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