HEMA_CVMS
ID HEMA_CVMS Reviewed; 439 AA.
AC P31614; O55252;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2014, sequence version 2.
DT 02-JUN-2021, entry version 111.
DE RecName: Full=Hemagglutinin-esterase {ECO:0000255|HAMAP-Rule:MF_04207};
DE Short=HE protein {ECO:0000255|HAMAP-Rule:MF_04207};
DE EC=3.1.1.53 {ECO:0000255|HAMAP-Rule:MF_04207};
DE AltName: Full=E3 glycoprotein {ECO:0000255|HAMAP-Rule:MF_04207};
DE Flags: Precursor;
GN Name=HE {ECO:0000255|HAMAP-Rule:MF_04207}; ORFNames=2b;
OS Murine coronavirus (strain S) (MHV-S) (Murine hepatitis virus).
OC Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC Nidovirales; Cornidovirineae; Coronaviridae; Orthocoronavirinae;
OC Betacoronavirus; Embecovirus.
OX NCBI_TaxID=11145;
OH NCBI_TaxID=10090; Mus musculus (Mouse).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA], AND CHARACTERIZATION.
RC STRAIN=S;
RX PubMed=15507445; DOI=10.1074/jbc.m409683200;
RA Smits S.L., Gerwig G.J., van Vliet A.L., Lissenberg A., Briza P.,
RA Kamerling J.P., Vlasak R., de Groot R.J.;
RT "Nidovirus sialate-O-acetylesterases: evolution and substrate specificity
RT of coronaviral and toroviral receptor-destroying enzymes.";
RL J. Biol. Chem. 280:6933-6941(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=S;
RX PubMed=16306576; DOI=10.1128/jvi.79.24.15054-15063.2005;
RA Lissenberg A., Vrolijk M.M., van Vliet A.L., Langereis M.A.,
RA de Groot-Mijnes J.D., Rottier P.J., de Groot R.J.;
RT "Luxury at a cost? Recombinant mouse hepatitis viruses expressing the
RT accessory hemagglutinin esterase protein display reduced fitness in
RT vitro.";
RL J. Virol. 79:15054-15063(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=DVIM;
RA Sugiyama K., Morita E., Ebina H., Muto A., Himeno H.;
RT "Murine hepatitis virus DVIM strain hemagglutinin-esterase glycoprotein
RT gene, complete cds.";
RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-434.
RC STRAIN=S;
RX PubMed=1649505; DOI=10.1016/0042-6822(91)90994-m;
RA Yokomori K., Banner L.R., Lai M.M.C.;
RT "Heterogeneity of gene expression of the hemagglutinin-esterase (HE)
RT protein of murine coronaviruses.";
RL Virology 183:647-657(1991).
RN [5]
RP CHARACTERIZATION.
RX PubMed=11807232; DOI=10.1099/0022-1317-83-2-395;
RA Wurzer W.J., Obojes K., Vlasak R.;
RT "The sialate-4-O-acetylesterases of coronaviruses related to mouse
RT hepatitis virus: a proposal to reorganize group 2 Coronaviridae.";
RL J. Gen. Virol. 83:395-402(2002).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 25-403 OF PROTEIN MUTANT ALA-45
RP AND IN COMPLEX WITH RECEPTOR ANALOG, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT,
RP ACTIVE SITE, GLYCOSYLATION AT ASN-94; ASN-152; ASN-196; ASN-246; ASN-316;
RP ASN-331; ASN-360 AND ASN-374, DISULFIDE BONDS, AND MUTAGENESIS OF SER-45;
RP LEU-119; ILE-166; PHE-212; LEU-260 AND TYR-281.
RC STRAIN=S;
RX PubMed=22291594; DOI=10.1371/journal.ppat.1002492;
RA Langereis M.A., Zeng Q., Heesters B.A., Huizinga E.G., de Groot R.J.;
RT "The murine coronavirus hemagglutinin-esterase receptor-binding site: a
RT major shift in ligand specificity through modest changes in architecture.";
RL PLoS Pathog. 8:E1002492-E1002492(2012).
