ID HEMA_I59A0 Reviewed; 564 AA. AC P09345; Q0A2H6; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 13-NOV-2007, sequence version 2. DT 09-JAN-2013, entry version 97. DE RecName: Full=Hemagglutinin; DE Contains: DE RecName: Full=Hemagglutinin HA1 chain; DE Contains: DE RecName: Full=Hemagglutinin HA2 chain; DE Flags: Precursor; GN Name=HA; OS Influenza A virus (strain A/Chicken/Scotland/1959 H5N1). OC Viruses; ssRNA negative-strand viruses; Orthomyxoviridae; OC Influenzavirus A. OX NCBI_TaxID=402527; OH NCBI_TaxID=8782; Aves. OH NCBI_TaxID=9685; Felis catus (Cat) (Felis silvestris catus). OH NCBI_TaxID=9606; Homo sapiens (Human). OH NCBI_TaxID=9691; Panthera pardus (Leopard). OH NCBI_TaxID=9694; Panthera tigris (Tiger). OH NCBI_TaxID=9823; Sus scrofa (Pig). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX MEDLINE=88234030; PubMed=3375087; DOI=10.1093/nar/16.9.4181; RA De B.K., Brownlee G.G., Kendal A.P., Shaw M.W.; RT "Complete sequence of a cDNA clone of the hemagglutinin gene of RT influenza A/Chicken/Scotland/59 (H5N1) virus: comparison with RT contemporary North American and European strains."; RL Nucleic Acids Res. 16:4181-4182(1988). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=16439620; DOI=10.1126/science.1121586; RA Obenauer J.C., Denson J., Mehta P.K., Su X., Mukatira S., RA Finkelstein D.B., Xu X., Wang J., Ma J., Fan Y., Rakestraw K.M., RA Webster R.G., Hoffmann E., Krauss S., Zheng J., Zhang Z., Naeve C.W.; RT "Large-scale sequence analysis of avian influenza isolates."; RL Science 311:1576-1580(2006). CC -!- FUNCTION: Binds to sialic acid-containing receptors on the cell CC surface, bringing about the attachment of the virus particle to CC the cell. This attachment induces virion internalization of about CC two third of the virus particles through clathrin-dependent CC endocytosis and about one third through a clathrin- and caveolin- CC independent pathway. Plays a major role in the determination of CC host range restriction and virulence. Class I viral fusion CC protein. Responsible for penetration of the virus into the cell CC cytoplasm by mediating the fusion of the membrane of the CC endocytosed virus particle with the endosomal membrane. Low pH in CC endosomes induces an irreversible conformational change in HA2, CC releasing the fusion hydrophobic peptide. Several trimers are CC required to form a competent fusion pore. CC -!- SUBUNIT: Homotrimer of disulfide-linked HA1-HA2. CC -!- SUBCELLULAR LOCATION: Virion membrane; Single-pass type I membrane CC protein (Potential). Host apical cell membrane; Single-pass type I CC membrane protein. 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 -!- 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 CC identified protease that may be involved in this process is CC secreted in lungs by Clara cells (By similarity). CC -!- PTM: Palmitoylated (By similarity). CC -!- MISCELLANEOUS: Major glycoprotein, comprises over 80% of the CC envelope proteins present in virus particle. CC -!- MISCELLANEOUS: The extent of infection into host organism is CC determined by HA. Influenza viruses bud from the apical surface of CC polarized epithelial cells (e.g. bronchial epithelial cells) into CC lumen of lungs and are therefore usually pneumotropic. The reason CC is that HA is cleaved by tryptase clara which is restricted to CC lungs. However, HAs of H5 and H7 pantropic avian viruses subtypes CC can be cleaved by furin and subtilisin-type enzymes, allowing the CC virus to grow in other organs than lungs. CC -!- MISCELLANEOUS: The influenza A genome consist of 8 RNA segments. CC Genetic variation of hemagglutinin and/or neuraminidase genes CC results in the emergence of new influenza strains. The mechanism CC of variation can be the result of point mutations or the result of CC genetic reassortment between segments of two different strains. CC -!- SIMILARITY: Belongs to the influenza viruses hemagglutinin family. 