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ST_POVJC
ID   ST_POVJC                Reviewed;         172 AA.
AC   P03083;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   03-AUG-2022, entry version 103.
DE   RecName: Full=Small t antigen;
DE            Short=ST;
DE            Short=ST-AG;
OS   JC polyomavirus (JCPyV) (JCV).
OC   Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Papovaviricetes;
OC   Sepolyvirales; Polyomaviridae; Betapolyomavirus.
OX   NCBI_TaxID=10632;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=6086957; DOI=10.1128/jvi.51.2.458-469.1984;
RA   Frisque R.J., Bream G.L., Cannella M.T.;
RT   "Human polyomavirus JC virus genome.";
RL   J. Virol. 51:458-469(1984).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33.
RX   PubMed=6304771;
RA   Frisque R.J.;
RT   "Regulatory sequences and virus-cell interactions of JC virus.";
RL   Prog. Clin. Biol. Res. 105:41-59(1983).
RN   [3]
RP   FUNCTION, AND INTERACTION WITH AGNOPROTEIN AND HOST PPP2R1A.
RX   PubMed=18353419; DOI=10.1016/j.virol.2008.02.020;
RA   Sariyer I.K., Khalili K., Safak M.;
RT   "Dephosphorylation of JC virus agnoprotein by protein phosphatase 2A:
RT   inhibition by small t antigen.";
RL   Virology 375:464-479(2008).
RN   [4]
RP   FUNCTION, INTERACTION WITH HOST PPP2R1A; RBL1 AND RBL2, AND MUTAGENESIS OF
RP   PRO-99.
RX   PubMed=20485545; DOI=10.1371/journal.pone.0010606;
RA   Bollag B., Hofstetter C.A., Reviriego-Mendoza M.M., Frisque R.J.;
RT   "JC virus small T antigen binds phosphatase PP2A and Rb family proteins and
RT   is required for efficient viral DNA replication activity.";
RL   PLoS ONE 5:e10606-e10606(2010).
RN   [5]
RP   FUNCTION, AND MUTAGENESIS OF PRO-99.
RX   PubMed=25744060; DOI=10.1093/mutage/gev004;
RA   Huang J.L., Lin C.S., Chang C.C., Lu Y.N., Hsu Y.L., Wong T.Y., Wang Y.F.;
RT   "Human JC virus small tumour antigen inhibits nucleotide excision repair
RT   and sensitises cells to DNA-damaging agents.";
RL   Mutagenesis 30:475-485(2015).
RN   [6]
RP   FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH HOST SMARCA5 AND SDHB.
RX   PubMed=33092197; DOI=10.3390/v12101192;
RA   Saribas S., Safak M.;
RT   "A Comprehensive Proteomics Analysis of the JC Virus (JCV) Large and Small
RT   Tumor Antigen Interacting Proteins: Large T Primarily Targets the Host
RT   Protein Complexes with V-ATPase and Ubiquitin Ligase Activities While Small
RT   t Mostly Associates with Those Having Phosphatase and Chromatin-Remodeling
RT   Functions.";
RL   Viruses 12:0-0(2020).
RN   [7]
RP   FUNCTION, AND INTERACTION WITH HOST TRIM25.
RX   PubMed=33849980; DOI=10.1128/mbio.00620-21;
RA   Chiang C., Dvorkin S., Chiang J.J., Potter R.B., Gack M.U.;
RT   "The Small t Antigen of JC Virus Antagonizes RIG-I-Mediated Innate Immunity
RT   by Inhibiting TRIM25's RNA Binding Ability.";
RL   MBio 12:0-0(2021).
CC   -!- FUNCTION: Promotes efficient viral genome replication by modulating
CC       several host signaling pathways including transport network, interferon
CC       production or cell cycle progression (PubMed:20485545, PubMed:33092197,
CC       PubMed:33849980). Inhibits host PP2A phosphatase activity and thereby
CC       prevents agnoprotein dephosphorylation (PubMed:20485545,
CC       PubMed:18353419). Inactivation of PP2A also results in the
CC       transactivation of cyclin A and cyclin D1 promoters (By similarity). In
CC       addition, antagonizes the RIG-I/DDX58-mediated IFN response through
CC       interaction with E3 ligase TRIM25 leading to the inhibition of 'Lys-
CC       63'-linked ubiquitination of DDX58. Inhibits nucleotide excision repair
CC       (NER) pathway which leads to DNA strand breaks during DNA replication
CC       and micronuclei formation (PubMed:25744060).
