ID HEMA_INCP2 Reviewed; 642 AA. AC P07967; DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1988, sequence version 1. DT 27-MAR-2024, entry version 114. 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; Fragment; GN Name=HE {ECO:0000255|HAMAP-Rule:MF_04072}; OS Influenza C virus (strain C/Pig/Beijing/115/1981). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina; OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Gammainfluenzavirus; OC Gammainfluenzavirus influenzae; Influenza C virus. OX NCBI_TaxID=203231; OH NCBI_TaxID=9606; Homo sapiens (Human). OH NCBI_TaxID=9823; Sus scrofa (Pig). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=3855244; DOI=10.1016/0042-6822(85)90006-6; RA Buonagurio D.A., Nakada S., Desselberger U., Krystal M., Palese P.; RT "Noncumulative sequence changes in the hemagglutinin genes of influenza C RT virus isolates."; RL Virology 146:221-232(1985). 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; M11644; AAA43793.1; -; Genomic_RNA. DR SMR; P07967; -. DR GlyCosmos; P07967; 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-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: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-KW. DR GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:InterPro. 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; 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 CHAIN 1..433 FT /note="Hemagglutinin-esterase-fusion glycoprotein chain 1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT /id="PRO_0000440765" FT CHAIN 434..642 FT /note="Hemagglutinin-esterase-fusion glycoprotein chain 2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT /id="PRO_0000039165" FT TOPO_DOM 1..617 FT /note="Extracellular" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT TRANSMEM 618..638 FT /note="Helical" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT TOPO_DOM 639..642 FT /note="Cytoplasmic" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT REGION 83..297 FT /note="N-acetyl-9-O-acetylneuraminic acid binding" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT REGION 297..351 FT /note="Esterase domain-2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT REGION 352..637 FT /note="Fusion domain-2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT ACT_SITE 353 FT /note="Charge relay system" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT ACT_SITE 356 FT /note="Charge relay system" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 13 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 48 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 131 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 176 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 382 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 539 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 590 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT DISULFID 197..239 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT DISULFID 216..303 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT DISULFID 224..276 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT NON_TER 1 SQ SEQUENCE 642 AA; 70719 MW; 4F4CFA6E9D71EAC0 CRC64; AEKIKICLQK QVNSSFSLHN GFGGNLYATE EKRMFELVKP KAGASVLNQS TWICFGDSRT DQSNSAFPRS ADVSAKTAEK FRSLSGGSLM LSMFGPPGKV DYLYQGCGKH KVFYEGVNWS PHTAIDCYRK NWTDIKLNFQ KSIYELASQS HCMSLVNALD KTIPLQATKG VAKNCNNSFL KNPALYTQEV KPLEQICGEE NLAFFTLPTQ FGTYECKLHL VASCYFIYDS KEVYNKRGCG NYFQVIYDSS GKVVGGLDNR VSPYTGNSGD TPTMQCDMLQ LKPGRYSVRS SPRFLLMPER SYCFDMKEKG LVTAVQSIWG KGRKSDYAVD QACLSTPGCM LIQKQKPYIG EADDHHGDQE MRELLSGLDY EARCISQSGW VNETSPFTEE YLLPPKFGRC PLAAKEESIP KIPDGLLIPT SGTDTTVTKP KSRIFGIDDL IIGLLFVAIV EAGIGGYLLG SRKESGGGVT KESAEKGFEK IGNDIQILRS STNIAIEKLN DRISHDEQAI RDLTLEIENA RSEALLGELG IIRALLVGNI SIGLQESLWE LASEITNRAG DLAVEVSPGC WIIDNNICDQ SCQNFIFKFN ETAPVPTIPP LDTKIDLQSD PFYWGSSLGL AITTPISLAA LVISGIAICR TK //