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HAMAP rule MF_04072

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General rule information [?]

Accession MF_04072
Dates 20-APR-2017 (Created)
29-SEP-2022 (Last updated, Version 7)
Name INFV_HEMA
Scope(s) Viruses
Orthomyxoviridae
Template(s) P03452 (HEMA_I34A1); P03465 (HEMA_INCCA); [ Recover all ]
Triggered by HAMAP; MF_04072 (Get profile general information and statistics)

Propagated annotation [?]

Identifier, protein and gene names [?]

Identifier HEMA
case <OC:Alphainfluenzavirus> or <OC:Betainfluenzavirus>
Protein name RecName: Full=Hemagglutinin;
                 Contains:
RecName: Full=Hemagglutinin HA1 chain;
                 Contains:
RecName: Full=Hemagglutinin HA2 chain;
                 Flags: Precursor;
Gene name Name=HA;
else
Protein name RecName: Full=Hemagglutinin-esterase-fusion glycoprotein;
                 Short=HEF;
                 EC=3.1.1.53;
                 Contains:
RecName: Full=Hemagglutinin-esterase-fusion glycoprotein chain 1;
                 Short=HEF1;
                 Contains:
RecName: Full=Hemagglutinin-esterase-fusion glycoprotein chain 2;
                 Short=HEF2;
                 Flags: Precursor;
Gene name Name=HE;
end case

Comments [?]

case <OC:Alphainfluenzavirus>
FUNCTIONBinds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. This attachment induces virion internalization either through clathrin-dependent endocytosis or through clathrin- and caveolin- independent pathway. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in HA2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore.
SUBUNITHomotrimer of disulfide-linked HA1-HA2.
SUBCELLULAR LOCATIONVirion membrane; Single-pass type I membrane protein. Host apical cell membrane; Single-pass type I membrane protein. Note=Targeted to the apical plasma membrane in epithelial polarized cells through a signal present in the transmembrane domain. Associated with glycosphingolipid- and cholesterol-enriched detergent- resistant lipid rafts.
PTMIn natural infection, inactive HA is matured into HA1 and HA2 outside the cell by one or more trypsin-like, arginine-specific endoprotease secreted by the bronchial epithelial cells. One identified protease that may be involved in this process is secreted in lungs by club cells.
PTMPalmitoylated.
else case <OC:Betainfluenzavirus>
FUNCTIONBinds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induce an irreversible conformational change in HA2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore.
SUBUNITHomotrimer of disulfide-linked HA1-HA2.
SUBCELLULAR LOCATIONVirion membrane; Single-pass type I membrane protein. Host apical cell membrane; Single-pass type I membrane protein. Note=Targeted to the apical plasma membrane in epithelial polarized cells through a signal present in the transmembrane domain. Associated with glycosphingolipid- and cholesterol-enriched detergent- resistant lipid rafts.
PTMIn natural infection, inactive HA is matured into HA1 and HA2 outside the cell by one or more trypsin-like, arginine-specific endoprotease secreted by the bronchial epithelial cells. One identified protease that may be involved in this process is secreted in lungs by club cells.
PTMPalmitoylated.
else case <OC:Gammainfluenzavirus>
FUNCTIONBinds to the N-acetyl-9-O-acetylneuraminic acid residues on the cell surface, bringing about the attachment of the virus particle to the cell. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induce an irreversible conformational change in HEF2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore. Displays a receptor-destroying activity which is a neuraminidate-O- acetyl esterase. This activity cleaves off any receptor on the cell surface, which would otherwise prevent virions release. These cleavages prevent self-aggregation and ensure the efficient spread of the progeny virus from cell to cell.
CATALYTIC ACTIVITY Reaction=H2O + N-acetyl-9-O-acetylneuraminate = acetate + H(+) + N- acetylneuraminate; Xref=Rhea:RHEA:22600, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28999, ChEBI:CHEBI:30089, ChEBI:CHEBI:35418; EC=3.1.1.53;
CATALYTIC ACTIVITY Reaction=H2O + N-acetyl-4-O-acetylneuraminate = acetate + H(+) + N- acetylneuraminate; Xref=Rhea:RHEA:25564, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29006, ChEBI:CHEBI:30089, ChEBI:CHEBI:35418; EC=3.1.1.53;
SUBUNITHomotrimer of disulfide-linked HEF1-HEF2.
SUBCELLULAR LOCATIONVirion membrane; Single-pass type I membrane protein. Host cell membrane; Single-pass type I membrane protein.
PTMIn natural infection, inactive HEF is matured into HEF1 and HEF2 outside the cell by one or more trypsin-like, arginine-specific endoprotease.
end case
SIMILARITYBelongs to the influenza viruses hemagglutinin family.

