HEMA_I56A1
ID HEMA_I56A1 Reviewed; 564 AA.
AC P19696; Q9EA20;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 2.
DT 02-JUN-2021, entry version 125.
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/Czechoslovakia/1956 H4N6).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=385590;
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].
RX PubMed=2705304; DOI=10.1016/0042-6822(89)90166-9;
RA Donis R.O., Bean W.J., Kawaoka Y., Webster R.G.;
RT "Distinct lineages of influenza virus H4 hemagglutinin genes in different
RT regions of the world.";
RL Virology 169:408-417(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10725545; DOI=10.1016/s0168-1702(99)00131-8;
RA Kaverin N.V., Matrosovich M.N., Gambaryan A.S., Rudneva I.A., Shilov A.A.,
RA Varich N.L., Makarova N.V., Kropotkina E.A., Sinitsin B.V.;
RT "Intergenic HA-NA interactions in influenza A virus: postreassortment
RT substitutions of charged amino acid in the hemagglutinin of different
RT subtypes.";
RL Virus Res. 66:123-129(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.
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; M25283; AAA43216.1; -; Genomic_RNA.
DR EMBL; D90302; BAA14332.1; -; Genomic_RNA.
DR EMBL; AF290436; AAF99711.1; -; mRNA.
DR PIR; A34214; HMIVF1.
DR PDB; 5XL8; X-ray; 2.00 A; A/B/C=17-519.
DR PDB; 5XL9; X-ray; 2.39 A; A/B/C=17-519.
DR PDB; 5XLA; X-ray; 2.10 A; A/B=17-519.
DR PDBsum; 5XL8; -.
DR PDBsum; 5XL9; -.
DR PDBsum; 5XLA; -.
DR SMR; P19696; -.
DR Proteomes; UP000008434; Genome.
DR Proteomes; UP000108613; Genome.
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_0000440388"
FT CHAIN 17..342
FT /note="Hemagglutinin HA1 chain"
FT /id="PRO_0000038912"
FT CHAIN 344..564
FT /note="Hemagglutinin HA2 chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="PRO_0000038913"
FT TOPO_DOM 17..527
FT /note="Extracellular"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT TRANSMEM 528..548
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT TOPO_DOM 549..564
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 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 14
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 18
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 34
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 178
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 310
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 26..480
FT /note="Interchain (between HA1 and HA2 chains)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 64..291
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 76..88
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 109..151
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 157
FT /note="D -> N (in Ref. 2; BAA14332)"
FT /evidence="ECO:0000305"
FT CONFLICT 176
FT /note="L -> F (in Ref. 3; AAF99711)"
FT /evidence="ECO:0000305"
FT CONFLICT 201
FT /note="S -> D (in Ref. 2; BAA14332)"
FT /evidence="ECO:0000305"
FT CONFLICT 205
FT /note="T -> I (in Ref. 3; AAF99711)"
FT /evidence="ECO:0000305"
FT CONFLICT 214
FT /note="R -> S (in Ref. 2; BAA14332)"
FT /evidence="ECO:0000305"
FT CONFLICT 229
FT /note="D -> N (in Ref. 2; BAA14332)"
FT /evidence="ECO:0000305"
FT CONFLICT 270
FT /note="H -> Y (in Ref. 2; BAA14332)"
FT /evidence="ECO:0000305"
FT CONFLICT 389
FT /note="D -> N (in Ref. 3; AAF99711)"
FT /evidence="ECO:0000305"
FT CONFLICT 425
FT /note="N -> K (in Ref. 2; BAA14332)"
FT /evidence="ECO:0000305"
FT CONFLICT 489
FT /note="N -> Y (in Ref. 2; BAA14332)"
FT /evidence="ECO:0000305"
FT CONFLICT 511
FT /note="N -> D (in Ref. 3; AAF99711)"
FT /evidence="ECO:0000305"
FT STRAND 24..30
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 46..49
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 51..53
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 70..72
FT /evidence="ECO:0007829|PDB:5XL8"
FT HELIX 78..83
FT /evidence="ECO:0007829|PDB:5XL8"
FT HELIX 89..91
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 97..101
FT /evidence="ECO:0007829|PDB:5XL8"
FT HELIX 117..127
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 132..134
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 141..143
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 148..153
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 177..182
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 185..187
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 189..197
FT /evidence="ECO:0007829|PDB:5XL8"
FT HELIX 201..208
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 209..212
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 214..218
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 223..226
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 242..250
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 255..262
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 264..272
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 280..283
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 294..297
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 300..302
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 307..309
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 315..318
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 329..331
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 352..354
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 364..371
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 374..380
FT /evidence="ECO:0007829|PDB:5XL8"
FT HELIX 381..391
FT /evidence="ECO:0007829|PDB:5XL8"
FT HELIX 394..397
FT /evidence="ECO:0007829|PDB:5XL8"
FT HELIX 419..469
FT /evidence="ECO:0007829|PDB:5XL8"
FT HELIX 470..472
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 473..475
FT /evidence="ECO:0007829|PDB:5XL8"
FT STRAND 477..483
FT /evidence="ECO:0007829|PDB:5XL8"
FT HELIX 489..496
FT /evidence="ECO:0007829|PDB:5XL8"
FT HELIX 502..504
FT /evidence="ECO:0007829|PDB:5XL8"
FT HELIX 506..514
FT /evidence="ECO:0007829|PDB:5XL8"
SQ SEQUENCE 564 AA; 63160 MW; 81A274926B649DBD CRC64;
MLSIVILFLL IAENSSQNYT GNPVICMGHH AVANGTMVKT LADDQVEVVT AQELVESQNL
PELCPSPLRL VDGQTCDIIN GALGSPGCDH LNGAEWDVFI ERPNAVDTCY PFDVPEYQSL
RSILANNGKF EFIAEEFQWN TVKQNGKSGA CKRANVDDFF NRLNWLVKSD GNAYPLQNLT
KINNGDYARL YIWGVHHPST STEQTNLYKN NPGRVTVSTK TSQTSVVPDI GSRPLVRGQS
GRVSFYWTIV EPGDLIVFNT IGNLIAPRGH YKLNNQKKST ILNTAIPIGS CVSKCHTDKG
SLSTTKPFQN ISRIAVGDCP RYVKQGSLKL ATGMRNIPEK ASRGLFGAIA GFIENGWQGL
IDGWYGFRHQ NAEGTGTAAD LKSTQAAIDQ INGKLNRLIE KTNDKYHQIE KEFEQVEGRI
QDLENYVEDT KIDLWSYNAE LLVALENQHT IDVTDSEMNK LFERVRRQLR ENAEDKGNGC
FEIFHKCDNN CIESIRNGTY DHDIYRDEAI NNRFQIQGVK LTQGYKDIIL WISFSISCFL
LVALLLAFIL WACQNGNIRC QICI
