivanyi-Nagy R., Soto-Rifo R., Ohlmann T., Lopez-Lastra M.,
Darlix J.L.;
"Mechanism of HIV-1 Tat RNA translation and its activation by the Tat
protein.";
Retrovirology 6:74-74(2009).
[44]
STRUCTURE BY NMR OF 46-55 IN COMPLEX WITH PCAF BROMODOMAIN.
PubMed=11931765; DOI=10.1016/S1097-2765(02)00483-5;
Mujtaba S., He Y., Zeng L., Farooq A., Carlson J.E., Ott M.,
Verdin E., Zhou M.-M.;
"Structural basis of lysine-acetylated HIV-1 Tat recognition by PCAF
bromodomain.";
Mol. Cell 9:575-586(2002).
[45]
STRUCTURE BY NMR.
PubMed=11098404; DOI=10.1016/S0764-4469(00)01228-2;
Peloponese J.M. Jr., Gregoire C., Opi S., Esquieu D., Sturgis J.,
Lebrun E., Meurs E., Collette Y., Olive D., Aubertin A.M., Witvrow M.,
Pannecouque C., De Clercq E., Bailly C., Lebreton J., Loret E.P.;
"1H-13C nuclear magnetic resonance assignment and structural
characterization of HIV-1 Tat protein.";
C. R. Acad. Sci. III, Sci. Vie 323:883-894(2000).
-!- 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 and other Tat-activated kinases hyperphosphorylate 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 by
interacting with host RELA. Through its interaction with host TBP,
Tat may also modulate transcription initiation. Tat can reactivate
a latently infected cell by penetrating in it and transactivating
its LTR promoter. In the cytoplasm, Tat is thought to act as a
translational activator of HIV-1 mRNAs. {ECO:0000255|HAMAP-
Rule:MF_04079}.
-!- FUNCTION: Extracellular circulating Tat can be endocytosed by
surrounding uninfected cells via the binding to several surface
receptors such as CD26, CXCR4, heparan sulfate proteoglycans
(HSPG) or LDLR. Neurons are rarely infected, but they internalize
Tat via their LDLR. Through its interaction with nuclear HATs, Tat
is potentially able to control the acetylation-dependent cellular
gene expression. Modulates the expression of many cellular genes
involved in cell survival, proliferation or in coding for
cytokines or cytokine receptors. Tat plays a role in T-cell and
neurons apoptosis. Tat induced neurotoxicity and apoptosis
probably contribute to neuroAIDS. 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. {ECO:0000255|HAMAP-
Rule:MF_04079}.
-!- SUBUNIT: Interacts with host CCNT1. Associates with the P-TEFb
complex composed at least of Tat, P-TEFb (CDK9 and CCNT1), TAR
RNA, RNA Pol II. Recruits the HATs CREBBP, TAF1/TFIID, EP300, PCAF
and GCN5L2. Interacts with host KAT5/Tip60; this interaction
targets the latter to degradation. Interacts with the host
deacetylase SIRT1. Interacts with host capping enzyme RNGTT; this
interaction stimulates RNGTT. Binds to host KDR, and to the host
integrins ITGAV/ITGB3 and ITGA5/ITGB1. Interacts with host
KPNB1/importin beta-1 without previous binding to KPNA1/importin
alpha-1. Interacts with EIF2AK2. Interacts with host nucleosome
assembly protein NAP1L1; this interaction may be required for the
transport of Tat within the nucleus, since the two proteins
interact at the nuclear rim. Interacts with host C1QBP/SF2P32;
this interaction involves lysine-acetylated Tat. Interacts with
the host chemokine receptors CCR2, CCR3 and CXCR4. Interacts with
host DPP4/CD26; this interaction may trigger an anti-proliferative
effect. Interacts with host LDLR. Interacts with the host
extracellular matrix metalloproteinase MMP1. Interacts with host
PRMT6; this interaction mediates Tat's methylation. Interacts
with, and is ubiquitinated by MDM2/Hdm2. Interacts with host PSMC3
and HTATIP2. Interacts with STAB1; this interaction may overcome
SATB1-mediated repression of IL2 and IL2RA (interleukin) in T
cells by binding to the same domain than HDAC1. Interacts (when
acetylated) with human CDK13, thereby increasing HIV-1 mRNA
splicing and promoting the production of the doubly spliced HIV-1
protein Nef.Interacts with host TBP; this interaction modulates
the activity of transcriptional pre-initiation complex. Interacts
with host RELA. {ECO:0000255|HAMAP-Rule:MF_04079,
ECO:0000269|PubMed:10329125, ECO:0000269|PubMed:10364329,
ECO:0000269|PubMed:10397733, ECO:0000269|PubMed:10590123,
ECO:0000269|PubMed:11024024, ECO:0000269|PubMed:11027346,
ECO:0000269|PubMed:11278368, ECO:0000269|PubMed:11384967,
ECO:0000269|PubMed:11931765, ECO:0000269|PubMed:12032084,
ECO:0000269|PubMed:12486002, ECO:0000269|PubMed:12883554,
ECO:0000269|PubMed:15713622, ECO:0000269|PubMed:15719057,
ECO:0000269|PubMed:15719058, ECO:0000269|PubMed:16001085,
ECO:0000269|PubMed:16807369, ECO:0000269|PubMed:2194290,
ECO:0000269|PubMed:7608968, ECO:0000269|PubMed:7912830,
ECO:0000269|PubMed:8121496, ECO:0000269|PubMed:8607265,
ECO:0000269|PubMed:9482853, ECO:0000269|PubMed:9649438,
ECO:0000269|PubMed:9789057, ECO:0000269|PubMed:9891055}.
