P0C6M9 (LHDAG_HDVWO) 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 Woodchuck) (HDV) [Complete proteome]
Taxonomic identifier	31764 [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 transcript 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 By similarity.
Subunit structure	Homodimer. Homooctamer. Interacts with HBV HBsAg. May interact with clathrin to induce virion budding By similarity.
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 By similarity.
Post-translational modification	Prenylated by host farnesyl-transferase in the cytoplasm prior to nucleus translocation By similarity. Phosphorylated at serines by host CK2 and other kinases. phosphorylation does not seem to be important for its function By similarity.
Miscellaneous	This strain belongs to the genotype I found in North America, Europe, Africa, East and West Asia and the South Pacific.
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 P29997), 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. Ref.2

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
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_0000038158
	Propeptide	212 – 214	3	Removed in mature form By similarity		PRO_0000396678
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 By similarity
	Modified residue	13	1	Omega-N-methylated arginine; by host By similarity
	Modified residue	72	1	N6-acetyllysine; by host By similarity
	Modified residue	123	1	Phosphoserine; by host By similarity
	Modified residue	177	1	Phosphoserine; by host By similarity
	Modified residue	211	1	Cysteine methyl ester; by host By similarity
	Lipidation	211	1	S-farnesyl cysteine; by host By similarity
Natural variations
	Natural variant	11	1	G → R in strain: Isolate Woodchuck5.
	Natural variant	86	1	R → G in strain: Isolate Woodchuck5.
	Natural variant	96	1	D → E in strain: Isolate Woodchuck5.

Sequences

	Sequence		Length	Mass (Da)
	P0C6M9 [UniParc]. Last modified April 14, 2009. Version 1. Checksum: 44360B6EF6870B5C	FASTA	214	24,078
	10 20 30 40 50 60 MSRSESRKNR GGREEILEQW VAGRKKLEEL ERDLRKTKKK LKKIEDENPW LGNIKGILGK 70 80 90 100 110 120 KDKDGEGAPP AKRARTDQME VDSGPRKRPL RGGFTDKERQ DHRRRKALEN KKKQLSAGGK 130 140 150 160 170 180 NLSKEEEEEL RRLTEEDERR ERRVAGPPVG GVNPLEGGSR GAPGGGFVPN LQGVPESPFS 190 200 210 RTGEGLDIRG NQGFPWDILF PADPPFSPQS CRPQ

References

[1]	"Molecular cloning of hepatitis delta virus RNA from an infected woodchuck liver: sequence, structure, and applications." Kuo M.Y.P., Goldberg J., Coates L., Mason W., Gerin J., Taylor J. J. Virol. 62:1855-1861(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Nucleotide sequence analysis of three different hepatitis delta viruses isolated from a woodchuck and humans." Deny P., Zignego A.L., Rascalou N., Ponzetto A., Tiollais P., Brechot C. J. Gen. Virol. 72:735-739(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA], RNA EDITING. Strain: Isolate Woodchuck5.
[3]	"Hepatitis D." Husa P., Linhartova A., Nemecek V., Husova L. Acta Virol. 49:219-225(2005) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[4]	"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.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M21012 Genomic RNA. Translation: AAA45723.1. Different termination. AJ307077 Genomic RNA. Translation: CAC32838.1.
PIR	SAVLWC. A30054.
3D structure databases
ProteinModelPortal	P0C6M9.
SMR	P0C6M9. 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_HDVWO

Accession

Primary (citable) accession number: P0C6M9

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 14, 2009
Last sequence update:	April 14, 2009
Last modified:	April 3, 2013
This is version 14 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program