ID HEMA_CVBM Reviewed; 424 AA. AC P15776; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1990, sequence version 1. DT 27-MAR-2024, entry version 136. 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 Bovine coronavirus (strain Mebus) (BCoV) (BCV). OC Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes; OC Nidovirales; Cornidovirineae; Coronaviridae; Orthocoronavirinae; OC Betacoronavirus; Embecovirus; Betacoronavirus 1. OX NCBI_TaxID=11132; OH NCBI_TaxID=9913; Bos taurus (Bovine). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA], AND SUBCELLULAR LOCATION. RX PubMed=2319653; DOI=10.1128/jvi.64.4.1834-1838.1990; RA Kienzle T.E., Abraham S., Hogue B.G., Brian D.A.; RT "Structure and orientation of expressed bovine coronavirus hemagglutinin- RT esterase protein."; RL J. Virol. 64:1834-1838(1990). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=2103108; DOI=10.1007/978-1-4684-5823-7_14; RA Kienzle T.E., Abraham S., Hogue B.G., Brian D.A.; RT "Structure and expression of the bovine coronavirus hemagglutinin RT protein."; RL Adv. Exp. Med. Biol. 276:95-102(1990). RN [3] RP PROTEIN SEQUENCE OF 19-27. RX PubMed=2732694; DOI=10.1099/0022-1317-70-2-345; RA Hogue B.G., Kienzle T.E., Brian D.A.; RT "Synthesis and processing of the bovine enteric coronavirus haemagglutinin RT protein."; RL J. Gen. Virol. 70:345-352(1989). RN [4] RP CHARACTERIZATION. 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 [5] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 19-388 OF APOPROTEIN AND MUTANT RP ALA-40 IN COMPLEX WITH RECEPTOR, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, RP ACTIVE SITES, GLYCOSYLATION AT ASN-54; ASN-89; ASN-236; ASN-301; ASN-316 RP AND ASN-358, DISULFIDE BONDS, AND MUTAGENESIS OF SER-40; TYR-184; PHE-211; RP LEU-266 AND LEU-267. RX PubMed=18550812; DOI=10.1073/pnas.0800502105; RA Zeng Q., Langereis M.A., van Vliet A.L., Huizinga E.G., de Groot R.J.; RT "Structure of coronavirus hemagglutinin-esterase offers insight into corona RT and influenza virus evolution."; RL Proc. Natl. Acad. Sci. U.S.A. 105:9065-9069(2008). 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:18550812}. 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:18550812}; 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:18550812}; 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:18550812}. 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, ECO:0000269|PubMed:2319653}. CC -!- PTM: N-glycosylated in the host RER. {ECO:0000255|HAMAP-Rule:MF_04207, CC ECO:0000269|PubMed:18550812}. CC -!- SIMILARITY: Belongs to the influenza type C/coronaviruses CC hemagglutinin-esterase family. {ECO:0000255|HAMAP-Rule:MF_04207}. 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; U00735; AAA66393.1; -; Genomic_RNA. DR EMBL; S50936; AAB19562.1; -; Genomic_RNA. DR PIR; A34666; HMIHBC. DR PDB; 3CL4; X-ray; 2.10 A; A=19-388. DR PDB; 3CL5; X-ray; 1.80 A; A=19-388. DR PDBsum; 3CL4; -. DR PDBsum; 3CL5; -. DR SMR; P15776; -. DR UniLectin; P15776; -. DR GlyCosmos; P15776; 8 sites, No reported glycans. DR iPTMnet; P15776; -. DR BRENDA; 3.1.1.53; 8724. DR EvolutionaryTrace; P15776; -. DR Proteomes; UP000007554; Genome. 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; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. 