Keywords [?]


Gene Ontology [?]

GO:0020002; Cellular component:host cell plasma membrane
GO:0016020; Cellular component:membrane
GO:0019031; Cellular component:viral envelope
GO:0046789; Molecular function:host cell surface receptor binding
case <OCellular component:Alphainfluenzavirus>
GO:0075512; Biological process:clathrin-dependent endocytosis of virus by host cell
end case
GO:0039654; Biological process:fusion of virus membrane with host endosome membrane
GO:0046761; Biological process:viral budding from plasma membrane

Cross-references [?]

PROSITE PS00001; ASN_GLYCOSYLATION; 0-unlimited;
Pfam PF00509; Hemagglutinin; 1;
Pfam PF03996; Hema_esterase; 1;
Pfam PF02710; Hema_HEFG; 1;
Pfam PF08720; Hema_stalk; 1;
PRINTS PR00330; HEMAGGLUTN1; 1;
PRINTS PR00329; HEMAGGLUTN12; 1;
PRINTS PR00331; HEMAGGLUTN2; 1;
General Signal; -; 1;
General Transmembrane; -; 1;
ADD_TOPO_DOMAIN Extracellular; -; 1;
ADD_TOPO_DOMAIN Cytoplasmic; -; 1;

Features [?]

From: HEMA_I34A1 (P03452)
Key From To Description Tag Condition FTGroup
case <OC:Alphainfluenzavirus> or <OC:Betainfluenzavirus>
CHAIN 18 343 /note="Hemagglutinin HA1 chain"
CHAIN 344 565 /note="Hemagglutinin HA2 chain"
SITE 343 344 /note="Cleavage; by host" R-G
LIPID 554 554 /note="S-palmitoyl cysteine; by host" C
LIPID 561 561 /note="S-palmitoyl cysteine; by host" C
LIPID 564 564 /note="S-palmitoyl cysteine; by host" C
DISULFID 21 480 /note="Interchain (between HA1 and HA2 chains)" C-x*-C
DISULFID 59 291 C-x*-C
DISULFID 72 84 C-x*-C
DISULFID 107 152 C-x*-C
DISULFID 295 319 C-x*-C
DISULFID 487 491 C-x*-C
end case
From: HEMA_INCAA (P03465)
Key From To Description Tag Condition FTGroup
case <OC:Gammainfluenzavirus>
CHAIN 15 446 /note="Hemagglutinin-esterase-fusion glycoprotein chain 1"
CHAIN 447 655 /note="Hemagglutinin-esterase-fusion glycoprotein chain 2"
REGION 15 40 /note="Fusion domain-1"
REGION 41 150 /note="Esterase domain-1"
REGION 150 310 /note="N-acetyl-9-O-acetylneuraminic acid binding"
REGION 310 364 /note="Esterase domain-2"
REGION 365 650 /note="Fusion domain-2"
ACT_SITE 71 71 /note="Nucleophile"
ACT_SITE 366 366 /note="Charge relay system"
ACT_SITE 369 369 /note="Charge relay system"
DISULFID 20 583 /note="Interchain (between HEF1 and HEF2 chains)" C-x*-C
DISULFID 120 165 C-x*-C
DISULFID 140 188 C-x*-C
DISULFID 210 252 C-x*-C
DISULFID 229 316 C-x*-C
DISULFID 237 289 C-x*-C
DISULFID 345 351 C-x*-C
end case

Additional information [?]

Size range 560-655 amino acids
Related rules None
Fusion Nter: None Cter: None



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