ID HEMA_INCAA Reviewed; 655 AA. AC P68762; P07969; Q6I7C1; DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot. DT 12-DEC-2006, sequence version 2. DT 27-MAR-2024, entry version 92. 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/Ann Arbor/1/1950). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina; OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Gammainfluenzavirus; OC Gammainfluenzavirus influenzae; Influenza C virus. OX NCBI_TaxID=11553; OH NCBI_TaxID=9606; Homo sapiens (Human). OH NCBI_TaxID=9823; Sus scrofa (Pig). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=15218173; DOI=10.1099/vir.0.79937-0; RA Muraki Y., Washioka H., Sugawara K., Matsuzaki Y., Takashita E., Hongo S.; RT "Identification of an amino acid residue on influenza C virus M1 protein RT responsible for formation of the cord-like structures of the virus."; RL J. Gen. Virol. 85:1885-1893(2004). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 14-655. 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; AB126194; BAD24940.1; -; Genomic_RNA. DR EMBL; M11638; AAA43782.1; -; Genomic_RNA. DR RefSeq; YP_089655.1; NC_006310.1. DR SMR; P68762; -. DR GlyCosmos; P68762; 7 sites, No reported glycans. DR DNASU; 3077359; -. DR GeneID; 3077359; -. DR KEGG; vg:3077359; -. DR OrthoDB; 2655at10239; -. DR Proteomes; UP000008286; 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; 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; Reference proteome; 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..655 FT /note="Hemagglutinin-esterase-fusion glycoprotein" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT /id="PRO_0000440551" FT CHAIN 15..446 FT /note="Hemagglutinin-esterase-fusion glycoprotein chain 1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT /id="PRO_0000039142" FT CHAIN 447..655 FT /note="Hemagglutinin-esterase-fusion glycoprotein chain 2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT /id="PRO_0000039143" FT TOPO_DOM 15..630 FT /note="Extracellular" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT TRANSMEM 631..651 FT /note="Helical" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT TOPO_DOM 652..655 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..158 FT /note="Esterase domain-1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT REGION 158..310 FT /note="N-acetyl-9-O-acetylneuraminic acid binding" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT REGION 310..364 FT /note="Esterase domain-2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT REGION 365..650 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 366 FT /note="Charge relay system" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT ACT_SITE 369 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 144 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 189 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 395 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 552 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 603 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT DISULFID 20..583 FT /note="Interchain (between HEF1 and HEF2 chains)" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT DISULFID 210..252 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT DISULFID 229..316 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT DISULFID 237..289 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CONFLICT 207..209 FT /note="VEK -> EEI (in Ref. 2; AAA43782)" FT /evidence="ECO:0000305" FT CONFLICT 214 FT /note="N -> Y (in Ref. 2; AAA43782)" FT /evidence="ECO:0000305" FT CONFLICT 263 FT /note="S -> Y (in Ref. 2; AAA43782)" FT /evidence="ECO:0000305" FT CONFLICT 324 FT /note="P -> L (in Ref. 2; AAA43782)" FT /evidence="ECO:0000305" FT CONFLICT 346 FT /note="C -> Y (in Ref. 2; AAA43782)" FT /evidence="ECO:0000305" FT CONFLICT 458 FT /note="L -> F (in Ref. 2; AAA43782)" FT /evidence="ECO:0000305" FT CONFLICT 477 FT /note="V -> E (in Ref. 2; AAA43782)" FT /evidence="ECO:0000305" FT CONFLICT 637..638 FT /note="AA -> TP (in Ref. 2; AAA43782)" FT /evidence="ECO:0000305" SQ SEQUENCE 655 AA; 71956 MW; 81869FEDA9CD8943 CRC64; MFFSLLLMLG LTEAEKIKIC LQKQVNSSFS LHNGFGGNLY ATEEKRMFEL VKPKAGASVL NQSTWIGFGD SRTDKSNSAF PRSADVSAKT ADKFRSLSGG SLMLSMFGPP GKVDYLYQGC GKHKVFYEGV NWSPHAAINC YRKNWTDIKL NFQKNIYELA SQSHCMSLVN ALDKTIPLQA TAGVAKNCNN SFLKNPALYT QEVNPSVEKC GKENLAFFTL PTQFGTYECK LHLVASCYFI YDSKEVYNKR GCDNYFQVIY DSSGKVVGGL DNRVSPYTGN SGDTPTMQCD MLQLKPGRYS VRSSPRFLLM PERSYCFDMK EKGPVTAVQS IWGKGRESDH AVDQACLSTP GCMLIQKQKP YIGEADDHHG DQEMRELLSG LDYEARCISQ SGWVNETSPF TEEYLLPPKF GRCPLAAKEE SIPKIPDGLL IPTSGTDTTV TKPKSRIFGI DDLIIGLLFV AIVEAGIGGY LLGSRKVSGG GVTKESAEKG FEKIGNDIQI LRSSTNIAIE KLNDRISHDE QAIRDLTLEI ENARSEALLG ELGIIRALLV GNISIGLQES LWELASEITN RAGDLAVEVS PGCWVIDNNI CDQSCQNFIF KFNETAPVPT IPPLDTKIDL QSDPFYWGSS LGLAITAAIS LAALVISGIA ICRTK //