ID HEMA_INCHY Reviewed; 641 AA. AC P17003; DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1990, sequence version 1. DT 27-MAR-2024, entry version 114. DE RecName: Full=Hemagglutinin-esterase-fusion glycoprotein; DE Short=HEF; DE EC=3.1.1.53; DE Contains: DE RecName: Full=Hemagglutinin-esterase-fusion glycoprotein chain 1; DE Short=HEF1; DE Contains: DE RecName: Full=Hemagglutinin-esterase-fusion glycoprotein chain 2; DE Short=HEF2; DE Flags: Precursor; Fragment; GN Name=HE; OS Influenza C virus (strain C/Hyogo/1/1983). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina; OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Gammainfluenzavirus; OC Gammainfluenzavirus influenzae; Influenza C virus. OX NCBI_TaxID=203225; OH NCBI_TaxID=9606; Homo sapiens (Human). OH NCBI_TaxID=9823; Sus scrofa (Pig). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=2773313; DOI=10.1016/0042-6822(89)90114-1; RA Adachi K., Kitame F., Sugawara K., Nishimura H., Nakamura K.; RT "Antigenic and genetic characterization of three influenza C strains RT isolated in the Kinki district of Japan in 1982-1983."; RL Virology 172:125-133(1989). CC -!- FUNCTION: Binds to the N-acetyl-9-O-acetylneuraminic acid residues on CC the cell surface, bringing about the attachment of the virus particle CC to the cell. Plays a major role in the determination of host range CC restriction and virulence. Class I viral fusion protein. Responsible CC for penetration of the virus into the cell cytoplasm by mediating the CC fusion of the membrane of the endocytosed virus particle with the CC endosomal membrane. Low pH in endosomes induce an irreversible CC conformational change in HEF2, releasing the fusion hydrophobic CC peptide. Several trimers are required to form a competent fusion pore. CC Displays a receptor-destroying activity which is a neuraminidate-O- CC acetyl esterase. This activity cleaves off any receptor on the cell CC surface, which would otherwise prevent virions release. These cleavages CC prevent self-aggregation and ensure the efficient spread of the progeny CC virus from cell to cell (By similarity). {ECO:0000250}. 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; 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; CC -!- SUBUNIT: Homotrimer of disulfide-linked HEF1-HEF2. {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000305}; Single-pass type I CC membrane protein {ECO:0000305}. Host cell membrane {ECO:0000250}; CC Single-pass type I membrane protein {ECO:0000250}. CC -!- PTM: In natural infection, inactive HEF is matured into HEF1 and HEF2 CC outside the cell by one or more trypsin-like, arginine-specific CC endoprotease. {ECO:0000250}. CC -!- SIMILARITY: Belongs to the influenza type C/coronaviruses CC hemagglutinin-esterase family. {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; M25363; AAA43787.1; -; Genomic_RNA. DR PIR; C32665; HMIVEC. DR GlyCosmos; P17003; 4 sites, No reported glycans. DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW. DR GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW. DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell. DR GO; GO:0046789; F:host cell surface receptor binding; IEA:InterPro. 