TAT_HV2ST
ID TAT_HV2ST Reviewed; 130 AA.
AC P20880;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 23-FEB-2022, entry version 109.
DE RecName: Full=Protein Tat;
DE AltName: Full=Transactivating regulatory protein;
GN Name=tat;
OS Human immunodeficiency virus type 2 subtype A (isolate ST) (HIV-2).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX NCBI_TaxID=11721;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2296086; DOI=10.1128/jvi.64.2.890-901.1990;
RA Kumar P., Hui H., Kappes J.C., Haggarty B.S., Hoxie J.A., Arya S.K.,
RA Shaw G.M., Hahn B.H.;
RT "Molecular characterization of an attenuated human immunodeficiency virus
RT type 2 isolate.";
RL J. Virol. 64:890-901(1990).
RN [2]
RP PHOSPHORYLATION AT THR-85; THR-89 AND SER-94 BY HOST CDK9, AND MUTAGENESIS
RP OF THR-3; SER-11; THR-22; SER-23; CYS-59; THR-85; THR-89 AND SER-94.
RX PubMed=8676484; DOI=10.1128/jvi.70.7.4576-4584.1996;
RA Yang X., Herrmann C.H., Rice A.P.;
RT "The human immunodeficiency virus Tat proteins specifically associate with
RT TAK in vivo and require the carboxyl-terminal domain of RNA polymerase II
RT for function.";
RL J. Virol. 70:4576-4584(1996).
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: 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=P20880-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P20880-2; Sequence=VSP_022446;
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:0000269|PubMed:8676484}.
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; M31113; AAB01356.1; -; Genomic_DNA.
DR PIR; F33943; TNLJST.
DR iPTMnet; P20880; -.
DR Proteomes; UP000007713; 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 1: Evidence at protein level;
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_0000085375"
FT REGION 1..29
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 13..29
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 85
FT /note="Phosphothreonine; by host CDK9"
FT /evidence="ECO:0000269|PubMed:8676484"
FT MOD_RES 89
FT /note="Phosphothreonine; by host CDK9"
FT /evidence="ECO:0000269|PubMed:8676484"
FT MOD_RES 94
FT /note="Phosphoserine; by host CDK9"
FT /evidence="ECO:0000269|PubMed:8676484"
FT VAR_SEQ 100..130
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000305"
FT /id="VSP_022446"
FT MUTAGEN 3
FT /note="T->A: No effect on P-TEFb binding and Tat
FT phosphorylation; when associated with A-11."
FT /evidence="ECO:0000269|PubMed:8676484"
FT MUTAGEN 11
FT /note="S->A: No effect on P-TEFb binding and Tat
FT phosphorylation; when associated with A-3."
FT /evidence="ECO:0000269|PubMed:8676484"
FT MUTAGEN 22
FT /note="T->A: No effect on P-TEFb binding and Tat
FT phosphorylation; when associated with A-23."
FT /evidence="ECO:0000269|PubMed:8676484"
FT MUTAGEN 23
FT /note="S->A: No effect on P-TEFb binding and Tat
FT phosphorylation; when associated with A-22."
FT /evidence="ECO:0000269|PubMed:8676484"
FT MUTAGEN 59
FT /note="C->A: Complete loss of P-TEFb binding and reduced
FT Tat phosphorylation."
FT /evidence="ECO:0000269|PubMed:8676484"
FT MUTAGEN 85
FT /note="T->A: No effect on P-TEFb binding and reduced Tat
FT phosphorylation; when associated with A-89 and A-94."
FT /evidence="ECO:0000269|PubMed:8676484"
FT MUTAGEN 89
FT /note="T->A: No effect on P-TEFb binding and reduced Tat
FT phosphorylation; when associated with A-85 and A-94."
FT /evidence="ECO:0000269|PubMed:8676484"
FT MUTAGEN 94
FT /note="S->A: No effect on P-TEFb binding and reduced Tat
FT phosphorylation; when associated with A-85 and A-89."
FT /evidence="ECO:0000269|PubMed:8676484"
SQ SEQUENCE 130 AA; 14383 MW; 1AA63DE911DD9DEC CRC64;
METPLKAPEG SLGSYNEPSS CTSEQDAAAQ GLVSPGDEIL YQLYQPLEAC DNKCYCKKCC
YHCQMCFLNK GLGIWYERKG RRRRTPKKTK AHSSSASDKS ISTRTGNSQP EKKQKKTLET
ALETIGGPGR
