HEMA_I68A6
ID HEMA_I68A6 Reviewed; 566 AA.
AC P03436; Q67095; Q84107;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 02-JUN-2021, entry version 129.
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/Northern Territory/60/1968 H3N2) (Influenza A
OS virus (strain NT60)) (Influenza A virus (strain A/NT/60/1968 H3N2)).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=384505;
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 [MRNA].
RC STRAIN=Subtype 29C;
RX PubMed=6253883; DOI=10.1093/nar/8.12.2561;
RA Both G.W., Sleigh M.J.;
RT "Complete nucleotide sequence of the haemagglutinin gene from a human
RT influenza virus of the Hong Kong subtype.";
RL Nucleic Acids Res. 8:2561-2575(1980).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 237-261.
RC STRAIN=Subtype 29C;
RX PubMed=388351; DOI=10.1093/nar/7.4.879;
RA Sleigh M.J., Both G.W., Brownlee G.G.;
RT "The influenza virus haemagglutinin gene: cloning and characterisation of a
RT double-stranded DNA copy.";
RL Nucleic Acids Res. 7:879-893(1979).
RN [3]
RP DISULFIDE BONDS.
RX PubMed=6768586; DOI=10.1016/0014-5793(80)80067-6;
RA Dopheide T.A., Ward C.W.;
RT "The disulphide bonds of a Hong Kong influenza virus hemagglutinin.";
RL FEBS Lett. 110:181-183(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, ECO:0000269|PubMed:6768586}.
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA24291.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; V01103; CAA24290.1; ALT_TERM; mRNA.
DR EMBL; V01103; CAA24291.1; ALT_INIT; mRNA.
DR EMBL; M25434; AAA43163.1; -; Genomic_RNA.
DR PIR; A93705; HMIVH.
DR PDB; 5T6N; X-ray; 2.54 A; B/D/F=346-519.
DR PDB; 6BKM; X-ray; 2.20 A; B/D/F=346-519.
DR PDB; 6CEX; X-ray; 2.57 A; B/D/F=346-519.
DR PDBsum; 5T6N; -.
DR PDBsum; 6BKM; -.
DR PDBsum; 6CEX; -.
DR BMRB; P03436; -.
DR SMR; P03436; -.
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..566
FT /note="Hemagglutinin"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="PRO_0000440417"
FT CHAIN 17..344
FT /note="Hemagglutinin HA1 chain"
FT /id="PRO_0000039032"
FT CHAIN 346..566
FT /note="Hemagglutinin HA2 chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="PRO_0000039033"
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..566
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT SITE 345..346
FT /note="Cleavage; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT LIPID 555
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT LIPID 562
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT LIPID 565
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 38
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 54
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 97
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 181
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 301
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 499
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 30..482
FT /note="Interchain (between HA1 and HA2 chains)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072,
FT ECO:0000269|PubMed:6768586"
FT DISULFID 68..293
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072,
FT ECO:0000269|PubMed:6768586"
FT DISULFID 80..92
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072,
FT ECO:0000269|PubMed:6768586"
FT DISULFID 113..155
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 297..321
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072,
FT ECO:0000269|PubMed:6768586"
FT DISULFID 489..493
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT TURN 352..354
FT /evidence="ECO:0007829|PDB:6BKM"
FT STRAND 366..373
FT /evidence="ECO:0007829|PDB:6BKM"
FT STRAND 376..381
FT /evidence="ECO:0007829|PDB:6BKM"
FT HELIX 383..400
FT /evidence="ECO:0007829|PDB:6BKM"
FT STRAND 406..409
FT /evidence="ECO:0007829|PDB:5T6N"
FT HELIX 421..470
FT /evidence="ECO:0007829|PDB:6BKM"
FT TURN 471..473
FT /evidence="ECO:0007829|PDB:6BKM"
FT STRAND 474..477
FT /evidence="ECO:0007829|PDB:6BKM"
FT STRAND 479..485
FT /evidence="ECO:0007829|PDB:6BKM"
FT HELIX 491..498
FT /evidence="ECO:0007829|PDB:6BKM"
FT HELIX 504..515
FT /evidence="ECO:0007829|PDB:6BKM"
SQ SEQUENCE 566 AA; 63488 MW; 9A187F6A5E383671 CRC64;
MKTIIALSYI FCLALGQDLP GNDNNTATLC LGHHAVPNGT LVKTITDDQI EVTNATELVQ
SSSTGKICNN PHRILDGIDC TLIDALLGDP HCDVFQNETW DLFVERSKAF SNCYPYDVPD
YASLRSLVAS SGTLEFITEG FTWTGVTQNG GSNACKRGPD SGFFSRLNWL TKSGSTYPVL
NVTMPNNDNF DKLYIWGVHH PSTNQEQTSL YVQASGRVTV STRRSQQTII PNIGSRPWVR
GQSSRISIYW TIVKPGDVLV INSNGNLIAP RGYFKMRTGK SSIMRSDAPI DTCISECITP
NGSIPNDKPF QNVNKITYGA CPKYVKQNTL KLATGMRNVP EKQTRGLFGA IAGFIENGWE
GMIDGWYGFR HQNSEGTGQA ADLKSTQAAI DQINGKLNRV IEKTNEKFHQ IEKEFSEVEG
RIQDLEKYVE DTKIDLWSYN AELLVALENQ HTIDLTDSEM NKLFEKTRRQ LRENAEDMGN
GCFKIYHKCD NACIESIRNG TYDHDVYRDE ALNNRFQIKG VELKSGYKDW ILWISFAISC
FLLCVVLLGF IMWACQRGNI RCNICI
