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 27-MAR-2024, entry version 116. 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; Murine coronavirus. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 GlyCosmos; P31614; 9 sites, No reported glycans. DR iPTMnet; P31614; -. DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C: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:RHEA. DR GO; GO:0106330; F:sialate 9-O-acetylesterase activity; IEA:RHEA. 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; SSF52266; SGNH hydrolase; 1. DR SUPFAM; SSF49818; Viral protein domain; 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 //