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TAT_HV1H2
ID   TAT_HV1H2               Reviewed;          86 AA.
AC   P04608; O09778;
DT   13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT   15-JUL-1999, sequence version 2.
DT   03-AUG-2022, entry version 160.
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 HXB2)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX   NCBI_TaxID=11706;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=2990041; DOI=10.1126/science.2990041;
RA   Sodroski J., Patarca R., Rosen C., Wong-Staal F., Haseltine W.;
RT   "Location of the trans-activating region on the genome of human T-cell
RT   lymphotropic virus type III.";
RL   Science 229:74-77(1985).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=3040055; DOI=10.1089/aid.1987.3.57;
RA   Ratner L., Fisher A., Jagodzinski L.L., Mitsuya H., Liou R.-S., Gallo R.C.,
RA   Wong-Staal F.;
RT   "Complete nucleotide sequences of functional clones of the AIDS virus.";
RL   AIDS Res. Hum. Retroviruses 3:57-69(1987).
RN   [3]
RP   SEQUENCE REVISION.
RA   Ratner L., Fisher A., Jagodzinski L.L., Mitsuya H., Liou R.-S., Gallo R.C.,
RA   Wong-Staal F.;
RL   Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA   Chappey C.;
RL   Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   FUNCTION.
RX   PubMed=1756726; DOI=10.1002/j.1460-2075.1991.tb04997.x;
RA   Marciniak R.A., Sharp P.A.;
RT   "HIV-1 Tat protein promotes formation of more-processive elongation
RT   complexes.";
RL   EMBO J. 10:4189-4196(1991).
RN   [6]
RP   FUNCTION, AND INTERACTION WITH HOST 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   [7]
RP   PHOSPHORYLATION, INTERACTION WITH HOST EIF2AK2, AND FUNCTION.
RX   PubMed=9079663; DOI=10.1074/jbc.272.13.8388;
RA   Brand S.R., Kobayashi R., Mathews M.B.;
RT   "The Tat protein of human immunodeficiency virus type 1 is a substrate and
RT   inhibitor of the interferon-induced, virally activated protein kinase,
RT   PKR.";
RL   J. Biol. Chem. 272:8388-8395(1997).
RN   [8]
RP   FUNCTION, AND INTERACTION WITH HOST CCNT1.
RX   PubMed=9491887; DOI=10.1016/s0092-8674(00)80939-3;
RA   Wei P., Garber M.E., Fang S.-M., Fischer W.H., Jones K.A.;
RT   "A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat
RT   and mediates its high-affinity, loop-specific binding to TAR RNA.";
RL   Cell 92:451-462(1998).
RN   [9]
RP   INTERACTION WITH HOST CREBBP AND EP300.
RX   PubMed=9811832; DOI=10.1073/pnas.95.23.13519;
RA   Marzio G., Tyagi M., Gutierrez M.I., Giacca M.;
RT   "HIV-1 tat transactivator recruits p300 and CREB-binding protein histone
RT   acetyltransferases to the viral promoter.";
RL   Proc. Natl. Acad. Sci. U.S.A. 95:13519-13524(1998).
RN   [10]
RP   FUNCTION.
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   [11]
RP   INTERACTION WITH HUMAN LDLR.
RX   PubMed=11100124; DOI=10.1038/82199;
RA   Liu Y., Jones M., Hingtgen C.M., Bu G., Laribee N., Tanzi R.E., Moir R.D.,
RA   Nath A., He J.J.;
RT   "Uptake of HIV-1 tat protein mediated by low-density lipoprotein receptor-
RT   related protein disrupts the neuronal metabolic balance of the receptor
RT   ligands.";
RL   Nat. Med. 6:1380-1387(2000).
RN   [12]
RP   UBIQUITINATION BY HOST MDM2.
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   [13]
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   [14]
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   [15]
RP   FUNCTION.
