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P03452 (HEMA_I34A1) Reviewed, UniProtKB/Swiss-Prot

Last modified May 14, 2014. Version 117. 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/Puerto Rico/8/1934 H1N1) [Reference proteome]
Taxonomic identifier211044 [NCBI]
Taxonomic lineageVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]

Protein attributes

Sequence length565 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 By similarity.

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.

Ontologies

Keywords
   Biological processClathrin- 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
   Cellular componentHost cell membrane
Host membrane
Membrane
Viral envelope protein
Virion
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionHemagglutinin
   PTMDisulfide bond
Glycoprotein
Lipoprotein
Palmitate
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processclathrin-mediated endocytosis of virus by host cell

Inferred from electronic annotation. Source: UniProtKB-KW

fusion of virus membrane with host endosome membrane

Inferred from electronic annotation. Source: UniProtKB-KW

fusion of virus membrane with host plasma membrane

Traceable author statement. Source: Reactome

intracellular transport of viral protein in host cell

Traceable author statement. Source: Reactome

receptor-mediated endocytosis of virus by host cell

Traceable author statement. Source: Reactome

uncoating of virus

Traceable author statement. Source: Reactome

viral entry into host cell

Traceable author statement. Source: Reactome

viral genome packaging

Traceable author statement. Source: Reactome

viral life cycle

Traceable author statement. Source: Reactome

viral process

Traceable author statement. Source: Reactome

viral release from host cell

Traceable author statement. Source: Reactome

viral transcription

Traceable author statement. Source: Reactome

virion assembly

Traceable author statement. Source: Reactome

virion attachment to host cell

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentGolgi membrane

Traceable author statement. Source: Reactome

endocytic vesicle membrane

Traceable author statement. Source: Reactome

endoplasmic reticulum membrane

Traceable author statement. Source: Reactome

endosome lumen

Traceable author statement. Source: Reactome

extracellular region

Traceable author statement. Source: Reactome

host cell plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Traceable author statement. Source: Reactome

viral envelope

Inferred from electronic annotation. Source: UniProtKB-KW

virion membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717 Potential
Chain18 – 342325Hemagglutinin HA1 chain
PRO_0000039034
Chain344 – 565222Hemagglutinin HA2 chain
PRO_0000039035

Regions

Topological domain18 – 528511Extracellular Potential
Transmembrane529 – 54921Helical; Potential
Topological domain550 – 56516Cytoplasmic Potential

Sites

Site343 – 3442Cleavage; by host By similarity

Amino acid modifications

Lipidation5541S-palmitoyl cysteine; by host By similarity
Lipidation5611S-palmitoyl cysteine; by host By similarity
Lipidation5641S-palmitoyl cysteine; by host By similarity
Glycosylation271N-linked (GlcNAc...); by host Potential
Glycosylation281N-linked (GlcNAc...); by host Potential
Glycosylation401N-linked (GlcNAc...); by host Potential
Glycosylation2851N-linked (GlcNAc...); by host Potential
Glycosylation3031N-linked (GlcNAc...); by host Potential
Glycosylation4971N-linked (GlcNAc...); by host Potential
Disulfide bond21 ↔ 480Interchain (between HA1 and HA2 chains) By similarity
Disulfide bond59 ↔ 291 By similarity
Disulfide bond72 ↔ 84 By similarity
Disulfide bond107 ↔ 152 By similarity
Disulfide bond295 ↔ 319 By similarity
Disulfide bond487 ↔ 491 By similarity

Experimental info

Sequence conflict101C → S in AAM75158. Ref.2
Sequence conflict1461N → TK in CAA24272. Ref.1
Sequence conflict1551E → A in CAA24272. Ref.1
Sequence conflict1991P → S in CAA24272. Ref.1
Sequence conflict2031E → D in CAA24272. Ref.1
Sequence conflict2071L → I in CAA24272. Ref.1
Sequence conflict2071L → I in AAM75158. Ref.2
Sequence conflict2681M → R in CAA24272. Ref.1
Sequence conflict3081Y → F in CAA24272. Ref.1
Sequence conflict3371I → N in ABO21709. Ref.3
Sequence conflict3971T → S in CAA24272. Ref.1

Secondary structure

............................................................................... 565
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P03452 [UniParc].