-!- SUBCELLULAR LOCATION: Host nucleus, host nucleolus
{ECO:0000255|HAMAP-Rule:MF_04079}. Host cytoplasm
{ECO:0000255|HAMAP-Rule:MF_04079}. Secreted {ECO:0000255|HAMAP-
Rule:MF_04079}. Note=Probably localizes to both nuclear and
nucleolar compartments. Nuclear localization is mediated through
the interaction of the nuclear localization signal with importin
KPNB1. Secretion occurs through a Golgi-independent pathway. Tat
is released from infected cells to the extracellular space where
it remains associated to the cell membrane, or is secreted into
the cerebrospinal fluid and sera. Extracellular Tat can be
endocytosed by surrounding uninfected cells via binding to several
receptors depending on the cell type. {ECO:0000255|HAMAP-
Rule:MF_04079}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=Long;
IsoId=P04610-1; Sequence=Displayed;
Name=Short;
IsoId=P04610-2; Sequence=VSP_022299;
Note=No experimental confirmation available. Expressed in the
late stage of the infection cycle, when unspliced viral RNAs are
exported to the cytoplasm by the viral Rev protein.;
-!- DOMAIN: The cell attachment site mediates the interaction with
ITGAV/ITGB3 and ITGA5/ITGB1 integrins, leading to vascular cell
migration and invasion. This interaction also provides endothelial
cells with the adhesion signal they require to grow in response to
mitogens. {ECO:0000255|HAMAP-Rule:MF_04079,
ECO:0000269|PubMed:10397733}.
-!- DOMAIN: The Cys-rich region may bind 2 zinc ions. This region is
involved in binding to KAT5. {ECO:0000255|HAMAP-Rule:MF_04079}.
-!- DOMAIN: The transactivation domain mediates the interaction with
CCNT1, GCN5L2, and MDM2. {ECO:0000255|HAMAP-Rule:MF_04079}.
-!- DOMAIN: The Arg-rich RNA-binding region binds the TAR RNA. This
region also mediates the nuclear localization through direct
binding to KPNB1 and is involved in Tat's transfer across cell
membranes (protein transduction). The same region is required for
the interaction with EP300, PCAF, EIF2AK2 and KDR.
-!- PTM: Asymmetrical arginine methylation by host PRMT6 seems to
diminish the transactivation capacity of Tat and affects the
interaction with host CCNT1. {ECO:0000255|HAMAP-Rule:MF_04079}.
-!- PTM: Acetylation by EP300, CREBBP, GCN5L2/GCN5 and PCAF regulates
the transactivation activity of Tat. EP300-mediated acetylation of
Lys-50 promotes dissociation of Tat from the TAR RNA through the
competitive binding to PCAF's bromodomain. In addition, the non-
acetylated Tat's N-terminus can also interact with PCAF. PCAF-
mediated acetylation of Lys-28 enhances Tat's binding to CCNT1.
Lys-50 is deacetylated by SIRT1. {ECO:0000255|HAMAP-
Rule:MF_04079}.
-!- PTM: Polyubiquitination by host MDM2 does not target Tat to
degradation, but activates its transactivation function and
fosters interaction with CCNT1 and TAR RNA. {ECO:0000255|HAMAP-
Rule:MF_04079, ECO:0000269|PubMed:12883554}.
