HEMA_INCCA
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 03-AUG-2022, 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;
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.
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=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 PIR; A04076; HMIVC8.
DR SMR; P03465; -.
DR PRIDE; P03465; -.
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..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
