P03148 (CAPSD_HBVA3) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Capsid protein

Alternative name(s):
Core antigen
Core protein
HBcAg
p21.5

Gene names

Name:

C

Organism

Hepatitis B virus genotype A2 subtype adw2 (strain Rutter 1979) (HBV-A) [Complete proteome]

Taxonomic identifier

480116 [NCBI]

Taxonomic lineage

Viruses › Retro-transcribing viruses › Hepadnaviridae › Orthohepadnavirus › Hepatitis B virus › Hepatitis B virus subtype adw › Hepatitis B virus subtype adw2

Virus host

Homo sapiens (Human) [TaxID: 9606]
Pan troglodytes (Chimpanzee) [TaxID: 9598]

Protein attributes

Sequence length	185 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Self assembles to form an icosahedral capsid. Most capsid appear to be large particles with a icosahedral symmetry of T=4 and consist of 240 copies of capsid protein, though a fraction forms smaller T=3 particles consisting of 180 capsid proteins. Entering capsid are transported along microtubules to the nucleus. Phosphorylation of the capsid is thought to induce exposure of nuclear localization signal in the C-terminal portion of the capsid protein that allows binding to the nuclear pore complex via the importin (karyopherin-) alpha and beta. Capsids are imported in intact form through the nuclear pore into the nuclear basket, where it probably binds NUP153. Only capsids that contain the mature viral genome can release the viral DNA and capsid protein into the nucleoplasm. Immature capsids get stucked in the basket. Capsids encapsulate the pre-genomic RNA and the P protein. Pre-genomic RNA is reverse transcribed into DNA while the capsid is still in the cytoplasm. The capsid can then either be directed to the nucleus, providing more genome for transcription, or bud through the endoplasmic reticulum to provide new virions By similarity. Ref.6 Encapsidates hepatitis delta genome. Ref.6
Subunit structure	Homodimerizes, then multimerizes. Interacts with cytosol exposed regions of viral L glycoprotein present in the reticulum-to-Golgi compartment. Interacts with human FLNB. Ref.5 Ref.10
Subcellular location	Capsid protein: Virion. Host cytoplasm Ref.2.
Post-translational modification	Phosphorylated by host SRPK1, SRPK2, and maybe protein kinase C or GAPDH. Phosphorylation is critical for pregenomic RNA packaging. Protein kinase C phosphorylation is stimulated by HBx protein and may play a role in transport of the viral genome to the nucleus at the late step during viral replication cycle. Ref.7 Ref.8
Sequence similarities	Belongs to the orthohepadnavirus core antigen family.

Ontologies

Keywords
Biological process	Cytoplasmic inwards viral transport Host-virus interaction Microtubular inwards viral transport Viral penetration into host nucleus Virus entry into host cell
Cellular component	Host cytoplasm Virion
Coding sequence diversity	Alternative initiation
Domain	Repeat
Ligand	DNA-binding RNA-binding
Molecular function	Capsid protein T=4 icosahedral capsid protein
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological_process	pathogenesis Inferred from electronic annotation. Source: InterPro 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	T=4 icosahedral viral capsid Inferred from electronic annotation. Source: UniProtKB-KW host cell cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW RNA binding Inferred from electronic annotation. Source: UniProtKB-KW structural molecule activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative initiation. [Align] [Select]

Isoform Capsid protein (identifier: P03148-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform External core antigen (identifier: P0C625-1)

The sequence of this isoform can be found in the external entry P0C625.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 185	185	Capsid protein		PRO_0000222308
Regions
	Repeat	157 – 163	7	1; half-length
	Repeat	164 – 171	8	2
	Repeat	172 – 179	8	3
	Region	157 – 179	23	3 X 8 AA repeats of S-P-R-R-R-[PR]-S-Q
	Region	179 – 185	7	RNA binding
	Motif	160 – 177	18	Bipartite nuclear localization signal Potential
Amino acid modifications
	Modified residue	157	1	Phosphoserine; by host Ref.7
	Modified residue	164	1	Phosphoserine; by host Ref.7
	Modified residue	172	1	Phosphoserine; by host Ref.7
Natural variations
	Natural variant	93	1	V → M.
	Natural variant	97	1	I → L Frequent mutation in chronic HBV carriers. Ref.9
	Natural variant	169	1	R → P.
Experimental info
	Mutagenesis	48	1	C → A: No effect on dimer or capsid formation. Ref.4
	Mutagenesis	61	1	C → A: No effect on dimer or capsid formation. Ref.4
	Mutagenesis	107	1	C → A: No effect on dimer or capsid formation. Ref.4
	Mutagenesis	157	1	S → A: Increases nuclear localization. Ref.7
	Mutagenesis	164	1	S → A: Increases nuclear localization. Ref.7
	Mutagenesis	172	1	S → A: Increases nuclear localization. Ref.7
	Mutagenesis	185	1	C → A: No effect on dimer or capsid formation. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform Capsid protein [UniParc]. Last modified January 15, 2008. Version 3. Checksum: 32423C338B507F5C	FASTA	185	21,332
	10 20 30 40 50 60 MDIDPYKEFG ATVELLSFLP SDFFPSVRDL LDTASALYRE ALESPEHCSP HHTALRQAIL 70 80 90 100 110 120 CWGELMTLAT WVGNNLEDPA SRDLVVNYVN TNVGLKIRQL LWFHISCLTF GRETVLEYLV 130 140 150 160 170 180 SFGVWIRTPP AYRPPNAPIL STLPETTVVR RRDRGRSPRR RTPSPRRRRS PSPRRRRSQS RESQC
	Isoform External core antigen [UniParc]. See P0C625.		–	–

