HEMA_I76A2
ID HEMA_I76A2 Reviewed; 564 AA.
AC P03446;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1991, sequence version 2.
DT 25-MAY-2022, entry version 126.
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/Duck/Alberta/60/1976 H12N5).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=385582;
OH NCBI_TaxID=8782; Aves.
OH NCBI_TaxID=9823; Sus scrofa (Pig).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=2024485; DOI=10.1016/0042-6822(91)90588-3;
RA Nobusawa E., Aoyama T., Kato H., Suzuki Y., Tateno Y., Nakajima K.;
RT "Comparison of complete amino acid sequences and receptor-binding
RT properties among 13 serotypes of hemagglutinins of influenza A viruses.";
RL Virology 182:475-485(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-101.
RX PubMed=6174976; DOI=10.1073/pnas.78.12.7639;
RA Air G.M.;
RT "Sequence relationships among the hemagglutinin genes of 12 subtypes of
RT influenza A virus.";
RL Proc. Natl. Acad. Sci. U.S.A. 78:7639-7643(1981).
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. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the influenza viruses hemagglutinin family.
CC {ECO:0000255|HAMAP-Rule:MF_04072}.
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DR EMBL; D90307; BAA14337.1; -; Genomic_RNA.
DR EMBL; J02104; AAA43180.1; -; Genomic_RNA.
DR PDB; 7A9D; X-ray; 2.70 A; B/D=343-509.
DR PDBsum; 7A9D; -.
DR SMR; P03446; -.
DR PRIDE; P03446; -.
DR PRO; PR:P03446; -.
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 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..564
FT /note="Hemagglutinin"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="PRO_0000440448"
FT CHAIN 18..341
FT /note="Hemagglutinin HA1 chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="PRO_0000038906"
FT CHAIN 343..564
FT /note="Hemagglutinin HA2 chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="PRO_0000038907"
FT TOPO_DOM 17..530
FT /note="Extracellular"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT TRANSMEM 531..551
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT TOPO_DOM 552..564
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 553
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT LIPID 560
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 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 140
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 151
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 152
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 222
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 309
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 496
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 523
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 21..479
FT /note="Interchain (between HA1 and HA2 chains)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 59..290
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 72..84
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 107..150
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 294..318
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 486..490
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CONFLICT 39
FT /note="Q -> L (in Ref. 2; AAA43180)"
FT /evidence="ECO:0000305"
FT CONFLICT 52
FT /note="R -> G (in Ref. 2; AAA43180)"
FT /evidence="ECO:0000305"
FT STRAND 19..25
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 39..44
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 58..61
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 67..72
FT /evidence="ECO:0007829|PDB:7A9D"
FT HELIX 74..79
FT /evidence="ECO:0007829|PDB:7A9D"
FT HELIX 85..87
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 94..98
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 108..112
FT /evidence="ECO:0007829|PDB:7A9D"
FT HELIX 115..124
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 125..132
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 138..142
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 147..151
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 161..165
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 176..181
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 184..186
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 188..196
FT /evidence="ECO:0007829|PDB:7A9D"
FT HELIX 200..206
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 214..217
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 222..225
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 235..237
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 241..249
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 254..261
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 264..274
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 280..282
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 287..291
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 293..298
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 306..308
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 314..317
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 328..330
FT /evidence="ECO:0007829|PDB:7A9D"
FT TURN 349..351
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 363..370
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 373..375
FT /evidence="ECO:0007829|PDB:7A9D"
FT HELIX 380..400
FT /evidence="ECO:0007829|PDB:7A9D"
FT HELIX 417..468
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 471..474
FT /evidence="ECO:0007829|PDB:7A9D"
FT STRAND 476..481
FT /evidence="ECO:0007829|PDB:7A9D"
FT HELIX 488..495
FT /evidence="ECO:0007829|PDB:7A9D"
FT HELIX 505..508
FT /evidence="ECO:0007829|PDB:7A9D"
SQ SEQUENCE 564 AA; 63713 MW; E4AB129865D9D678 CRC64;
MEKFIILSTV LAASFAYDKI CIGYQTNNST ETVNTLSEQN VPVTQVEELV HRGIDPILCG
TELGSPLVLD DCSLEGLILG NPKCDLYLNG REWSYIVERP KEMEGVCYPG SIENQEELRS
LFSSIKKYER VKMFDFTKWN VTYTGTSKAC NNTSNQGSFY RSMRWLTLKS GQFPVQTDEY
KNTRDSDIVF TWAIHHPPTS DEQVKLYKNP DTLSSVTTVE INRSFKPNIG PRPLVRGQQG
RMDYYWAVLK PGQTVKIQTN GNLIAPEYGH LITGKSHGRI LKNNLPMGQC VTECQLNEGV
MNTSKPFQNT SKHYIGKCPK YIPSGSLKLA IGLRNVPQVQ DRGLFGAIAG FIEGGWPGLV
AGWYGFQHQN AEGTGIAADR DSTQRAIDNM QNKLNNVIDK MNKQFEVVNH EFSEVESRIN
MINSKIDDQI TDIWAYNAEL LVLLENQKTL DEHDANVRNL HDRVRRVLRE NAIDTGDGCF
EILHKCDNNC MDTIRNGTYN HKEYEEESKI ERQKVNGVKL EENSTYKILS IYSSVASSLV
LLLMIIGGFI FGCQNGNVRC TFCI
