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O56140

- HEMA_I97A1

UniProt

O56140 - HEMA_I97A1

Protein

Hemagglutinin

Gene

HA

Organism
Influenza A virus (strain A/Hong Kong/156/1997 H5N1 genotype Gs/Gd)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 90 (01 Oct 2014)
      Sequence version 2 (24 Jan 2006)
      Previous versions | rss
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    Functioni

    Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. This attachment induces virion internalization of about two third of the virus particles through clathrin-dependent endocytosis and about one third through a clathrin- and caveolin-independent pathway. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in HA2, releasing the fusion hydrophobic speptide. Several trimers are required to form a competent fusion pore.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei346 – 3472Cleavage; by host

    GO - Biological processi

    1. clathrin-mediated endocytosis of virus by host cell Source: UniProtKB-KW
    2. fusion of virus membrane with host endosome membrane Source: UniProtKB-KW
    3. fusion of virus membrane with host plasma membrane Source: InterPro
    4. virion attachment to host cell Source: UniProtKB-KW

    Keywords - Molecular functioni

    Hemagglutinin

    Keywords - Biological processi

    Clathrin- and caveolin-independent endocytosis of virus by host, Clathrin-mediated endocytosis of virus by host, Fusion of virus membrane with host endosomal membrane, Fusion of virus membrane with host membrane, Host-virus interaction, Viral attachment to host cell, Viral penetration into host cytoplasm, Virus endocytosis by host, Virus entry into host cell

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Hemagglutinin
    Cleaved into the following 2 chains:
    Gene namesi
    Name:HA
    OrganismiInfluenza A virus (strain A/Hong Kong/156/1997 H5N1 genotype Gs/Gd)
    Taxonomic identifieri130763 [NCBI]
    Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
    Virus hostiAves [TaxID: 8782]
    Felis catus (Cat) (Felis silvestris catus) [TaxID: 9685]
    Homo sapiens (Human) [TaxID: 9606]
    Panthera pardus (Leopard) (Felis pardus) [TaxID: 9691]
    Panthera tigris (Tiger) [TaxID: 9694]
    Sus scrofa (Pig) [TaxID: 9823]
    ProteomesiUP000008587: Genome

    Subcellular locationi

    Virion membrane Curated; Single-pass type I membrane protein Curated. Host apical cell membrane; Single-pass type I membrane protein
    Note: Targeted to the apical plasma membrane in epithelial polarized cells through a signal present in the transmembrane domain. Associated with glycosphingolipid- and cholesterol-enriched detergent-resistant lipid rafts.

    GO - Cellular componenti

    1. host cell plasma membrane Source: UniProtKB-SubCell
    2. integral component of membrane Source: UniProtKB-KW
    3. viral envelope Source: UniProtKB-KW
    4. virion membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Host cell membrane, Host membrane, Membrane, Viral envelope protein, Virion

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1616Sequence AnalysisAdd
    BLAST
    Chaini17 – 338322Hemagglutinin HA1 chainPRO_0000043412Add
    BLAST
    Propeptidei339 – 3468Connecting peptidePRO_0000392214
    Chaini347 – 568222Hemagglutinin HA2 chainPRO_0000043413Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi20 ↔ 483Interchain (between HA1 and HA2 chains)By similarity
    Glycosylationi26 – 261N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi27 – 271N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi39 – 391N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi58 ↔ 290By similarity
    Disulfide bondi71 ↔ 83By similarity
    Disulfide bondi106 ↔ 151By similarity
    Glycosylationi181 – 1811N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi294 ↔ 318By similarity
    Glycosylationi302 – 3021N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi490 ↔ 494By similarity
    Glycosylationi500 – 5001N-linked (GlcNAc...); by hostSequence Analysis
    Lipidationi557 – 5571S-palmitoyl cysteine; by hostBy similarity
    Lipidationi564 – 5641S-palmitoyl cysteine; by hostBy similarity
    Lipidationi567 – 5671S-palmitoyl cysteine; by hostBy similarity

    Post-translational modificationi

    In natural infection, inactive HA is matured into HA1 and HA2 outside the cell by one or more trypsin-like, arginine-specific endoprotease secreted by the bronchial epithelial cells. One identified protease that may be involved in this process is secreted in lungs by Clara cells By similarity.By similarity
    Palmitoylated.By similarity

    Keywords - PTMi

    Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

    Interactioni

    Subunit structurei

    Homotrimer of disulfide-linked HA1-HA2.

    Structurei

    3D structure databases

    ProteinModelPortaliO56140.
    SMRiO56140. Positions 17-337, 347-520.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini17 – 531515ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini553 – 56816CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei532 – 55221HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Family and domain databases

    Gene3Di2.10.77.10. 1 hit.
    3.90.20.10. 1 hit.
    3.90.209.20. 1 hit.
    InterProiIPR008980. Capsid_hemagglutn.
    IPR013828. Hemagglutn_HA1_a/b_dom.
    IPR013827. Hemagglutn_HA1_b-rbn_dom.
    IPR000149. Hemagglutn_influenz_A.
    IPR001364. Hemagglutn_influenz_A/B.
    IPR013829. Hemagglutn_stalk.
    [Graphical view]
    PfamiPF00509. Hemagglutinin. 1 hit.
    [Graphical view]
    PRINTSiPR00330. HEMAGGLUTN1.
    PR00329. HEMAGGLUTN12.
    SUPFAMiSSF49818. SSF49818. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    O56140-1 [UniParc]FASTAAdd to Basket