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:0001681; F:sialate O-acetylesterase activity; IDA:UniProtKB. DR GO; GO:0005102; F:signaling receptor binding; IDA:UniProtKB. DR GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule. DR GO; GO:0002683; P:negative regulation of immune system process; IDA:UniProtKB. DR GO; GO:0046813; P:receptor-mediated virion attachment to host cell; IDA:UniProtKB. 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; Direct protein sequencing; Disulfide bond; Glycoprotein; KW Hemagglutinin; Host cell membrane; Host membrane; Hydrolase; Membrane; KW Signal; Transmembrane; Transmembrane helix; Viral envelope protein; Virion. FT SIGNAL 1..18 FT /evidence="ECO:0000269|PubMed:2732694" FT SIGNAL 1..16 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207" FT CHAIN 17..424 FT /note="Hemagglutinin-esterase" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207" FT /id="PRO_0000037138" FT TOPO_DOM 17..392 FT /note="Virion surface" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207" FT TRANSMEM 393..413 FT /note="Helical" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207" FT TOPO_DOM 414..424 FT /note="Intravirion" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207" FT REGION 7..127 FT /note="Esterase domain 1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207" FT REGION 128..266 FT /note="Receptor binding" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207" FT REGION 267..379 FT /note="Esterase domain 2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207" FT ACT_SITE 40 FT /note="Nucleophile" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207, FT ECO:0000269|PubMed:18550812" FT ACT_SITE 326 FT /note="Charge relay system" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207" FT ACT_SITE 329 FT /note="Charge relay system" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207" FT CARBOHYD 54 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207, FT ECO:0000269|PubMed:18550812" FT CARBOHYD 89 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207, FT ECO:0000269|PubMed:18550812" FT CARBOHYD 153 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207" FT CARBOHYD 236 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207, FT ECO:0000269|PubMed:18550812" FT CARBOHYD 301 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207, FT ECO:0000269|PubMed:18550812" FT CARBOHYD 316 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207, FT ECO:0000269|PubMed:18550812" FT CARBOHYD 358 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207, FT ECO:0000269|PubMed:18550812" FT CARBOHYD 417 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207" FT DISULFID 44..65 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207, FT ECO:0000269|PubMed:18550812" FT DISULFID 113..162 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207, FT ECO:0000269|PubMed:18550812" FT DISULFID 197..276 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207, FT ECO:0000269|PubMed:18550812" FT DISULFID 205..249 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207, FT ECO:0000269|PubMed:18550812" FT DISULFID 307..312 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207, FT ECO:0000269|PubMed:18550812" FT DISULFID 347..371 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04207, FT ECO:0000269|PubMed:18550812" FT