CC -!- FUNCTION: Structural protein that makes short spikes at the surface of
CC the virus. Contains receptor binding and receptor-destroying
CC activities. Mediates de-O-acetylation of N-acetyl-4-O-acetylneuraminic
CC acid, which is probably the receptor determinant recognized by the
CC virus on the surface of erythrocytes and susceptible cells. This
CC receptor-destroying activity is important for virus release as it
CC probably helps preventing self-aggregation and ensures the efficient
CC spread of the progeny virus from cell to cell. May serve as a secondary
CC viral attachment protein for initiating infection, the spike protein
CC being the major one. May become a target for both the humoral and the
CC cellular branches of the immune system. {ECO:0000255|HAMAP-
CC Rule:MF_04207, ECO:0000269|PubMed:22291594}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-acetyl-9-O-acetylneuraminate = acetate + H(+) + N-
CC acetylneuraminate; Xref=Rhea:RHEA:22600, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:28999, ChEBI:CHEBI:30089,
CC ChEBI:CHEBI:35418; EC=3.1.1.53; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_04207, ECO:0000269|PubMed:22291594};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-acetyl-4-O-acetylneuraminate = acetate + H(+) + N-
CC acetylneuraminate; Xref=Rhea:RHEA:25564, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29006, ChEBI:CHEBI:30089,
CC ChEBI:CHEBI:35418; EC=3.1.1.53; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_04207, ECO:0000269|PubMed:22291594};
CC -!- SUBUNIT: Homodimer; disulfide-linked. Forms a complex with the M
CC protein in the pre-Golgi. Associates then with S-M complex to form a
CC ternary complex S-M-HE. {ECO:0000255|HAMAP-Rule:MF_04207,
CC ECO:0000269|PubMed:22291594}.
CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000255|HAMAP-
CC Rule:MF_04207}; Single-pass type I membrane protein {ECO:0000255|HAMAP-
CC Rule:MF_04207}. Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04207};
CC Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04207}.
CC Note=In infected cells becomes incorporated into the envelope of
CC virions during virus assembly at the endoplasmic reticulum and cis
CC Golgi. However, some may escape incorporation into virions and
CC subsequently migrate to the cell surface. {ECO:0000255|HAMAP-
CC Rule:MF_04207}.
CC -!- PTM: N-glycosylated in the host RER. {ECO:0000255|HAMAP-Rule:MF_04207,
CC ECO:0000269|PubMed:22291594}.
CC -!- SIMILARITY: Belongs to the influenza type C/coronaviruses
CC hemagglutinin-esterase family. {ECO:0000255|HAMAP-Rule:MF_04207,
CC ECO:0000305}.
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DR EMBL; AY771997; AAX08110.1; -; Genomic_RNA.
DR EMBL; AB008939; BAA23718.1; -; Genomic_RNA.
DR EMBL; M64316; AAA46460.1; -; Genomic_RNA.
DR PIR; A40476; HMIHMS.
DR PDB; 4C7L; X-ray; 2.10 A; A/B=25-403.
DR PDB; 4C7W; X-ray; 2.50 A; A/B=25-403.
DR PDBsum; 4C7L; -.
DR PDBsum; 4C7W; -.
DR SMR; P31614; -.
DR iPTMnet; P31614; -.
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:0046789; F:host cell surface receptor binding; IEA:UniProtKB-UniRule.
DR GO; GO:0106331; F:sialate 4-O-acetylesterase activity; IEA:UniProtKB-EC.
DR GO; GO:0106330; F:sialate 9-O-acetylesterase activity; IEA:UniProtKB-EC.
DR GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR HAMAP; MF_04207; BETA_CORONA_HE; 1.
DR InterPro; IPR008980; Capsid_hemagglutn.
DR InterPro; IPR042545; HEMA.
DR InterPro; IPR007142; Hemagglutn-estrase_core.
DR InterPro; IPR003860; Hemagglutn-estrase_hemagglutn.
DR Pfam; PF03996; Hema_esterase; 1.
DR Pfam; PF02710; Hema_HEFG; 1.
DR SUPFAM; SSF49818; SSF49818; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Glycoprotein; Hemagglutinin;
KW Host cell membrane; Host membrane; Hydrolase; Membrane; Signal;
KW Transmembrane; Transmembrane helix; Viral envelope protein; Virion.
