LHDAG_HDVD3
ID LHDAG_HDVD3 Reviewed; 214 AA.
AC P29996;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2004, sequence version 2.
DT 29-SEP-2021, entry version 96.
DE RecName: Full=Large delta antigen;
DE Short=L-HDAg;
DE AltName: Full=p27;
DE Flags: Precursor;
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 ISOPRENYLATION AT CYS-211, AND INTERACTION WITH HBV HBSAG.
RX PubMed=8230486; DOI=10.1128/jvi.67.12.7659-7662.1993;
RA Hwang S.B., Lai M.M.;
RT "Isoprenylation mediates direct protein-protein interactions between
RT hepatitis large delta antigen and hepatitis B virus surface antigen.";
RL J. Virol. 67:7659-7662(1993).
RN [4]
RP ISOPRENYLATION AT CYS-211, AND METHYLATION AT CYS-211.
RX PubMed=8617711; DOI=10.1074/jbc.271.9.4569;
RA Otto J.C., Casey P.J.;
RT "The hepatitis delta virus large antigen is farnesylated both in vitro and
RT in animal cells.";
RL J. Biol. Chem. 271:4569-4572(1996).
RN [5]
RP PHOSPHORYLATION AT SER-2; SER-123 AND SER-177.
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 [6]
RP FUNCTION.
RX PubMed=12208968; DOI=10.1128/jvi.76.19.9910-9919.2002;
RA Macnaughton T.B., Lai M.M.;
RT "Large hepatitis delta antigen is not a suppressor of hepatitis delta virus
RT RNA synthesis once RNA replication is established.";
RL J. Virol. 76:9910-9919(2002).
RN [7]
RP SUBUNIT.
RX PubMed=12970416; DOI=10.1128/jvi.77.19.10314-10326.2003;
RA Cornillez-Ty C.T., Lazinski D.W.;
RT "Determination of the multimerization state of the hepatitis delta virus
RT antigens in vivo.";
RL J. Virol. 77:10314-10326(2003).
RN [8]
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 [9]
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 [10]
RP FUNCTION.
RX PubMed=17376909; DOI=10.1128/jvi.02809-06;
RA Huang C., Chang S.C., Yu I.C., Tsay Y.G., Chang M.F.;
RT "Large hepatitis delta antigen is a novel clathrin adaptor-like protein.";
RL J. Virol. 81:5985-5994(2007).
RN [11]
RP NUCLEAR LOCALIZATION SIGNAL, AND RNA-BINDING.
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: Following virus entry into host cell, provides nuclear import
CC of HDV RNPs thanks to its nuclear localization signal. Needs co-
CC infection with hepatitis B virus to provide surface proteins, otherwise
CC there is no packaging or budding. Packages the HDV ribonucleoprotein in
CC hepatitis B virus empty particles. Interacts with both HDV genomic RNA
CC and cytoplasmic tail of HBsAg. May inhibit viral RNA replication.
CC {ECO:0000269|PubMed:12208968, ECO:0000269|PubMed:17376909}.
CC -!- SUBUNIT: Homodimer. Homooctamer. Interacts with HBV HBsAg. May interact
CC with clathrin to induce virion budding. {ECO:0000269|PubMed:12970416,
CC ECO:0000269|PubMed:8230486}.
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000269|PubMed:1731113}. Host
CC nucleus, host nucleolus {ECO:0000269|PubMed:1731113}.
CC Note=isoprenylated in the cytoplasm, and translocates in the nucleus
CC possibly after phosphorylation. Translocates after to nuclear speckle,
CC then to the ER membrane where interaction with Hepatitis B virus
CC antigene takes place.
CC -!- PTM: Prenylated by host farnesyl-transferase in the cytoplasm prior to
CC nucleus translocation. {ECO:0000269|PubMed:8230486,
CC ECO:0000269|PubMed:8617711}.
CC -!- PTM: Phosphorylated at serines by host CK2 and other kinases.
CC phosphorylation does not seem to be important for its function.
CC {ECO:0000269|PubMed:10559375}.
CC -!- RNA EDITING: Modified_positions=196 {ECO:0000250}; Note=Partially
CC edited. RNA editing at this position occurs on the antigenomic strand
CC and consists of a conversion of A to G catalyzed by the cellular enzyme
CC ADAR1. The unedited RNA version gives rise to the small delta antigen
CC (AC P0C6L3), which ends with a nonsense codon at position 196. In the
CC edited version, this amber codon is modified to a tryptophan codon and
CC gives rise to the large delta antigen protein. S-HDAg suppresses
CC editing of non-replicating antigenomic RNA, thereby regulating the
CC extent of editing (By similarity). {ECO:0000250};
CC -!- SIMILARITY: Belongs to the hepatitis delta antigen family.
CC {ECO:0000305}.
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DR EMBL; D01075; BAA00874.1; ALT_TERM; Genomic_RNA.
DR SMR; P29996; -.
DR iPTMnet; P29996; -.
DR Proteomes; UP000006675; 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:0039675; P:exit of virus from host cell nucleus through nuclear pore; IDA:UniProtKB.
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; Lipoprotein; Methylation; Phosphoprotein;
KW Prenylation; Reference proteome; RNA editing; RNA-binding;
KW Viral penetration into host nucleus; Virion; Virus entry into host cell.
FT CHAIN 1..211
FT /note="Large delta antigen"
FT /id="PRO_0000038130"
FT PROPEP 212..214
FT /note="Removed in mature form"
FT /evidence="ECO:0000305"
FT /id="PRO_0000396787"
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..214
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"
FT /evidence="ECO:0000269|PubMed:10559375"
FT MOD_RES 13
FT /note="Omega-N-methylated arginine; by host"
FT /evidence="ECO:0000250|UniProtKB:P0C6L3"
FT MOD_RES 72
FT /note="N6-acetyllysine; by host"
FT /evidence="ECO:0000250|UniProtKB:P0C6L3"
FT MOD_RES 123
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000269|PubMed:10559375"
FT MOD_RES 177
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000269|PubMed:10559375"
FT MOD_RES 211
FT /note="Cysteine methyl ester; by host"
FT /evidence="ECO:0000305|PubMed:8617711"
FT LIPID 211
FT /note="S-farnesyl cysteine; by host"
FT /evidence="ECO:0000269|PubMed:8230486,
FT ECO:0000269|PubMed:8617711"
SQ SEQUENCE 214 AA; 24060 MW; 4A4C6AAAF90A388E CRC64;
MSRPEGRKNR GGREEVLEQW VSGRKKLEEL ERDLRKVKKK IKKLEDEHPW LGNIKGILGK
KDKDGEGAPP AKRARTDQME VDSGPRKRPS RGGFTDKERQ DHRRRKALEN KRKQLSAGGK
NLSKEEEEEL RRLTEEDERR ERRIAGPQVG GVNPLEGGTR GAPGGGFVPS MQGVPESPFT
RTGEGLDIRG SQGFPWDILF PADPPSSPQS CRPQ
