HEMA_I34A1
ID HEMA_I34A1 Reviewed; 565 AA.
AC P03452; A4GXH4; Q20N38; Q83964; Q8JUU5;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 2.
DT 23-FEB-2022, entry version 158.
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/Puerto Rico/8/1934 H1N1).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=211044;
OH NCBI_TaxID=8782; Aves.
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9823; Sus scrofa (Pig).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=7278968; DOI=10.1038/292072a0;
RA Winter G., Fields S., Brownlee G.G.;
RT "Nucleotide sequence of the haemagglutinin gene of a human influenza virus
RT H1 subtype.";
RL Nature 292:72-75(1981).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=11779399; DOI=10.1098/rstb.2001.0979;
RA Schickli J.H., Flandorfer A., Nakaya T., Martinez-Sobrido L.,
RA Garcia-Sastre A., Palese P.;
RT "Plasmid-only rescue of influenza A virus vaccine candidates.";
RL Philos. Trans. R. Soc. Lond., B, Biol. Sci. 356:1965-1973(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA], AND REVERSE GENETICS.
RX PubMed=15163504; DOI=10.1016/j.virusres.2004.02.028;
RA de Wit E., Spronken M.I.J., Bestebroer T.M., Rimmelzwaan G.F.,
RA Osterhaus A.D.M.E., Fouchier R.A.M.;
RT "Efficient generation and growth of influenza virus A/PR/8/34 from eight
RT cDNA fragments.";
RL Virus Res. 103:155-161(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Isolate EE12/E1;
RA Ghedin E., Spiro D., Miller N., Zaborsky J., Feldblyum T., Subbu V.,
RA Shumway M., Sparenborg J., Groveman L., Halpin R., Sitz J., Koo H.,
RA Salzberg S.L., Webster R.G., Hoffmann E., Krauss S., Naeve C., Bao Y.,
RA Bolotov P., Dernovoy D., Kiryutin B., Lipman D.J., Tatusova T.;
RT "The NIAID influenza genome sequencing project.";
RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 18-343.
RX PubMed=6186384; DOI=10.1016/0092-8674(82)90135-0;
RA Caton A.J., Brownlee G.G., Yewdell J.W., Gerhard W.;
RT "The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (H1
RT subtype).";
RL Cell 31:417-427(1982).
RN [6]
RP INTERACTION WITH HUMAN CACNA1C.
RX PubMed=29779930; DOI=10.1016/j.chom.2018.04.015;
RA Fujioka Y., Nishide S., Ose T., Suzuki T., Kato I., Fukuhara H.,
RA Fujioka M., Horiuchi K., Satoh A.O., Nepal P., Kashiwagi S., Wang J.,
RA Horiguchi M., Sato Y., Paudel S., Nanbo A., Miyazaki T., Hasegawa H.,
RA Maenaka K., Ohba Y.;
RT "Channel Binds Hemagglutinin and Mediates Influenza A Virus Entry into
RT Mammalian Cells.";
RL Cell Host Microbe 23:809-818(2018).
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. Interacts with human
CC CACNA1C (PubMed:29779930). {ECO:0000255|HAMAP-Rule:MF_04072,
CC ECO:0000269|PubMed:29779930}.
CC -!- INTERACTION:
CC P03452; PRO_0000000092 [P05067]: APP; Xeno; NbExp=2; IntAct=EBI-2548105, EBI-821758;
CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000255|HAMAP-Rule:MF_04072,
CC ECO:0000305}; Single-pass type I membrane protein {ECO:0000255|HAMAP-
CC Rule:MF_04072, ECO:0000305}. Host apical cell membrane
CC {ECO:0000255|HAMAP-Rule:MF_04072}; Single-pass type I membrane protein
CC {ECO:0000255|HAMAP-Rule:MF_04072, ECO:0000305}. Note=Targeted to the
CC apical plasma membrane in epithelial polarized cells through a signal
CC present in the transmembrane domain. Associated with
CC glycosphingolipid- and cholesterol-enriched detergent-resistant lipid
CC rafts. {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. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the influenza viruses hemagglutinin family.