References

[1]	"The nucleotide sequence of the hepatitis B viral genome and the identification of the major viral genes." Valenzuela P., Quiroga M., Zaldivar J., Gray P., Rutter W.J. (In) Field B.N., Jaenisch R., Fox C.F. (eds.); Animal virus genetics, pp.57-70, Academic Press, New York (1980) Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Hepatitis B virus gene function: the precore region targets the core antigen to cellular membranes and causes the secretion of the e antigen." Ou J.H., Laub O., Rutter W.J. Proc. Natl. Acad. Sci. U.S.A. 83:1578-1582(1986) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[3]	"RNA- and DNA-binding activities in hepatitis B virus capsid protein: a model for their roles in viral replication." Hatton T., Zhou S., Standring D.N. J. Virol. 66:5232-5241(1992) [PubMed] [Europe PMC] [Abstract] Cited for: RNA AND DNA-BINDING.
[4]	"Cys residues of the hepatitis B virus capsid protein are not essential for the assembly of viral core particles but can influence their stability." Zhou S., Standring D.N. J. Virol. 66:5393-5398(1992) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF CYS-48; CYS-61; CYS-107 AND CYS-185.
[5]	"Hepatitis B virus capsid particles are assembled from core-protein dimer precursors." Zhou S., Standring D.N. Proc. Natl. Acad. Sci. U.S.A. 89:10046-10050(1992) [PubMed] [Europe PMC] [Abstract] Cited for: DIMERIZATION.
[6]	"A protease-sensitive hinge linking the two domains of the hepatitis B virus core protein is exposed on the viral capsid surface." Seifer M., Standring D.N. J. Virol. 68:5548-5555(1994) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[7]	"Phosphorylation and nuclear localization of the hepatitis B virus core protein: significance of serine in the three repeated SPRRR motifs." Liao W., Ou J.H. J. Virol. 69:1025-1029(1995) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-157; SER-164 AND SER-172, MUTAGENESIS OF SER-157; SER-164 AND SER-172.
[8]	"Phosphorylation of the hepatitis B virus core protein by glyceraldehyde-3-phosphate dehydrogenase protein kinase activity." Duclos-Vallee J.C., Capel F., Mabit H., Petit M.A. J. Gen. Virol. 79:1665-1670(1998) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY HUMAN GAPDH.
[9]	"Subtype-independent immature secretion and subtype-dependent replication deficiency of a highly frequent, naturally occurring mutation of human hepatitis B virus core antigen." Yuan T.T., Tai P.C., Shih C. J. Virol. 73:10122-10128(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LEU-97.
[10]	"Hepatitis B virus core protein interacts with the C-terminal region of actin-binding protein." Huang C.J., Chen Y.H., Ting L.P. J. Biomed. Sci. 7:160-168(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HUMAN FLNB.
[11]	"Envelopment of the hepatitis B virus nucleocapsid." Bruss V. Virus Res. 106:199-209(2004) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.

Web resources

HepSEQ

Hepatitis virus B database

Cross-references

Sequence databases
EMBL GenBank DDBJ	X02763 Genomic DNA. Translation: CAA26537.1.
3D structure databases
ProteinModelPortal	P03148.
SMR	P03148. Positions 1-143.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
InterPro	IPR002006. Viral_capsid_core_Hepatitis. [Graphical view]
Pfam	PF00906. Hepatitis_core. 1 hit. [Graphical view]
SUPFAM	SSF47852. Viral_capsid_core_Hepatitis. 1 hit.
ProtoNet	Search...

Entry information

Entry name

CAPSD_HBVA3

Accession

Primary (citable) accession number: P03148
Secondary accession number(s): Q67868

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 15, 2008
Last modified:	January 9, 2013
This is version 53 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program