-!- PTM: Phosphorylated by EIF2AK2 on serine and threonine residues
adjacent to the basic region important for TAR RNA binding and
function. Phosphorylation of Tat by EIF2AK2 is dependent on the
prior activation of EIF2AK2 by dsRNA. {ECO:0000255|HAMAP-
Rule:MF_04079}.
-!- MISCELLANEOUS: The infectious clone pNL4-3 is a chimeric provirus
that consists of DNA from HIV isolates NY5 (5' half) and BRU (3'
half).
-!- MISCELLANEOUS: This truncated variant has a premature stop codon.
It may have arose as a consequence of tissue culture passaging.
{ECO:0000255|HAMAP-Rule:MF_04079}.
-!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M
(for Major), O (for Outlier), and N (for New, or Non-M, Non-O).
The vast majority of strains found worldwide belong to the group
M. Group O seems to be endemic to and largely confined to Cameroon
and neighboring countries in West Central Africa, where these
viruses represent a small minority of HIV-1 strains. The group N
is represented by a limited number of isolates from Cameroonian
persons. The group M is further subdivided in 9 clades or subtypes
(A to D, F to H, J and K). {ECO:0000255|HAMAP-Rule:MF_04079}.
-!- SIMILARITY: Belongs to the lentiviruses Tat family.
{ECO:0000255|HAMAP-Rule:MF_04079}.
-----------------------------------------------------------------------
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
Distributed under the Creative Commons Attribution-NoDerivs License
-----------------------------------------------------------------------
EMBL; K02013; AAB59745.1; -; Genomic_RNA.
EMBL; M19921; AAA44985.1; -; Genomic_RNA.
PIR; A25700; A25700.
PDB; 1JFW; NMR; -; A=1-86.
PDB; 1JM4; NMR; -; A=46-55.
PDBsum; 1JFW; -.
PDBsum; 1JM4; -.
ProteinModelPortal; P04610; -.
SMR; P04610; -.
IntAct; P04610; 3.
MINT; MINT-7908963; -.
iPTMnet; P04610; -.
EvolutionaryTrace; P04610; -.
Proteomes; UP000007692; Genome.
GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
GO; GO:0044196; C:host cell nucleolus; IEA:UniProtKB-SubCell.
GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
GO; GO:0001070; F:RNA binding transcription factor activity; IEA:InterPro.
GO; GO:0060081; P:membrane hyperpolarization; IDA:CACAO.
GO; GO:0039525; P:modulation by virus of host chromatin organization; IEA:UniProtKB-KW.
GO; GO:0039586; P:modulation by virus of host PP1 activity; IEA:UniProtKB-KW.
GO; GO:0052312; P:modulation of transcription in other organism involved in symbiotic interaction; IDA:CACAO.
GO; GO:1901856; P:negative regulation of cellular respiration; IDA:CACAO.
GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:CACAO.
GO; GO:1900182; P:positive regulation of protein localization to nucleus; IDA:CACAO.
GO; GO:0050434; P:positive regulation of viral transcription; IEA:InterPro.
GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
Gene3D; 4.10.20.10; -; 1.
HAMAP; MF_04079; HIV_TAT; 1.
InterPro; IPR001831; IV_Tat.
InterPro; IPR036963; Tat_dom_sf.
Pfam; PF00539; Tat; 1.
PRINTS; PR00055; HIVTATDOMAIN.
1: Evidence at protein level;
3D-structure; Acetylation; Activator; AIDS; Alternative splicing;
Apoptosis; Complete proteome; Host cytoplasm; Host nucleus;
Host-virus interaction;
Inhibition of host innate immune response by virus;
Inhibition of host interferon signaling pathway by virus;
Isopeptide bond; Metal-binding; Methylation;
Modulation of host chromatin by virus;
Modulation of host PP1 activity by virus; Phosphoprotein; RNA-binding;
Secreted; Transcription; Transcription regulation; Ubl conjugation;
Viral immunoevasion; Zinc.
CHAIN 1 86 Protein Tat.
/FTId=PRO_0000085346.
REGION 1 48 Transactivation. {ECO:0000255|HAMAP-
Rule:MF_04079}.
REGION 1 24 Interaction with human CREBBP.
{ECO:0000255|HAMAP-Rule:MF_04079}.
REGION 22 37 Cysteine-rich. {ECO:0000255|HAMAP-
Rule:MF_04079}.
REGION 38 48 Core. {ECO:0000255|HAMAP-Rule:MF_04079}.
REGION 49 86 Interaction with the host capping enzyme
RNGTT. {ECO:0000255|HAMAP-Rule:MF_04079}.
