P29996 (LHDAG_HDVD3) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Large delta antigen Short name=L-HDAg Alternative name(s): p27
Organism	Hepatitis delta virus genotype I (isolate D380) (HDV) [Reference proteome]
Taxonomic identifier	31762 [NCBI]
Taxonomic lineage	Viruses › Deltavirus › Hepatitis delta virus
Virus host	Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	214 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Following virus entry into host cell, provides nuclear import of HDV RNPs thanks to its nuclear localization signal. Needs co-infection with hepatitis B virus to provide surface proteins, otherwise there is no packaging or budding. Packages the HDV ribonucleoprotein in hepatitis B virus empty particles. Interacts with both HDV genomic RNA and cytoplasmic tail of HBsAg. May inhibit viral RNA replication. Ref.6 Ref.10
Subunit structure	Homodimer. Homooctamer. Interacts with HBV HBsAg. May interact with clathrin to induce virion budding. Ref.3 Ref.7
Subcellular location	Virion. Host nucleus › host nucleolus. Note: isoprenylated in the cytoplasm, and translocates in the nucleus possibly after phosphorylation. Translocates after to nuclear speckle, then to the ER membrane where interaction with Hepatitis B virus antigene takes place. Ref.2
Post-translational modification	Prenylated by host farnesyl-transferase in the cytoplasm prior to nucleus translocation. Phosphorylated at serines by host CK2 and other kinases. phosphorylation does not seem to be important for its function. Ref.5
Sequence similarities	Belongs to the hepatitis delta antigen family.
RNA editing	Edited at position 196. Partially edited. RNA editing at this position occurs on the antigenomic strand and consists of a conversion of A to G catalyzed by the cellular enzyme ADAR1. The unedited RNA version gives rise to the small delta antigen (AC P0C6L3), which ends with a nonsense codon at position 196. In the edited version, this amber codon is modified to a tryptophan codon and gives rise to the large delta antigen protein. S-HDAg suppresses editing of non-replicating antigenomic RNA, thereby regulating the extent of editing By similarity.

Ontologies

Keywords
Biological process	Viral penetration into host nucleus Virus entry into host cell
Cellular component	Host nucleus Virion
Coding sequence diversity	RNA editing
Ligand	RNA-binding
PTM	Acetylation Lipoprotein Methylation Phosphoprotein Prenylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	viral entry into host cell Inferred from electronic annotation. Source: UniProtKB-KW viral penetration into host nucleus Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	host cell nucleolus Inferred from electronic annotation. Source: UniProtKB-SubCell virion Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 211	211	Large delta antigen		PRO_0000038130
	Propeptide	212 – 214	3	Removed in mature form Probable		PRO_0000396787
Regions
	Region	12 – 60	49	Dimerization Potential
	Region	97 – 107	11	RNA-binding Potential
	Region	136 – 146	11	RNA-binding Potential
	Motif	66 – 75	10	Nuclear localization signal By similarity
Amino acid modifications
	Modified residue	2	1	Phosphoserine; by host
	Modified residue	13	1	Omega-N-methylated arginine; by host
	Modified residue	72	1	N6-acetyllysine; by host
	Modified residue	123	1	Phosphoserine; by host
	Modified residue	177	1	Phosphoserine; by host
	Modified residue	211	1	Cysteine methyl ester; by host Probable
	Lipidation	211	1	S-farnesyl cysteine; by host Ref.3 Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P29996 [UniParc]. Last modified March 1, 2004. Version 2. Checksum: 4A4C6AAAF90A388E	FASTA	214	24,060
	10 20 30 40 50 60 MSRPEGRKNR GGREEVLEQW VSGRKKLEEL ERDLRKVKKK IKKLEDEHPW LGNIKGILGK 70 80 90 100 110 120 KDKDGEGAPP AKRARTDQME VDSGPRKRPS RGGFTDKERQ DHRRRKALEN KRKQLSAGGK 130 140 150 160 170 180 NLSKEEEEEL RRLTEEDERR ERRIAGPQVG GVNPLEGGTR GAPGGGFVPS MQGVPESPFT 190 200 210 RTGEGLDIRG SQGFPWDILF PADPPSSPQS CRPQ

References

[1]	"Cloning and sequencing of RNA of hepatitis delta virus isolated from human serum." Saldanha J.A., Thomas H.C., Monjardino J.P. J. Gen. Virol. 71:1603-1606(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Characterization of nuclear targeting signal of hepatitis delta antigen: nuclear transport as a protein complex." Xia Y.-P., Yeh C.-T., Ou J.-H., Lai M.M.C. J. Virol. 66:914-921(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEAR LOCALIZATION SIGNAL, SUBCELLULAR LOCATION.
[3]	"Isoprenylation mediates direct protein-protein interactions between hepatitis large delta antigen and hepatitis B virus surface antigen." Hwang S.B., Lai M.M. J. Virol. 67:7659-7662(1993) [PubMed] [Europe PMC] [Abstract] Cited for: ISOPRENYLATION AT CYS-211, INTERACTION WITH HBV HBSAG.
[4]	"The hepatitis delta virus large antigen is farnesylated both in vitro and in animal cells." Otto J.C., Casey P.J. J. Biol. Chem. 271:4569-4572(1996) [PubMed] [Europe PMC] [Abstract] Cited for: ISOPRENYLATION AT CYS-211.
[5]	"Characterization of the phosphorylated forms and the phosphorylated residues of hepatitis delta virus delta antigens." Mu J.J., Wu H.L., Chiang B.L., Chang R.P., Chen D.S., Chen P.J. J. Virol. 73:10540-10545(1999) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION.
[6]	"Large hepatitis delta antigen is not a suppressor of hepatitis delta virus RNA synthesis once RNA replication is established." Macnaughton T.B., Lai M.M. J. Virol. 76:9910-9919(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[7]	"Determination of the multimerization state of the hepatitis delta virus antigens in vivo." Cornillez-Ty C.T., Lazinski D.W. J. Virol. 77:10314-10326(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT.
[8]	"Hepatitis D." Husa P., Linhartova A., Nemecek V., Husova L. Acta Virol. 49:219-225(2005) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[9]	"Post-translational modification of delta antigen of hepatitis D virus." Huang W.H., Chen C.W., Wu H.L., Chen P.J. Curr. Top. Microbiol. Immunol. 307:91-112(2006) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[10]	"Large hepatitis delta antigen is a novel clathrin adaptor-like protein." Huang C., Chang S.C., Yu I.C., Tsay Y.G., Chang M.F. J. Virol. 81:5985-5994(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"Characterization of the nuclear localization signal of the hepatitis delta virus antigen." Alves C., Freitas N., Cunha C. Virology 370:12-21(2008) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEAR LOCALIZATION SIGNAL, RNA-BINDING.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D01075 Genomic RNA. Translation: BAA00874.1. Different termination.
3D structure databases
ProteinModelPortal	P29996.
SMR	P29996. Positions 12-60.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
InterPro	IPR002506. HDV_ag. [Graphical view]
Pfam	PF01517. HDV_ag. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

LHDAG_HDVD3

Accession

Primary (citable) accession number: P29996

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	March 1, 2004
Last modified:	April 3, 2013
This is version 59 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program