SPIKE_CVM4
ID SPIKE_CVM4 Reviewed; 1376 AA.
AC P22432;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1991, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Spike glycoprotein {ECO:0000255|HAMAP-Rule:MF_04099};
DE Short=S glycoprotein {ECO:0000255|HAMAP-Rule:MF_04099};
DE AltName: Full=E2 {ECO:0000255|HAMAP-Rule:MF_04099};
DE AltName: Full=Peplomer protein {ECO:0000255|HAMAP-Rule:MF_04099};
DE Contains:
DE RecName: Full=Spike protein S1 {ECO:0000255|HAMAP-Rule:MF_04099};
DE Contains:
DE RecName: Full=Spike protein S2 {ECO:0000255|HAMAP-Rule:MF_04099};
DE Contains:
DE RecName: Full=Spike protein S2' {ECO:0000255|HAMAP-Rule:MF_04099};
DE Flags: Precursor;
GN Name=S {ECO:0000255|HAMAP-Rule:MF_04099}; ORFNames=3;
OS Murine coronavirus (strain 4) (MHV-4) (Murine hepatitis virus).
OC Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC Nidovirales; Cornidovirineae; Coronaviridae; Orthocoronavirinae;
OC Betacoronavirus; Embecovirus.
OX NCBI_TaxID=12760;
OH NCBI_TaxID=10090; Mus musculus (Mouse).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=2556846; DOI=10.1016/0042-6822(89)90579-5;
RA Parker S.E., Gallagher T.M., Buchmeier M.J.;
RT "Sequence analysis reveals extensive polymorphism and evidence of deletions
RT within the E2 glycoprotein gene of several strains of murine hepatitis
RT virus.";
RL Virology 173:664-673(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=1966429; DOI=10.1007/978-1-4684-5823-7_54;
RA Parker S.E., Buchmeier M.J.;
RT "RNA sequence analysis of the E2 genes of wildtype and neuroattenuated
RT mutants of MHV-4 reveals a hypervariable domain.";
RL Adv. Exp. Med. Biol. 276:395-402(1990).
RN [3]
RP FUNCTION.
RX PubMed=9201212; DOI=10.1006/viro.1997.8609;
RA Nash T.C., Buchmeier M.J.;
RT "Entry of mouse hepatitis virus into cells by endosomal and nonendosomal
RT pathways.";
RL Virology 233:1-8(1997).
CC -!- FUNCTION: [Spike protein S1]: Attaches the virion to the cell membrane
CC by interacting with host receptor, initiating the infection.
CC {ECO:0000255|HAMAP-Rule:MF_04099}.
CC -!- FUNCTION: [Spike protein S2]: Mediates fusion of the virion and
CC cellular membranes by acting as a class I viral fusion protein. Under
CC the current model, the protein has at least three conformational
CC states: pre-fusion native state, pre-hairpin intermediate state, and
CC post-fusion hairpin state. During viral and target cell membrane
CC fusion, the coiled coil regions (heptad repeats) assume a trimer-of-
CC hairpins structure, positioning the fusion peptide in close proximity
CC to the C-terminal region of the ectodomain. The formation of this
CC structure appears to drive apposition and subsequent fusion of viral
CC and target cell membranes. {ECO:0000255|HAMAP-Rule:MF_04099,
CC ECO:0000269|PubMed:9201212}.
CC -!- FUNCTION: [Spike protein S2']: Acts as a viral fusion peptide which is
CC unmasked following S2 cleavage occurring upon virus endocytosis.
CC {ECO:0000255|HAMAP-Rule:MF_04099}.
CC -!- SUBUNIT: Homotrimer; each monomer consists of a S1 and a S2 subunit.
CC The resulting peplomers protrude from the virus surface as spikes.
CC {ECO:0000255|HAMAP-Rule:MF_04099}.
CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000255|HAMAP-
CC Rule:MF_04099}; Single-pass type I membrane protein {ECO:0000255|HAMAP-
CC Rule:MF_04099}. Host endoplasmic reticulum-Golgi intermediate
CC compartment membrane {ECO:0000255|HAMAP-Rule:MF_04099}; Single-pass
CC type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04099}. Host cell
CC membrane {ECO:0000255|HAMAP-Rule:MF_04099}; Single-pass type I membrane
CC protein {ECO:0000255|HAMAP-Rule:MF_04099}. Note=Accumulates in the
CC endoplasmic reticulum-Golgi intermediate compartment, where it
CC participates in virus particle assembly. Some S oligomers are
CC transported to the host plasma membrane, where they may mediate cell-
CC cell fusion. {ECO:0000255|HAMAP-Rule:MF_04099}.
CC -!- DOMAIN: Fusion peptide 1 (FP1) and fusion peptide 2 (FP2) function
CC cooperatively and have a membrane-ordering effect on lipid headgroups
CC and shallow hydrophobic regions of target bilayers. They are considered
CC as two domains of an extended, bipartite FP. The membrane-ordering
CC activity is calcium-dependent and also dependent on correct folding,
CC which is maintained by an internal disulfide bond in FP2.