FT SIGNAL 1..22
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207"
FT CHAIN 23..439
FT /note="Hemagglutinin-esterase"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207"
FT /id="PRO_0000037148"
FT TOPO_DOM 23..407
FT /note="Virion surface"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207"
FT TRANSMEM 408..428
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207"
FT TOPO_DOM 429..439
FT /note="Intravirion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207"
FT REGION 12..132
FT /note="Esterase domain 1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207"
FT REGION 133..281
FT /note="Receptor binding"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207"
FT REGION 282..395
FT /note="Esterase domain 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207"
FT ACT_SITE 45
FT /note="Nucleophile"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207,
FT ECO:0000269|PubMed:22291594"
FT ACT_SITE 342
FT /note="Charge relay system"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207,
FT ECO:0000269|PubMed:22291594"
FT ACT_SITE 345
FT /note="Charge relay system"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207,
FT ECO:0000269|PubMed:22291594"
FT CARBOHYD 94
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207,
FT ECO:0000269|PubMed:22291594"
FT CARBOHYD 152
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207,
FT ECO:0000269|PubMed:22291594"
FT CARBOHYD 196
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207,
FT ECO:0000269|PubMed:22291594"
FT CARBOHYD 246
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207,
FT ECO:0000269|PubMed:22291594"
FT CARBOHYD 309
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207"
FT CARBOHYD 316
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207,
FT ECO:0000269|PubMed:22291594"
FT CARBOHYD 331
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207,
FT ECO:0000269|PubMed:22291594"
FT CARBOHYD 360
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207,
FT ECO:0000269|PubMed:22291594"
FT CARBOHYD 374
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207,
FT ECO:0000269|PubMed:22291594"
FT DISULFID 49..70
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207,
FT ECO:0000269|PubMed:22291594"
FT DISULFID 118..167
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207,
FT ECO:0000269|PubMed:22291594"
FT DISULFID 202..291
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207,
FT ECO:0000269|PubMed:22291594"
FT DISULFID 210..264
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207,
FT ECO:0000269|PubMed:22291594"
FT DISULFID 322..327
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207,
FT ECO:0000269|PubMed:22291594"
FT DISULFID 363..387
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207,
FT ECO:0000269|PubMed:22291594"
FT DISULFID 400
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:22291594"
FT MUTAGEN 45
FT /note="S->A: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:22291594"
FT MUTAGEN 119
FT /note="L->A: Decreased receptor-binding activity."
FT /evidence="ECO:0000269|PubMed:22291594"
FT MUTAGEN 166
FT /note="I->A: Decreased receptor-binding activity."
FT /evidence="ECO:0000269|PubMed:22291594"
FT MUTAGEN 212
FT /note="F->A: Decreased receptor-binding activity."
FT /evidence="ECO:0000269|PubMed:22291594"
FT MUTAGEN 260
FT /note="L->A: Decreased receptor-binding activity."
FT /evidence="ECO:0000269|PubMed:22291594"
FT MUTAGEN 281
FT /note="Y->A: Decreased receptor-binding activity."
