TAT_HV2D1
ID TAT_HV2D1 Reviewed; 130 AA.
AC P17759;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 1.
DT 23-FEB-2022, entry version 95.
DE RecName: Full=Protein Tat;
DE AltName: Full=Transactivating regulatory protein;
GN Name=tat;
OS Human immunodeficiency virus type 2 subtype A (isolate D194) (HIV-2).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX NCBI_TaxID=11713;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2467304; DOI=10.1073/pnas.86.7.2383;
RA Kuehnel H., von Briesen H., Dietrich U., Adamski M., Mix D., Biesert L.,
RA Kreutz R., Immelmann A., Henco K., Meichsner C., Andreesen R.,
RA Gelderblom H., Ruebsamen-Waigmann H.;
RT "Molecular cloning of two west African human immunodeficiency virus type 2
RT isolates that replicate well in macrophages: a Gambian isolate, from a
RT patient with neurologic acquired immunodeficiency syndrome, and a highly
RT divergent Ghanian isolate.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:2383-2387(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2235509; DOI=10.1093/nar/18.20.6142;
RA Kuehnel H., Kreutz R., Ruebsamen-Waigmann H.;
RT "Nucleotide sequence of HIV-2D194, an isolate from a Gambian case of
RT 'neuro-AIDS', which showed excellent growth in macrophages.";
RL Nucleic Acids Res. 18:6142-6142(1990).
RN [3]
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: Binds human CCNT1. Binds also to CCNT2, but the resulting
CC complex is unable to bind to TAR RNA. May participate in the formation
CC of a complex composed at least of Tat, P-TEFb, TAR RNA, RNA Pol II (By
CC 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=P17759-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P17759-2; Sequence=VSP_022439;
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: This isolate is from a Gambian case of 'neuro-AIDS'.
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; J04542; AAA76845.1; -; Genomic_DNA.
DR EMBL; X52223; CAA36469.1; -; Genomic_DNA.
DR PIR; S12157; S12157.
DR Proteomes; UP000007422; 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..130
FT /note="Protein Tat"
FT /id="PRO_0000085366"
FT REGION 1..33
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 50..66
FT /note="Cysteine-rich"
FT /evidence="ECO:0000250"
FT REGION 67..77
FT /note="Core"
FT /evidence="ECO:0000250"
FT REGION 78..130
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 78..90
FT /note="Nuclear localization signal, and RNA-binding (TAR)"
FT /evidence="ECO:0000250"
FT COMPBIAS 9..26
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 85
FT /note="Phosphothreonine; by host CDK9"
FT /evidence="ECO:0000250"
FT MOD_RES 89
FT /note="Phosphothreonine; by host CDK9"
FT /evidence="ECO:0000250"
FT VAR_SEQ 100..130
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000305"
FT /id="VSP_022439"
SQ SEQUENCE 130 AA; 14598 MW; 1A659CB2F933C537 CRC64;
METPLKEPES SLESYNEPSS CTSERDVTAQ ERAKQGEELL AQLHRPLEAC TNSCYCKQCS
YHCQLCFLKK GLGIWYARQG RRRRTPRKTK THPPPASDKS ISTRTGDSQP TKKQKKTPET
TVVSACGLGH