RX   PubMed=16687403; DOI=10.1074/jbc.m603336200;
RA   Mahmoudi T., Parra M., Vries R.G., Kauder S.E., Verrijzer C.P., Ott M.,
RA   Verdin E.;
RT   "The SWI/SNF chromatin-remodeling complex is a cofactor for Tat
RT   transactivation of the HIV promoter.";
RL   J. Biol. Chem. 281:19960-19968(2006).
RN   [16]
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   [17]
RP   INTERACTION WITH HUMAN C1QBP.
RX   PubMed=16537587; DOI=10.1128/jvi.80.7.3189-3204.2006;
RA   Berro R., Kehn K., de la Fuente C., Pumfery A., Adair R., Wade J.,
RA   Colberg-Poley A.M., Hiscott J., Kashanchi F.;
RT   "Acetylated Tat regulates human immunodeficiency virus type 1 splicing
RT   through its interaction with the splicing regulator p32.";
RL   J. Virol. 80:3189-3204(2006).
RN   [18]
RP   FUNCTION, AND METHYLATION AT ARG-52 AND ARG-53.
RX   PubMed=17267505; DOI=10.1128/jvi.01888-06;
RA   Xie B., Invernizzi C.F., Richard S., Wainberg M.A.;
RT   "Arginine methylation of the human immunodeficiency virus type 1 Tat
RT   protein by PRMT6 negatively affects Tat Interactions with both cyclin T1
RT   and the Tat transactivation region.";
RL   J. Virol. 81:4226-4234(2007).
RN   [19]
RP   FUNCTION.
RX   PubMed=17360663; DOI=10.1073/pnas.0611699104;
RA   Eugenin E.A., King J.E., Nath A., Calderon T.M., Zukin R.S., Bennett M.V.,
RA   Berman J.W.;
RT   "HIV-tat induces formation of an LRP-PSD-95- NMDAR-nNOS complex that
RT   promotes apoptosis in neurons and astrocytes.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:3438-3443(2007).
RN   [20]
RP   FUNCTION, INTERACTION WITH HUMAN CDK13, ACETYLATION AT LYS-50 AND LYS-51,
RP   AND MUTAGENESIS OF 50-LYS-LYS-51.
RX   PubMed=18480452; DOI=10.1128/jvi.02543-07;
RA   Berro R., Pedati C., Kehn-Hall K., Wu W., Klase Z., Even Y.,
RA   Geneviere A.M., Ammosova T., Nekhai S., Kashanchi F.;
RT   "CDK13, a new potential human immunodeficiency virus type 1 inhibitory
RT   factor regulating viral mRNA splicing.";
RL   J. Virol. 82:7155-7166(2008).
RN   [21]
RP   INTERACTION WITH HUMAN NAP1L1.
RX   PubMed=18226242; DOI=10.1186/1742-4690-5-8;
RA   Vardabasso C., Manganaro L., Lusic M., Marcello A., Giacca M.;
RT   "The histone chaperone protein Nucleosome Assembly Protein-1 (hNAP-1) binds
RT   HIV-1 Tat and promotes viral transcription.";
RL   Retrovirology 5:8-8(2008).
RN   [22]
RP   SUBCELLULAR LOCATION, AND INTERACTION WITH HUMAN NAP1L1.
RX   PubMed=19888548; DOI=10.1007/s00726-009-0378-9;
RA   De Marco A., Dans P.D., Knezevich A., Maiuri P., Pantano S., Marcello A.;
RT   "Subcellular localization of the interaction between the human
RT   immunodeficiency virus transactivator Tat and the nucleosome assembly
RT   protein 1.";
RL   Amino Acids 38:1583-1593(2010).
RN   [23]
RP   FUNCTION, AND INTERACTION WITH HOST RELA.
RX   PubMed=22187158; DOI=10.1093/nar/gkr1224;
RA   Fiume G., Vecchio E., De Laurentiis A., Trimboli F., Palmieri C.,
RA   Pisano A., Falcone C., Pontoriero M., Rossi A., Scialdone A.,
RA   Fasanella Masci F., Scala G., Quinto I.;
RT   "Human immunodeficiency virus-1 Tat activates NF-kappaB via physical
RT   interaction with IkappaB-alpha and p65.";
RL   Nucleic Acids Res. 40:3548-3562(2012).
