CAPSD_HBVA3
ID CAPSD_HBVA3 Reviewed; 185 AA.
AC P03148; Q67868;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 3.
DT 29-SEP-2021, entry version 91.
DE RecName: Full=Capsid protein {ECO:0000255|HAMAP-Rule:MF_04076};
DE AltName: Full=Core antigen {ECO:0000255|HAMAP-Rule:MF_04076};
DE AltName: Full=Core protein {ECO:0000255|HAMAP-Rule:MF_04076};
DE AltName: Full=HBcAg {ECO:0000255|HAMAP-Rule:MF_04076};
DE AltName: Full=p21.5 {ECO:0000255|HAMAP-Rule:MF_04076};
GN Name=C {ECO:0000255|HAMAP-Rule:MF_04076};
OS Hepatitis B virus genotype A2 subtype adw2 (strain Rutter 1979) (HBV-A).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Blubervirales; Hepadnaviridae; Orthohepadnavirus.
OX NCBI_TaxID=480116;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9598; Pan troglodytes (Chimpanzee).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Valenzuela P., Quiroga M., Zaldivar J., Gray P., Rutter W.J.;
RT "The nucleotide sequence of the hepatitis B viral genome and the
RT identification of the major viral genes.";
RL (In) Field B.N., Jaenisch R., Fox C.F. (eds.);
RL Animal virus genetics, pp.57-70, Academic Press, New York (1980).
RN [2]
RP SUBCELLULAR LOCATION.
RX PubMed=3006057; DOI=10.1073/pnas.83.6.1578;
RA Ou J.H., Laub O., Rutter W.J.;
RT "Hepatitis B virus gene function: the precore region targets the core
RT antigen to cellular membranes and causes the secretion of the e antigen.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:1578-1582(1986).
RN [3]
RP RNA AND DNA-BINDING.
RX PubMed=1501273; DOI=10.1128/jvi.66.9.5232-5241.1992;
RA Hatton T., Zhou S., Standring D.N.;
RT "RNA- and DNA-binding activities in hepatitis B virus capsid protein: a
RT model for their roles in viral replication.";
RL J. Virol. 66:5232-5241(1992).
RN [4]
RP MUTAGENESIS OF CYS-48; CYS-61; CYS-107 AND CYS-185.
RX PubMed=1501280; DOI=10.1128/jvi.66.9.5393-5398.1992;
RA Zhou S., Standring D.N.;
RT "Cys residues of the hepatitis B virus capsid protein are not essential for
RT the assembly of viral core particles but can influence their stability.";
RL J. Virol. 66:5393-5398(1992).
RN [5]
RP DIMERIZATION.
RX PubMed=1438193; DOI=10.1073/pnas.89.21.10046;
RA Zhou S., Standring D.N.;
RT "Hepatitis B virus capsid particles are assembled from core-protein dimer
RT precursors.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:10046-10050(1992).
RN [6]
RP FUNCTION.
RX PubMed=7520091; DOI=10.1128/jvi.68.9.5548-5555.1994;
RA Seifer M., Standring D.N.;
RT "A protease-sensitive hinge linking the two domains of the hepatitis B
RT virus core protein is exposed on the viral capsid surface.";
RL J. Virol. 68:5548-5555(1994).
RN [7]
RP PHOSPHORYLATION AT SER-157; SER-164 AND SER-172, AND MUTAGENESIS OF
RP SER-157; SER-164 AND SER-172.
RX PubMed=7815479; DOI=10.1128/jvi.69.2.1025-1029.1995;
RA Liao W., Ou J.H.;
RT "Phosphorylation and nuclear localization of the hepatitis B virus core
RT protein: significance of serine in the three repeated SPRRR motifs.";
RL J. Virol. 69:1025-1029(1995).
RN [8]
RP PHOSPHORYLATION BY HUMAN GAPDH.
RX PubMed=9680129; DOI=10.1099/0022-1317-79-7-1665;
RA Duclos-Vallee J.C., Capel F., Mabit H., Petit M.A.;
RT "Phosphorylation of the hepatitis B virus core protein by glyceraldehyde-3-
RT phosphate dehydrogenase protein kinase activity.";
RL J. Gen. Virol. 79:1665-1670(1998).
RN [9]
RP VARIANT LEU-97.
