SHDAG_HDVD3
ID SHDAG_HDVD3 Reviewed; 195 AA.
AC P0C6L3;
DT 10-FEB-2009, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2009, sequence version 1.
DT 25-MAY-2022, entry version 54.
DE RecName: Full=Small delta antigen;
DE Short=S-HDAg;
DE AltName: Full=p24;
OS Hepatitis delta virus genotype I (isolate D380) (HDV).
OC Viruses; Ribozyviria; Kolmioviridae; Deltavirus.
OX NCBI_TaxID=31762;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=2374010; DOI=10.1099/0022-1317-71-7-1603;
RA Saldanha J.A., Thomas H.C., Monjardino J.P.;
RT "Cloning and sequencing of RNA of hepatitis delta virus isolated from human
RT serum.";
RL J. Gen. Virol. 71:1603-1606(1990).
RN [2]
RP NUCLEAR LOCALIZATION SIGNAL, AND SUBCELLULAR LOCATION.
RX PubMed=1731113; DOI=10.1128/jvi.66.2.914-921.1992;
RA Xia Y.-P., Yeh C.-T., Ou J.-H., Lai M.M.C.;
RT "Characterization of nuclear targeting signal of hepatitis delta antigen:
RT nuclear transport as a protein complex.";
RL J. Virol. 66:914-921(1992).
RN [3]
RP MUTAGENESIS OF SER-2 AND SER-123, AND PHOSPHORYLATION AT SER-2 AND SER-123.
RX PubMed=8709245; DOI=10.1128/jvi.70.9.6190-6198.1996;
RA Yeh T.S., Lo S.J., Chen P.J., Lee Y.H.;
RT "Casein kinase II and protein kinase C modulate hepatitis delta virus RNA
RT replication but not empty viral particle assembly.";
RL J. Virol. 70:6190-6198(1996).
RN [4]
RP PHOSPHORYLATION.
RX PubMed=10559375; DOI=10.1128/jvi.73.12.10540-10545.1999;
RA Mu J.J., Wu H.L., Chiang B.L., Chang R.P., Chen D.S., Chen P.J.;
RT "Characterization of the phosphorylated forms and the phosphorylated
RT residues of hepatitis delta virus delta antigens.";
RL J. Virol. 73:10540-10545(1999).
RN [5]
RP MUTAGENESIS OF SER-177.
RX PubMed=11533172; DOI=10.1128/jvi.75.19.9087-9095.2001;
RA Mu J.J., Chen D.S., Chen P.J.;
RT "The conserved serine 177 in the delta antigen of hepatitis delta virus is
RT one putative phosphorylation site and is required for efficient viral RNA
RT replication.";
RL J. Virol. 75:9087-9095(2001).
RN [6]
RP INTERACTION WITH HOST NPM1.
RX PubMed=11309377; DOI=10.1074/jbc.m010087200;
RA Huang W.H., Yung B.Y., Syu W.J., Lee Y.H.;
RT "The nucleolar phosphoprotein B23 interacts with hepatitis delta antigens
RT and modulates the hepatitis delta virus RNA replication.";
RL J. Biol. Chem. 276:25166-25175(2001).
RN [7]
RP PHOSPHORYLATION AT SER-177 AND THR-182.
RX PubMed=12060652; DOI=10.1074/jbc.m200613200;
RA Chen C.W., Tsay Y.G., Wu H.L., Lee C.H., Chen D.S., Chen P.J.;
RT "The double-stranded RNA-activated kinase, PKR, can phosphorylate hepatitis
RT D virus small delta antigen at functional serine and threonine residues.";
RL J. Biol. Chem. 277:33058-33067(2002).
RN [8]
RP ACETYLATION AT LYS-72, AND MUTAGENESIS OF LYS-72.
RX PubMed=14967488; DOI=10.1016/j.virol.2003.10.024;
RA Mu J.J., Tsay Y.G., Juan L.J., Fu T.F., Huang W.H., Chen D.S., Chen P.J.;
RT "The small delta antigen of hepatitis delta virus is an acetylated protein
RT and acetylation of lysine 72 may influence its cellular localization and
RT viral RNA synthesis.";
RL Virology 319:60-70(2004).
