HAMAP rule MF_04072

Accession	MF_04072
Dates	20-APR-2017 (Created) 29-SEP-2022 (Last updated, Version 7)

Name

INFV_HEMA

Scope

Viruses; Orthomyxoviridae

Templates

P03452 (HEMA_I34A1); P03465 (HEMA_INCCA): [Recover all]

Triggered by

HAMAP; MF_04072 (Get profile general information and statistics)

Identifier

HEMA

Protein name

RecName: Full=Hemagglutinin; Contains: RecName: Full=Hemagglutinin HA1 chain; Contains: RecName: Full=Hemagglutinin HA2 chain; Flags: Precursor;

Gene name

HA

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

HE

Function	Binds 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.
Subunit	Homotrimer of disulfide-linked HA1-HA2.
Subcellular location	Virion 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.
Ptm	In 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.
	Palmitoylated.

Function	Binds 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.
Subunit	Homotrimer of disulfide-linked HA1-HA2.
Subcellular location	Virion 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.
Ptm	In 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.
	Palmitoylated.

Function	Binds 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	RHEA:22600: H2O + N-acetyl-9-O-acetylneuraminate = acetate + H(+) + N-acetylneuraminate EC 3.1.1.53
	RHEA:25564: H2O + N-acetyl-4-O-acetylneuraminate = acetate + H(+) + N-acetylneuraminate EC 3.1.1.53
Subunit	Homotrimer of disulfide-linked HEF1-HEF2.
Subcellular location	Virion membrane; Single-pass type I membrane protein. Host cell membrane; Single-pass type I membrane protein.
Ptm	In natural infection, inactive HEF is matured into HEF1 and HEF2 outside the cell by one or more trypsin-like, arginine-specific endoprotease.

Similarity

Belongs to the influenza viruses hemagglutinin family.

Clathrin- and caveolin-independent endocytosis of virus by host
Clathrin-mediated endocytosis of virus by host

Lipoprotein
Palmitate

Hydrolase

Disulfide bond
Fusion of virus membrane with host endosomal membrane
Fusion of virus membrane with host membrane
Glycoprotein
Hemagglutinin
Host cell membrane
Host membrane
Host-virus interaction
Membrane
Signal
Transmembrane
Transmembrane helix
Viral attachment to host cell
Viral envelope protein
Viral penetration into host cytoplasm
Virion
Virus endocytosis by host
Virus entry into host cell

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.

GO:0075512; Biological process: clathrin-dependent endocytosis of virus by host cell.

GO:0039654; Biological process: fusion of virus membrane with host endosome membrane.
GO:0046761; Biological process: viral budding from plasma membrane.

PROSITE	PS00001; ASN_GLYCOSYLATION; 0-unlimited; trigger=PRU00498;
Pfam	PF00509; Hemagglutinin; 1;
	PF03996; Hema_esterase; 1;
	PF02710; Hema_HEFG; 1;
	PF08720; Hema_stalk; 1;
PRINTS	PR00330; HEMAGGLUTN1; 1;
	PR00329; HEMAGGLUTN12; 1;
	PR00331; HEMAGGLUTN2; 1;

General	Signal; -; 1; trigger=yes;
	Transmembrane; -; 1; trigger=yes;
ADD_TOPO_DOMAIN	Extracellular; -; 1; trigger=yes;
	Cytoplasmic; -; 1; trigger=yes;

From: HEMA_I34A1 (P03452)

Key

From

To

Description

Tag

Condition

FTGroup

CHAIN

18

343

Hemagglutinin HA1 chain

CHAIN

344

565

Hemagglutinin HA2 chain

SITE

343

344

Cleavage; by host

R-G

LIPID

554

554

S-palmitoyl cysteine; by host

C

LIPID

561

561

S-palmitoyl cysteine; by host

C

LIPID

564

564

S-palmitoyl cysteine; by host

C

DISULFID

21

480

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

From: HEMA_INCAA (P03465)
CHAIN		15		446		Hemagglutinin-esterase-fusion glycoprotein chain 1
CHAIN		447		655		Hemagglutinin-esterase-fusion glycoprotein chain 2
REGION		15		40		Fusion domain-1
REGION		41		150		Esterase domain-1
REGION		150		310		N-acetyl-9-O-acetylneuraminic acid binding
REGION		310		364		Esterase domain-2
REGION		365		650		Fusion domain-2
ACT_SITE		71		71		Nucleophile
ACT_SITE		366		366		Charge relay system
ACT_SITE		369		369		Charge relay system
DISULFID		20		583		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

Size range	560-655 amino acids
Related rules	None
Fusion	None

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