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P04664

- HEMA_I69A0

UniProt

P04664 - HEMA_I69A0

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Protein

Hemagglutinin

Gene
HA
Organism
Influenza A virus (strain A/England/878/1969 H3N2)
Status
Reviewed - Annotation score: 4 out of 5 - Experimental evidence at protein leveli

Functioni

Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. This attachment induces virion internalization of about two third of the virus particles through clathrin-dependent endocytosis and about one third through a clathrin- and caveolin-independent pathway. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in HA2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore.

GO - Biological processi

  1. clathrin-mediated endocytosis of virus by host cell Source: UniProtKB-KW
  2. fusion of virus membrane with host endosome membrane Source: UniProtKB-KW
  3. fusion of virus membrane with host plasma membrane Source: InterPro
  4. virion attachment to host cell Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Hemagglutinin

Keywords - Biological processi

Clathrin- and caveolin-independent endocytosis of virus by host, Clathrin-mediated endocytosis of virus by host, Fusion of virus membrane with host endosomal membrane, Fusion of virus membrane with host membrane, Host-virus interaction, Viral attachment to host cell, Viral penetration into host cytoplasm, Virus endocytosis by host, Virus entry into host cell

Names & Taxonomyi

Protein namesi
Recommended name:
Hemagglutinin
Cleaved into the following chain:
Gene namesi
Name:HA
OrganismiInfluenza A virus (strain A/England/878/1969 H3N2)
Taxonomic identifieri387147 [NCBI]
Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Mysticeti (baleen whales) [TaxID: 9761]
Phocidae (true seals) [TaxID: 9709]
Sus scrofa (Pig) [TaxID: 9823]

Subcellular locationi

Virion membrane; Single-pass type I membrane protein Reviewed prediction. Host apical cell membrane; Single-pass type I membrane protein
Note: Targeted to the apical plasma membrane in epithelial polarized cells through a signal present in the transmembrane domain. Associated with glycosphingolipid- and cholesterol-enriched detergent-resistant lipid rafts.

GO - Cellular componenti

  1. host cell plasma membrane Source: UniProtKB-SubCell
  2. integral component of membrane Source: UniProtKB-KW
  3. viral envelope Source: UniProtKB-KW
  4. virion membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Viral envelope protein, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 328328Hemagglutinin HA1 chainPRO_0000038948Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi8 – 81N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi22 – 221N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi38 – 381N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi52 ↔ 277 By similarity
Glycosylationi63 – 631N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi64 ↔ 76 By similarity
Disulfide bondi97 ↔ 139 By similarity
Glycosylationi165 – 1651N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi281 ↔ 305 By similarity
Glycosylationi285 – 2851N-linked (GlcNAc...); by host Reviewed prediction

Post-translational modificationi

In natural infection, inactive HA is matured into HA1 and HA2 outside the cell by one or more trypsin-like, arginine-specific endoprotease secreted by the bronchial epithelial cells. One identified protease that may be involved in this process is secreted in lungs by Clara cells By similarity.
Palmitoylated By similarity.

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Interactioni

Subunit structurei

Homotrimer of disulfide-linked HA1-HA2.

Structurei

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1DLHX-ray2.80C/F306-318[»]
2G9HX-ray2.00C306-318[»]
ProteinModelPortaliP04664.
SMRiP04664. Positions 1-328.

Miscellaneous databases

EvolutionaryTraceiP04664.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane

Family and domain databases

Gene3Di2.10.77.10. 1 hit.
3.90.209.20. 1 hit.
InterProiIPR008980. Capsid_hemagglutn.
IPR013828. Hemagglutn_HA1_a/b_dom.
IPR013827. Hemagglutn_HA1_b-rbn_dom.
IPR000149. Hemagglutn_influenz_A.
IPR001364. Hemagglutn_influenz_A/B.
[Graphical view]
PfamiPF00509. Hemagglutinin. 1 hit.
[Graphical view]
PRINTSiPR00330. HEMAGGLUTN1.
PR00329. HEMAGGLUTN12.
SUPFAMiSSF49818. SSF49818. 1 hit.

