AC   MF_04072;
DC   Protein; auto
TR   HAMAP; MF_04072; -; 1; level=0
XX
Names: INFV_HEMA
XX
ID   HEMA
case <OC:Alphainfluenzavirus> or <OC:Betainfluenzavirus>
DE   RecName: Full=Hemagglutinin;
DE   Contains:
DE     RecName: Full=Hemagglutinin HA1 chain;
DE   Contains:
DE     RecName: Full=Hemagglutinin HA2 chain;
DE   Flags: Precursor;
GN   Name=HA;
else
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;
GN   Name=HE;
end case
XX
case <OC:Alphainfluenzavirus>
CC   -!- FUNCTION: Binds to sialic acid-containing receptors on the cell
CC       surface, bringing about the attachment of the virus particle to the
CC       cell. This attachment induces virion internalization either through
CC       clathrin-dependent endocytosis or through clathrin- and caveolin-
CC       independent pathway. Plays a major role in the determination of host
CC       range restriction and virulence. Class I viral fusion protein.
CC       Responsible for penetration of the virus into the cell cytoplasm by
CC       mediating the fusion of the membrane of the endocytosed virus particle
CC       with the endosomal membrane. Low pH in endosomes induces an
CC       irreversible conformational change in HA2, releasing the fusion
CC       hydrophobic peptide. Several trimers are required to form a competent
CC       fusion pore.
CC   -!- SUBUNIT: Homotrimer of disulfide-linked HA1-HA2.
CC   -!- SUBCELLULAR LOCATION: Virion membrane; Single-pass type I membrane
CC       protein. Host apical cell membrane; Single-pass type I membrane
CC       protein. Note=Targeted to the apical plasma membrane in epithelial
CC       polarized cells through a signal present in the transmembrane domain.
CC       Associated with glycosphingolipid- and cholesterol-enriched detergent-
CC       resistant lipid rafts.
CC   -!- PTM: In natural infection, inactive HA is matured into HA1 and HA2
CC       outside the cell by one or more trypsin-like, arginine-specific
CC       endoprotease secreted by the bronchial epithelial cells. One identified
CC       protease that may be involved in this process is secreted in lungs by
CC       club cells.
CC   -!- PTM: Palmitoylated.
else case <OC:Betainfluenzavirus>
CC   -!- FUNCTION: Binds to sialic acid-containing receptors on the cell
CC       surface, bringing about the attachment of the virus particle to the
CC       cell. Plays a major role in the determination of host range restriction
CC       and virulence. Class I viral fusion protein. Responsible for
CC       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 HA2, releasing the fusion hydrophobic peptide.
CC       Several trimers are required to form a competent fusion pore.
CC   -!- SUBUNIT: Homotrimer of disulfide-linked HA1-HA2.
CC   -!- SUBCELLULAR LOCATION: Virion membrane; Single-pass type I membrane
CC       protein. Host apical cell membrane; Single-pass type I membrane
CC       protein. Note=Targeted to the apical plasma membrane in epithelial
CC       polarized cells through a signal present in the transmembrane domain.
CC       Associated with glycosphingolipid- and cholesterol-enriched detergent-
CC       resistant lipid rafts.
CC   -!- PTM: In natural infection, inactive HA is matured into HA1 and HA2
CC       outside the cell by one or more trypsin-like, arginine-specific
CC       endoprotease secreted by the bronchial epithelial cells. One identified
CC       protease that may be involved in this process is secreted in lungs by
CC       club cells.
CC   -!- PTM: Palmitoylated.
else case <OC:Gammainfluenzavirus>
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.
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.
CC   -!- SUBCELLULAR LOCATION: Virion membrane; Single-pass type I membrane
CC       protein. Host cell membrane; Single-pass type I membrane protein.
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.
end case
CC   -!- SIMILARITY: Belongs to the influenza viruses hemagglutinin family.