FT /evidence="ECO:0000269|PubMed:22291594"
FT CONFLICT 76
FT /note="S -> Y (in Ref. 4; AAA46460)"
FT /evidence="ECO:0000305"
FT CONFLICT 208
FT /note="P -> T (in Ref. 4; AAA46460)"
FT /evidence="ECO:0000305"
FT CONFLICT 212
FT /note="F -> S (in Ref. 4; AAA46460)"
FT /evidence="ECO:0000305"
FT CONFLICT 218
FT /note="G -> S (in Ref. 4; AAA46460)"
FT /evidence="ECO:0000305"
FT CONFLICT 231
FT /note="S -> A (in Ref. 4; AAA46460)"
FT /evidence="ECO:0000305"
FT CONFLICT 403
FT /note="D -> E (in Ref. 4; AAA46460)"
FT /evidence="ECO:0000305"
FT STRAND 29..31
FT /evidence="ECO:0007829|PDB:4C7L"
FT STRAND 35..37
FT /evidence="ECO:0007829|PDB:4C7L"
FT STRAND 39..45
FT /evidence="ECO:0007829|PDB:4C7L"
FT HELIX 61..63
FT /evidence="ECO:0007829|PDB:4C7L"
FT TURN 68..71
FT /evidence="ECO:0007829|PDB:4C7L"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:4C7L"
FT HELIX 83..88
FT /evidence="ECO:0007829|PDB:4C7L"
FT STRAND 89..91
FT /evidence="ECO:0007829|PDB:4C7L"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:4C7W"
FT STRAND 100..106
FT /evidence="ECO:0007829|PDB:4C7L"
FT TURN 112..114
FT /evidence="ECO:0007829|PDB:4C7L"
FT HELIX 124..141
FT /evidence="ECO:0007829|PDB:4C7L"
FT TURN 142..144
FT /evidence="ECO:0007829|PDB:4C7L"
FT STRAND 145..152
FT /evidence="ECO:0007829|PDB:4C7L"
FT STRAND 176..180
FT /evidence="ECO:0007829|PDB:4C7L"
FT STRAND 187..189
FT /evidence="ECO:0007829|PDB:4C7L"
FT STRAND 193..199
FT /evidence="ECO:0007829|PDB:4C7L"
FT STRAND 201..214
FT /evidence="ECO:0007829|PDB:4C7L"
FT STRAND 220..222
FT /evidence="ECO:0007829|PDB:4C7L"
FT STRAND 231..236
FT /evidence="ECO:0007829|PDB:4C7L"
FT TURN 237..239
FT /evidence="ECO:0007829|PDB:4C7L"
FT STRAND 241..246
FT /evidence="ECO:0007829|PDB:4C7L"
FT STRAND 253..257
FT /evidence="ECO:0007829|PDB:4C7L"
FT STRAND 261..269
FT /evidence="ECO:0007829|PDB:4C7L"
FT STRAND 271..285
FT /evidence="ECO:0007829|PDB:4C7L"
FT STRAND 287..295
FT /evidence="ECO:0007829|PDB:4C7L"
FT STRAND 301..305
FT /evidence="ECO:0007829|PDB:4C7L"
FT HELIX 317..321
FT /evidence="ECO:0007829|PDB:4C7L"
FT TURN 324..326
FT /evidence="ECO:0007829|PDB:4C7L"
FT STRAND 327..330
FT /evidence="ECO:0007829|PDB:4C7L"
FT HELIX 350..356
FT /evidence="ECO:0007829|PDB:4C7L"
FT STRAND 362..365
FT /evidence="ECO:0007829|PDB:4C7L"
FT STRAND 368..371
FT /evidence="ECO:0007829|PDB:4C7L"
FT STRAND 373..375
FT /evidence="ECO:0007829|PDB:4C7L"
FT STRAND 384..386
FT /evidence="ECO:0007829|PDB:4C7L"
FT STRAND 399..401
FT /evidence="ECO:0007829|PDB:4C7L"
SQ SEQUENCE 439 AA; 49205 MW; 68CC6EC9CD108FAA CRC64;
MGCMCIAMAP RTLLLLIGCQ LVFGFNEPLN IVSHLNDDWF LFGDSRSDCT YVENNGHPKL
DWLDLDPKLC NSGRISAKSG NSLFRSFHFI DFYNYSGEGD QVIFYEGVNF SPSHGFKCLA
YGDNKRWMGN KARFYARVYE KMAQYRSLSF VNVSYAYGGN AKPTSICKDK TLTLNNPTFI
SKESNYVDYY YESEANFTLQ GCDEFIVPLC VFNGHSKGSS SDPANKYYTD SQSYYNMDTG
VLYGFNSTLD VGNTVQNPGL DLTCRYLALT PGNYKAVSLE YLLSLPSKAI CLRKPKSFMP
VQVVDSRWNS TRQSDNMTAV ACQLPYCFFR NTSADYSGGT HDVHHGDFHF RQLLSGLLYN
VSCIAQQGAF VYNNVSSSWP AYGYGHCPTA ANIGYMAPVC IYDPLPVILL GVLLGIAVLI
IVFLMFYFMT DSGVRLHEA
