Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P03437 (HEMA_I68A0) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Hemagglutinin

Cleaved into the following 2 chains:

  1. Hemagglutinin HA1 chain
  2. Hemagglutinin HA2 chain
Gene names
Name:HA
OrganismInfluenza A virus (strain A/Aichi/2/1968 H3N2)
Taxonomic identifier387139 [NCBI]
Taxonomic lineageVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostAves [TaxID: 8782]
Cetacea (whales) [TaxID: 9721]
Homo sapiens (Human) [TaxID: 9606]
Phocidae (true seals) [TaxID: 9709]
Sus scrofa (Pig) [TaxID: 9823]

Protein attributes

Sequence length566 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

Homotrimer of disulfide-linked HA1-HA2.

Subcellular location

Virion membrane; Single-pass type I membrane protein Potential. 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.

Post-translational modification

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.

Palmitoylated By similarity.

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.

Sequence similarities

Belongs to the influenza viruses hemagglutinin family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1616 Potential
Chain17 – 344328Hemagglutinin HA1 chain
PRO_0000038885
Chain346 – 566221Hemagglutinin HA2 chain
PRO_0000038886

Regions

Topological domain17 – 530514Extracellular Potential
Transmembrane531 – 55121Helical; Potential
Topological domain552 – 56615Cytoplasmic Potential

Sites

Site345 – 3462Cleavage; by host

Amino acid modifications

Lipidation5551S-palmitoyl cysteine; by host By similarity
Lipidation5621S-palmitoyl cysteine; by host By similarity
Lipidation5651S-palmitoyl cysteine; by host By similarity
Glycosylation241N-linked (GlcNAc...); by host
Glycosylation381N-linked (GlcNAc...); by host
Glycosylation541N-linked (GlcNAc...); by host
Glycosylation971N-linked (GlcNAc...); by host
Glycosylation1811N-linked (GlcNAc...); by host
Glycosylation3011N-linked (GlcNAc...); by host
Glycosylation4991N-linked (GlcNAc...); by host
Disulfide bond30 ↔ 482Interchain (between HA1 and HA2 chains)
Disulfide bond68 ↔ 293
Disulfide bond80 ↔ 92
Disulfide bond113 ↔ 155
Disulfide bond297 ↔ 321
Disulfide bond489 ↔ 493

Experimental info

Sequence conflict141A → P in AAA43239. Ref.2
Sequence conflict151L → I in BAF37221. Ref.3
Sequence conflict1601G → S in BAF37221. Ref.3
Sequence conflict1981I → V in BAF37221. Ref.3
Sequence conflict2401R → G in BAF37221. Ref.3
Sequence conflict4771E → D in BAF37221. Ref.3

Secondary structure

.......................................................................................... 566
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P03437 [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: E395659C23CAFECA

FASTA56663,416
        10         20         30         40         50         60 
MKTIIALSYI FCLALGQDLP GNDNSTATLC LGHHAVPNGT LVKTITDDQI EVTNATELVQ 

        70         80         90        100        110        120 
SSSTGKICNN PHRILDGIDC TLIDALLGDP HCDVFQNETW DLFVERSKAF SNCYPYDVPD 

       130        140        150        160        170        180 
YASLRSLVAS SGTLEFITEG FTWTGVTQNG GSNACKRGPG SGFFSRLNWL TKSGSTYPVL 

       190        200        210        220        230        240 
NVTMPNNDNF DKLYIWGIHH PSTNQEQTSL YVQASGRVTV STRRSQQTII PNIGSRPWVR 

       250        260        270        280        290        300 
GLSSRISIYW TIVKPGDVLV INSNGNLIAP RGYFKMRTGK SSIMRSDAPI DTCISECITP 

       310        320        330        340        350        360 
NGSIPNDKPF QNVNKITYGA CPKYVKQNTL KLATGMRNVP EKQTRGLFGA IAGFIENGWE 

       370        380        390        400        410        420 
GMIDGWYGFR HQNSEGTGQA ADLKSTQAAI DQINGKLNRV IEKTNEKFHQ IEKEFSEVEG 

       430        440        450        460        470        480 
RIQDLEKYVE DTKIDLWSYN AELLVALENQ HTIDLTDSEM NKLFEKTRRQ LRENAEEMGN 

       490        500        510        520        530        540 
GCFKIYHKCD NACIESIRNG TYDHDVYRDE ALNNRFQIKG VELKSGYKDW ILWISFAISC 

