ID HEMA_I45A0 Reviewed; 566 AA. AC A4U6V2; DT 05-MAY-2009, integrated into UniProtKB/Swiss-Prot. DT 15-MAY-2007, sequence version 1. DT 08-NOV-2023, entry version 71. 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/USA:Huston/AA/1945 H1N1). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina; OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus; OC Alphainfluenzavirus influenzae; Influenza A virus. OX NCBI_TaxID=425551; OH NCBI_TaxID=8782; Aves. OH NCBI_TaxID=9606; Homo sapiens (Human). OH NCBI_TaxID=9823; Sus scrofa (Pig). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RA Ghedin E., Spiro D., Miller N., Zaborsky J., Feldblyum T., Subbu V., RA Shumway M., Sparenborg J., Groveman L., Halpin R., Sitz J., Koo H., RA Salzberg S.L., Webster R.G., Hoffmann E., Krauss S., Naeve C., Bao Y., RA Bolotov P., Dernovoy D., Kiryutin B., Lipman D.J., Tatusova T.; RT "The NIAID influenza genome sequencing project."; RL Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RG The NIAID Influenza Genome Sequencing Consortium; RL Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases. 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. Interacts with human CC CACNA1C. {ECO:0000250|UniProtKB:Q289M7}. 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 club 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; CY021709; ABP49327.1; -; Viral_cRNA. DR SMR; A4U6V2; -. DR GlyCosmos; A4U6V2; 9 sites, No reported glycans. DR PRO; PR:A4U6V2; -. DR Proteomes; UP000008433; Genome. DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C: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; 3.90.20.10; -; 1. DR Gene3D; 3.90.209.20; -; 1. DR Gene3D; 2.10.77.10; Hemagglutinin Chain A, Domain 2; 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; SSF58064; Influenza hemagglutinin (stalk); 1. DR SUPFAM; SSF49818; Viral protein domain; 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..17 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CHAIN 18..566 FT /note="Hemagglutinin" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT /id="PRO_0000440382" FT CHAIN 18..343 FT /note="Hemagglutinin HA1 chain" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT /id="PRO_0000372881" FT CHAIN 345..566 FT /note="Hemagglutinin HA2 chain" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT /id="PRO_0000372882" FT TOPO_DOM 18..529 FT /note="Extracellular" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT TRANSMEM 530..550 FT /note="Helical" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT TOPO_DOM 551..566 FT /note="Cytoplasmic" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT SITE 344..345 FT /note="Cleavage; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT LIPID 555 FT /note="S-palmitoyl cysteine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT LIPID 562 FT /note="S-palmitoyl cysteine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT LIPID 565 FT /note="S-palmitoyl cysteine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 27 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 28 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 40 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 104 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 144 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 179 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 286 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 304 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 498 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT DISULFID 21..481 FT /note="Interchain (between HA1 and HA2 chains)" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT DISULFID 59..292 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT DISULFID 72..84 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT DISULFID 107..153 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT DISULFID 296..320 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT DISULFID 488..492 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" SQ SEQUENCE 566 AA; 63573 MW; 2F0468D2817E18AD CRC64; MKARLLVLLC ALAATDADTI CIGYHANNST DTVDTVLEKN VTVTHSVNLL EDSHNGKLCR LKGIAPLQLR KCNIAGWILG NPECESLLSE RSWSYIVETP NSENGTCYPG DFTNYEELRE QLSSVSSFER FEIFPKESSW PKHNTTRGVT AACSHAGKSS FYRNLLWLTE KDGSYPNLNN SYVNKKGKEV LVLWGVHHPS NIKDQQTLYQ KENAYVSVVS SNYNRRFTPE IAERPKVRGQ AGRMNYYWTL LKPGDTIMFE ANGNLIAPWY AFALSRGFGS GIITSNASMH ECDTKCQTPQ GAINSSLPFQ NIHPVTIGEC PKYVRSTKLR MVTGLRNIPS IQSRGLFGAI AGFIEGGWTG MIDGWYGYHH QNEQGSGYAA DQKSTQNAIN GITNKVNSVI EKMNTQFTAV GKEFNNLEKR MENLNKKVDD GFLDIWTYNA ELLILLENER TLDFHDSNVK NLYEKVKSQL RNNAKEIGNG CFEFYHKCNN ECMESVKNGT YDYPKYSEES KLNREKIDGV KLESMGVYQI LAIYSTVASS LVLLVSLGAI SFWMCSNGSL QCRICI //