ID   LHDAG_HDVS2             Reviewed;         214 AA.
AC   P0C6M0;
DT   14-APR-2009, integrated into UniProtKB/Swiss-Prot.
DT   14-APR-2009, sequence version 1.
DT   29-SEP-2021, entry version 46.
DE   RecName: Full=Large delta antigen;
DE            Short=L-HDAg;
DE   AltName: Full=p27;
DE   Flags: Precursor;
OS   Hepatitis delta virus genotype I (isolate Japanese S-2) (HDV).
OC   Viruses; Ribozyviria; Kolmioviridae; Deltavirus.
OX   NCBI_TaxID=10428;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=2214027; DOI=10.1128/jvi.64.11.5594-5599.1990;
RA   Imazeki F., Omata M., Ohto M.;
RT   "Heterogeneity and evolution rates of delta virus RNA sequences.";
RL   J. Virol. 64:5594-5599(1990).
RN   [2]
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   [3]
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).
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 (By
CC       similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Homodimer. Homooctamer. Interacts with HBV HBsAg. May interact
CC       with clathrin to induce virion budding (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Virion. Host nucleus, host nucleolus.
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 (By similarity). {ECO:0000250}.
CC   -!- PTM: Prenylated by host farnesyl-transferase in the cytoplasm prior to
CC       nucleus translocation. {ECO:0000250}.
CC   -!- PTM: Phosphorylated at serines by host CK2 and other kinases.
CC       phosphorylation does not seem to be important for its function (By
CC       similarity). {ECO:0000250}.
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 P25884), 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   -!- 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; D90193; BAA14217.1; ALT_TERM; Genomic_RNA.
DR   SMR; P0C6M0; -.
DR   Proteomes; UP000008112; 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: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   3: Inferred from homology;
KW   Acetylation; Host nucleus; Lipoprotein; Methylation; Phosphoprotein;
KW   Prenylation; RNA editing; RNA-binding; Viral penetration into host nucleus;
KW   Virion; Virus entry into host cell.
FT   CHAIN           1..211
FT                   /note="Large delta antigen"
FT                   /id="PRO_0000038146"
FT   PROPEP          212..214
FT                   /note="Removed in mature form"
FT                   /evidence="ECO:0000250|UniProtKB:P29996"
FT                   /id="PRO_0000396676"
FT   DOMAIN          21..195
FT                   /note="HDAg"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01183"
FT   REGION          13..60
FT                   /note="Dimerization"
FT                   /evidence="ECO:0000255"
FT   REGION          59..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:0000250|UniProtKB:P29996"
FT   COMPBIAS        65..147
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:0000250|UniProtKB:P29996"
FT   MOD_RES         14
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:0000250|UniProtKB:P29996"
FT   MOD_RES         177
FT                   /note="Phosphoserine; by host"
FT                   /evidence="ECO:0000250|UniProtKB:P29996"
FT   MOD_RES         211
FT                   /note="Cysteine methyl ester; by host"
FT                   /evidence="ECO:0000250|UniProtKB:P29996"
FT   LIPID           211
FT                   /note="S-farnesyl cysteine; by host"
FT                   /evidence="ECO:0000250|UniProtKB:P29996"
SQ   SEQUENCE   214 AA;  24070 MW;  A65F9AF85381D1F3 CRC64;
     MSQSETRRGR RGTREETLEK WITARKKAEE LEKDLRKARK TIKKLEEENP WLGNILGIIR
     KGKDGEGAPP AKRPRTDQME VDSGPGKRPH KSGFTDKERE DHRRRKALEN KKKQLSAGGK
     ILSKEEEEEL RRLTDEDEER KRRVAGPRVG DVNPSRGGPR GAPGGGFVPQ MAGVPESPFS
     RTGEGLDIRG TQGFPWVSPS PPQQRLPLLE CTPQ