HEMA_I76A1
ID HEMA_I76A1 Reviewed; 564 AA.
AC P03443;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 2.
DT 23-FEB-2022, entry version 123.
DE RecName: Full=Hemagglutinin {ECO:0000255|HAMAP-Rule:MF_04072};
DE Contains:
DE RecName: Full=Hemagglutinin HA1 chain {ECO:0000255|HAMAP-Rule:MF_04072};
DE Contains:
DE RecName: Full=Hemagglutinin HA2 chain {ECO:0000255|HAMAP-Rule:MF_04072};
DE Flags: Precursor;
GN Name=HA {ECO:0000255|HAMAP-Rule:MF_04072};
OS Influenza A virus (strain A/Duck/Alberta/28/1976 H4N6).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=385638;
OH NCBI_TaxID=8782; Aves.
OH NCBI_TaxID=9823; Sus scrofa (Pig).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=2705304; DOI=10.1016/0042-6822(89)90166-9;
RA Donis R.O., Bean W.J., Kawaoka Y., Webster R.G.;
RT "Distinct lineages of influenza virus H4 hemagglutinin genes in different
RT regions of the world.";
RL Virology 169:408-417(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-101.
RX PubMed=6174976; DOI=10.1073/pnas.78.12.7639;
RA Air G.M.;
RT "Sequence relationships among the hemagglutinin genes of 12 subtypes of
RT influenza A virus.";
RL Proc. Natl. Acad. Sci. U.S.A. 78:7639-7643(1981).
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 of about two third
CC of the virus particles through clathrin-dependent endocytosis and about
CC one third through a clathrin- and caveolin-independent pathway. Plays a
CC major role in the determination of host range restriction and
CC virulence. Class I viral fusion protein. Responsible for penetration of
CC the virus into the cell cytoplasm by mediating the fusion of the
CC membrane of the endocytosed virus particle with the endosomal membrane.
CC Low pH in endosomes induces an irreversible conformational change in
CC HA2, releasing the fusion hydrophobic peptide. Several trimers are
CC required to form a competent fusion pore.
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. {ECO:0000255|HAMAP-Rule:MF_04072}.
CC -!- SUBUNIT: Homotrimer of disulfide-linked HA1-HA2. {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 apical cell membrane {ECO:0000255|HAMAP-
CC Rule:MF_04072}; Single-pass type I membrane protein {ECO:0000255|HAMAP-
CC Rule:MF_04072}. Note=Targeted to the apical plasma membrane in
CC epithelial polarized cells through a signal present in the
CC transmembrane domain. Associated with glycosphingolipid- and
CC cholesterol-enriched detergent-resistant lipid rafts.
CC {ECO:0000255|HAMAP-Rule:MF_04072}.
CC -!- PTM: Palmitoylated. {ECO:0000255|HAMAP-Rule:MF_04072}.
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 Clara cells. {ECO:0000255|HAMAP-Rule:MF_04072}.
CC -!- MISCELLANEOUS: Major glycoprotein, comprises over 80% of the envelope
CC proteins present in virus particle.
CC -!- MISCELLANEOUS: The extent of infection into host organism is determined
CC by HA. Influenza viruses bud from the apical surface of polarized
CC epithelial cells (e.g. bronchial epithelial cells) into lumen of lungs
CC and are therefore usually pneumotropic. The reason is that HA is
CC cleaved by tryptase clara which is restricted to lungs. However, HAs of
CC H5 and H7 pantropic avian viruses subtypes can be cleaved by furin and
CC subtilisin-type enzymes, allowing the virus to grow in other organs
CC than lungs.
CC -!- MISCELLANEOUS: The influenza A genome consist of 8 RNA segments.
CC Genetic variation of hemagglutinin and/or neuraminidase genes results
CC in the emergence of new influenza strains. The mechanism of variation
CC can be the result of point mutations or the result of genetic
CC reassortment between segments of two different strains. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the influenza viruses hemagglutinin family.
CC {ECO:0000255|HAMAP-Rule:MF_04072}.
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DR EMBL; M25287; AAA43220.1; -; Genomic_RNA.
DR EMBL; J02102; AAA43179.1; -; Genomic_RNA.
DR PIR; A04054; HMIVH4.
DR SMR; P03443; -.
DR ABCD; P03443; 1 sequenced antibody.
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:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
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 Gene3D; 3.90.209.20; -; 1.
DR HAMAP; MF_04072; INFV_HEMA; 1.
DR InterPro; IPR008980; Capsid_hemagglutn.
DR InterPro; IPR013828; Hemagglutn_HA1_a/b_dom_sf.
DR InterPro; IPR000149; Hemagglutn_influenz_A.
DR InterPro; IPR001364; Hemagglutn_influenz_A/B.
DR Pfam; PF00509; Hemagglutinin; 1.
DR PRINTS; PR00330; HEMAGGLUTN1.
DR PRINTS; PR00329; HEMAGGLUTN12.
DR SUPFAM; SSF49818; SSF49818; 1.
PE 3: Inferred from homology;
KW Clathrin- and caveolin-independent endocytosis of virus by host;
KW Clathrin-mediated endocytosis of virus by host; Disulfide bond;
KW 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; Lipoprotein;
KW Membrane; Palmitate; 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..16
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CHAIN 17..564
FT /note="Hemagglutinin"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="PRO_0000440446"
FT CHAIN 17..342
FT /note="Hemagglutinin HA1 chain"
FT /id="PRO_0000038904"
FT CHAIN 344..564
FT /note="Hemagglutinin HA2 chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="PRO_0000038905"
FT TOPO_DOM 17..527
FT /note="Extracellular"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT TRANSMEM 528..548
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT TOPO_DOM 549..564
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT SITE 343..344
FT /note="Cleavage; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT LIPID 553
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT LIPID 560
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT LIPID 563
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 18
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 34
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 178
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 310
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 497
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 26..480
FT /note="Interchain (between HA1 and HA2 chains)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 64..291
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 76..88
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 109..151
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 295..319
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 487..491
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CONFLICT 69
FT /note="R -> K (in Ref. 2; AAA43179)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 564 AA; 63382 MW; 808C4BE89E15C94D CRC64;
MLSITILFLL IAEGSSQNYT GNPVICLGHH AVSNGTMVKT LTDDQVEVVT AQELVESQHL
PELCPSPLRL VDGQTCDIVN GALGSPGCDH LNGAEWDVFI ERPTAVDTCY PFDVPDYQSL
RSILANNGKF EFIAEEFQWN TVKQNGKSGA CKRANVNDFF NRLNWLTKSD GDAYPLQNLT
KVNNGDYARL YIWGVHHPST DTEQTNLYKN NPGRVTVSTK TSQTSVVPNI GSRPWVRGQS
GRISFYWTIV EPGDLIVFNT IGNLIAPRGH YKLNSQKKST ILNTAVPIGS CVSKCHTDRG
SISTTKPFQN ISRISIRDCP KYVKQGSLKL ATGMRNIPEK ATRGLFGAIA GFIENGWQGL
IDGWYGFRHQ NAEGTGTAAD LKSTQAAIDQ INGKLNRLIE KTNEKYHQIE KEFEQVEGRI
QDLEKYVEDT KIDLWSYNAE FLVALENQHT IDVTDSEMNK LFERVRRQLR ENAEDKGNGC
FEIFHQCDNN CIESIRNGTY DHDIYRDEAI NNRFQIQGVK LTQGYKDIIL WISFSISCFL
LVALLLAFIL WACQNGNIRC QICI