Sequencei

Sequence statusi: Fragment.

Sequence processingi: The displayed sequence is further processed into a mature form.

P04664-1 [UniParc]FASTAAdd to Basket

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QDLPGNDNST ATLCLGHHAV PNGTLVKTIT NDQIEVTNAT ELVQSSSTGK    50
ICNNPHRILD GINCTLIDAL LGDPHCDVFQ DETWDLFVER SKAFSNCYPY 100
DVPDYASLRS LVASSGTLEF ITEGFTWTGV TQNGGSNACK RGPDSGFFSR 150
LNWLTKSGST YPVLNVTMPN NDNFDKLYIW GVHHPSTNQE QTSLYVQASG 200
RVTVSTRRSQ QTIIPNIGSR PWVRGLSSRI SIYWTIVKPG DVLVINSNGN 250
LIAPRGYFKM RTGKSSIMRS DAPIDTCISE CITPNGSIPN DKPFQNVNKI 300
TYGACPKYVK QNTLKLATGM RNVPEKQT 328
Length:328
Mass (Da):36,073
Last modified:August 13, 1987 - v1
Checksum:i9C3A86B3A8D856FE
GO

Non-terminal residue

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Non-terminal residuei1 – 11
Non-terminal residuei328 – 3281

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
K03335 Genomic RNA. Translation: AAA43184.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
K03335 Genomic RNA. Translation: AAA43184.1 .

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1DLH X-ray 2.80 C/F 306-318 [» ]
2G9H X-ray 2.00 C 306-318 [» ]
ProteinModelPortali P04664.
SMRi P04664. Positions 1-328.
ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Miscellaneous databases

EvolutionaryTracei P04664.

Family and domain databases

Gene3Di 2.10.77.10. 1 hit.
3.90.209.20. 1 hit.
InterProi IPR008980. Capsid_hemagglutn.
IPR013828. Hemagglutn_HA1_a/b_dom.
IPR013827. Hemagglutn_HA1_b-rbn_dom.
IPR000149. Hemagglutn_influenz_A.
IPR001364. Hemagglutn_influenz_A/B.
[Graphical view ]
Pfami PF00509. Hemagglutinin. 1 hit.
[Graphical view ]
PRINTSi PR00330. HEMAGGLUTN1.
PR00329. HEMAGGLUTN12.
SUPFAMi SSF49818. SSF49818. 1 hit.
ProtoNeti Search...

Publicationsi

  1. "Antigenic drift in the hemagglutinin of the Hong Kong influenza subtype: correlation of amino acid changes with alterations in viral antigenicity."
    Sleigh M.J., Both G.W., Underwood P.A., Bender V.J.
    J. Virol. 37:845-853(1981) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. "Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide."
    Stern L.J., Brown J.H., Jardetzky T.J., Gorga J.C., Urban R.G., Strominger J.L., Wiley D.C.
    Nature 368:215-221(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 306-318.

Entry informationi

Entry nameiHEMA_I69A0
AccessioniPrimary (citable) accession number: P04664
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: August 13, 1987
Last modified: February 19, 2014
This is version 98 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Miscellaneous

Major glycoprotein, comprises over 80% of the envelope proteins present in virus particle.
The extent of infection into host organism is determined by HA. Influenza viruses bud from the apical surface of polarized epithelial cells (e.g. bronchial epithelial cells) into lumen of lungs and are therefore usually pneumotropic. The reason is that HA is cleaved by tryptase clara which is restricted to lungs. However, HAs of H5 and H7 pantropic avian viruses subtypes can be cleaved by furin and subtilisin-type enzymes, allowing the virus to grow in other organs than lungs.
The influenza A genome consist of 8 RNA segments. Genetic variation of hemagglutinin and/or neuraminidase genes results in the emergence of new influenza strains. The mechanism of variation can be the result of point mutations or the result of genetic reassortment between segments of two different strains.

Keywords - Technical termi

3D-structure

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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