HEMA_I57A0
ID HEMA_I57A0 Reviewed; 562 AA.
AC P03451;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 133.
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/Japan/305/1957 H2N2).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=387161;
OH NCBI_TaxID=8782; Aves.
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=7421990; DOI=10.1038/287301a0;
RA Gething M.-J., Bye J., Skehel J.J., Waterfield M.;
RT "Cloning and DNA sequence of double-stranded copies of haemagglutinin genes
RT from H2 and H3 strains elucidates antigenic shift and drift in human
RT influenza virus.";
RL Nature 287:301-306(1980).
RN [2]
RP PALMITOYLATION AT CYS-551; CYS-558 AND CYS-561, AND MUTAGENESIS OF SER-519;
RP SER-520; CYS-551; CYS-558 AND CYS-561.
RX PubMed=2249653; DOI=10.1002/j.1460-2075.1990.tb07604.x;
RA Naeve C.W., Williams D.;
RT "Fatty acids on the A/Japan/305/57 influenza virus hemagglutinin have a
RT role in membrane fusion.";
RL EMBO J. 9:3857-3866(1990).
RN [3]
RP FUNCTION.
RX PubMed=2271610; DOI=10.1021/bi00493a027;
RA Ellens H., Bentz J., Mason D., Zhang F., White J.M.;
RT "Fusion of influenza hemagglutinin-expressing fibroblasts with glycophorin-
RT bearing liposomes: role of hemagglutinin surface density.";
RL Biochemistry 29:9697-9707(1990).
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. {ECO:0000269|PubMed:2271610}.
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 ECO:0000269|PubMed:2249653}.
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; J02127; AAA43185.1; -; Genomic_RNA.
DR PIR; A04062; HMIV2.
DR PDB; 4HFU; X-ray; 3.11 A; A=15-340, B=341-514.
DR PDB; 4HG4; X-ray; 3.20 A; A/B/C/D/E/F/G/H/I=15-340, a/b/c/d/e/f/g/h/i=341-514.
DR PDBsum; 4HFU; -.
DR PDBsum; 4HG4; -.
DR SMR; P03451; -.
DR DIP; DIP-60235N; -.
DR PRIDE; P03451; -.
DR ABCD; P03451; 4 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: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..15
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CHAIN 16..562
FT /note="Hemagglutinin"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="PRO_0000440392"
FT CHAIN 16..339
FT /note="Hemagglutinin HA1 chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="PRO_0000039010"
FT CHAIN 341..562
FT /note="Hemagglutinin HA2 chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="PRO_0000039011"
FT TOPO_DOM 16..525
FT /note="Extracellular"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT TRANSMEM 526..546
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT TOPO_DOM 547..562
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT SITE 340..341
FT /note="Cleavage; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT LIPID 551
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072,
FT ECO:0000269|PubMed:2249653"
FT LIPID 558
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072,
FT ECO:0000269|PubMed:2249653"
FT LIPID 561
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072,
FT ECO:0000269|PubMed:2249653"
FT CARBOHYD 25
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 26
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 38
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 179
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 180
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 300
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 494
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 19..477
FT /note="Interchain (between HA1 and HA2 chains)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 57..288
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 70..82
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 105..149
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 292..316
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 484..488
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT MUTAGEN 519
FT /note="S->A: No effect on palmitoylation."
FT /evidence="ECO:0000269|PubMed:2249653"
FT MUTAGEN 520
FT /note="S->A: No effect on palmitoylation."
FT /evidence="ECO:0000269|PubMed:2249653"
FT MUTAGEN 551
FT /note="C->A: Loss of palmitoylation."
FT /evidence="ECO:0000269|PubMed:2249653"
FT MUTAGEN 558
FT /note="C->A: Loss of palmitoylation."
FT /evidence="ECO:0000269|PubMed:2249653"
FT MUTAGEN 561
FT /note="C->A: Loss of palmitoylation."
FT /evidence="ECO:0000269|PubMed:2249653"
FT STRAND 16..23
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 37..42
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 44..46
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 65..68
FT /evidence="ECO:0007829|PDB:4HG4"
FT HELIX 72..77
FT /evidence="ECO:0007829|PDB:4HFU"
FT HELIX 80..86
FT /evidence="ECO:0007829|PDB:4HG4"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:4HG4"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:4HFU"
FT HELIX 113..119
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 122..132
FT /evidence="ECO:0007829|PDB:4HFU"
FT HELIX 134..136
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 138..141
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 146..151
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 154..156
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 161..163
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 167..169
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 174..179
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 182..194
FT /evidence="ECO:0007829|PDB:4HFU"
FT HELIX 198..205
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 206..209
FT /evidence="ECO:0007829|PDB:4HG4"
FT STRAND 212..215
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 220..223
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 239..247
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 252..259
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 261..271
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 278..280
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 289..294
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 297..299
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 303..306
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 313..315
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 326..328
FT /evidence="ECO:0007829|PDB:4HFU"
FT TURN 347..349
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 361..367
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 373..376
FT /evidence="ECO:0007829|PDB:4HFU"
FT HELIX 378..397
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 403..405
FT /evidence="ECO:0007829|PDB:4HFU"
FT HELIX 415..466
FT /evidence="ECO:0007829|PDB:4HFU"
FT HELIX 467..469
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 470..472
FT /evidence="ECO:0007829|PDB:4HFU"
FT STRAND 474..482
FT /evidence="ECO:0007829|PDB:4HFU"
FT HELIX 486..493
FT /evidence="ECO:0007829|PDB:4HFU"
FT HELIX 499..510
FT /evidence="ECO:0007829|PDB:4HFU"
SQ SEQUENCE 562 AA; 63119 MW; 6B7FD0C038993630 CRC64;
MAIIYLILLF TAVRGDQICI GYHANNSTEK VDTNLERNVT VTHAKDILEK THNGKLCKLN
GIPPLELGDC SIAGWLLGNP ECDRLLSVPE WSYIMEKENP RDGLCYPGSF NDYEELKHLL
SSVKHFEKVK ILPKDRWTQH TTTGGSRACA VSGNPSFFRN MVWLTKEGSD YPVAKGSYNN
TSGEQMLIIW GVHHPIDETE QRTLYQNVGT YVSVGTSTLN KRSTPEIATR PKVNGQGGRM
EFSWTLLDMW DTINFESTGN LIAPEYGFKI SKRGSSGIMK TEGTLENCET KCQTPLGAIN
TTLPFHNVHP LTIGECPKYV KSEKLVLATG LRNVPQIESR GLFGAIAGFI EGGWQGMVDG
WYGYHHSNDQ GSGYAADKES TQKAFDGITN KVNSVIEKMN TQFEAVGKEF GNLERRLENL
NKRMEDGFLD VWTYNAELLV LMENERTLDF HDSNVKNLYD KVRMQLRDNV KELGNGCFEF
YHKCDDECMN SVKNGTYDYP KYEEESKLNR NEIKGVKLSS MGVYQILAIY ATVAGSLSLA
IMMAGISFWM CSNGSLQCRI CI