RX PubMed=10559327; DOI=10.1128/jvi.73.12.10122-10128.1999;
RA Yuan T.T., Tai P.C., Shih C.;
RT "Subtype-independent immature secretion and subtype-dependent replication
RT deficiency of a highly frequent, naturally occurring mutation of human
RT hepatitis B virus core antigen.";
RL J. Virol. 73:10122-10128(1999).
RN [10]
RP INTERACTION WITH HUMAN FLNB.
RX PubMed=10754391; DOI=10.1159/000025442;
RA Huang C.J., Chen Y.H., Ting L.P.;
RT "Hepatitis B virus core protein interacts with the C-terminal region of
RT actin-binding protein.";
RL J. Biomed. Sci. 7:160-168(2000).
RN [11]
RP REVIEW.
RX PubMed=15567498; DOI=10.1016/j.virusres.2004.08.016;
RA Bruss V.;
RT "Envelopment of the hepatitis B virus nucleocapsid.";
RL Virus Res. 106:199-209(2004).
RN [12]
RP INTERACTION WITH THE LARGE ENVELOPE PROTEIN.
RX PubMed=31700077; DOI=10.1038/s41598-019-52824-z;
RA Pastor F., Herrscher C., Patient R., Eymieux S., Moreau A.,
RA Burlaud-Gaillard J., Seigneuret F., de Rocquigny H., Roingeard P.,
RA Hourioux C.;
RT "Direct interaction between the hepatitis B virus core and envelope
RT proteins analyzed in a cellular context.";
RL Sci. Rep. 9:16178-16178(2019).
CC -!- FUNCTION: Self assembles to form an icosahedral capsid. Most capsids
CC appear to be large particles with an icosahedral symmetry of T=4 and
CC consist of 240 copies of capsid protein, though a fraction forms
CC smaller T=3 particles consisting of 180 capsid proteins. Entering
CC capsids are transported along microtubules to the nucleus.
CC Phosphorylation of the capsid is thought to induce exposure of nuclear
CC localization signal in the C-terminal portion of the capsid protein
CC that allows binding to the nuclear pore complex via the importin
CC (karyopherin-) alpha and beta. Capsids are imported in intact form
CC through the nuclear pore into the nuclear basket, where it probably
CC binds NUP153. Only capsids that contain the mature viral genome can
CC release the viral DNA and capsid protein into the nucleoplasm. Immature
CC capsids get stuck in the basket. Capsids encapsulate the pre-genomic
CC RNA and the P protein. Pre-genomic RNA is reverse-transcribed into DNA
CC while the capsid is still in the cytoplasm. The capsid can then either
CC be directed to the nucleus, providing more genomes for transcription,
CC or bud through the endoplasmic reticulum to provide new virions.
CC {ECO:0000255|HAMAP-Rule:MF_04076}.
CC -!- SUBUNIT: Homodimerizes, then multimerizes. Interacts with cytosol
CC exposed regions of viral L glycoprotein present in the reticulum-to-
CC Golgi compartment (PubMed:31700077). Interacts with human FLNB
CC (PubMed:10754391). Phosphorylated form interacts with host importin
CC alpha; this interaction depends on the exposure of the NLS, which
CC itself depends upon genome maturation and/or phosphorylation of the
CC capsid protein. Interacts with host NUP153. {ECO:0000255|HAMAP-
CC Rule:MF_04076, ECO:0000269|PubMed:10754391,
CC ECO:0000269|PubMed:31700077}.
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000255|HAMAP-Rule:MF_04076,
CC ECO:0000269|PubMed:3006057}. Host cytoplasm {ECO:0000255|HAMAP-
CC Rule:MF_04076, ECO:0000269|PubMed:3006057}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=Capsid protein;
CC IsoId=P03148-1; Sequence=Displayed;
CC Name=External core antigen;
CC IsoId=P0C625-1; Sequence=External;
CC -!- PTM: Phosphorylated by host SRPK1, SRPK2, and maybe protein kinase C or
CC GAPDH. Phosphorylation is critical for pregenomic RNA packaging.
CC Protein kinase C phosphorylation is stimulated by HBx protein and may
CC play a role in transport of the viral genome to the nucleus at the late
CC step during the viral replication cycle. {ECO:0000255|HAMAP-
CC Rule:MF_04076, ECO:0000269|PubMed:7815479, ECO:0000269|PubMed:9680129}.