CC {ECO:0000255|HAMAP-Rule:MF_04099}.
CC -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins. The
CC precursor is processed into S1 and S2 by host cell furin or another
CC cellular protease to yield the mature S1 and S2 proteins. Additionally,
CC a second cleavage leads to the release of a fusion peptide after viral
CC attachment to host cell receptor. {ECO:0000255|HAMAP-Rule:MF_04099}.
CC -!- PTM: The cytoplasmic Cys-rich domain is palmitoylated. Spike
CC glycoprotein is digested within host endosomes. {ECO:0000255|HAMAP-
CC Rule:MF_04099}.
CC -!- MISCELLANEOUS: The viral fusion process requires lipid rafts of the
CC host plasma membrane (By similarity). This strain is apparently capable
CC of entering cells either through direct fusion at the cell surface or
CC through endocytosis. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the betacoronaviruses spike protein family.
CC {ECO:0000255|HAMAP-Rule:MF_04099}.
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DR EMBL; M32789; AAA46456.1; -; Genomic_RNA.
DR EMBL; S51114; AAB19590.1; -; Genomic_RNA.
DR PIR; A33748; VGIHJ2.
DR SMR; P22432; -.
DR GO; GO:0044173; C:host cell endoplasmic reticulum-Golgi intermediate compartment membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0019031; C:viral envelope; IEA:UniProtKB-UniRule.
DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0075509; P:endocytosis involved in viral entry into host cell; IEA:UniProtKB-UniRule.
DR GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0046813; P:receptor-mediated virion attachment to host cell; IEA:UniProtKB-UniRule.
DR CDD; cd21625; MHV-like_Spike_S1_NTD; 1.
DR Gene3D; 2.60.120.960; -; 1.
DR HAMAP; MF_04099; BETA_CORONA_SPIKE; 1.
DR InterPro; IPR032500; bCoV_S1_N.
DR InterPro; IPR042578; BETA_CORONA_SPIKE.
DR InterPro; IPR043607; CoV_S1_C.
DR InterPro; IPR043473; S2_sf_CoV.
DR InterPro; IPR043002; Spike_N_sf.
DR InterPro; IPR044339; Spike_S1_NTD_MHV-like.
DR InterPro; IPR018548; Spike_S1_RBD_bCoV.
DR InterPro; IPR036326; Spike_S1_RBD_sf_bCoV.
DR InterPro; IPR002552; Spike_S2_CoV.
DR InterPro; IPR043614; Spike_S2_CoV_C.
DR InterPro; IPR044873; Spike_S2_CoV_HR1.
DR InterPro; IPR044874; Spike_S2_CoV_HR2.
DR Pfam; PF16451; bCoV_S1_N; 1.
DR Pfam; PF09408; bCoV_S1_RBD; 1.
DR Pfam; PF19209; CoV_S1_C; 1.
DR Pfam; PF01601; CoV_S2; 1.
DR Pfam; PF19214; CoV_S2_C; 1.
DR SUPFAM; SSF111474; SSF111474; 2.
DR SUPFAM; SSF143587; SSF143587; 1.
DR PROSITE; PS51921; BCOV_S1_CTD; 1.
DR PROSITE; PS51922; BCOV_S1_NTD; 1.
DR PROSITE; PS51923; COV_S2_HR1; 1.
PE 3: Inferred from homology;
KW Coiled coil; Disulfide bond;
KW Fusion of virus membrane with host endosomal membrane;
KW Fusion of virus membrane with host membrane; Glycoprotein;
KW Host cell membrane; Host membrane; Host-virus interaction; Lipoprotein;
KW Membrane; Palmitate; Signal; Transmembrane; Transmembrane helix;
KW Viral attachment to host cell; Viral envelope protein;
KW Viral penetration into host cytoplasm; Virion; Virulence;
KW Virus entry into host cell.
