ID HEMA_INCYB Reviewed; 648 AA. AC P87691; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1997, sequence version 1. DT 27-MAR-2024, entry version 113. DE RecName: Full=Hemagglutinin-esterase-fusion glycoprotein {ECO:0000255|HAMAP-Rule:MF_04072}; DE Short=HEF {ECO:0000255|HAMAP-Rule:MF_04072}; DE EC=3.1.1.53 {ECO:0000255|HAMAP-Rule:MF_04072}; DE Contains: DE RecName: Full=Hemagglutinin-esterase-fusion glycoprotein chain 1 {ECO:0000255|HAMAP-Rule:MF_04072}; DE Short=HEF1 {ECO:0000255|HAMAP-Rule:MF_04072}; DE Contains: DE RecName: Full=Hemagglutinin-esterase-fusion glycoprotein chain 2 {ECO:0000255|HAMAP-Rule:MF_04072}; DE Short=HEF2 {ECO:0000255|HAMAP-Rule:MF_04072}; DE Flags: Precursor; GN Name=HE {ECO:0000255|HAMAP-Rule:MF_04072}; OS Influenza C virus (strain C/Yamagata/4/1988). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina; OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Gammainfluenzavirus; OC Gammainfluenzavirus influenzae; Influenza C virus. OX NCBI_TaxID=127958; OH NCBI_TaxID=9606; Homo sapiens (Human). OH NCBI_TaxID=9823; Sus scrofa (Pig). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=1641987; DOI=10.1016/0042-6822(92)90597-i; RA Umetsu Y., Sugawara K., Nishimura H., Hongo S., Matsuzaki M., Kitame F., RA Nakamura K.; RT "Selection of antigenically distinct variants of influenza C viruses by the RT host cell."; RL Virology 189:740-744(1992). 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. {ECO:0000255|HAMAP-Rule:MF_04072}. 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_04072}; 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_04072}; CC -!- SUBUNIT: Homotrimer of disulfide-linked HEF1-HEF2. {ECO:0000255|HAMAP- CC Rule:MF_04072}. CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000255|HAMAP- CC Rule:MF_04072}; Single-pass type I membrane protein {ECO:0000255|HAMAP- CC Rule:MF_04072}. Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04072}; CC Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04072}. 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:0000255|HAMAP-Rule:MF_04072}. CC -!- SIMILARITY: Belongs to the influenza viruses hemagglutinin family. CC {ECO:0000255|HAMAP-Rule:MF_04072}. 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; D63503; BAA09781.1; -; Genomic_RNA. DR SMR; P87691; -. DR GlyCosmos; P87691; 7 sites, No reported glycans. 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:0075509; P:endocytosis involved in viral entry into host cell; IEA:UniProtKB-KW. 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:InterPro. DR GO; GO:0046761; P:viral budding from plasma membrane; IEA:UniProtKB-UniRule. 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 HAMAP; MF_04072; INFV_HEMA; 1. DR InterPro; IPR008980; Capsid_hemagglutn. DR InterPro; IPR007142; Hemagglutn-estrase_core. DR InterPro; IPR003860; Hemagglutn-estrase_hemagglutn. DR InterPro; IPR001364; Hemagglutn_influenz_A/B. 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; Signal; Transmembrane; Transmembrane helix; KW Viral attachment to host cell; Viral envelope protein; KW Viral penetration into host cytoplasm; Virion; Virus endocytosis by host; KW Virus entry into host cell. FT SIGNAL 1..7 FT /evidence="ECO:0000250" FT CHAIN 8..439 FT /note="Hemagglutinin-esterase-fusion glycoprotein chain 1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT /id="PRO_0000039172" FT CHAIN 440..648 FT /note="Hemagglutinin-esterase-fusion glycoprotein chain 2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT /id="PRO_0000039173" FT TOPO_DOM 8..623 FT /note="Extracellular" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT TRANSMEM 624..644 FT /note="Helical" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT TOPO_DOM 645..648 FT /note="Cytoplasmic" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT REGION 8..33 FT /note="Fusion domain-1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT REGION 34..151 FT /note="Esterase domain-1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT REGION 151..303 FT /note="N-acetyl-9-O-acetylneuraminic acid binding" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT REGION 303..357 FT /note="Esterase domain-2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT REGION 358..643 FT /note="Fusion domain-2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT ACT_SITE 64 FT /note="Nucleophile" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT ACT_SITE 359 FT /note="Charge relay system" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT ACT_SITE 362 FT /note="Charge relay system" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 19 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 54 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 137 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 182 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 388 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 545 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 596 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT DISULFID 13..576 FT /note="Interchain (between HEF1 and HEF2 chains)" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT DISULFID 203..245 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT DISULFID 222..309 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT DISULFID 230..282 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT VARIANT 276 FT /note="D -> N (in HMV-II adapted variant)" SQ SEQUENCE 648 AA; 71142 MW; A0AE7820D26F3263 CRC64; MLGLTEAEKI KICLQKQVNS SFSLHNGFGG NLYATEEKRM FELVKPKAGA SVLNQSTWIG FGDSRTDQSN SAFPRSADVS AKTADKFRSL SGGSLMLSMF GPPGKVDYLY QGCGKHKVFY EGVNWSPHAA IDCYRKNWTD IKLNFQKSIY ELASQSHCMS LVNALDKTIP LQVTKGVAKN CNNSFLKNPA LYTQEVKPLE QICGEENLAF FTLPTQFGTY ECKLHLVASC YFIYDSKEVY NKRGCGNYFQ VIYDSSGKVV GGLDNRVSPY TGNSGDTPTM QCDMLQLKPG RYSVRSSPRF LLMPERSYCF DMKEKGPVTA VQSIWGKGRE SDTAVDQACS STPGCMLIQK QKPYIGEADD HHGDQEMREL LSGLDYEARC ISQSGWVNET SPFTEEYLLP PKFGRCPLAA KEESIPKIPD GLLIPTSGTD TTVTKPKSRI FGIDDLIIGL LFVAIVEAGI GGYLLGSRKE SGGGVTKESA EKGFEKIGND IQILRSSTNI AIEKLNDRIS HDEQAIRDLT LEIENARSEA LLGELGIIRA LLVGNISIGL QESLWELASE ITNRAGDLAV EVSPGCWIID NNICDQSCQN FIFKFNETAP VPTIPPLDTK IDLQSDPFYW GSSLGLAITA AISLAALVIS GIAICRTK //