MUTAGEN 40 FT /note="S->A: Loss of enzyme activity." FT /evidence="ECO:0000269|PubMed:18550812" FT MUTAGEN 184 FT /note="Y->A: Decreased receptor binding." FT /evidence="ECO:0000269|PubMed:18550812" FT MUTAGEN 211 FT /note="F->A: Loss of receptor binding." FT /evidence="ECO:0000269|PubMed:18550812" FT MUTAGEN 266 FT /note="L->A: Loss of receptor binding; when associated with FT A-267." FT /evidence="ECO:0000269|PubMed:18550812" FT MUTAGEN 267 FT /note="L->A: Loss of receptor binding; when associated with FT A-266." FT /evidence="ECO:0000269|PubMed:18550812" FT STRAND 23..25 FT /evidence="ECO:0007829|PDB:3CL4" FT STRAND 29..32 FT /evidence="ECO:0007829|PDB:3CL5" FT STRAND 34..39 FT /evidence="ECO:0007829|PDB:3CL5" FT HELIX 40..42 FT /evidence="ECO:0007829|PDB:3CL5" FT HELIX 44..49 FT /evidence="ECO:0007829|PDB:3CL5" FT STRAND 50..52 FT /evidence="ECO:0007829|PDB:3CL5" FT HELIX 55..57 FT /evidence="ECO:0007829|PDB:3CL4" FT HELIX 62..64 FT /evidence="ECO:0007829|PDB:3CL5" FT STRAND 70..73 FT /evidence="ECO:0007829|PDB:3CL5" FT HELIX 78..83 FT /evidence="ECO:0007829|PDB:3CL5" FT STRAND 84..86 FT /evidence="ECO:0007829|PDB:3CL5" FT STRAND 95..100 FT /evidence="ECO:0007829|PDB:3CL5" FT HELIX 107..109 FT /evidence="ECO:0007829|PDB:3CL5" FT HELIX 119..137 FT /evidence="ECO:0007829|PDB:3CL5" FT STRAND 140..147 FT /evidence="ECO:0007829|PDB:3CL5" FT STRAND 150..152 FT /evidence="ECO:0007829|PDB:3CL4" FT STRAND 162..164 FT /evidence="ECO:0007829|PDB:3CL5" FT STRAND 167..169 FT /evidence="ECO:0007829|PDB:3CL5" FT STRAND 171..175 FT /evidence="ECO:0007829|PDB:3CL5" FT STRAND 182..184 FT /evidence="ECO:0007829|PDB:3CL5" FT STRAND 188..207 FT /evidence="ECO:0007829|PDB:3CL5" FT STRAND 211..213 FT /evidence="ECO:0007829|PDB:3CL5" FT STRAND 216..218 FT /evidence="ECO:0007829|PDB:3CL5" FT STRAND 221..226 FT /evidence="ECO:0007829|PDB:3CL5" FT TURN 227..229 FT /evidence="ECO:0007829|PDB:3CL5" FT STRAND 232..236 FT /evidence="ECO:0007829|PDB:3CL5" FT STRAND 242..244 FT /evidence="ECO:0007829|PDB:3CL5" FT STRAND 247..270 FT /evidence="ECO:0007829|PDB:3CL5" FT STRAND 273..280 FT /evidence="ECO:0007829|PDB:3CL5" FT STRAND 286..289 FT /evidence="ECO:0007829|PDB:3CL5" FT HELIX 302..306 FT /evidence="ECO:0007829|PDB:3CL5" FT TURN 309..311 FT /evidence="ECO:0007829|PDB:3CL5" FT STRAND 312..315 FT /evidence="ECO:0007829|PDB:3CL5" FT STRAND 323..326 FT /evidence="ECO:0007829|PDB:3CL5" FT STRAND 329..331 FT /evidence="ECO:0007829|PDB:3CL5" FT HELIX 332..338 FT /evidence="ECO:0007829|PDB:3CL5" FT HELIX 339..342 FT /evidence="ECO:0007829|PDB:3CL5" FT STRAND 346..349 FT /evidence="ECO:0007829|PDB:3CL5" FT STRAND 352..355 FT /evidence="ECO:0007829|PDB:3CL5" FT STRAND 357..359 FT /evidence="ECO:0007829|PDB:3CL5" FT STRAND 368..370 FT /evidence="ECO:0007829|PDB:3CL5" SQ SEQUENCE 424 AA; 47695 MW; FDEF70542F91F305 CRC64; MFLLLRFVLV SCIIGSLGFD NPPTNVVSHL NGDWFLFGDS RSDCNHVVNT NPRNYSYMDL NPALCDSGKI SSKAGNSIFR SFHFTDFYNY TGEGQQIIFY EGVNFTPYHA FKCTTSGSND IWMQNKGLFY TQVYKNMAVY RSLTFVNVPY VYNGSAQSTA LCKSGSLVLN NPAYIAREAN FGDYYYKVEA DFYLSGCDEY IVPLCIFNGK FLSNTKYYDD SQYYFNKDTG VIYGLNSTET ITTGFDFNCH YLVLPSGNYL AISNELLLTV PTKAICLNKR KDFTPVQVVD SRWNNARQSD NMTAVACQPP YCYFRNSTTN YVGVYDINHG DAGFTSILSG LLYDSPCFSQ QGVFRYDNVS SVWPLYSYGR CPTAADINTP DVPICVYDPL PLILLGILLG VAVIIIVVLL LYFMVDNGTR LHDA //