ID Q5DL24_9INFA Unreviewed; 564 AA. AC Q5DL24; DT 29-MAR-2005, integrated into UniProtKB/TrEMBL. DT 29-MAR-2005, sequence version 1. DT 27-MAR-2024, entry version 111. DE RecName: Full=Hemagglutinin {ECO:0000256|HAMAP-Rule:MF_04072}; DE Contains: DE RecName: Full=Hemagglutinin HA1 chain {ECO:0000256|HAMAP-Rule:MF_04072}; DE Contains: DE RecName: Full=Hemagglutinin HA2 chain {ECO:0000256|HAMAP-Rule:MF_04072}; GN Name=HA {ECO:0000256|HAMAP-Rule:MF_04072, GN ECO:0000313|EMBL:AAV91214.1}; OS Influenza A virus (A/black-headed gull/Sweden/2/99(H16N3)). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina; OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus; OC Alphainfluenzavirus influenzae; Influenza A virus. OX NCBI_TaxID=304362 {ECO:0000313|EMBL:AAV91214.1}; RN [1] {ECO:0000313|EMBL:AAV91214.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=A/black-headed gull/Sweden/2/99 {ECO:0000313|EMBL:AAV91214.1}; RA Tajne S.S.; RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases. RN [2] {ECO:0000313|EMBL:AAV91214.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=A/black-headed gull/Sweden/2/99 {ECO:0000313|EMBL:AAV91214.1}; RX PubMed=15709000; DOI=10.1128/JVI.79.5.2814-2822.2005; RA Fouchier R.A., Munster V., Wallensten A., Bestebroer T.M., Herfst S., RA Smith D., Rimmelzwaan G.F., Olsen B., Osterhaus A.D.; RT "Characterization of a novel influenza A virus hemagglutinin subtype (H16) RT obtained from black-headed gulls."; RL J. Virol. 79:2814-2822(2005). RN [3] {ECO:0007829|PDB:4F23, ECO:0007829|PDB:4FIU} RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 19-517, GLYCOSYLATION AT ASN-181 RP AND ASN-495, AND DISULFIDE BONDS. RX PubMed=22993148; DOI=10.1128/JVI.01606-12; RA Lu X., Shi Y., Gao F., Xiao H., Wang M., Qi J., Gao G.F.; RT "Insights into avian influenza virus pathogenicity: the hemagglutinin RT precursor HA0 of subtype H16 has an alpha-helix structure in its cleavage RT site with inefficient HA1/HA2 cleavage."; RL J. Virol. 86:12861-12870(2012). 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:0000256|HAMAP-Rule:MF_04072}. 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 {ECO:0000256|RuleBase:RU003324}. CC -!- SUBUNIT: Homotrimer of disulfide-linked HA1-HA2. {ECO:0000256|HAMAP- CC Rule:MF_04072, ECO:0000256|RuleBase:RU003324}. CC -!- SUBCELLULAR LOCATION: Apical cell membrane CC {ECO:0000256|ARBA:ARBA00004247}; Single-pass type I membrane protein CC {ECO:0000256|ARBA:ARBA00004247}. Cell membrane CC {ECO:0000256|ARBA:ARBA00004251}; Single-pass type I membrane protein CC {ECO:0000256|ARBA:ARBA00004251}. Host apical cell membrane CC {ECO:0000256|ARBA:ARBA00004310, ECO:0000256|HAMAP-Rule:MF_04072}; CC Single-pass type I membrane protein {ECO:0000256|ARBA:ARBA00004310, CC ECO:0000256|HAMAP-Rule:MF_04072}. Membrane CC {ECO:0000256|ARBA:ARBA00004479}; Single-pass type I membrane protein CC {ECO:0000256|ARBA:ARBA00004479}. Virion membrane {ECO:0000256|HAMAP- CC Rule:MF_04072}; Single-pass type I membrane protein {ECO:0000256|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:0000256|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:0000256|HAMAP-Rule:MF_04072}. CC -!- PTM: Palmitoylated. {ECO:0000256|HAMAP-Rule:MF_04072}. CC -!- SIMILARITY: Belongs to the influenza viruses hemagglutinin family. CC {ECO:0000256|ARBA:ARBA00006321, ECO:0000256|HAMAP-Rule:MF_04072, CC ECO:0000256|RuleBase:RU003324}. CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of CC feature annotation. {ECO:0000256|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; AY684888; AAV91214.1; -; Genomic_RNA. DR PDB; 4F23; X-ray; 1.70 A; A/B/C=14-519. DR PDB; 4FIU; X-ray; 2.00 A; A/B/C=14-519. DR PDBsum; 4F23; -. DR PDBsum; 4FIU; -. DR SMR; Q5DL24; -. DR GlyCosmos; Q5DL24; 2 sites, No reported glycans. DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell. 