HEMA_I75A3
ID HEMA_I75A3 Reviewed; 567 AA.
AC P03435;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 132.
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/Victoria/3/1975 H3N2).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=392809;
OH NCBI_TaxID=8782; Aves.
OH NCBI_TaxID=9721; Cetacea (whales).
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9709; Phocidae (true seals).
OH NCBI_TaxID=9823; Sus scrofa (Pig).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=6153930; DOI=10.1016/s0092-8674(80)80045-6;
RA Min Jou W., Verhoeyen M., Devos R., Saman E., Fang R., Huylebroeck D.,
RA Fiers W., Threlfall G., Barber C., Carey N., Emtage S.;
RT "Complete structure of the hemagglutinin gene from the human influenza
RT A/Victoria/3/75 (H3N2) strain as determined from cloned DNA.";
RL Cell 19:683-696(1980).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=7402351; DOI=10.1038/286771a0;
RA Verhoeyen M., Fang R., Jou W.M., Devos R., Huylebroeck D., Saman E.,
RA Fiers W.;
RT "Antigenic drift between the haemagglutinin of the Hong Kong influenza
RT strains A/Aichi/2/68 and A/Victoria/3/75.";
RL Nature 286:771-776(1980).
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 -!- INTERACTION:
CC P03435; P03435: HA; NbExp=2; IntAct=EBI-16015508, EBI-16015508;
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. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the influenza viruses hemagglutinin family.
CC {ECO:0000255|HAMAP-Rule:MF_04072}.
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DR EMBL; V01098; CAA24281.1; -; Genomic_RNA.
DR EMBL; V01086; CAA24270.1; -; Genomic_RNA.
DR PIR; A90794; HMIVV.
DR PDB; 4GMS; X-ray; 2.95 A; A/C/E=28-346, B/D/F=347-522.
DR PDB; 4O58; X-ray; 2.75 A; A=28-346, B=347-522.
DR PDB; 6R0E; X-ray; 1.91 A; CCC=323-335.
DR PDBsum; 4GMS; -.
DR PDBsum; 4O58; -.
DR PDBsum; 6R0E; -.
DR SMR; P03435; -.
DR DIP; DIP-60078N; -.
DR ABCD; P03435; 7 sequenced antibodies.
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:0042802; F:identical protein binding; IPI:IntAct.
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 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; 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..16
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CHAIN 17..567
FT /note="Hemagglutinin"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="PRO_0000440442"
FT CHAIN 17..345
FT /note="Hemagglutinin HA1 chain"
FT /id="PRO_0000039065"
FT CHAIN 347..567
FT /note="Hemagglutinin HA2 chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="PRO_0000039066"
FT TOPO_DOM 17..531
FT /note="Extracellular"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT TRANSMEM 532..552
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT TOPO_DOM 553..567
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT SITE 346..347
FT /note="Cleavage; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT LIPID 556
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT LIPID 563
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT LIPID 566
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 24
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 25
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 39
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 55
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 80
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 143
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 182
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 302
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 500
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 31..483
FT /note="Interchain (between HA1 and HA2 chains)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 69..294
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 81..93
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 114..156
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 298..322
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 490..494
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT STRAND 28..35
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 41..43
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 49..54
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 56..58
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 66..73
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:4O58"
FT HELIX 83..88
FT /evidence="ECO:0007829|PDB:4O58"
FT HELIX 91..96
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 102..106
FT /evidence="ECO:0007829|PDB:4O58"
FT HELIX 122..132
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 146..148
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 152..158
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 161..163
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 168..170
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 172..174
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 181..186
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 189..191
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 193..201
FT /evidence="ECO:0007829|PDB:4O58"
FT HELIX 205..212
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 213..216
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 219..222
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 227..230
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 246..254
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 259..266
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 268..276
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 283..286
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 291..295
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 297..300
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 303..305
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 308..312
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 319..321
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 332..334
FT /evidence="ECO:0007829|PDB:4O58"
FT TURN 353..355
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 367..374
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 377..382
FT /evidence="ECO:0007829|PDB:4O58"
FT HELIX 384..401
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 406..408
FT /evidence="ECO:0007829|PDB:4GMS"
FT HELIX 422..472
FT /evidence="ECO:0007829|PDB:4O58"
FT HELIX 473..475
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 476..478
FT /evidence="ECO:0007829|PDB:4O58"
FT STRAND 480..486
FT /evidence="ECO:0007829|PDB:4O58"
FT HELIX 492..500
FT /evidence="ECO:0007829|PDB:4O58"
FT HELIX 505..516
FT /evidence="ECO:0007829|PDB:4O58"
SQ SEQUENCE 567 AA; 63423 MW; 824D98A880EC5DEF CRC64;
MKTIIALSYI FCLVFAQDLP GNDNNSTATL CLGHHAVPNG TLVKTITNDQ IEVTNATELV
QSSSTGKICN NPHRILDGIN CTLIDALLGD PHCDGFQNEK WDLFVERSKA FSNCYPYDVP
DYASLRSLVA SSGTLEFINE GFNWTGVTQN GGSSACKRGP DSGFFSRLNW LYKSGSTYPV
QNVTMPNNDN SDKLYIWGVH HPSTDKEQTN LYVQASGKVT VSTKRSQQTI IPNVGSRPWV
RGLSSRISIY WTIVKPGDIL VINSNGNLIA PRGYFKMRTG KSSIMRSDAP IGTCSSECIT
PNGSIPNDKP FQNVNKITYG ACPKYVKQNT LKLATGMRNV PEKQTRGIFG AIAGFIENGW
EGMIDGWYGF RHQNSEGTGQ AADLKSTQAA IDQINGKLNR VIEKTNEKFH QIEKEFSEVE
GRIQDLEKYV EDTKIDLWSY NAELLVALEN QHTIDLTDSE MNKLFEKTRR QLRENAEDMG
NGCFKIYHKC DNACIGSIRN GTYDHDVYRD EALNNRFQIK GVELKSGYKD WILWISFAIS
CFLLCVVLLG FIMWACQKGN IRCNICI