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    MEKTVLLLAT VSLVKSDQIC IGYHANNSTE QVDTIMEKNV TVTHAQDILE    50
    RTHNGKLCDL NGVKPLILRD CSVAGWLLGN PMCDEFINVP EWSYIVEKAS 100
    PANDLCYPGN FNDYEELKHL LSRINHFEKI QIIPKSSWSN HDASSGVSSA 150
    CPYLGRSSFF RNVVWLIKKN SAYPTIKRSY NNTNQEDLLV LWGIHHPNDA 200
    AEQTKLYQNP TTYISVGTST LNQRLVPEIA TRPKVNGQSG RMEFFWTILK 250
    PNDAINFESN GNFIAPEYAY KIVKKGDSTI MKSELEYGNC NTKCQTPMGA 300
    INSSMPFHNI HPLTIGECPK YVKSNRLVLA TGLRNTPQRE RRRKKRGLFG 350
    AIAGFIEGGW QGMVDGWYGY HHSNEQGSGY AADKESTQKA IDGVTNKVNS 400
    IINKMNTQFE AVGREFNNLE RRIENLNKKM EDGFLDVWTY NAELLVLMEN 450
    ERTLDFHDSN VKNLYDKVRL QLRDNAKELG NGCFEFYHKC DNECMESVKN 500
    GTYDYPQYSE EARLNREEIS GVKLESMGTY QILSIYSTVA SSLALAIMVA 550
    GLSLWMCSNG SLQCRICI 568
    Length:568
    Mass (Da):64,277
    Last modified:January 24, 2006 - v2
    Checksum:iD99BD1729B730A40
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti3 – 31K → R in AAC40508. (PubMed:9482438)Curated
    Sequence conflicti194 – 1941I → V in AAC40508. (PubMed:9482438)Curated
    Sequence conflicti379 – 3813GYA → CYS in AAC40508. (PubMed:9482438)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF028709 mRNA. Translation: AAC40508.1.
    AF046088 Genomic RNA. Translation: AAC32088.1.
    AF036356 Genomic RNA. Translation: AAC34263.1.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF028709 mRNA. Translation: AAC40508.1 .
    AF046088 Genomic RNA. Translation: AAC32088.1 .
    AF036356 Genomic RNA. Translation: AAC34263.1 .

    3D structure databases

    ProteinModelPortali O56140.
    SMRi O56140. Positions 17-337, 347-520.
    ModBasei Search...
    MobiDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Family and domain databases

    Gene3Di 2.10.77.10. 1 hit.
    3.90.20.10. 1 hit.
    3.90.209.20. 1 hit.
    InterProi IPR008980. Capsid_hemagglutn.
    IPR013828. Hemagglutn_HA1_a/b_dom.
    IPR013827. Hemagglutn_HA1_b-rbn_dom.
    IPR000149. Hemagglutn_influenz_A.
    IPR001364. Hemagglutn_influenz_A/B.
    IPR013829. Hemagglutn_stalk.
    [Graphical view ]
    Pfami PF00509. Hemagglutinin. 1 hit.
    [Graphical view ]
    PRINTSi PR00330. HEMAGGLUTN1.
    PR00329. HEMAGGLUTN12.
    SUPFAMi SSF49818. SSF49818. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus."
      Claas E.C.J., Osterhaus A.D., van Beek R., De Jong J.C., Rimmelzwaan G.F., Senne D.A., Krauss S., Shortridge K.F., Webster R.G.
      Lancet 351:472-477(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Comparisons of highly virulent H5N1 influenza A viruses isolated from humans and chickens from Hong Kong."
      Suarez D.L., Perdue M.L., Cox N., Rowe T., Bender C., Huang J., Swayne D.E.
      J. Virol. 72:6678-6688(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    3. "Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness."
      Subbarao K., Klimov A., Katz J., Regnery H., Lim W., Hall H., Perdue M., Swayne D., Bender C., Huang J., Hemphill M., Rowe T., Shaw M., Xu X., Fukuda K., Cox N.
      Science 279:393-396(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 17-568.

    Entry informationi

    Entry nameiHEMA_I97A1
    AccessioniPrimary (citable) accession number: O56140
    Secondary accession number(s): O56262, Q9WAA0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 6, 2005
    Last sequence update: January 24, 2006
    Last modified: October 1, 2014
    This is version 90 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programViral Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Major glycoprotein, comprises over 80% of the envelope proteins present in virus particle.
    The extent of infection into host organism is determined by HA. Influenza viruses bud from the apical surface of polarized epithelial cells (e.g. bronchial epithelial cells) into lumen of lungs and are therefore usually pneumotropic. The reason is that HA is cleaved by tryptase clara which is restricted to lungs. However, HAs of H5 and H7 pantropic avian viruses subtypes can be cleaved by furin and subtilisin-type enzymes, allowing the virus to grow in other organs than lungs.
    The influenza A genome consist of 8 RNA segments. Genetic variation of hemagglutinin and/or neuraminidase genes results in the emergence of new influenza strains. The mechanism of variation can be the result of point mutations or the result of genetic reassortment between segments of two different strains.

    Keywords - Technical termi

    Complete proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3