RN   [24]
RP   STRUCTURE BY NMR OF 1-24 IN COMPLEX WITH CREBBP KIX DOMAIN.
RX   PubMed=14744133; DOI=10.1021/bi035612l;
RA   Vendel A.C., Lumb K.J.;
RT   "NMR mapping of the HIV-1 Tat interaction surface of the KIX domain of the
RT   human coactivator CBP.";
RL   Biochemistry 43:904-908(2004).
RN   [25]
RP   X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH ZINC.
RX   PubMed=20535204; DOI=10.1038/nature09131;
RA   Tahirov T.H., Babayeva N.D., Varzavand K., Cooper J.J., Sedore S.C.,
RA   Price D.H.;
RT   "Crystal structure of HIV-1 Tat complexed with human P-TEFb.";
RL   Nature 465:747-751(2010).
RN   [26]
RP   X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 1-48 IN COMPLEX WITH ZINC.
RX   PubMed=24727379; DOI=10.4161/cc.28756;
RA   Gu J., Babayeva N.D., Suwa Y., Baranovskiy A.G., Price D.H., Tahirov T.H.;
RT   "Crystal structure of HIV-1 Tat complexed with human P-TEFb and AFF4.";
RL   Cell Cycle 13:1788-1797(2014).
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       ECO:0000269|PubMed:16687403, ECO:0000269|PubMed:17267505,
CC       ECO:0000269|PubMed:1756726, ECO:0000269|PubMed:22187158,
CC       ECO:0000269|PubMed:7608968, ECO:0000269|PubMed:9491887}.
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-Rule:MF_04079,
CC       ECO:0000269|PubMed:10397733, ECO:0000269|PubMed:17360663,
CC       ECO:0000269|PubMed:9079663}.
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:11100124, ECO:0000269|PubMed:14744133,
CC       ECO:0000269|PubMed:16537587, ECO:0000269|PubMed:18226242,
CC       ECO:0000269|PubMed:18480452, ECO:0000269|PubMed:19888548,
CC       ECO:0000269|PubMed:22187158, ECO:0000269|PubMed:7608968,
CC       ECO:0000269|PubMed:9079663, ECO:0000269|PubMed:9491887,
CC       ECO:0000269|PubMed:9811832}.
CC   -!- INTERACTION:
CC       P04608; P04578: env; NbExp=4; IntAct=EBI-6164389, EBI-6163496;
CC       P04608; P51825: AFF1; Xeno; NbExp=3; IntAct=EBI-6164389, EBI-2610180;
CC       P04608; Q9UHB7: AFF4; Xeno; NbExp=4; IntAct=EBI-6164389, EBI-395282;
CC       P04608; O43865: AHCYL1; Xeno; NbExp=5; IntAct=EBI-6164389, EBI-2371423;
CC       P04608; O60563: CCNT1; Xeno; NbExp=9; IntAct=EBI-6164389, EBI-2479671;
CC       P04608; P50750: CDK9; Xeno; NbExp=8; IntAct=EBI-6164389, EBI-1383449;
CC       P04608; Q92793: CREBBP; Xeno; NbExp=2; IntAct=EBI-6164389, EBI-81215;
CC       P04608; Q9NXF7: DCAF16; Xeno; NbExp=2; IntAct=EBI-6164389, EBI-2559096;
CC       P04608; O00571: DDX3X; Xeno; NbExp=4; IntAct=EBI-6164389, EBI-353779;
CC       P04608; Q09472: EP300; Xeno; NbExp=3; IntAct=EBI-6164389, EBI-447295;
CC       P04608; Q9UK99: FBXO3; Xeno; NbExp=3; IntAct=EBI-6164389, EBI-2509901;
CC       P04608; P55209: NAP1L1; Xeno; NbExp=6; IntAct=EBI-6164389, EBI-356392;
CC       P04608; Q99733: NAP1L4; Xeno; NbExp=3; IntAct=EBI-6164389, EBI-2255116;
CC       P04608; O75607: NPM3; Xeno; NbExp=2; IntAct=EBI-6164389, EBI-721544;