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; X07826; CAA30680.1; -; Genomic_RNA. DR EMBL; X07869; CAA30719.1; -; mRNA. DR EMBL; CY015081; ABI85106.1; -; Genomic_RNA. DR ProteinModelPortal; P09345; -. DR SMR; P09345; 17-337, 343-516. DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016021; C:integral to 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:0019062; P:viral attachment to host cell; IEA:UniProtKB-KW. DR GO; GO:0075512; P:viral entry into host cell via clathrin-mediated endocytosis; IEA:UniProtKB-KW. DR GO; GO:0019064; P:viral entry into host cell via membrane fusion with the plasma membrane; IEA:InterPro. DR Gene3D; 3.90.209.20; Haemagglutn_HA1_a/b; 1. DR Gene3D; 2.10.77.10; Haemagglutn_HA1_b-ribbon; 1. DR Gene3D; 3.90.20.10; Haemagglutn_stalk; 1. DR InterPro; IPR008980; Capsid_hemagglutn. DR InterPro; IPR013828; Hemagglutn_HA1_a/b_dom. DR InterPro; IPR013827; Hemagglutn_HA1_b-rbn_dom. DR InterPro; IPR000149; Hemagglutn_influenz_A. DR InterPro; IPR001364; Hemagglutn_influenz_A/B. DR InterPro; IPR013829; Hemagglutn_stalk. DR Pfam; PF00509; Hemagglutinin; 1. DR PRINTS; PR00330; HEMAGGLUTN1. DR PRINTS; PR00329; HEMAGGLUTN12. DR SUPFAM; SSF49818; Capsid_hemag; 1. PE 2: Evidence at transcript level; KW Clathrin- and caveolin-independent endocytosis of virus by host; KW Clathrin-mediated endocytosis of virus by host; KW Cleavage on pair of basic residues; Complete proteome; Disulfide bond; KW Fusion of virus membrane with host endosomal membrane; KW Fusion of virus membrane with host membrane; Glycoprotein; KW Hemagglutinin; Host cell membrane; Host membrane; KW Host-virus interaction; Lipoprotein; Membrane; Palmitate; Signal; KW Transmembrane; Transmembrane helix; Viral attachment to host cell; KW Viral envelope protein; Viral penetration into host cytoplasm; Virion; KW Virus endocytosis by host; Virus entry into host cell. FT SIGNAL 1 16 Potential. FT CHAIN 17 338 Hemagglutinin HA1 chain. FT /FTId=PRO_0000038899. FT PROPEP 339 342 Connecting peptide. FT /FTId=PRO_0000392211. FT CHAIN 343 564 Hemagglutinin HA2 chain. FT /FTId=PRO_0000038900. FT TOPO_DOM 17 527 Extracellular (Potential). FT TRANSMEM 528 548 Helical; (Potential). FT TOPO_DOM 549 564 Cytoplasmic (Potential). FT SITE 342 343 Cleavage; by host (By similarity). FT LIPID 553 553 S-palmitoyl cysteine; by host (By FT similarity). FT LIPID 560 560 S-palmitoyl cysteine; by host (By FT similarity). FT LIPID 563 563 S-palmitoyl cysteine; by host (By FT similarity). FT CARBOHYD 26 26 N-linked (GlcNAc...); by host FT (Potential). FT CARBOHYD 39 39 N-linked (GlcNAc...); by host FT (Potential). FT CARBOHYD 181 181 N-linked (GlcNAc...); by host FT (Potential). FT CARBOHYD 302 302 N-linked (GlcNAc...); by host FT (Potential). FT CARBOHYD 496 496 N-linked (GlcNAc...); by host FT (Potential). FT DISULFID 20 479 Interchain (between HA1 and HA2 chains) FT (By similarity). FT DISULFID 58 290 By similarity. FT DISULFID 71 83 By similarity. FT DISULFID 106 151 By similarity. FT DISULFID 294 318 By similarity. FT DISULFID 486 490 By similarity. FT CONFLICT 89 89 V -> L (in Ref. 1; CAA30719/CAA30680). FT CONFLICT 93 93 S -> L (in Ref. 1; CAA30719/CAA30680). FT CONFLICT 119 119 H -> Y (in Ref. 1; CAA30719/CAA30680). FT CONFLICT 131 131 Q -> R (in Ref. 1; CAA30719/CAA30680). FT CONFLICT 160 160 F -> L (in Ref. 1; CAA30719/CAA30680). FT CONFLICT 170 172 DNA -> NNT (in Ref. 1; CAA30719/ FT CAA30680). FT CONFLICT 267 267 E -> R (in Ref. 1; CAA30719/CAA30680). FT CONFLICT 300 300 A -> E (in Ref. 1; CAA30719/CAA30680). FT CONFLICT 404 406 QFK -> RFE (in Ref. 1; CAA30719/ FT CAA30680). FT CONFLICT 458 458 K -> N (in Ref. 1; CAA30719/CAA30680). SQ SEQUENCE 564 AA; 63671 MW; 5C57790D6B76255F CRC64; MERIVLLLAI VSLVKSDQIC IGYHANKSTK QVDTIMEKNV TVTHAQDILE RTHNGKLCSL NGVKPLILRD CSVAGWLLGN PMCDEFLNVP EWSYIVEKDN PINSLCYPGD FNDYEELKHL LSSTNHFEKI QIIPRSSWSN HDASSGVSSA CPYIGRSSFF RNVVWLIKKD NAYPTIKRSY NNTNQEDLLI LWGIHHPNDA AEQTKLYQNP TTYVSVGTST LNQRSIPEIA TRPKVNGQSG RMEFFWTILK PNDAINFESN GNFIAPEYAY KIVKKGDSAI MKSGLAYGNC DTKCQTPVGA INSSMPFHNI HPHTIGECPK YVKSDRLVLA TGLRNVPQRK KRGLFGAIAG FIEGGWQGMV DGWYGYHHSN EQGSGYAADK ESTQKAIDGI TNKVNSIIDK MNTQFKAVGK EFNNLERRVE NLNKKMEDGF LDVWTYNVEL LVLMENERTL DFHDSNVKNL YDKVRLQLKD NARELGNGCF EFYHKCDNEC MESVRNGTYD YPQYSEEARL NREEISGVKL ESMGVYQILS IYSTVASSLA LAIMIAGLSF WMCSNGSLQC RICI //