Last modified March 6, 2007. Version 2.
Checksum: 47F34821748F494E

FASTA56563,353
        10         20         30         40         50         60 
MKANLLVLLC ALAAADADTI CIGYHANNST DTVDTVLEKN VTVTHSVNLL EDSHNGKLCR 

        70         80         90        100        110        120 
LKGIAPLQLG KCNIAGWLLG NPECDPLLPV RSWSYIVETP NSENGICYPG DFIDYEELRE 

       130        140        150        160        170        180 
QLSSVSSFER FEIFPKESSW PNHNTNGVTA ACSHEGKSSF YRNLLWLTEK EGSYPKLKNS 

       190        200        210        220        230        240 
YVNKKGKEVL VLWGIHHPPN SKEQQNLYQN ENAYVSVVTS NYNRRFTPEI AERPKVRDQA 

       250        260        270        280        290        300 
GRMNYYWTLL KPGDTIIFEA NGNLIAPMYA FALSRGFGSG IITSNASMHE CNTKCQTPLG 

       310        320        330        340        350        360 
AINSSLPYQN IHPVTIGECP KYVRSAKLRM VTGLRNIPSI QSRGLFGAIA GFIEGGWTGM 

       370        380        390        400        410        420 
IDGWYGYHHQ NEQGSGYAAD QKSTQNAING ITNKVNTVIE KMNIQFTAVG KEFNKLEKRM 

       430        440        450        460        470        480 
ENLNKKVDDG FLDIWTYNAE LLVLLENERT LDFHDSNVKN LYEKVKSQLK NNAKEIGNGC 

       490        500        510        520        530        540 
FEFYHKCDNE CMESVRNGTY DYPKYSEESK LNREKVDGVK LESMGIYQIL AIYSTVASSL 

       550        560 
VLLVSLGAIS FWMCSNGSLQ CRICI 

« Hide

References

[1]"Nucleotide sequence of the haemagglutinin gene of a human influenza virus H1 subtype."
Winter G., Fields S., Brownlee G.G.
Nature 292:72-75(1981) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]"Plasmid-only rescue of influenza A virus vaccine candidates."
Schickli J.H., Flandorfer A., Nakaya T., Martinez-Sobrido L., Garcia-Sastre A., Palese P.
Philos. Trans. R. Soc. Lond., B, Biol. Sci. 356:1965-1973(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[3]"Efficient generation and growth of influenza virus A/PR/8/34 from eight cDNA fragments."
de Wit E., Spronken M.I.J., Bestebroer T.M., Rimmelzwaan G.F., Osterhaus A.D.M.E., Fouchier R.A.M.
Virus Res. 103:155-161(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA], REVERSE GENETICS.
[4]"The NIAID influenza genome sequencing project."
Ghedin E., Spiro D., Miller N., Zaborsky J., Feldblyum T., Subbu V., Shumway M., Sparenborg J., Groveman L., Halpin R., Sitz J., Koo H., Salzberg S.L., Webster R.G., Hoffmann E., Krauss S., Naeve C., Bao Y. expand/collapse author list , Bolotov P., Dernovoy D., Kiryutin B., Lipman D.J., Tatusova T.
Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
Strain: Isolate EE12/E1.
[5]"The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (H1 subtype)."
Caton A.J., Brownlee G.G., Yewdell J.W., Gerhard W.
Cell 31:417-427(1982) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 18-343.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
V01088 Genomic RNA. Translation: CAA24272.1.
AF389118 Genomic RNA. Translation: AAM75158.1.
EF467821 Genomic RNA. Translation: ABO21709.1.
CY009444 Genomic RNA. Translation: ABD77675.1.
J02144 Genomic RNA. Translation: AAA43194.1.
RefSeqNP_040980.1. NC_002017.1.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1RU7X-ray2.30A/C/E/G/I/K18-338[»]
B/D/F/H/J/L344-503[»]
1RVXX-ray2.20A/C/E/G/I/K14-338[»]
B/D/F/H/J/L344-503[»]
1RVZX-ray2.25A/C/E/G/I/K14-338[»]
B/D/F/H/J/L344-503[»]
ProteinModelPortalP03452.
SMRP03452. Positions 18-339, 344-518.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP03452. 8 interactions.
MINTMINT-3375119.

Chemistry

BindingDBP03452.
ChEMBLCHEMBL1075313.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID956529.

Enzyme and pathway databases

ReactomeREACT_116125. Disease.

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

EvolutionaryTraceP03452.

Entry information

Entry nameHEMA_I34A1
AccessionPrimary (citable) accession number: P03452
Secondary accession number(s): A4GXH4 expand/collapse secondary AC list , Q20N38, Q83964, Q8JUU5
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: March 6, 2007
Last modified: May 14, 2014
This is version 117 of the entry and version 2 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