CC       {ECO:0000250|UniProtKB:P03081, ECO:0000269|PubMed:18353419,
CC       ECO:0000269|PubMed:20485545, ECO:0000269|PubMed:25744060,
CC       ECO:0000269|PubMed:33092197, ECO:0000269|PubMed:33849980}.
CC   -!- SUBUNIT: Interacts with host PPP2R1A; the interaction inhibits PP2A
CC       activity (PubMed:20485545). Interacts with agnoprotein; this
CC       interaction prevents agnoprotein dephosphorylation by host PP2A
CC       (PubMed:18353419). Interacts with host RBL1 and RBL2 (PubMed:20485545).
CC       Interacts with SMARCA5 (PubMed:33092197). Interacts with SDHB
CC       (PubMed:33092197). {ECO:0000269|PubMed:18353419,
CC       ECO:0000269|PubMed:20485545, ECO:0000269|PubMed:33092197}.
CC   -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000269|PubMed:33092197}.
CC       Host nucleus {ECO:0000269|PubMed:33092197}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=Small t antigen;
CC         IsoId=P03083-1; Sequence=Displayed;
CC       Name=Large T antigen;
CC         IsoId=P03072-1; Sequence=External;
CC   -!- DOMAIN: The common region of ST and LT proteins comprises the J domain.
CC       This domain is essential for multiple viral activities, including
CC       virion assembly, viral DNA replication, transformation and
CC       transcriptional activation. This domain is also required for cyclin A-
CC       transactivating activity of ST. {ECO:0000250|UniProtKB:P03081}.
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DR   EMBL; J02226; AAA82103.1; -; Genomic_DNA.
DR   EMBL; M34921; AAA46891.2; -; Genomic_DNA.
DR   PIR; A03620; TVVPAJ.
DR   RefSeq; NP_043513.1; NC_001699.1. [P03083-1]
DR   SMR; P03083; -.
DR   GeneID; 1489521; -.
DR   KEGG; vg:1489521; -.
DR   Proteomes; UP000008478; Genome.
DR   GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0039540; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of host RIG-I activity; IEA:UniProtKB-KW.
DR   CDD; cd06257; DnaJ; 1.
DR   Gene3D; 1.10.287.110; -; 1.
DR   Gene3D; 1.20.120.1860; -; 1.
DR   InterPro; IPR001623; DnaJ_domain.
DR   InterPro; IPR036869; J_dom_sf.
DR   InterPro; IPR003354; Papo_T_antigen.
DR   InterPro; IPR036092; Papo_T_antigensf.
DR   Pfam; PF02380; Papo_T_antigen; 1.
DR   SMART; SM00271; DnaJ; 1.
DR   SUPFAM; SSF161240; SSF161240; 1.
DR   SUPFAM; SSF46565; SSF46565; 1.
DR   PROSITE; PS50076; DNAJ_2; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Activator; Alternative splicing; Early protein;
KW   Host cytoplasm; Host nucleus; Host-virus interaction;
KW   Inhibition of host innate immune response by virus;
KW   Inhibition of host RIG-I by virus; Inhibition of host RLR pathway by virus;
KW   Metal-binding; Oncogene; Phosphoprotein; Transcription;
KW   Transcription regulation; Viral immunoevasion; Zinc; Zinc-finger.
FT   CHAIN           1..172
FT                   /note="Small t antigen"
FT                   /id="PRO_0000115056"
FT   DOMAIN          12..75
FT                   /note="J"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00286"
FT   ZN_FING         101..114
FT                   /note="C4-type; atypical"
FT   ZN_FING         120..141
FT                   /note="H1C3-type; atypical"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine; by host"
FT                   /evidence="ECO:0000250|UniProtKB:P03081"
FT   MUTAGEN         99
FT                   /note="P->A: Loss of interaction with host PPP2R1A and
FT                   significant reduction of viral DNA replication. The
FT                   nucleotide excision repair (NER) pathway is no longer
FT                   inhibited."
FT                   /evidence="ECO:0000269|PubMed:20485545,
FT                   ECO:0000269|PubMed:25744060"
FT   CONFLICT        33
FT                   /note="A -> L (in Ref. 2)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   172 AA;  20238 MW;  5D040CE468BF29E3 CRC64;
     MDKVLNREES MELMDLLGLD RSAWGNIPVM RKAYLKKCKE LHPDKGGDED KMKRMNFLYK
     KMEQGVKVAH QPDFGTWNSS EVGCDFPPNS DTLYCKEWPN CATNPSVHCP CLMCMLKLRH
     RNRKFLRSSP LVWIDCYCFD CFRQWFGCDL TQEALHCWEK VLGDTPYRDL KL
 
 
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