HEMA_I34A0
ID HEMA_I34A0 Reviewed; 563 AA.
AC P03459; Q67087;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 23-FEB-2022, entry version 137.
DE RecName: Full=Hemagglutinin {ECO:0000255|HAMAP-Rule:MF_04072};
DE Contains:
DE RecName: Full=Hemagglutinin HA1 chain {ECO:0000255|HAMAP-Rule:MF_04072};
DE Contains:
DE RecName: Full=Hemagglutinin HA2 chain {ECO:0000255|HAMAP-Rule:MF_04072};
DE Flags: Precursor;
GN Name=HA {ECO:0000255|HAMAP-Rule:MF_04072};
OS Influenza A virus (strain A/Fowl plague virus/Rostock/8/1934 H7N1).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=392810;
OH NCBI_TaxID=8782; Aves.
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=503226; DOI=10.1038/282471a0;
RA Porter A.G., Barber C., Carey N.H., Hallewell R.A., Threlfall G.,
RA Emtage J.S.;
RT "Complete nucleotide sequence of an influenza virus haemagglutinin gene
RT from cloned DNA.";
RL Nature 282:471-477(1979).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Mutant ts1, and mutant ts651;
RX PubMed=3840634; DOI=10.1016/0264-410x(85)90112-4;
RA Garten W., Kuroda K., Schuy W., Naruse H., Scholtissek C., Klenk H.D.;
RT "Haemagglutinin transport mutants.";
RL Vaccine 3:227-229(1985).
RN [3]
RP MUTANTS TS1 AND TS227.
RC STRAIN=Mutant ts1, and mutant ts227;
RX PubMed=3024963; DOI=10.1002/j.1460-2075.1986.tb04576.x;
RA Schuy W., Will C., Kuroda K., Scholtissek C., Garten W., Klenk H.-D.;
RT "Mutations blocking the transport of the influenza virus hemagglutinin
RT between the rough endoplasmic reticulum and the Golgi apparatus.";
RL EMBO J. 5:2831-2836(1986).
RN [4]
RP GLYCOSYLATION AT ASN-424 AND ASN-496, AND STRUCTURE OF CARBOHYDRATES.
RA Geyer R., Diabate S., Geyer H., Klenk H.-D., Niemann H., Stirm S.;
RT "Carbohydrates of influenza virus. Structure of the oligosaccharides linked
RT to asparagines 406 and 478 in the hemagglutinin of fowl plague virus,
RT strain Dutch.";
RL Glycoconj. J. 4:17-32(1987).
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 -!- 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:0000255|HAMAP-Rule:MF_04072}.
CC -!- SUBUNIT: Homotrimer of disulfide-linked HA1-HA2. {ECO:0000255|HAMAP-
CC Rule:MF_04072}.
CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000255|HAMAP-
CC Rule:MF_04072}; Single-pass type I membrane protein {ECO:0000255|HAMAP-
CC Rule:MF_04072}. Host apical cell membrane {ECO:0000255|HAMAP-
CC Rule:MF_04072}; Single-pass type I membrane protein {ECO:0000255|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:0000255|HAMAP-Rule:MF_04072}.
CC -!- PTM: Palmitoylated. {ECO:0000255|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 Clara cells. {ECO:0000255|HAMAP-Rule:MF_04072}.
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 -!- MISCELLANEOUS: Mutants ts1 and ts227 have a temperature-sensitive
CC defect in the transport of the hemagglutinin from the rough endoplasmic
CC reticulum to the Golgi apparatus. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the influenza viruses hemagglutinin family.
CC {ECO:0000255|HAMAP-Rule:MF_04072}.
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DR EMBL; V01105; CAA24294.1; -; Genomic_RNA.
DR EMBL; M24457; AAA43150.1; -; Genomic_RNA.
DR SMR; P03459; -.
DR IntAct; P03459; 1.
DR MINT; P03459; -.
DR GlyConnect; 209; 16 N-Linked glycans (7 sites).
DR SwissPalm; P03459; -.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-UniRule.
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; 3.90.209.20; -; 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; SSF49818; SSF49818; 1.
