CAPSD_HEVPA
ID CAPSD_HEVPA Reviewed; 660 AA.
AC P33426; Q77EC8;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 25-MAY-2022, entry version 85.
DE RecName: Full=Secreted protein ORF2;
DE AltName: Full=Protein ORF2;
DE Short=pORF2;
GN ORFNames=ORF2;
OS Hepatitis E virus genotype 1 (isolate Human/Pakistan/Sar-55) (HEV-1).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Alsuviricetes;
OC Hepelivirales; Hepeviridae; Orthohepevirus; Hepatitis E virus.
OX NCBI_TaxID=33774;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=1731327; DOI=10.1073/pnas.89.2.559;
RA Tsarev S.A., Emerson S.U., Reyes G.R., Tsareva T.S., Legters L.J.,
RA Malik I.A., Iqbal M., Purcell R.H.;
RT "Characterization of a prototype strain of hepatitis E virus.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:559-563(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Isolate pSK-HEV-2, and Isolate pSK-HEV-3;
RX PubMed=11742081; DOI=10.1073/pnas.251555098;
RA Emerson S.U., Zhang M., Meng X.J., Nguyen H., St Claire M.,
RA Govindarajan S., Huang Y.K., Purcell R.H.;
RT "Recombinant hepatitis E virus genomes infectious for primates: importance
RT of capping and discovery of a cis-reactive element.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:15270-15275(2001).
RN [3]
RP MUTAGENESIS OF ASN-137; ASN-310; ASN-445 AND ASN-562.
RC STRAIN=Isolate pSK-HEV-2;
RX PubMed=18032496; DOI=10.1128/jvi.01219-07;
RA Graff J., Zhou Y.-H., Torian U., Nguyen H., St Claire M., Yu C.,
RA Purcell R.H., Emerson S.U.;
RT "Mutations within potential glycosylation sites in the capsid protein of
RT hepatitis E virus prevent the formation of infectious virus particles.";
RL J. Virol. 82:1185-1194(2008).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 455-602.
RX PubMed=19662165; DOI=10.1371/journal.ppat.1000537;
RA Li S., Tang X., Seetharaman J., Yang C., Gu Y., Zhang J., Du H., Shih J.W.,
RA Hew C.L., Sivaraman J., Xia N.;
RT "Dimerization of hepatitis E virus capsid protein E2s domain is essential
RT for virus-host interaction.";
RL PLoS Pathog. 5:E1000537-E1000537(2009).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 459-603.
RX PubMed=21642534; DOI=10.1073/pnas.1101309108;
RA Tang X., Yang C., Gu Y., Song C., Zhang X., Wang Y., Zhang J., Hew C.L.,
RA Li S., Xia N., Sivaraman J.;
RT "Structural basis for the neutralization and genotype specificity of
RT hepatitis E virus.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:10266-10271(2011).
CC -!- FUNCTION: [Isoform Secreted protein ORF2]: Plays a role in the
CC inhibition of host antibody-mediated neutralization without blocking
CC viral cell entry. {ECO:0000250|UniProtKB:Q81871}.
CC -!- FUNCTION: [Isoform Capsid protein ORF2]: Forms an icosahedral capsid
CC with a T=1 symmetry and a 34 nm diameter. The capsid is composed of 60
CC copies linked to each other. Binds to the 5' end of the genomic RNA to
CC mediate genome encapsidation (By similarity). Binds to heparin surface
CC proteoglycans (HSPGs) to mediate viral entry. Additionally, the
CC interactions with host ASGR1 and ASGR2 facilitate viral infection of
CC hepatocytes (By similarity). {ECO:0000250|UniProtKB:P29326,
CC ECO:0000250|UniProtKB:Q81871}.
CC -!- SUBUNIT: [Isoform Secreted protein ORF2]: Homodimers.
CC {ECO:0000250|UniProtKB:Q68985}.
CC -!- SUBUNIT: [Isoform Capsid protein ORF2]: Self-assembles to form the
CC capsid. The capsid is dominated by dimers that define the 30
CC morphological units. Interacts with phosphorylated protein ORF3 (By
CC similarity). Interacts with host TMEM134. Interacts with host ASGR1 and
CC ASGR2; these interactions facilitate infection of host hepatocytes (By
CC similarity). {ECO:0000250|UniProtKB:Q81871}.
CC -!- INTERACTION:
CC P33426; P33426: ORF2; NbExp=3; IntAct=EBI-15929932, EBI-15929932;
CC -!- SUBCELLULAR LOCATION: [Isoform Secreted protein ORF2]: Secreted
CC {ECO:0000250|UniProtKB:Q81871}.
CC -!- SUBCELLULAR LOCATION: [Isoform Capsid protein ORF2]: Virion
CC {ECO:0000250|UniProtKB:Q81871}. Host cytoplasm
CC {ECO:0000250|UniProtKB:Q81871}. Host endoplasmic reticulum
CC {ECO:0000250|UniProtKB:Q81871}. Host Golgi apparatus
CC {ECO:0000250|UniProtKB:Q81871}. Host cell surface
CC {ECO:0000250|UniProtKB:Q68985}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=Secreted protein ORF2;
CC IsoId=P33426-1; Sequence=Displayed;
CC Name=Capsid protein ORF2;
CC IsoId=P33426-2; Sequence=VSP_059889;
CC -!- PTM: Isoform Secreted protein ORF2; Exists as a glycosylated dimer.
