ID   HEMA_I60A0              Reviewed;         339 AA.
AC   Q9IFF7;
DT   26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   29-SEP-2021, entry version 91.
DE   RecName: Full=Hemagglutinin;
DE   Contains:
DE     RecName: Full=Hemagglutinin HA1 chain;
DE   Flags: Precursor; Fragment;
GN   Name=HA;
OS   Influenza A virus (strain A/Ann Arbor/6/1960 H2N2).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC   Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX   NCBI_TaxID=384498;
OH   NCBI_TaxID=8782; Aves.
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=10954551; DOI=10.1128/jvi.74.18.8502-8512.2000;
RA   Matrosovich M., Tuzikov A., Bovin N., Gambaryan A., Klimov A.,
RA   Castrucci M.R., Donatelli I., Kawaoka Y.;
RT   "Early alterations of the receptor-binding properties of H1, H2, and H3
RT   avian influenza virus hemagglutinins after their introduction into
RT   mammals.";
RL   J. Virol. 74:8502-8512(2000).
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 (By similarity).
CC       {ECO:0000250}.
CC   -!- SUBUNIT: Homotrimer of disulfide-linked HA1-HA2. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000305}; Single-pass type I
CC       membrane protein {ECO:0000305}. Host apical cell membrane; Single-pass
CC       type I 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 (By similarity).
CC       {ECO:0000250}.
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       Clara cells (By similarity). {ECO:0000250}.
CC   -!- PTM: Palmitoylated. {ECO:0000250}.
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:0000305}.
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DR   EMBL; AF270721; AAF82105.1; -; Genomic_RNA.
DR   SMR; Q9IFF7; -.
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; 3.90.209.20; -; 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; SSF49818; SSF49818; 1.
PE   3: Inferred from homology;
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; Signal; 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..15
FT                   /evidence="ECO:0000255"
FT   CHAIN           16..339
FT                   /note="Hemagglutinin HA1 chain"
FT                   /id="PRO_0000318719"
FT   TOPO_DOM        16..>339
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        25
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        26
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        38
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        179
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        180
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        300
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   DISULFID        57..288
FT                   /evidence="ECO:0000250"
FT   DISULFID        70..82
FT                   /evidence="ECO:0000250"
FT   DISULFID        105..149
FT                   /evidence="ECO:0000250"
FT   DISULFID        292..316
FT                   /evidence="ECO:0000250"
FT   NON_TER         339
SQ   SEQUENCE   339 AA;  37896 MW;  FECE7718D2628F0E CRC64;
     MAIIYLILLF TAVRGDQICI GYHANNSTET VDTILERNVT VTHAKDILEK THNGKLCKLN
     GIPPLELGDC SIAGWLLGNP ECDRLLSVPE WSYIMEKENP RNGLCYPGNF NDYEELKHLL
     SSVKHFEKVK ILPKDRWTQH TTTGGSQACA VSGNPSFFRN MVWLTEKESN YPVAKGSYNN
     TSGEQMLIIW GVHHPIDEKE QRTLYQNVGT YVSVGTSTLN KRSTPEIATR PKVNGLGSRM
     EFSWTLLDMW DTITFESTGN LIAPEYGFKI SKRGSSGIMK TEGTLENCET KCQTPLGAIN
     TTLPFHNVHP LTIGECPKYV KSEKLVLATG LRNVPQIES