MOTIF 49 57 Nuclear localization signal, RNA-binding
(TAR), and protein transduction.
{ECO:0000255|HAMAP-Rule:MF_04079,
ECO:0000269|PubMed:9891055}.
MOTIF 78 80 Cell attachment site. {ECO:0000255|HAMAP-
Rule:MF_04079}.
METAL 22 22 Zinc 1. {ECO:0000255|HAMAP-
Rule:MF_04079}.
METAL 25 25 Zinc 2. {ECO:0000255|HAMAP-
Rule:MF_04079}.
METAL 27 27 Zinc 2. {ECO:0000255|HAMAP-
Rule:MF_04079}.
METAL 30 30 Zinc 2. {ECO:0000255|HAMAP-
Rule:MF_04079}.
METAL 33 33 Zinc 1; via pros nitrogen.
{ECO:0000255|HAMAP-Rule:MF_04079}.
METAL 34 34 Zinc 1. {ECO:0000255|HAMAP-
Rule:MF_04079}.
METAL 37 37 Zinc 1. {ECO:0000255|HAMAP-
Rule:MF_04079}.
SITE 11 11 Essential for Tat translocation through
the endosomal membrane.
{ECO:0000255|HAMAP-Rule:MF_04079}.
MOD_RES 28 28 N6-acetyllysine; by host PCAF.
{ECO:0000255|HAMAP-Rule:MF_04079,
ECO:0000269|PubMed:10545121}.
MOD_RES 50 50 N6-acetyllysine; by host EP300 and
GCN5L2. {ECO:0000255|HAMAP-Rule:MF_04079,
ECO:0000269|PubMed:10545121,
ECO:0000269|PubMed:11080476,
ECO:0000269|PubMed:11384967}.
MOD_RES 51 51 N6-acetyllysine; by host EP300 and
GCN5L2. {ECO:0000255|HAMAP-Rule:MF_04079,
ECO:0000269|PubMed:11080476,
ECO:0000269|PubMed:11384967}.
MOD_RES 52 52 Asymmetric dimethylarginine; by host
PRMT6. {ECO:0000255|HAMAP-Rule:MF_04079}.
MOD_RES 53 53 Asymmetric dimethylarginine; by host
PRMT6. {ECO:0000255|HAMAP-Rule:MF_04079}.
CROSSLNK 71 71 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in ubiquitin).
{ECO:0000255|HAMAP-Rule:MF_04079,
ECO:0000269|PubMed:12883554}.
VAR_SEQ 73 86 Missing (in isoform Short).
/FTId=VSP_022299.
VARIANT 24 24 T -> N (in strain: Clone pNL4-3).
VARIANT 39 39 T -> M (in strain: Clone pNL4-3).
VARIANT 58 61 PPQG -> AHQN (in strain: Clone pNL4-3).
VARIANT 67 67 V -> A (in strain: Clone pNL4-3).
VARIANT 77 77 P -> S (in strain: Clone pNL4-3).
MUTAGEN 28 28 K->A: Strong decrease in Tat
transactivation.
{ECO:0000269|PubMed:10545121}.
MUTAGEN 50 50 K->A: Strong decrease in Tat
transactivation.
{ECO:0000269|PubMed:10545121,
ECO:0000269|PubMed:11080476}.
MUTAGEN 51 51 K->A: Strong decrease in Tat
transactivation.
{ECO:0000269|PubMed:11080476}.
STRAND 16 18 {ECO:0000244|PDB:1JFW}.
STRAND 20 23 {ECO:0000244|PDB:1JFW}.
TURN 26 29 {ECO:0000244|PDB:1JFW}.
STRAND 32 35 {ECO:0000244|PDB:1JFW}.
TURN 39 41 {ECO:0000244|PDB:1JFW}.
STRAND 42 44 {ECO:0000244|PDB:1JFW}.
STRAND 47 50 {ECO:0000244|PDB:1JFW}.
STRAND 60 62 {ECO:0000244|PDB:1JFW}.
STRAND 69 73 {ECO:0000244|PDB:1JFW}.
STRAND 78 82 {ECO:0000244|PDB:1JFW}.
SEQUENCE 86 AA; 9769 MW; 9B1B4A915FAF8A14 CRC64;
MEPVDPRLEP WKHPGSQPKT ACTTCYCKKC CFHCQVCFTT KALGISYGRK KRRQRRRPPQ
GSQTHQVSLS KQPTSQPRGD PTGPKE


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