CC {ECO:0000255|HAMAP-Rule:MF_04072}.
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DR EMBL; V01088; CAA24272.1; -; Genomic_RNA.
DR EMBL; AF389118; AAM75158.1; -; Genomic_RNA.
DR EMBL; EF467821; ABO21709.1; -; Genomic_RNA.
DR EMBL; CY009444; ABD77675.1; -; Genomic_RNA.
DR EMBL; J02144; AAA43194.1; -; Genomic_RNA.
DR RefSeq; NP_040980.1; NC_002017.1.
DR PDB; 1RU7; X-ray; 2.30 A; A/C/E/G/I/K=18-338, B/D/F/H/J/L=344-503.
DR PDB; 1RVX; X-ray; 2.20 A; A/C/E/G/I/K=14-338, B/D/F/H/J/L=344-503.
DR PDB; 1RVZ; X-ray; 2.25 A; A/C/E/G/I/K=14-338, B/D/F/H/J/L=344-503.
DR PDBsum; 1RU7; -.
DR PDBsum; 1RVX; -.
DR PDBsum; 1RVZ; -.
DR SMR; P03452; -.
DR IntAct; P03452; 38.
DR MINT; P03452; -.
DR BindingDB; P03452; -.
DR ChEMBL; CHEMBL1075313; -.
DR UniLectin; P03452; -.
DR ABCD; P03452; 1 sequenced antibody.
DR GeneID; 956529; -.
DR KEGG; vg:956529; -.
DR Reactome; R-HSA-168255; Influenza Infection.
DR Reactome; R-HSA-168275; Entry of Influenza Virion into Host Cell via Endocytosis.
DR Reactome; R-HSA-168288; Fusion of the Influenza Virion to the Host Cell Endosome.
DR Reactome; R-HSA-168298; Release.
DR Reactome; R-HSA-168302; Budding.
DR Reactome; R-HSA-168303; Packaging of Eight RNA Segments.
DR Reactome; R-HSA-168316; Assembly of Viral Components at the Budding Site.
DR Reactome; R-HSA-168336; Uncoating of the Influenza Virion.
DR Reactome; R-HSA-168874; Transport of HA trimer, NA tetramer and M2 tetramer from the endoplasmic reticulum to the Golgi Apparatus.
DR Reactome; R-HSA-192823; Viral mRNA Translation.
DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR EvolutionaryTrace; P03452; -.
DR PRO; PR:P03452; -.
DR Proteomes; UP000009255; Genome.
DR Proteomes; UP000116373; Genome.
DR Proteomes; UP000170967; Genome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
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:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0019031; C:viral envelope; IEA:UniProtKB-UniRule.
DR GO; GO:0055036; C:virion membrane; TAS:Reactome.
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; IDA:UniProtKB.