CC       P04608; Q86U86: PBRM1; Xeno; NbExp=2; IntAct=EBI-6164389, EBI-637807;
CC       P04608; O15355: PPM1G; Xeno; NbExp=3; IntAct=EBI-6164389, EBI-725702;
CC       P04608; Q96EB6: SIRT1; Xeno; NbExp=3; IntAct=EBI-6164389, EBI-1802965;
CC       P04608; P51784: USP11; Xeno; NbExp=3; IntAct=EBI-6164389, EBI-306876;
CC   -!- SUBCELLULAR LOCATION: Host nucleus, host nucleolus {ECO:0000255|HAMAP-
CC       Rule:MF_04079, ECO:0000269|PubMed:19888548}. Host cytoplasm
CC       {ECO:0000255|HAMAP-Rule:MF_04079, ECO:0000269|PubMed:19888548}.
CC       Secreted {ECO:0000255|HAMAP-Rule:MF_04079,
CC       ECO:0000269|PubMed:19888548}. Note=Probably localizes to both nuclear
CC       and nucleolar compartments. Nuclear localization is mediated through
CC       the interaction of the nuclear localization signal with importin KPNB1.
CC       Secretion occurs through a Golgi-independent pathway. Tat is released
CC       from infected cells to the extracellular space where it remains
CC       associated to the cell membrane, or is secreted into the cerebrospinal
CC       fluid and sera. Extracellular Tat can be endocytosed by surrounding
CC       uninfected cells via binding to several receptors depending on the cell
CC       type.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=Long;
CC         IsoId=P04608-1; Sequence=Displayed;
CC       Name=Short;
CC         IsoId=P04608-2; Sequence=VSP_022300;
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   -!- 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. {ECO:0000255|HAMAP-Rule:MF_04079}.
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       ECO:0000269|PubMed:17267505}.
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, ECO:0000269|PubMed:18480452}.
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       ECO:0000269|PubMed:9079663}.
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; K03455; AAB50256.1; -; Genomic_RNA.
DR   EMBL; AF033819; AAC82591.1; -; Genomic_RNA.
DR   RefSeq; NP_057853.1; NC_001802.1.
DR   PDB; 3MI9; X-ray; 2.10 A; C=1-86.
DR   PDB; 3MIA; X-ray; 3.00 A; C=1-86.
DR   PDB; 4OR5; X-ray; 2.90 A; C/H=1-48.
DR   PDB; 5V61; X-ray; 2.20 A; I=49-57.
DR   PDB; 6CYT; X-ray; 3.50 A; D=1-57.
DR   PDB; 6MCE; NMR; -; B=44-60.
DR   PDB; 6MCF; NMR; -; B=44-60.
DR   PDBsum; 3MI9; -.
DR   PDBsum; 3MIA; -.
DR   PDBsum; 4OR5; -.
DR   PDBsum; 5V61; -.
DR   PDBsum; 6CYT; -.
DR   PDBsum; 6MCE; -.
DR   PDBsum; 6MCF; -.
DR   SMR; P04608; -.
DR   BioGRID; 1205541; 333.
DR   IntAct; P04608; 34.
DR   MINT; P04608; -.
DR   BindingDB; P04608; -.
DR   ChEMBL; CHEMBL4011; -.
DR   iPTMnet; P04608; -.
DR   PRIDE; P04608; -.
DR   GeneID; 155871; -.
DR   KEGG; vg:155871; -.
DR   Reactome; R-HSA-167200; Formation of HIV-1 elongation complex containing HIV-1 Tat.
DR   Reactome; R-HSA-167238; Pausing and recovery of Tat-mediated HIV elongation.