PE 1: Evidence at protein level;
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; Transmembrane; Transmembrane helix;
KW Viral attachment to host cell; Viral envelope protein;
KW Viral penetration into host cytoplasm; Virion; Virus endocytosis by host;
KW Virus entry into host cell.
FT SIGNAL 1..18
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CHAIN 19..563
FT /note="Hemagglutinin"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="PRO_0000440375"
FT CHAIN 19..341
FT /note="Hemagglutinin HA1 chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="PRO_0000440376"
FT CHAIN 343..563
FT /note="Hemagglutinin HA2 chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="PRO_0000038953"
FT TOPO_DOM 19..529
FT /note="Extracellular"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT TRANSMEM 530..550
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT TOPO_DOM 551..563
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT SITE 342..343
FT /note="Cleavage; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT LIPID 559
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT LIPID 562
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 30
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="CAR_000098"
FT CARBOHYD 46
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="CAR_000099"
FT CARBOHYD 141
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="CAR_000100"
FT CARBOHYD 167
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="CAR_000101"
FT CARBOHYD 249
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="CAR_000102"
FT CARBOHYD 424
FT /note="N-linked (GlcNAc...) (high mannose) asparagine; by
FT host"
FT /evidence="ECO:0000269|Ref.4"
FT /id="CAR_000103"
FT CARBOHYD 424
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 496
FT /note="N-linked (GlcNAc...) (high mannose) asparagine; by
FT host"
FT /evidence="ECO:0000269|Ref.4"
FT /id="CAR_000104"
FT CARBOHYD 496
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 22..479
FT /note="Interchain (between HA1 and HA2 chains)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 60..286
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 72..84
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 105..147
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 290..314
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 486..490
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT VARIANT 113
FT /note="E -> G (in strain: mutant ts227)"
FT VARIANT 293
FT /note="S -> G (in strain: mutant ts1)"
FT VARIANT 416
FT /note="E -> G (in strain: mutant ts1)"
FT VARIANT 475
FT /note="D -> N (in strain: mutant ts227)"
FT CONFLICT 340
FT /note="E -> K (in Ref. 2; AAA43150)"
FT /evidence="ECO:0000305"
FT CONFLICT 429
FT /note="F -> S (in Ref. 2; AAA43150)"
FT /evidence="ECO:0000305"
FT CONFLICT 441
FT /note="L -> I (in Ref. 2; AAA43150)"
FT /evidence="ECO:0000305"
FT CONFLICT 459
FT /note="K -> R (in Ref. 2; AAA43150)"
FT /evidence="ECO:0000305"
FT CONFLICT 545
FT /note="V -> M (in Ref. 2; AAA43150)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 563 AA; 62703 MW; 544C0520B83714E2 CRC64;
MNTQILVFAL VAVIPTNADK ICLGHHAVSN GTKVNTLTER GVEVVNATET VERTNIPKIC
SKGKRTTDLG QCGLLGTITG PPQCDQFLEF SADLIIERRE GNDVCYPGKF VNEEALRQIL
RGSGGIDKET MGFTYSGIRT NGTTSACRRS GSSFYAEMEW LLSNTDNASF PQMTKSYKNT
RRESALIVWG IHHSGSTTEQ TKLYGSGNKL ITVGSSKYHQ SFVPSPGTRP QINGQSGRID
FHWLILDPND TVTFSFNGAF IAPNRASFLR GKSMGIQSDV QVDANCEGEC YHSGGTITSR
LPFQNINSRA VGKCPRYVKQ ESLLLATGMK NVPEPSKKRE KRGLFGAIAG FIENGWEGLV
DGWYGFRHQN AQGEGTAADY KSTQSAIDQI TGKLNRLIEK TNQQFELIDN EFTEVEKQIG
NLINWTKDFI TEVWSYNAEL LVAMENQHTI DLADSEMNKL YERVRKQLRE NAEEDGTGCF
EIFHKCDDDC MASIRNNTYD HSKYREEAMQ NRIQIDPVKL SSGYKDVILW FSFGASCFLL
LAIAVGLVFI CVKNGNMRCT ICI