CC -!- SIMILARITY: Belongs to the orthohepadnavirus core antigen family.
CC {ECO:0000255|HAMAP-Rule:MF_04076}.
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DR EMBL; X02763; CAA26537.1; -; Genomic_DNA.
DR SMR; P03148; -.
DR iPTMnet; P03148; -.
DR Proteomes; UP000008766; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0039619; C:T=4 icosahedral viral capsid; IEA:UniProtKB-UniRule.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-UniRule.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-UniRule.
DR GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR GO; GO:0075521; P:microtubule-dependent intracellular transport of viral material towards nucleus; IEA:UniProtKB-UniRule.
DR GO; GO:0046718; P:viral entry into host cell; IEA:UniProtKB-UniRule.
DR GO; GO:0075732; P:viral penetration into host nucleus; IEA:UniProtKB-UniRule.
DR Gene3D; 1.10.4090.10; -; 1.
DR HAMAP; MF_04076; HBV_HBEAG; 1.
DR InterPro; IPR002006; Hepatitis_core.
DR InterPro; IPR036459; Viral_capsid_core_dom_sf_HBV.
DR Pfam; PF00906; Hepatitis_core; 3.
DR SUPFAM; SSF47852; SSF47852; 1.
PE 1: Evidence at protein level;
KW Alternative initiation; Capsid protein;
KW Cytoplasmic inwards viral transport; DNA-binding; Host cytoplasm;
KW Host-virus interaction; Microtubular inwards viral transport;
KW Phosphoprotein; Repeat; RNA-binding; T=4 icosahedral capsid protein;
KW Viral penetration into host nucleus; Virion; Virus entry into host cell.
FT CHAIN 1..185
FT /note="Capsid protein"
FT /id="PRO_0000222308"
FT REPEAT 157..163
FT /note="1; half-length"
FT REPEAT 164..171
FT /note="2"
FT REPEAT 172..179
FT /note="3"
FT REGION 136..185
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 157..179
FT /note="3 X 8 AA repeats of S-P-R-R-R-[PR]-S-Q"
FT REGION 179..185
FT /note="RNA binding"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04076"
FT MOTIF 160..177
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04076"
FT COMPBIAS 153..175
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 157
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04076,
FT ECO:0000269|PubMed:7815479"
FT MOD_RES 164
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04076,
FT ECO:0000269|PubMed:7815479"
FT MOD_RES 172
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04076,
FT ECO:0000269|PubMed:7815479"
FT VARIANT 93
FT /note="V -> M"
FT VARIANT 97
FT /note="I -> L (frequent mutation in chronic HBV carriers)"
FT /evidence="ECO:0000269|PubMed:10559327"
FT VARIANT 169
FT /note="R -> P"
FT MUTAGEN 48
FT /note="C->A: No effect on dimer or capsid formation."
FT /evidence="ECO:0000269|PubMed:1501280"
FT MUTAGEN 61
FT /note="C->A: No effect on dimer or capsid formation."
FT /evidence="ECO:0000269|PubMed:1501280"
FT MUTAGEN 107
FT /note="C->A: No effect on dimer or capsid formation."
FT /evidence="ECO:0000269|PubMed:1501280"
FT MUTAGEN 157
FT /note="S->A: Increases nuclear localization."
FT /evidence="ECO:0000269|PubMed:7815479"
FT MUTAGEN 164
FT /note="S->A: Increases nuclear localization."
FT /evidence="ECO:0000269|PubMed:7815479"
FT MUTAGEN 172
FT /note="S->A: Increases nuclear localization."
FT /evidence="ECO:0000269|PubMed:7815479"
FT MUTAGEN 185
FT /note="C->A: No effect on dimer or capsid formation."
FT /evidence="ECO:0000269|PubMed:1501280"
SQ SEQUENCE 185 AA; 21332 MW; 32423C338B507F5C CRC64;
MDIDPYKEFG ATVELLSFLP SDFFPSVRDL LDTASALYRE ALESPEHCSP HHTALRQAIL
CWGELMTLAT WVGNNLEDPA SRDLVVNYVN TNVGLKIRQL LWFHISCLTF GRETVLEYLV
SFGVWIRTPP AYRPPNAPIL STLPETTVVR RRDRGRSPRR RTPSPRRRRS PSPRRRRSQS
RESQC