FT SIGNAL 1..13
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT CHAIN 14..1376
FT /note="Spike glycoprotein"
FT /id="PRO_0000037211"
FT CHAIN 14..769
FT /note="Spike protein S1"
FT /id="PRO_0000037212"
FT CHAIN 770..1376
FT /note="Spike protein S2"
FT /id="PRO_0000037213"
FT CHAIN 922..1376
FT /note="Spike protein S2'"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT /id="PRO_0000444083"
FT TOPO_DOM 14..1317
FT /note="Extracellular"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT TRANSMEM 1318..1338
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT TOPO_DOM 1339..1376
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT DOMAIN 15..296
FT /note="BetaCoV S1-NTD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01270"
FT DOMAIN 327..618
FT /note="BetaCoV S1-CTD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01269"
FT REGION 15..330
FT /note="Receptor binding site"
FT REGION 429..599
FT /note="Important for the neurovirulence"
FT REGION 922..943
FT /note="Fusion peptide 1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT REGION 941..961
FT /note="Fusion peptide 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT REGION 1022..1072
FT /note="Heptad repeat 1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT REGION 1266..1306
FT /note="Heptad repeat 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT COILED 1051..1095
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT COILED 1279..1307
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT MOTIF 1372..1376
FT /note="KxHxx"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT SITE 769..770
FT /note="Cleavage; by host"
FT /evidence="ECO:0000250"
FT SITE 921..922
FT /note="Cleavage"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT CARBOHYD 31
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT CARBOHYD 60
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT CARBOHYD 134
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT CARBOHYD 192
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT CARBOHYD 357
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT CARBOHYD 435
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT CARBOHYD 582
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT CARBOHYD 677
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT CARBOHYD 709
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT CARBOHYD 717
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT CARBOHYD 740
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT CARBOHYD 789
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT CARBOHYD 806
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT CARBOHYD 945
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT CARBOHYD 1232
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT CARBOHYD 1242
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT CARBOHYD 1261
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT CARBOHYD 1277
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT CARBOHYD 1298
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
FT DISULFID 21..158
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01270"
FT DISULFID 153..187
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01270"
FT DISULFID 165..246
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01270"
FT DISULFID 284..294
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01270"
FT DISULFID 329..354
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01269"
FT DISULFID 372..425
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01269"
FT DISULFID 384..616
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01269"
FT DISULFID 946..957
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04099"
SQ SEQUENCE 1376 AA; 151882 MW; 88C01B97B252094E CRC64;
MLFVFILLLP SCLGYIGDFR CIQTVNYNGN NASAPSISTE AVDVSKGLGT YYVLDRVYLN
ATLLLTGYYP VDGSNYRNLA LTGTNTLSLT WFKPPFLSEF NDGIFAKVQN LKTNTPTGAT
SYFPTIVIGS LFGNTSYTVV LEPYNNIIMA SVCTYTICQL PYTPCKPNTN GNRVIGFWHT
DVKPPICLLK RNFTFNVNAP WLYFHFYQQG GTFYAYYADK PSATTFLFSV YIGDILTQYF
VLPFICTPTA GSTLLPLYWV TPLLKRQYLF NFNEKGVITS AVDCASSYIS EIKCKTQSLL
PSTGVYDLSG YTVQPVGVVY RRVPNLPDCK IEEWLTAKSV PSPLNWERRT FQNCNFNLSS
LLRYVQAESL SCNNIDASKV YGMCFGSVSV DKFAIPRSRQ IDLQIGNSGF LQTANYKIDT
AATSCQLYYS LPKNNVTINN YNPSSWNRRY GFNDAGVFGK SKHDVAYAQQ CFTVRPSYCP
CAQPDIVSAC TSQTKPMSAY CPTGTIHREC SLWNGPHLRS ARVGSGTYTC ECTCKPNPFD
TYDLRCGQIK TIVNVGDHCE GLGVLEDKCG NSDPHKGCSC ANDSFIGWSH DTCLVNDRCQ
IFANILLNGI NSGTTCSTDL QLPNTEVATG VCVRYDLYGI TGQGVFKEVK ADYYNSWQAL
LYDVNGNLNG FRDLTTNKTY TIRSCYSGRV SAAYHKEAPE PALLYRNINC SYVFTNNISR
EENPLNYFDS YLGCVVNADN RTDEALPNCD LRMGAGLCVD YSKSRRARRS VSTGYRLTTF
EPYMPMLVND SVQSVGGLYE MQIPTNFTIG HHEEFIQIRA PKVTIDCAAF VCGDNAACRQ
QLVEYGSFCD NVNAILNEVN NLLDNMQLQV ASALMQGVTI SSRLPDGISG PIDDINFSPL
LGCIGSTCAE DGNGPSAIRG RSAIEDLLFD KVKLSDVGFV EAYNNCTGGQ EVRDLLCVQS
FNGIKVLPPV LSESQISGYT AGATAAAMFP PWTAAAGVPF SLNVQYRING LGVTMNVLSE
NQKMIASAFN NALGAIQEGF DATNSALGKI QSVVNANAEA LNNLLNQLSN RFGAISASLQ
EILTRLDAVE AKAQIDRLIN GRLTALNAYI SKQLSDSTLI KFSAAQAIEK VNECVKSQTT
RINFCGNGNH ILSLVQNAPY GLCFIHFSYV PTSFKTANVS PGLCISGDRG LAPKAGYFVQ
DNGEWKFTGS NYYYPEPITD KNSVVMISCA VNYTKAPEVF LNNSIPNLPD FKEELDKWFK
NQTSIAPDLS LDFEKLNVTF LDLTYEMNRI QDAIKKLNES YINLKEVGTY EMYVKWPWYV
WLLIGLAGVA VCVLLFFICC CTGCGSCCFR KCGSCCDEYG GHQDSIVIHN ISAHED