DR   Reactome; R-HSA-167243; Tat-mediated HIV elongation arrest and recovery.
DR   Reactome; R-HSA-167246; Tat-mediated elongation of the HIV-1 transcript.
DR   Reactome; R-HSA-176034; Interactions of Tat with host cellular proteins.
DR   EvolutionaryTrace; P04608; -.
DR   Proteomes; UP000002241; Genome.
DR   Proteomes; UP000105453; 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:0042025; C:host cell nucleus; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0042805; F:actinin binding; IPI:BHF-UCL.
DR   GO; GO:0030332; F:cyclin binding; IPI:ParkinsonsUK-UCL.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0019904; F:protein domain specific binding; IPI:CAFA.
DR   GO; GO:0001070; F:RNA-binding transcription regulator activity; TAS:ParkinsonsUK-UCL.
DR   GO; GO:1990970; F:trans-activation response element binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0039525; P:modulation by virus of host chromatin organization; IDA:UniProtKB.
DR   GO; GO:0039586; P:modulation by virus of host PP1 activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; IMP:CAFA.
DR   GO; GO:0032968; P:positive regulation of transcription elongation from RNA polymerase II promoter; IDA:UniProtKB.
DR   GO; GO:0050434; P:positive regulation of viral transcription; IDA:BHF-UCL.
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   DisProt; DP00929; -.
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_0000085364"
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          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          48..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   MOTIF           78..80
FT                   /note="Cell attachment site"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04079"
FT   COMPBIAS        61..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                   ECO:0000269|PubMed:20535204, ECO:0000269|PubMed:24727379"
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                   ECO:0000269|PubMed:20535204, ECO:0000269|PubMed:24727379"
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                   ECO:0000269|PubMed:20535204, ECO:0000269|PubMed:24727379"
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                   ECO:0000269|PubMed:20535204, ECO:0000269|PubMed:24727379"
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                   ECO:0000269|PubMed:20535204, ECO:0000269|PubMed:24727379"
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                   ECO:0000269|PubMed:20535204, ECO:0000269|PubMed:24727379"
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                   ECO:0000269|PubMed:20535204, ECO:0000269|PubMed:24727379"
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   MOD_RES         50
FT                   /note="N6-acetyllysine; by host EP300 and GCN5L2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04079,
FT                   ECO:0000269|PubMed:18480452"
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:18480452"
FT   MOD_RES         52
FT                   /note="Asymmetric dimethylarginine; by host PRMT6"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04079,
FT                   ECO:0000269|PubMed:17267505"
FT   MOD_RES         53
FT                   /note="Asymmetric dimethylarginine; by host PRMT6"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04079,
FT                   ECO:0000269|PubMed:17267505"
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   VAR_SEQ         73..86
FT                   /note="Missing (in isoform Short)"
FT                   /id="VSP_022300"
FT   MUTAGEN         50..51
FT                   /note="KK->AA: Reduced virus production."
FT                   /evidence="ECO:0000269|PubMed:18480452"
FT   HELIX           10..12
FT                   /evidence="ECO:0007829|PDB:3MI9"
FT   HELIX           30..32
FT                   /evidence="ECO:0007829|PDB:3MI9"
FT   HELIX           35..40
FT                   /evidence="ECO:0007829|PDB:3MI9"
FT   TURN            41..43
FT                   /evidence="ECO:0007829|PDB:3MIA"
FT   TURN            52..54
FT                   /evidence="ECO:0007829|PDB:6MCF"
FT   TURN            57..59
FT                   /evidence="ECO:0007829|PDB:6MCF"
SQ   SEQUENCE   86 AA;  9837 MW;  4DDC56D979769115 CRC64;
     MEPVDPRLEP WKHPGSQPKT ACTNCYCKKC CFHCQVCFIT KALGISYGRK KRRQRRRAHQ
     NSQTHQASLS KQPTSQPRGD PTGPKE
 
 
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