CC {ECO:0000250|UniProtKB:Q81871}.
CC -!- SIMILARITY: Belongs to the hepevirus capsid protein family.
CC {ECO:0000305}.
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DR EMBL; M80581; AAA45727.1; -; Genomic_RNA.
DR EMBL; AF444002; AAL50056.1; -; Genomic_RNA.
DR EMBL; AF444003; AAL50059.1; -; Genomic_RNA.
DR PDB; 3GGQ; X-ray; 2.00 A; A=455-602.
DR PDB; 3RKD; X-ray; 1.90 A; A/B=459-603.
DR PDB; 6LAT; EM; 3.40 A; A=129-605.
DR PDB; 6LB0; EM; 3.60 A; A=129-605.
DR PDBsum; 3GGQ; -.
DR PDBsum; 3RKD; -.
DR PDBsum; 6LAT; -.
DR PDBsum; 6LB0; -.
DR SMR; P33426; -.
DR DIP; DIP-59683N; -.
DR ABCD; P33426; 1 sequenced antibody.
DR EvolutionaryTrace; P33426; -.
DR Proteomes; UP000001322; Genome.
DR Proteomes; UP000008498; Genome.
DR Proteomes; UP000180763; Genome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0044165; C:host cell endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0044177; C:host cell Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0044228; C:host cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0039615; C:T=1 icosahedral viral capsid; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0098670; P:entry receptor-mediated virion attachment to host cell; IEA:UniProtKB-KW.
DR GO; GO:0046718; P:viral entry into host cell; IEA:UniProtKB-KW.
DR Gene3D; 2.60.120.20; -; 1.
DR InterPro; IPR004261; SP2.
DR InterPro; IPR029053; Viral_coat.
DR Pfam; PF03014; SP2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative initiation; Capsid protein; Glycoprotein;
KW Host cytoplasm; Host endoplasmic reticulum; Host Golgi apparatus;
KW Host-virus interaction; RNA-binding; Secreted;
KW T=1 icosahedral capsid protein; Viral attachment to host cell;
KW Viral attachment to host entry receptor; Virion;
KW Virus entry into host cell.
FT CHAIN 1..660
FT /note="Secreted protein ORF2"
FT /id="PRO_0000445489"
FT REGION 18..44
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 66..127
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 368..394
FT /note="particle formation"
FT /evidence="ECO:0000250"
FT REGION 585..610
FT /note="Oligomerization"
FT /evidence="ECO:0000250"
FT CARBOHYD 137
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000250|UniProtKB:Q81871"
FT CARBOHYD 310
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000250|UniProtKB:Q81871"
FT CARBOHYD 562
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000250|UniProtKB:Q81871"
FT VAR_SEQ 1..15
FT /note="Missing (in isoform Capsid protein ORF2)"
FT /id="VSP_059889"
FT MUTAGEN 137
FT /note="N->Q: Complete loss of infectivity. Inhibition of
FT capsid assembly."
FT /evidence="ECO:0000269|PubMed:18032496"
FT MUTAGEN 310
FT /note="N->Q: Complete loss of infectivity. Inhibition of
FT capsid assembly."
FT /evidence="ECO:0000269|PubMed:18032496"
FT MUTAGEN 445
FT /note="N->Q: Complete loss of infectivity."
FT /evidence="ECO:0000269|PubMed:18032496"
FT MUTAGEN 562
FT /note="N->Q: Complete loss of infectivity. Loss of
FT dimerization."