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 3D-structure;
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; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix; 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..17
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CHAIN 18..565
FT /note="Hemagglutinin"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="PRO_0000440377"
FT CHAIN 18..342
FT /note="Hemagglutinin HA1 chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="PRO_0000039034"
FT CHAIN 344..565
FT /note="Hemagglutinin HA2 chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="PRO_0000039035"
FT TOPO_DOM 18..528
FT /note="Extracellular"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT TRANSMEM 529..549
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT TOPO_DOM 550..565
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT SITE 343..344
FT /note="Cleavage; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT LIPID 554
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT LIPID 561
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT LIPID 564
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 27
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 28
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 40
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 285
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 303
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 497
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 21..480
FT /note="Interchain (between HA1 and HA2 chains)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 59..291
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 72..84
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 107..152
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 295..319
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 487..491
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CONFLICT 10
FT /note="C -> S (in Ref. 2; AAM75158)"
FT /evidence="ECO:0000305"
FT CONFLICT 146
FT /note="N -> TK (in Ref. 1; CAA24272)"
FT /evidence="ECO:0000305"
FT CONFLICT 155
FT /note="E -> A (in Ref. 1; CAA24272)"
FT /evidence="ECO:0000305"
FT CONFLICT 199
FT /note="P -> S (in Ref. 1; CAA24272)"
FT /evidence="ECO:0000305"
FT CONFLICT 203
FT /note="E -> D (in Ref. 1; CAA24272)"
FT /evidence="ECO:0000305"
FT CONFLICT 207
FT /note="L -> I (in Ref. 1; CAA24272 and 2; AAM75158)"
FT /evidence="ECO:0000305"
FT CONFLICT 268
FT /note="M -> R (in Ref. 1; CAA24272)"
FT /evidence="ECO:0000305"
FT CONFLICT 308
FT /note="Y -> F (in Ref. 1; CAA24272)"
FT /evidence="ECO:0000305"
FT CONFLICT 337
FT /note="I -> N (in Ref. 3; ABO21709)"
FT /evidence="ECO:0000305"
FT CONFLICT 397
FT /note="T -> S (in Ref. 1; CAA24272)"
FT /evidence="ECO:0000305"
FT STRAND 19..25
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 39..44
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 56..61
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 67..70
FT /evidence="ECO:0007829|PDB:1RVX"
FT HELIX 74..79
FT /evidence="ECO:0007829|PDB:1RVX"
FT HELIX 82..87
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 94..98
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 107..110
FT /evidence="ECO:0007829|PDB:1RVX"
FT HELIX 115..122
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 125..134
FT /evidence="ECO:0007829|PDB:1RVX"
FT TURN 136..138
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 149..154
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 157..159
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 162..166
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 170..172
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 177..182
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 185..197
FT /evidence="ECO:0007829|PDB:1RVX"
FT HELIX 201..208
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 215..218
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 223..226
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 242..250
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 255..262
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 264..275
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 281..283
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 288..297
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 300..302
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 307..309
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 315..319
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 329..331
FT /evidence="ECO:0007829|PDB:1RVX"
FT TURN 350..352
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 364..367
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 376..379
FT /evidence="ECO:0007829|PDB:1RVZ"
FT HELIX 381..401
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 405..408
FT /evidence="ECO:0007829|PDB:1RVZ"
FT HELIX 418..469
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 472..475
FT /evidence="ECO:0007829|PDB:1RVX"
FT STRAND 477..485
FT /evidence="ECO:0007829|PDB:1RVX"
FT HELIX 491..496
FT /evidence="ECO:0007829|PDB:1RVX"
SQ SEQUENCE 565 AA; 63353 MW; 47F34821748F494E CRC64;
MKANLLVLLC ALAAADADTI CIGYHANNST DTVDTVLEKN VTVTHSVNLL EDSHNGKLCR
LKGIAPLQLG KCNIAGWLLG NPECDPLLPV RSWSYIVETP NSENGICYPG DFIDYEELRE
QLSSVSSFER FEIFPKESSW PNHNTNGVTA ACSHEGKSSF YRNLLWLTEK EGSYPKLKNS
YVNKKGKEVL VLWGIHHPPN SKEQQNLYQN ENAYVSVVTS NYNRRFTPEI AERPKVRDQA
GRMNYYWTLL KPGDTIIFEA NGNLIAPMYA FALSRGFGSG IITSNASMHE CNTKCQTPLG
AINSSLPYQN IHPVTIGECP KYVRSAKLRM VTGLRNIPSI QSRGLFGAIA GFIEGGWTGM
IDGWYGYHHQ NEQGSGYAAD QKSTQNAING ITNKVNTVIE KMNIQFTAVG KEFNKLEKRM
ENLNKKVDDG FLDIWTYNAE LLVLLENERT LDFHDSNVKN LYEKVKSQLK NNAKEIGNGC
FEFYHKCDNE CMESVRNGTY DYPKYSEESK LNREKVDGVK LESMGIYQIL AIYSTVASSL
VLLVSLGAIS FWMCSNGSLQ CRICI
