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TAT_HV2CA
ID   TAT_HV2CA               Reviewed;         133 AA.
AC   P24109;
DT   01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-1992, sequence version 1.
DT   23-FEB-2022, entry version 92.
DE   RecName: Full=Protein Tat;
DE   AltName: Full=Transactivating regulatory protein;
GN   Name=tat;
OS   Human immunodeficiency virus type 2 subtype A (isolate CAM2) (HIV-2).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX   NCBI_TaxID=11715;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2005437; DOI=10.1099/0022-1317-72-3-721;
RA   Tristem M., Hill F., Karpas A.;
RT   "Nucleotide sequence of a Guinea-Bissau-derived human immunodeficiency
RT   virus type 2 proviral clone (HIV-2CAM2).";
RL   J. Gen. Virol. 72:721-724(1991).
RN   [2]
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).
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 (By
CC       similarity). {ECO:0000250}.
CC   -!- FUNCTION: Extracellular circulating Tat can be endocytosed by
CC       surrounding uninfected cells via the binding to several surface
CC       receptors. Endosomal low pH allows Tat to cross the endosome membrane
CC       to enter the cytosol and eventually further translocate into the
CC       nucleus, thereby inducing severe cell dysfunctions ranging from cell
CC       activation to cell death. Through (By similarity). {ECO:0000250}.
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       Interacts with CCNT2; the resulting complex is unable to bind to TAR
CC       RNA (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Host nucleus, host nucleolus {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=Long;
CC         IsoId=P24109-1; Sequence=Displayed;
CC       Name=Short;
CC         IsoId=P24109-2; Sequence=VSP_022438;
CC   -!- DOMAIN: The Arg-rich RNA-binding region binds the TAR RNA. This region
CC       also mediates the nuclear localization (By similarity). {ECO:0000250}.
CC   -!- PTM: The phosphorylation by CDK9 does not seem to be important for
CC       transactivation function. {ECO:0000250}.
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:0000305}.
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DR   EMBL; D00835; BAA00714.1; -; Genomic_DNA.
DR   PIR; I38475; TNLJCA.
DR   PRIDE; P24109; -.
DR   Proteomes; UP000007421; Genome.
DR   GO; GO:0044196; C:host cell nucleolus; IEA:UniProtKB-SubCell.
DR   GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0001070; F:RNA-binding transcription regulator activity; IEA:InterPro.
DR   GO; GO:0050434; P:positive regulation of viral transcription; IEA:InterPro.
DR   Gene3D; 4.10.20.10; -; 1.
DR   InterPro; IPR001831; IV_Tat.
DR   InterPro; IPR036963; Tat_dom_sf.
DR   Pfam; PF00539; Tat; 1.
DR   PRINTS; PR00055; HIVTATDOMAIN.
PE   3: Inferred from homology;
KW   Activator; AIDS; Alternative splicing; Host nucleus;
KW   Host-virus interaction; Phosphoprotein; RNA-binding; Transcription;
KW   Transcription regulation.
FT   CHAIN           1..133
FT                   /note="Protein Tat"
FT                   /id="PRO_0000085368"
FT   REGION          1..34
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          53..69
FT                   /note="Cysteine-rich"
FT                   /evidence="ECO:0000250"
FT   REGION          70..80
FT                   /note="Core"
FT                   /evidence="ECO:0000250"
FT   REGION          83..133
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           81..93
FT                   /note="Nuclear localization signal, and RNA-binding (TAR)"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        12..33
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         88
FT                   /note="Phosphothreonine; by host CDK9"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         97
FT                   /note="Phosphoserine; by host CDK9"
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         103..133
FT                   /note="Missing (in isoform Short)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_022438"
SQ   SEQUENCE   133 AA;  14850 MW;  CFAB978387B3C1FD CRC64;
     MLDMETPLKE PESSLGSCNE PSSRTSGQDA TTQELAKLGE EILSQLYQPL EECDNSCYCK
     RCCYHCQLCF LKKGLGICYD RKGRRRRTPK KAKAHSSSAS DKSISTRTRN SQPAKKQKKT
     LEATVETDPG LGR
 
 
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