FT /evidence="ECO:0000269|PubMed:18032496"
FT STRAND 131..139
FT /evidence="ECO:0007829|PDB:6LAT"
FT STRAND 151..159
FT /evidence="ECO:0007829|PDB:6LAT"
FT STRAND 161..163
FT /evidence="ECO:0007829|PDB:6LAT"
FT STRAND 167..171
FT /evidence="ECO:0007829|PDB:6LAT"
FT HELIX 174..178
FT /evidence="ECO:0007829|PDB:6LAT"
FT TURN 179..181
FT /evidence="ECO:0007829|PDB:6LAT"
FT STRAND 182..196
FT /evidence="ECO:0007829|PDB:6LAT"
FT STRAND 207..213
FT /evidence="ECO:0007829|PDB:6LAT"
FT STRAND 215..217
FT /evidence="ECO:0007829|PDB:6LAT"
FT TURN 225..229
FT /evidence="ECO:0007829|PDB:6LAT"
FT STRAND 230..236
FT /evidence="ECO:0007829|PDB:6LAT"
FT HELIX 248..251
FT /evidence="ECO:0007829|PDB:6LAT"
FT HELIX 255..257
FT /evidence="ECO:0007829|PDB:6LAT"
FT STRAND 258..261
FT /evidence="ECO:0007829|PDB:6LAT"
FT STRAND 264..266
FT /evidence="ECO:0007829|PDB:6LAT"
FT STRAND 268..271
FT /evidence="ECO:0007829|PDB:6LAT"
FT STRAND 275..282
FT /evidence="ECO:0007829|PDB:6LAT"
FT TURN 287..289
FT /evidence="ECO:0007829|PDB:6LAT"
FT STRAND 298..308
FT /evidence="ECO:0007829|PDB:6LAT"
FT STRAND 322..327
FT /evidence="ECO:0007829|PDB:6LAT"
FT STRAND 330..333
FT /evidence="ECO:0007829|PDB:6LAT"
FT STRAND 335..342
FT /evidence="ECO:0007829|PDB:6LAT"
FT HELIX 348..350
FT /evidence="ECO:0007829|PDB:6LAT"
FT STRAND 352..354
FT /evidence="ECO:0007829|PDB:6LAT"
FT TURN 355..357
FT /evidence="ECO:0007829|PDB:6LAT"
FT STRAND 369..373
FT /evidence="ECO:0007829|PDB:6LAT"
FT HELIX 379..381
FT /evidence="ECO:0007829|PDB:6LAT"
FT TURN 386..388
FT /evidence="ECO:0007829|PDB:6LAT"
FT STRAND 389..393
FT /evidence="ECO:0007829|PDB:6LAT"
FT STRAND 395..401
FT /evidence="ECO:0007829|PDB:6LAT"
FT STRAND 404..406
FT /evidence="ECO:0007829|PDB:6LAT"
FT STRAND 409..414
FT /evidence="ECO:0007829|PDB:6LAT"
FT HELIX 416..421
FT /evidence="ECO:0007829|PDB:6LAT"
FT STRAND 435..444
FT /evidence="ECO:0007829|PDB:6LAT"
FT TURN 448..450
FT /evidence="ECO:0007829|PDB:6LAT"
FT STRAND 470..487
FT /evidence="ECO:0007829|PDB:3RKD"
FT STRAND 492..496
FT /evidence="ECO:0007829|PDB:3RKD"
FT STRAND 498..502
FT /evidence="ECO:0007829|PDB:3RKD"
FT TURN 503..505
FT /evidence="ECO:0007829|PDB:3RKD"
FT STRAND 508..510
FT /evidence="ECO:0007829|PDB:3RKD"
FT HELIX 511..513
FT /evidence="ECO:0007829|PDB:3RKD"
FT HELIX 516..518
FT /evidence="ECO:0007829|PDB:3RKD"
FT STRAND 528..531
FT /evidence="ECO:0007829|PDB:3RKD"
FT STRAND 534..543
FT /evidence="ECO:0007829|PDB:3RKD"
FT STRAND 546..549
FT /evidence="ECO:0007829|PDB:3RKD"
FT TURN 559..562
FT /evidence="ECO:0007829|PDB:3RKD"
FT STRAND 568..574
FT /evidence="ECO:0007829|PDB:3RKD"
FT STRAND 579..582
FT /evidence="ECO:0007829|PDB:3RKD"
FT STRAND 584..586
FT /evidence="ECO:0007829|PDB:3GGQ"
FT STRAND 593..601
FT /evidence="ECO:0007829|PDB:3RKD"
SQ SEQUENCE 660 AA; 70980 MW; 8085BC53CFB46FD3 CRC64;
MRPRPILLLL LMFLPMLPAP PPGQPSGRRR GRRSGGSGGG FWGDRVDSQP FAIPYIHPTN
PFAPDVTAAA GAGPRVRQPA RPLGSAWRDQ AQRPAAASRR RPTTAGAAPL TAVAPAHDTP
PVPDVDSRGA ILRRQYNLST SPLTSSVATG TNLVLYAAPL SPLLPLQDGT NTHIMATEAS
NYAQYRVARA TIRYRPLVPN AVGGYAISIS FWPQTTTTPT SVDMNSITST DVRILVQPGI
ASELVIPSER LHYRNQGWRS VETSGVAEEE ATSGLVMLCI HGSPVNSYTN TPYTGALGLL
DFALELEFRN LTPGNTNTRV SRYSSTARHR LRRGADGTAE LTTTAATRFM KDLYFTSTNG
VGEIGRGIAL TLFNLADTLL GGLPTELISS AGGQLFYSRP VVSANGEPTV KLYTSVENAQ
QDKGIAIPHD IDLGESRVVI QDYDNQHEQD RPTPSPAPSR PFSVLRANDV LWLSLTAAEY
DQSTYGSSTG PVYVSDSVTL VNVATGAQAV ARSLDWTKVT LDGRPLSTIQ QYSKTFFVLP
LRGKLSFWEA GTTKAGYPYN YNTTASDQLL VENAAGHRVA ISTYTTSLGA GPVSISAVAV
LAPHSVLALL EDTMDYPARA HTFDDFCPEC RPLGLQGCAF QSTVAELQRL KMKVGKTREL
