HEMA_INCNB
ID HEMA_INCNB Reviewed; 648 AA.
AC Q67387;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 10-FEB-2021, entry version 105.
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/Nara/2/1985).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Gammainfluenzavirus.
OX NCBI_TaxID=127957;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9823; Sus scrofa (Pig).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=7996155; DOI=10.1099/0022-1317-75-12-3619;
RA Peng G., Hongo S., Muraki Y., Sugawara K., Nishimura H., Kitame F.,
RA Nakamura K.;
RT "Genetic reassortment of influenza C viruses in man.";
RL J. Gen. Virol. 75:3619-3622(1994).
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}.
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DR EMBL; D30697; BAA06368.1; -; Genomic_RNA.
DR SMR; Q67387; -.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of 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:UniProtKB-EC.
DR GO; GO:0106330; F:sialate 9-O-acetylesterase activity; IEA:UniProtKB-EC.
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 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; SSF49818; SSF49818; 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_0000039160"
FT CHAIN 440..648
FT /note="Hemagglutinin-esterase-fusion glycoprotein chain 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="PRO_0000039161"
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"
SQ SEQUENCE 648 AA; 71229 MW; D6736996092E5DB9 CRC64;
MLGLTEAEKI KICLQKQVNS SFSLHNGFGG NLYATEEKRM FELVKPKAGA SVLNQSTWIG
FGDSRTDQSN SAFPRSADVS AKTADKFRSL SGGSLMLSMF GPPGKVDYLY QGCGKHKVFY
EGVNWSPHAA IDCYRKNWTD IKLNFQKSIY ELASQSHCMS LVNALDKTIP LQVTKGVAKN
CNNSFLKNPA LYTQEVKPLE QICGKENLAF FTLPTQFGTY ECKLHLVASC YFIYDSKEVY
NKRGCGNYFQ VIYDSSGKVV GGLDNRVSPY TGNSGDTPTM QCDMLQLKPG RYSVRSSPRF
LLMPERSYCF DMKEKGPVTA VQSIWGKGRE SDYAVDQACL 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