RN [9]
RP METHYLATION AT ARG-13 BY HOST PRMT1.
RX PubMed=15542683; DOI=10.1128/jvi.78.23.13325-13334.2004;
RA Li Y.J., Stallcup M.R., Lai M.M.;
RT "Hepatitis delta virus antigen is methylated at arginine residues, and
RT methylation regulates subcellular localization and RNA replication.";
RL J. Virol. 78:13325-13334(2004).
RN [10]
RP REVIEW.
RX PubMed=16402678;
RA Husa P., Linhartova A., Nemecek V., Husova L.;
RT "Hepatitis D.";
RL Acta Virol. 49:219-225(2005).
RN [11]
RP REVIEW.
RX PubMed=16903222; DOI=10.1007/3-540-29802-9_5;
RA Huang W.H., Chen C.W., Wu H.L., Chen P.J.;
RT "Post-translational modification of delta antigen of hepatitis D virus.";
RL Curr. Top. Microbiol. Immunol. 307:91-112(2006).
RN [12]
RP PHOSPHORYLATION AT SER-177.
RX PubMed=18632853; DOI=10.1128/jvi.00656-08;
RA Chen Y.S., Huang W.H., Hong S.Y., Tsay Y.G., Chen P.J.;
RT "ERK1/2-mediated phosphorylation of small hepatitis delta antigen at serine
RT 177 enhances hepatitis delta virus antigenomic RNA replication.";
RL J. Virol. 82:9345-9358(2008).
RN [13]
RP NUCLEAR LOCALIZATION SIGNAL.
RX PubMed=17897693; DOI=10.1016/j.virol.2007.07.034;
RA Alves C., Freitas N., Cunha C.;
RT "Characterization of the nuclear localization signal of the hepatitis delta
RT virus antigen.";
RL Virology 370:12-21(2008).
CC -!- FUNCTION: Promotes both transcription and replication of genomic RNA.
CC Following virus entry into host cell, provides nuclear import of HDV
CC RNPs thanks to its nuclear localization signal. May interact with host
CC RNA polymerase II thereby changing its template requirement from DNA to
CC RNA. RNA pol II complex would then acts as an RNA-directed RNA
CC polymerase, and transcribe and replicate HDV genome (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Homodimer (By similarity). Homooctamer (By similarity).
CC Interacts with host RNA polymerase II complex, and with host NPM1.
CC {ECO:0000250, ECO:0000269|PubMed:11309377}.
CC -!- INTERACTION:
CC P0C6L3; Q9HCE1: MOV10; Xeno; NbExp=2; IntAct=EBI-15709810, EBI-1055820;
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000269|PubMed:1731113}. Host nucleus
CC {ECO:0000269|PubMed:1731113}.
CC -!- PTM: Phosphorylated at serines and threonines by host MAPK1/3, PKR, and
CC CK2. {ECO:0000269|PubMed:10559375, ECO:0000269|PubMed:12060652,
CC ECO:0000269|PubMed:18632853}.
CC -!- PTM: Acetylation modulates nuclear localization. Neo-synthesized
CC genomic RNA migrates from the nucleus to the cytoplasm, where they
CC interact with S-HDAg, which once acetylated redirect both partners to
CC the nucleus. {ECO:0000269|PubMed:14967488}.
CC -!- PTM: Methylation plays a role in viral genome replication.
CC {ECO:0000269|PubMed:15542683}.
CC -!- RNA EDITING: Modified_positions=196; Note=Partially edited. RNA editing
CC at this position occurs on the antigenomic strand and consists of a
CC conversion of A to G catalyzed by the cellular enzyme ADAR1. The
CC unedited RNA version gives rise to the small delta antigen, which ends
CC with a nonsense codon at position 196. In the edited version, this
CC amber codon is modified to a tryptophan codon and gives rise to the
CC large delta antigen protein (AC P29996). S-HDAg suppresses editing of
CC non-replicating antigenomic RNA, thereby regulating the extent of
CC editing.;
CC -!- MISCELLANEOUS: This strain belongs to the genotype I found in North
CC America, Europe, Africa, East and West Asia and the South Pacific.
