HEMA_INCEN
ID HEMA_INCEN Reviewed; 642 AA.
AC P07973;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1988, sequence version 1.
DT 25-MAY-2022, entry version 107.
DE RecName: Full=Hemagglutinin-esterase-fusion glycoprotein;
DE Short=HEF;
DE EC=3.1.1.53;
DE Contains:
DE RecName: Full=Hemagglutinin-esterase-fusion glycoprotein chain 1;
DE Short=HEF1;
DE Contains:
DE RecName: Full=Hemagglutinin-esterase-fusion glycoprotein chain 2;
DE Short=HEF2;
DE Flags: Precursor; Fragment;
GN Name=HE;
OS Influenza C virus (strain C/England/892/1983).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Gammainfluenzavirus.
OX NCBI_TaxID=11556;
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 (By similarity). {ECO:0000250}.
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;
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;
CC -!- SUBUNIT: Homotrimer of disulfide-linked HEF1-HEF2. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}. Host cell membrane {ECO:0000250};
CC Single-pass type I membrane protein {ECO:0000250}.
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:0000250}.
CC -!- SIMILARITY: Belongs to the influenza type C/coronaviruses
CC hemagglutinin-esterase family. {ECO:0000305}.
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DR EMBL; M11642; AAA43783.1; -; Genomic_RNA.
DR SMR; P07973; -.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of 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:UniProtKB-EC.
DR GO; GO:0106330; F:sialate 9-O-acetylesterase activity; IEA:UniProtKB-EC.
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:0046718; P:viral entry into host cell; IEA:UniProtKB-KW.
DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW.
DR InterPro; IPR008980; Capsid_hemagglutn.
DR InterPro; IPR007142; Hemagglutn-estrase_core.
DR InterPro; IPR003860; Hemagglutn-estrase_hemagglutn.
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 entry into host cell.
FT SIGNAL <1..1
FT CHAIN 2..433
FT /note="Hemagglutinin-esterase-fusion glycoprotein chain 1"
FT /id="PRO_0000039146"
FT CHAIN 434..642
FT /note="Hemagglutinin-esterase-fusion glycoprotein chain 2"
FT /id="PRO_0000039147"
FT TOPO_DOM 2..617
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 618..638
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 639..642
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 2..27
FT /note="Fusion domain-1"
FT /evidence="ECO:0000250"
FT REGION 28..138
FT /note="Esterase domain-1"
FT /evidence="ECO:0000250"
FT REGION 138..297
FT /note="N-acetyl-9-O-acetylneuraminic acid binding"
FT /evidence="ECO:0000250"
FT REGION 298..352
FT /note="Esterase domain-2"
FT /evidence="ECO:0000250"
FT REGION 353..638
FT /note="Fusion domain-2"
FT /evidence="ECO:0000250"
FT ACT_SITE 58
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 353
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 356
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT CARBOHYD 13
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 48
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 131
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 382
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT DISULFID 7..570
FT /note="Interchain (between HEF1 and HEF2 chains)"
FT /evidence="ECO:0000250"
FT DISULFID 107..152
FT /evidence="ECO:0000250"
FT DISULFID 127..175
FT /evidence="ECO:0000250"
FT DISULFID 197..239
FT /evidence="ECO:0000250"
FT DISULFID 216..303
FT /evidence="ECO:0000250"
FT DISULFID 224..276
FT /evidence="ECO:0000250"
FT DISULFID 333..339
FT /evidence="ECO:0000250"
FT NON_TER 1
SQ SEQUENCE 642 AA; 70732 MW; F0D64E9143B14F67 CRC64;
AEKIKICLQK QVNSSFSLHN GFGGNLYATE EKRMFELVKP KAGASVLNQS TWICFGDSRT
DQSNSAFPRS ADVSAKTADK FRSLSGGSLM LSMFGPPGKV DYLYQGCGKH KVFYEGVNWS
PHAAIDCYRK NWTDIKLNFQ KSIYELASQS HCMSLVNALD KTIPLQVTKG VAKNCNNSFL
KNPALYTQEV KPLEQICGEE NLAFFTLPTQ FGTYECKLHL VASCYFIYDS KEVYNKRGCG
NYFQVIYDSS GKVVGGLDNR VSPYTGNTGD TPTMQCDMLQ LKPGRYSVRS SPRFLLMPER
SYCFDMKEKG LVTAVQSIWG KGRKSDYAVD QACLSTPGCM LIQKQKPYIG EADDHHGDQE
MRELLSGLDY EARCISQSGW VNETSPFTEE YLLPPKFGRC PLAAKEESIP KIPDGLLIPT
SGTDTTVTKP KSRIFGIDDL IIGLLFVAIV EAGIGGYLLG SRKESGGGVT KESAEKGFEK
IGNDIQILRS STNIAIEKLN DRITHDEQAI RDLTLEIENA RSEALLGELG IIRALLVGNI
SIGLQESLWE LASEITNRAG DLAVEVSPGC WIIDDNICDQ SCQNFIFKFN ETAPVPTIPP
LDTKIDLQSD PFYWGSSLGL AITTPISLAA LVISGIAICR TK
