ID HEMA_INCCA Reviewed; 654 AA. AC P03465; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 27-NOV-2024, entry version 121. 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/California/1978). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina; OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Gammainfluenzavirus; OC Gammainfluenzavirus influenzae; Influenza C virus. OX NCBI_TaxID=203224; OH NCBI_TaxID=9606; Homo sapiens (Human). OH NCBI_TaxID=9823; Sus scrofa (Pig). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=6699942; DOI=10.1128/jvi.50.1.118-124.1984; RA Nakada S., Creager R.S., Krystal M., Aaronson R.P., Palese P.; RT "Influenza C virus hemagglutinin: comparison with influenza A and B virus RT hemagglutinins."; RL J. Virol. 50:118-124(1984). 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=N-acetyl-9-O-acetylneuraminate + H2O = N-acetylneuraminate + CC acetate + H(+); 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=N-acetyl-4-O-acetylneuraminate + H2O = N-acetylneuraminate + CC acetate + H(+); 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 PIR; A04076; HMIVC8. DR SMR; P03465; -. DR GlyCosmos; P03465; 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..14 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CHAIN 15..654 FT /note="Hemagglutinin-esterase-fusion glycoprotein" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT /id="PRO_0000440552" FT CHAIN 15..445 FT /note="Hemagglutinin-esterase-fusion glycoprotein chain 1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT /id="PRO_0000440553" FT CHAIN 446..654 FT /note="Hemagglutinin-esterase-fusion glycoprotein chain 2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT /id="PRO_0000440554" FT TOPO_DOM 15..629 FT /note="Extracellular" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT TRANSMEM 630..650 FT /note="Helical" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT TOPO_DOM 651..654 FT /note="Cytoplasmic" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT REGION 15..40 FT /note="Fusion domain-1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT REGION 41..157 FT /note="Esterase domain-1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT REGION 157..309 FT /note="N-acetyl-9-O-acetylneuraminic acid binding" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT REGION 309..363 FT /note="Esterase domain-2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT REGION 364..654 FT /note="Fusion domain-2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT ACT_SITE 71 FT /note="Nucleophile" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT ACT_SITE 365 FT /note="Charge relay system" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT ACT_SITE 368 FT /note="Charge relay system" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 26 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 61 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 143 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 188 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 394 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 551 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 602 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT DISULFID 20..582 FT /note="Interchain (between HEF1 and HEF2 chains)" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT DISULFID 209..251 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT DISULFID 228..315 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT DISULFID 236..288 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" SQ SEQUENCE 654 AA; 72085 MW; 7F4C28D9EFD2E429 CRC64; MFFSLLLMLG LTEAEKIKIC LQKQVNSSFS LHNGFGGNLY ATEEKRMFEL VKPKAGASVL NQSTWIGFGD SRTDQSNSAF PRSLMSAKTA DKFRSLSGGS LMLSMFGPPG KVDYLYQGCG KHKVFYEGVN WSPHAAIDCY RKNWTDIKLN FQKSIYELAS QSHCMSLVNA LDKTIPLQVT KGVAKNCNNS FLKNPALYTQ EVKPLEQICG EENLAFFTLP TQFGTYECKL HLVASCYFIY DSKEVYNKRG CGNYFQVIYD SSGKVVGGLD NRVSPYTGNS GDTPTMQCDM LQLKPGRYSV RSSPRFLLMP ERSYCFDMKE KGPVTAVQSI WGKGRKSDYA VDQACLSTPG CMLIQKQKPY IGEADDHHGD QEMRELLSGL DYEARCISQS GWVNETSPFT EEYLLPPKFG RCPLAAKEES IPKIPDGLLI PTSGTDTTVT KPKSRIFGID DLIIGLLFVA IVEAGIGGYL LGSRKESGGG VTKESAEKGF EKIGNDIQIL RSSTNIAIEK LNDRISHDEQ AIRDLTLEIE NARSEALLGE LGIIRALLVG NISIGLQESL WELASEITNR AGDLAVEVSP GCWIIDNNIC DQSCQNFIFK FNETAPVPTI PPLDTKIDLQ SDPFYWGSSL GLAITAANLM AALVISGIAI CRTK //