CC -!- SIMILARITY: Belongs to the hepatitis delta antigen family.
CC {ECO:0000305}.
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DR EMBL; D01075; BAA00874.1; -; Genomic_RNA.
DR PIR; A35219; SAVLH1.
DR RefSeq; NP_077804.1; NC_001653.2.
DR SMR; P0C6L3; -.
DR IntAct; P0C6L3; 1.
DR iPTMnet; P0C6L3; -.
DR GeneID; 920835; -.
DR KEGG; vg:920835; -.
DR Proteomes; UP000006675; Genome.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0046718; P:viral entry into host cell; IEA:UniProtKB-KW.
DR GO; GO:0075732; P:viral penetration into host nucleus; IEA:UniProtKB-KW.
DR Gene3D; 4.10.220.40; -; 1.
DR InterPro; IPR027403; Delta_antigen_N.
DR InterPro; IPR037517; HDAG_dom.
DR InterPro; IPR002506; HDV_ag.
DR Pfam; PF01517; HDV_ag; 1.
DR SUPFAM; SSF58108; SSF58108; 1.
DR PROSITE; PS51838; HDAG; 1.
PE 1: Evidence at protein level;
KW Acetylation; Host nucleus; Host-virus interaction; Methylation;
KW Phosphoprotein; Reference proteome; RNA editing; RNA-binding;
KW Viral penetration into host nucleus; Virion; Virus entry into host cell.
FT CHAIN 1..195
FT /note="Small delta antigen"
FT /id="PRO_0000038131"
FT DOMAIN 20..195
FT /note="HDAg"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01183"
FT REGION 12..60
FT /note="Dimerization"
FT /evidence="ECO:0000255"
FT REGION 41..195
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 97..107
FT /note="RNA-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01183"
FT REGION 130..195
FT /note="RNAPII-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01183"
FT REGION 136..146
FT /note="RNA-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01183"
FT MOTIF 66..75
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:1731113,
FT ECO:0000269|PubMed:17897693"
FT COMPBIAS 57..105
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 118..145
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="Phosphoserine; by host CK2"
FT /evidence="ECO:0000269|PubMed:8709245"
FT MOD_RES 13
FT /note="Omega-N-methylated arginine; by host PRMT1"
FT /evidence="ECO:0000269|PubMed:15542683"
FT MOD_RES 72
FT /note="N6-acetyllysine; by host"
FT /evidence="ECO:0000269|PubMed:14967488"
FT MOD_RES 123
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000269|PubMed:8709245"
FT MOD_RES 177
FT /note="Phosphoserine; by host MAPK1 and MAPK3"
FT /evidence="ECO:0000269|PubMed:12060652,
FT ECO:0000269|PubMed:18632853"
FT MOD_RES 182
FT /note="Phosphothreonine; by host"
FT /evidence="ECO:0000269|PubMed:12060652"
FT MUTAGEN 2
FT /note="S->A: Reduces viral replication."
FT /evidence="ECO:0000269|PubMed:8709245"
FT MUTAGEN 72
FT /note="K->R: Complete loss of nuclear localization."
FT /evidence="ECO:0000269|PubMed:14967488"
FT MUTAGEN 123
FT /note="S->A: No effect on viral replication."
FT /evidence="ECO:0000269|PubMed:8709245"
FT MUTAGEN 177
FT /note="S->A: Reduces viral replication."
FT /evidence="ECO:0000269|PubMed:11533172"
SQ SEQUENCE 195 AA; 21937 MW; 8F09A9C62E9D2721 CRC64;
MSRPEGRKNR GGREEVLEQW VSGRKKLEEL ERDLRKVKKK IKKLEDEHPW LGNIKGILGK
KDKDGEGAPP AKRARTDQME VDSGPRKRPS RGGFTDKERQ DHRRRKALEN KRKQLSAGGK
NLSKEEEEEL RRLTEEDERR ERRIAGPQVG GVNPLEGGTR GAPGGGFVPS MQGVPESPFT
RTGEGLDIRG SQGFP