       550        560 
FLLCVVLLGF IMWACQRGNI RCNICI 

« Hide

References

[1]"Antigenic drift between the haemagglutinin of the Hong Kong influenza strains A/Aichi/2/68 and A/Victoria/3/75."
Verhoeyen M., Fang R., Jou W.M., Devos R., Huylebroeck D., Saman E., Fiers W.
Nature 286:771-776(1980) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]"Shift and drift in influenza viruses."
Min J.W., Verhoeyen M., Fang R.-X., Devos R., Huylebroeck D., Fiers W.
(In) Carlile M.J., Collins J.F., Moseley B.E.B. (eds.); Symposium of the Society for General Microbiology, pp.285-311, Cambridge University Press, New York (1981)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[3]"Effect of the addition of oligosaccharides on the biological activities and antigenicity of influenza A/H3N2 virus hemagglutinin."
Abe Y., Takashita E., Sugawara K., Matsuzaki Y., Muraki Y., Hongo S.
J. Virol. 78:9605-9611(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[4]"Human mucus protease inhibitor in airway fluids is a potential defensive compound against infection with influenza A and Sendai viruses."
Beppu Y., Imamura Y., Tashiro M., Towatari T., Ariga H., Kido H.
J. Biochem. 121:309-316(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: CLEAVAGE.
[5]"Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3-A resolution."
Wilson I.A., Skehel J.J., Wiley D.C.
Nature 289:366-373(1981) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
[6]"Structure of the influenza virus haemagglutinin complexed with its receptor, sialic acid."
Weis W.I., Brown J.H., Cusack S.C., Paulson J.C., Skehel J.J., Wiley D.C.
Nature 333:426-431(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
[7]"The structure of a membrane fusion mutant of the influenza virus haemagglutinin."
Weis W.I., Cusack S.C., Brown J.H., Daniels R.S., Skehel J.J., Wiley D.C.
EMBO J. 9:17-24(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF A MUTANT WITH GLY-457.
[8]"Refinement of the influenza virus hemagglutinin by simulated annealing."
Weis W.I., Bruenger A.T., Skehel J.J., Wiley D.C.
J. Mol. Biol. 212:737-761(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
[9]"Structure of influenza haemagglutinin at the pH of membrane fusion."
Bullough P.A., Hughson F.M., Skehel J.J., Wiley D.C.
Nature 371:37-43(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
[10]"Antigen distortion allows influenza virus to escape neutralization."
Fleury D., Wharton S.A., Skehel J.J., Knossow M., Bizebard T.
Nat. Struct. Biol. 5:119-123(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS).
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J02090 Genomic RNA. Translation: AAA43178.1.
V01085 Genomic RNA. Translation: CAA24269.1.
M55059 Genomic RNA. Translation: AAA43239.1.
AB284320 Genomic RNA. Translation: BAF37221.1.
PIRHMIVHA. A93231.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1EO8X-ray2.80A17-344[»]
B346-520[»]
1FYTX-ray2.60C322-334[»]
1HA0X-ray2.80A25-518[»]
1HGGX-ray2.90A/C/E17-344[»]
B/D/F346-520[»]
1HTMX-ray2.50A/C/E17-43[»]
B/D/F383-520[»]
1J8HX-ray2.40C322-334[»]
1QU1X-ray1.90A/B/C/D/E/F376-530[»]
2HMGX-ray3.00A/C/E17-344[»]
B/D/F346-520[»]
2VIRX-ray3.25C44-325[»]
2VISX-ray3.25C44-325[»]
2VITX-ray3.25C44-325[»]
2VIUX-ray2.50A17-344[»]
B346-520[»]
2YPGX-ray2.85A/C/E17-344[»]
B/D/F346-520[»]
3EYMX-ray2.80A/C/E25-345[»]
B/D/F346-517[»]
3HMGX-ray2.90A/C/E17-344[»]
B/D/F346-520[»]
3S4SX-ray2.40C/F322-334[»]
3S5LX-ray2.10C/F322-334[»]
3VUNX-ray3.00A/C/E17-345[»]
B/D/F346-520[»]
4HMGX-ray3.00A/C/E17-344[»]
B/D/F346-520[»]
5HMGX-ray3.20A/C/E17-344[»]
B/D/F346-520[»]
ProteinModelPortalP03437.
SMRP03437. Positions 17-520.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-45342N.
IntActP03437. 1 interaction.

Chemistry

BindingDBP03437.
ChEMBLCHEMBL1932897.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Family and domain databases

Gene3D2.10.77.10. 1 hit.
3.90.20.10. 1 hit.
3.90.209.20. 1 hit.
InterProIPR008980. Capsid_hemagglutn.
IPR013828. Hemagglutn_HA1_a/b_dom.
IPR013827. Hemagglutn_HA1_b-rbn_dom.
IPR000149. Hemagglutn_influenz_A.
IPR001364. Hemagglutn_influenz_A/B.
IPR013829. Hemagglutn_stalk.
[Graphical view]
PfamPF00509. Hemagglutinin. 1 hit.
[Graphical view]
PRINTSPR00330. HEMAGGLUTN1.
PR00329. HEMAGGLUTN12.
SUPFAMSSF49818. SSF49818. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceP03437.

Entry information

Entry nameHEMA_I68A0
AccessionPrimary (citable) accession number: P03437
Secondary accession number(s): A0PC85, Q67132
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: July 9, 2014
This is version 120 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references