ID HEMA_I78A9 Reviewed; 550 AA. AC P11133; Q84019; Q84020; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 15-JUL-1998, sequence version 2. DT 08-NOV-2023, entry version 121. 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; Fragment; GN Name=HA {ECO:0000255|HAMAP-Rule:MF_04072}; OS Influenza A virus (strain A/Swine/Hong Kong/81/1978 H3N2). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina; OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus; OC Alphainfluenzavirus influenzae; Influenza A virus. OX NCBI_TaxID=384484; OH NCBI_TaxID=8782; Aves. OH NCBI_TaxID=9721; Cetacea (whales). OH NCBI_TaxID=9606; Homo sapiens (Human). OH NCBI_TaxID=9709; Phocidae (true seals). OH NCBI_TaxID=9823; Sus scrofa (Pig). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=3336940; DOI=10.1016/0042-6822(88)90405-9; RA Kida H., Shortridge K.F., Webster R.G.; RT "Origin of the hemagglutinin gene of H3N2 influenza viruses from pigs in RT China."; RL Virology 162:160-166(1988). 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 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. 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; M19057; AAA43212.1; -; Genomic_RNA. DR PIR; B29971; HMIVS3. DR PDB; 1R5I; X-ray; 2.60 A; C/G=306-318. DR PDBsum; 1R5I; -. DR SMR; P11133; -. DR GlyCosmos; P11133; 6 sites, No reported glycans. DR EvolutionaryTrace; P11133; -. DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW. DR GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW. DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell. DR GO; GO:0046789; F:host cell surface receptor binding; IEA:InterPro. DR GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-KW. DR GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW. DR GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:InterPro. 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 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 1: Evidence at protein level; KW 3D-structure; 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; 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 CHAIN 1..329 FT /note="Hemagglutinin HA1 chain" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT /id="PRO_0000440842" FT CHAIN 330..550 FT /note="Hemagglutinin HA2 chain" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT /id="PRO_0000039076" FT TOPO_DOM 1..514 FT /note="Extracellular" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT TRANSMEM 515..535 FT /note="Helical" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT TOPO_DOM 536..550 FT /note="Cytoplasmic" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT SITE 329..330 FT /note="Cleavage; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT LIPID 539 FT /note="S-palmitoyl cysteine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT LIPID 546 FT /note="S-palmitoyl cysteine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT LIPID 549 FT /note="S-palmitoyl cysteine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 8 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 22 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 38 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 165 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 285 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT CARBOHYD 483 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT DISULFID 14..466 FT /note="Interchain (between HA1 and HA2 chains)" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT DISULFID 52..277 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT DISULFID 64..76 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT DISULFID 97..139 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT DISULFID 281..305 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT DISULFID 473..477 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072" FT NON_TER 1 SQ SEQUENCE 550 AA; 61437 MW; 1F2A7E758C531CE8 CRC64; QDLPGTDNST ATLCLGHHAV PNGTIVKTIT DDQIEVTNAT ELVQSSSTGK ICNNPHKILD GIDCTLIDAL LGDPHCDVFQ DETWDLFVER SNAFSNCYPY DVPDYASLRS LVASSGTLEF ITEGFTWTGV TQNGGSNACK RGPANGFFSR LNWLTKSGST YPVLNVTMPN NDNSDKLYIW GVHHPSTNQE QTNLYVQASG RVTVSTKRSQ QTMIPNAGSR PWVRGLSSRI SIYWTIVKPG DILVINSNGN LIAPRGYFKM RTGKSSIMRS DAPIGTCSSE CITPNGSIPN DKPFQNVNKI TYGACPKYVK QNTLKLATGM RNVPEKQTRG LFGAIAGFIE NGWEGMIDGW YGFRHQNSEG TGQAADLKST QAAIDLINGK VNRVIEKTNE KFHQIEKEFS EVEGRIQDLE KYVEDTKIDL WSYNADVLVA LENQHTIDLT DSEMNKLFEK TRRQLRENAE DMGNGCFKIY HKCDNACIES IRNGTYDHDI YRDEALNNRF QIKGVELKSG YKDWILWISF AISCFLLCVV LLGFIMWACQ RGNIRCNICI //