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:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW. DR GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:InterPro. DR GO; GO:0046718; P:viral entry into host cell; IEA:UniProtKB-KW. DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW. DR Gene3D; 2.20.70.20; -; 2. DR Gene3D; 3.90.20.10; -; 1. DR InterPro; IPR008980; Capsid_hemagglutn. DR InterPro; IPR007142; Hemagglutn-estrase_core. DR InterPro; IPR003860; Hemagglutn-estrase_hemagglutn. DR InterPro; IPR014831; Hemagglutn_stalk_influenz-C. DR Pfam; PF03996; Hema_esterase; 1. DR Pfam; PF02710; Hema_HEFG; 1. DR Pfam; PF08720; Hema_stalk; 1. DR SUPFAM; SSF58064; Influenza hemagglutinin (stalk); 1. DR SUPFAM; SSF52266; SGNH hydrolase; 1. DR SUPFAM; SSF49818; Viral protein domain; 1. PE 3: Inferred from homology; KW Disulfide bond; Fusion of virus membrane with host endosomal membrane; KW Fusion of virus membrane with host membrane; Glycoprotein; Hemagglutinin; KW Host cell membrane; Host membrane; Host-virus interaction; Hydrolase; KW Membrane; Transmembrane; Transmembrane helix; KW Viral attachment to host cell; Viral envelope protein; KW Viral penetration into host cytoplasm; Virion; Virus entry into host cell. FT CHAIN 1..432 FT /note="Hemagglutinin-esterase-fusion glycoprotein chain 1" FT /id="PRO_0000039150" FT CHAIN 433..641 FT /note="Hemagglutinin-esterase-fusion glycoprotein chain 2" FT /id="PRO_0000039151" FT TOPO_DOM 1..616 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 617..637 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 638..641 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 1..26 FT /note="Fusion domain-1" FT /evidence="ECO:0000250" FT REGION 27..137 FT /note="Esterase domain-1" FT /evidence="ECO:0000250" FT REGION 137..296 FT /note="N-acetyl-9-O-acetylneuraminic acid binding" FT /evidence="ECO:0000250" FT REGION 297..351 FT /note="Esterase domain-2" FT /evidence="ECO:0000250" FT REGION 352..637 FT /note="Fusion domain-2" FT /evidence="ECO:0000250" FT ACT_SITE 57 FT /note="Nucleophile" FT /evidence="ECO:0000250" FT ACT_SITE 352 FT /note="Charge relay system" FT /evidence="ECO:0000250" FT ACT_SITE 355 FT /note="Charge relay system" FT /evidence="ECO:0000250" FT CARBOHYD 12 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 47 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 130 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 381 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT DISULFID 6..569 FT /note="Interchain (between HEF1 and HEF2 chains)" FT /evidence="ECO:0000250" FT DISULFID 106..151 FT /evidence="ECO:0000250" FT DISULFID 126..174 FT /evidence="ECO:0000250" FT DISULFID 196..238 FT /evidence="ECO:0000250" FT DISULFID 215..302 FT /evidence="ECO:0000250" FT DISULFID 223..275 FT /evidence="ECO:0000250" FT DISULFID 332..338 FT /evidence="ECO:0000250" FT NON_TER 1 SQ SEQUENCE 641 AA; 70594 MW; DAA832F4C3B5FAC8 CRC64; EKIKICLQKQ VNSSFSLHNG FGGNLYATEE KRMFELVKPK AGASVLNQST WIGFGDSRTD KSNPNFPRSA DVSVKTANKF RSLTGGSLML SMFGPPGKVD YLYQGCGKHK VFYEGVNWSP HAAIDCYRKN WTDIKLNFQK NIYELASQSH CMSLVNALDK TIPLQATAGV AGNCNNSFLK NPALYTQKVT PPXXKCGKEN LAFFTLPTQF GTYECRLHLV ASCYFIYDSK EVYNKRGCDN YFQVIYDSSG KVVGGLDNRV SPYTGNSGDT PTMQCDMIQL KPGRYSVRSS PRFLLMPERS YCFDMKEKGP VTAVQSIWGK DRKSDYAVDQ ACLSTPGCML IQKQKPYTGE ADDHHGDQEM RELLSGLDYE ARCISQSGWV NETSPFTEEY LLPPKFGRCP LAAKEESIPK IPDGLLIPTS GTDTTVTKPK SRIFGIDDLI IGLFFVAIVE AGIGGYLLGS RKESGGGVTK ESAEKGFEKI GNDIQILRSS TNIAIEKLND RISHDEQAIR DLTLEIENAR SEALLGELGI IRALLVGNIS IGLQESLWEL ASEITNRAGD LAVEISPGCW IIDNNICDQS CQNFIFKFNE TAPVPTIPPL DTKIDLQSDP FYWGSSLGLA ITAAISLAAL VISGIAICRT K //