XX
DR   PROSITE; PS00001; ASN_GLYCOSYLATION; 0-unlimited; trigger=yes
DR   Pfam; PF00509; Hemagglutinin; 1; trigger=no
DR   Pfam; PF03996; Hema_esterase; 1; trigger=no
DR   Pfam; PF02710; Hema_HEFG; 1; trigger=no
DR   Pfam; PF08720; Hema_stalk; 1; trigger=no
DR   PRINTS; PR00330; HEMAGGLUTN1; 1; trigger=no
DR   PRINTS; PR00329; HEMAGGLUTN12; 1; trigger=no
DR   PRINTS; PR00331; HEMAGGLUTN2; 1; trigger=no
DR   General; Signal; -; 1; trigger=yes
DR   General; Transmembrane; -; 1; trigger=yes
DR   ADD_TOPO_DOMAIN; Extracellular; -; 1; trigger=yes
DR   ADD_TOPO_DOMAIN; Cytoplasmic; -; 1; trigger=yes
XX
case <OC:Alphainfluenzavirus>
KW   Clathrin- and caveolin-independent endocytosis of virus by host
KW   Clathrin-mediated endocytosis of virus by host
end case
case <OC:Alphainfluenzavirus> or <OC:Betainfluenzavirus>
KW   Lipoprotein
KW   Palmitate
end case
case <OC:Gammainfluenzavirus>
KW   Hydrolase
end case
KW   Disulfide bond
KW   Fusion of virus membrane with host endosomal membrane
KW   Fusion of virus membrane with host membrane
KW   Glycoprotein
KW   Hemagglutinin
KW   Host cell membrane
KW   Host membrane
KW   Host-virus interaction
KW   Membrane
KW   Signal
KW   Transmembrane
KW   Transmembrane helix
KW   Viral attachment to host cell
KW   Viral envelope protein
KW   Viral penetration into host cytoplasm
KW   Virion
KW   Virus endocytosis by host
KW   Virus entry into host cell
XX
GO   GO:0020002; C:host cell plasma membrane
GO   GO:0016020; C:membrane
GO   GO:0019031; C:viral envelope
GO   GO:0046789; F:host cell surface receptor binding
case <OC:Alphainfluenzavirus>
GO   GO:0075512; P:clathrin-dependent endocytosis of virus by host cell
end case
GO   GO:0039654; P:fusion of virus membrane with host endosome membrane
GO   GO:0046761; P:viral budding from plasma membrane
XX
FT   From: HEMA_I34A1 (P03452)
case <OC:Alphainfluenzavirus> or <OC:Betainfluenzavirus>
FT   CHAIN           18..343
FT                   /note="Hemagglutinin HA1 chain"
FT   CHAIN           344..565
FT                   /note="Hemagglutinin HA2 chain"
FT   SITE            343..344
FT                   /note="Cleavage; by host"
FT   Condition: R-G
FT   LIPID           554
FT                   /note="S-palmitoyl cysteine; by host"
FT   Condition: C
FT   LIPID           561
FT                   /note="S-palmitoyl cysteine; by host"
FT   Condition: C
FT   LIPID           564
FT                   /note="S-palmitoyl cysteine; by host"
FT   Condition: C
FT   DISULFID        21..480
FT                   /note="Interchain (between HA1 and HA2 chains)"
FT   Condition: C-x*-C
FT   DISULFID        59..291
FT   Condition: C-x*-C
FT   DISULFID        72..84
FT   Condition: C-x*-C
FT   DISULFID        107..152
FT   Condition: C-x*-C
FT   DISULFID        295..319
FT   Condition: C-x*-C
FT   DISULFID        487..491
FT   Condition: C-x*-C
end case
FT   From: HEMA_INCAA (P03465)
case <OC:Gammainfluenzavirus>
FT   CHAIN           15..446
FT                   /note="Hemagglutinin-esterase-fusion glycoprotein chain 1"
FT   CHAIN           447..655
FT                   /note="Hemagglutinin-esterase-fusion glycoprotein chain 2"
FT   REGION          15..40
FT                   /note="Fusion domain-1"
FT   REGION          41..150
FT                   /note="Esterase domain-1"
FT   REGION          150..310
FT                   /note="N-acetyl-9-O-acetylneuraminic acid binding"
FT   REGION          310..364
FT                   /note="Esterase domain-2"
FT   REGION          365..650
FT                   /note="Fusion domain-2"
FT   ACT_SITE        71
FT                   /note="Nucleophile"
FT   ACT_SITE        366
FT                   /note="Charge relay system"
FT   ACT_SITE        369
FT                   /note="Charge relay system"
FT   DISULFID        20..583
FT                   /note="Interchain (between HEF1 and HEF2 chains)"
FT   Condition: C-x*-C
FT   DISULFID        120..165
FT   Condition: C-x*-C
FT   DISULFID        140..188
FT   Condition: C-x*-C
FT   DISULFID        210..252
FT   Condition: C-x*-C
FT   DISULFID        229..316
FT   Condition: C-x*-C
FT   DISULFID        237..289
FT   Condition: C-x*-C
FT   DISULFID        345..351
FT   Condition: C-x*-C
end case
XX
Size: 560-655;
Related: None;
Template: P03452; P03465;
Scope:
 Viruses; Orthomyxoviridae
Fusion:
 Nter: None
 Cter: None
Duplicate: None
Plasmid: None
Comments: None
XX
# Revision 1.7 2022/09/29
//