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P04664

- HEMA_I69A0

UniProt

P04664 - HEMA_I69A0

Protein

Hemagglutinin

Gene

HA

Organism
Influenza A virus (strain A/England/878/1969 H3N2)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 99 (01 Oct 2014)
      Sequence version 1 (13 Aug 1987)
      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 peptide. Several trimers are required to form a competent fusion pore.

    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 chain:
    Gene namesi
    Name:HA
    OrganismiInfluenza A virus (strain A/England/878/1969 H3N2)
    Taxonomic identifieri387147 [NCBI]
    Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
    Virus hostiAves [TaxID: 8782]
    Homo sapiens (Human) [TaxID: 9606]
    Mysticeti (baleen whales) [TaxID: 9761]
    Phocidae (true seals) [TaxID: 9709]
    Sus scrofa (Pig) [TaxID: 9823]

    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
    Chaini1 – 328328Hemagglutinin HA1 chainPRO_0000038948Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi8 – 81N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi22 – 221N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi38 – 381N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi52 ↔ 277By similarity
    Glycosylationi63 – 631N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi64 ↔ 76By similarity
    Disulfide bondi97 ↔ 139By similarity
    Glycosylationi165 – 1651N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi281 ↔ 305By similarity
    Glycosylationi285 – 2851N-linked (GlcNAc...); by hostSequence Analysis

    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

    Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

    Interactioni

    Subunit structurei

    Homotrimer of disulfide-linked HA1-HA2.

    Structurei

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1DLHX-ray2.80C/F306-318[»]
    2G9HX-ray2.00C306-318[»]
    ProteinModelPortaliP04664.
    SMRiP04664. Positions 1-328.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP04664.

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane

    Family and domain databases

    Gene3Di2.10.77.10. 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.
    [Graphical view]
    PfamiPF00509. Hemagglutinin. 1 hit.
    [Graphical view]
    PRINTSiPR00330. HEMAGGLUTN1.
    PR00329. HEMAGGLUTN12.
    SUPFAMiSSF49818. SSF49818. 1 hit.

    Sequencei

    Sequence statusi: Fragment.

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

    P04664-1 [UniParc]FASTAAdd to Basket

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    QDLPGNDNST ATLCLGHHAV PNGTLVKTIT NDQIEVTNAT ELVQSSSTGK    50
    ICNNPHRILD GINCTLIDAL LGDPHCDVFQ DETWDLFVER SKAFSNCYPY 100
    DVPDYASLRS LVASSGTLEF ITEGFTWTGV TQNGGSNACK RGPDSGFFSR 150
    LNWLTKSGST YPVLNVTMPN NDNFDKLYIW GVHHPSTNQE QTSLYVQASG 200
    RVTVSTRRSQ QTIIPNIGSR PWVRGLSSRI SIYWTIVKPG DVLVINSNGN 250
    LIAPRGYFKM RTGKSSIMRS DAPIDTCISE CITPNGSIPN DKPFQNVNKI 300
    TYGACPKYVK QNTLKLATGM RNVPEKQT 328
    Length:328
    Mass (Da):36,073
    Last modified:August 13, 1987 - v1
    Checksum:i9C3A86B3A8D856FE
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Non-terminal residuei1 – 11
    Non-terminal residuei328 – 3281

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    K03335 Genomic RNA. Translation: AAA43184.1.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    K03335 Genomic RNA. Translation: AAA43184.1 .

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1DLH X-ray 2.80 C/F 306-318 [» ]
    2G9H X-ray 2.00 C 306-318 [» ]
    ProteinModelPortali P04664.
    SMRi P04664. Positions 1-328.
    ModBasei Search...
    MobiDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Miscellaneous databases

    EvolutionaryTracei P04664.

    Family and domain databases

    Gene3Di 2.10.77.10. 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.
    [Graphical view ]
    Pfami PF00509. Hemagglutinin. 1 hit.
    [Graphical view ]
    PRINTSi PR00330. HEMAGGLUTN1.
    PR00329. HEMAGGLUTN12.
    SUPFAMi SSF49818. SSF49818. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "Antigenic drift in the hemagglutinin of the Hong Kong influenza subtype: correlation of amino acid changes with alterations in viral antigenicity."
      Sleigh M.J., Both G.W., Underwood P.A., Bender V.J.
      J. Virol. 37:845-853(1981) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    2. "Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide."
      Stern L.J., Brown J.H., Jardetzky T.J., Gorga J.C., Urban R.G., Strominger J.L., Wiley D.C.
      Nature 368:215-221(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 306-318.

    Entry informationi

    Entry nameiHEMA_I69A0
    AccessioniPrimary (citable) accession number: P04664
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 13, 1987
    Last sequence update: August 13, 1987
    Last modified: October 1, 2014
    This is version 99 of the entry and version 1 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

    3D-structure

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3