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 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 {ECO:0007829|PDB:4F23, ECO:0007829|PDB:4FIU}; KW Clathrin- and caveolin-independent endocytosis of virus by host KW {ECO:0000256|ARBA:ARBA00023261, ECO:0000256|HAMAP-Rule:MF_04072}; KW Clathrin-mediated endocytosis of virus by host KW {ECO:0000256|ARBA:ARBA00022570, ECO:0000256|HAMAP-Rule:MF_04072}; KW Disulfide bond {ECO:0000256|ARBA:ARBA00023157, ECO:0000256|HAMAP- KW Rule:MF_04072}; KW Fusion of virus membrane with host endosomal membrane KW {ECO:0000256|ARBA:ARBA00022510, ECO:0000256|HAMAP-Rule:MF_04072}; KW Fusion of virus membrane with host membrane {ECO:0000256|ARBA:ARBA00022506, KW ECO:0000256|HAMAP-Rule:MF_04072}; KW Glycoprotein {ECO:0000256|ARBA:ARBA00023180, ECO:0000256|HAMAP- KW Rule:MF_04072}; KW Hemagglutinin {ECO:0000256|ARBA:ARBA00022546, ECO:0000256|HAMAP- KW Rule:MF_04072}; KW Host cell membrane {ECO:0000256|ARBA:ARBA00022511, ECO:0000256|HAMAP- KW Rule:MF_04072}; KW Host membrane {ECO:0000256|ARBA:ARBA00022870, ECO:0000256|HAMAP- KW Rule:MF_04072}; KW Host-virus interaction {ECO:0000256|ARBA:ARBA00022581, ECO:0000256|HAMAP- KW Rule:MF_04072}; KW Lipoprotein {ECO:0000256|ARBA:ARBA00023288, ECO:0000256|HAMAP- KW Rule:MF_04072}; KW Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|HAMAP-Rule:MF_04072}; KW Palmitate {ECO:0000256|ARBA:ARBA00023139, ECO:0000256|HAMAP-Rule:MF_04072}; KW Signal {ECO:0000256|HAMAP-Rule:MF_04072}; KW Transmembrane {ECO:0000256|HAMAP-Rule:MF_04072}; KW Transmembrane helix {ECO:0000256|HAMAP-Rule:MF_04072}; KW Viral attachment to host cell {ECO:0000256|ARBA:ARBA00022804, KW ECO:0000256|HAMAP-Rule:MF_04072}; KW Viral envelope protein {ECO:0000256|ARBA:ARBA00022879, ECO:0000256|HAMAP- KW Rule:MF_04072}; KW Viral penetration into host cytoplasm {ECO:0000256|ARBA:ARBA00022595, KW ECO:0000256|HAMAP-Rule:MF_04072}; KW Virion {ECO:0000256|ARBA:ARBA00022844, ECO:0000256|HAMAP-Rule:MF_04072}; KW Virus endocytosis by host {ECO:0000256|ARBA:ARBA00022890, KW ECO:0000256|HAMAP-Rule:MF_04072}; KW Virus entry into host cell {ECO:0000256|ARBA:ARBA00023296, KW ECO:0000256|HAMAP-Rule:MF_04072}. FT TRANSMEM 529..551 FT /note="Helical" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04072" FT SITE 341..342 FT /note="Cleavage; by host" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04072" FT LIPID 553 FT /note="S-palmitoyl cysteine; by host" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04072" FT LIPID 563 FT /note="S-palmitoyl cysteine; by host" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04072" FT CARBOHYD 495 FT /note="N-acetyl-D-glucosamine" FT /evidence="ECO:0007829|PDB:4F23, ECO:0007829|PDB:4FIU" FT CARBOHYD 495 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0007829|PDB:4F23, ECO:0007829|PDB:4FIU" FT DISULFID 22..478 FT /evidence="ECO:0007829|PDB:4F23, ECO:0007829|PDB:4FIU" FT DISULFID 60..289 FT /evidence="ECO:0007829|PDB:4F23, ECO:0007829|PDB:4FIU" FT DISULFID 73..85 FT /evidence="ECO:0000256|HAMAP-Rule:MF_04072, FT ECO:0007829|PDB:4F23" FT DISULFID 108..151 FT /evidence="ECO:0007829|PDB:4F23, ECO:0007829|PDB:4FIU" FT DISULFID 293..317 FT /evidence="ECO:0000256|HAMAP-Rule:MF_04072, FT ECO:0007829|PDB:4F23" FT DISULFID 485..489 FT /evidence="ECO:0000256|HAMAP-Rule:MF_04072, FT ECO:0007829|PDB:4F23" SQ SEQUENCE 564 AA; 63266 MW; 24ECBDF6D2233971 CRC64; MAKTLYLLVL IFVKYSRADK ICIGYLSNNS TDTVDTLTEN GVPVTSSIDL VETNHTGTYC SLNGVSPIHL GDCSFEGWIV GNPSCASNIN IREWSYLIED PNAPHKLCFP GEVDNNGELR HLFSGVNSFS RTELIPPSKW GDILEGTTAS CQNRGANSFY RNLIWLVNKL NKYPVVKGEY NNTTGRDVLV LWGIHHPDTE ATANKLYVNK NPYTLVSTKE WSRRYELEIG TRIGDGQRSW MKIYWHLMHP GERITFESSG GLLAPRYGYI IEKYGTGRIF QSGVRLAKCN TKCQTSMGGI NTNKTFQNIE RNALGDCPKY IKSGQLKLAT GLRNVPSIVE RGLFGAIAGF IEGGWPGLIN GWYGFQHQNE QGTGIAADKT STQKAINEIT TKINNIIEKM NGNYDSIRGE FNQVEKRINM IADRVDDAVT DIWSYNAKLL VLIENDRTLD LHDANVRNLH EQIKRALKDN AIDEGDGCFS ILHKCNDSCM ETIRNGTYNH EDYKEESQLK RQEIEGIKLK TEDNVYKILS IYSCIASSVV LVGLILAFIL WACSSGNCRF NVCI //