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Protein

Hemagglutinin

Gene

HA

Organism
Influenza A virus (strain A/Victoria/3/1975 H3N2)
Status
Reviewed-Annotation score: 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

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 2 chains:
Gene namesi
Name:HA
OrganismiInfluenza A virus (strain A/Victoria/3/1975 H3N2)
Taxonomic identifieri392809 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Cetacea (whales) [TaxID: 9721]
Homo sapiens (Human) [TaxID: 9606]
Phocidae (true seals) [TaxID: 9709]
Sus scrofa (Pig) [TaxID: 9823]

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini17 – 531515ExtracellularSequence analysisAdd
BLAST
Transmembranei532 – 55221HelicalSequence analysisAdd
BLAST
Topological domaini553 – 56715CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

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
Signal peptidei1 – 1616Sequence analysisAdd
BLAST
Chaini17 – 345329Hemagglutinin HA1 chainPRO_0000039065Add
BLAST
Chaini347 – 567221Hemagglutinin HA2 chainPRO_0000039066Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi24 – 241N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi25 – 251N-linked (GlcNAc...); by hostSequence analysis
Disulfide bondi31 ↔ 483Interchain (between HA1 and HA2 chains)By similarity
Glycosylationi39 – 391N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi55 – 551N-linked (GlcNAc...); by hostSequence analysis
Disulfide bondi69 ↔ 294By similarity
Glycosylationi80 – 801N-linked (GlcNAc...); by hostSequence analysis
Disulfide bondi81 ↔ 93By similarity
Disulfide bondi114 ↔ 156By similarity
Glycosylationi143 – 1431N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi182 – 1821N-linked (GlcNAc...); by hostSequence analysis
Disulfide bondi298 ↔ 322By similarity
Glycosylationi302 – 3021N-linked (GlcNAc...); by hostSequence analysis
Disulfide bondi490 ↔ 494By similarity
Glycosylationi500 – 5001N-linked (GlcNAc...); by hostSequence analysis
Lipidationi556 – 5561S-palmitoyl cysteine; by hostBy similarity
Lipidationi563 – 5631S-palmitoyl cysteine; by hostBy similarity
Lipidationi566 – 5661S-palmitoyl cysteine; by hostBy similarity

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).By similarity
Palmitoylated.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei346 – 3472Cleavage; by hostBy similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Interactioni

Subunit structurei

Homotrimer of disulfide-linked HA1-HA2.

Protein-protein interaction databases

DIPiDIP-60078N.

Structurei

Secondary structure

1
567
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi28 – 358Combined sources
Beta strandi41 – 433Combined sources
Beta strandi49 – 546Combined sources
Beta strandi56 – 583Combined sources
Beta strandi66 – 738Combined sources
Beta strandi75 – 773Combined sources
Helixi83 – 886Combined sources
Helixi91 – 966Combined sources
Beta strandi102 – 1065Combined sources
Helixi122 – 13211Combined sources
Beta strandi137 – 1393Combined sources
Beta strandi146 – 1483Combined sources
Beta strandi152 – 1587Combined sources
Beta strandi161 – 1633Combined sources
Beta strandi168 – 1703Combined sources
Beta strandi172 – 1743Combined sources
Beta strandi181 – 1866Combined sources
Beta strandi189 – 1913Combined sources
Beta strandi193 – 2019Combined sources
Helixi205 – 2128Combined sources
Beta strandi213 – 2164Combined sources
Beta strandi219 – 2224Combined sources
Beta strandi227 – 2304Combined sources
Beta strandi246 – 2549Combined sources
Beta strandi259 – 2668Combined sources
Beta strandi268 – 2769Combined sources
Beta strandi283 – 2864Combined sources
Beta strandi291 – 2955Combined sources
Beta strandi297 – 3004Combined sources
Beta strandi303 – 3053Combined sources
Beta strandi308 – 3125Combined sources
Beta strandi319 – 3213Combined sources
Beta strandi332 – 3343Combined sources
Turni353 – 3553Combined sources
Beta strandi367 – 3748Combined sources
Beta strandi377 – 3826Combined sources
Helixi384 – 40118Combined sources
Beta strandi406 – 4083Combined sources
Helixi422 – 47251Combined sources
Helixi473 – 4753Combined sources
Beta strandi476 – 4783Combined sources
Beta strandi480 – 4867Combined sources
Helixi492 – 5009Combined sources
Helixi505 – 51612Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4GMSX-ray2.95A/C/E28-346[»]
B/D/F347-522[»]
4O58X-ray2.75A28-346[»]
B347-522[»]
ProteinModelPortaliP03435.
SMRiP03435. Positions 26-519.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Family and domain databases

Gene3Di2.10.77.10. 1 hit.
3.90.20.10. 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.
IPR013829. Hemagglutn_stalk.
[Graphical view]
PfamiPF00509. Hemagglutinin. 1 hit.
[Graphical view]
PRINTSiPR00330. HEMAGGLUTN1.
PR00329. HEMAGGLUTN12.
SUPFAMiSSF49818. SSF49818. 1 hit.

Sequencei

Sequence statusi: Complete.

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

P03435-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKTIIALSYI FCLVFAQDLP GNDNNSTATL CLGHHAVPNG TLVKTITNDQ
60 70 80 90 100
IEVTNATELV QSSSTGKICN NPHRILDGIN CTLIDALLGD PHCDGFQNEK
110 120 130 140 150
WDLFVERSKA FSNCYPYDVP DYASLRSLVA SSGTLEFINE GFNWTGVTQN
160 170 180 190 200
GGSSACKRGP DSGFFSRLNW LYKSGSTYPV QNVTMPNNDN SDKLYIWGVH
210 220 230 240 250
HPSTDKEQTN LYVQASGKVT VSTKRSQQTI IPNVGSRPWV RGLSSRISIY
260 270 280 290 300
WTIVKPGDIL VINSNGNLIA PRGYFKMRTG KSSIMRSDAP IGTCSSECIT
310 320 330 340 350
PNGSIPNDKP FQNVNKITYG ACPKYVKQNT LKLATGMRNV PEKQTRGIFG
360 370 380 390 400
AIAGFIENGW EGMIDGWYGF RHQNSEGTGQ AADLKSTQAA IDQINGKLNR
410 420 430 440 450
VIEKTNEKFH QIEKEFSEVE GRIQDLEKYV EDTKIDLWSY NAELLVALEN
460 470 480 490 500
QHTIDLTDSE MNKLFEKTRR QLRENAEDMG NGCFKIYHKC DNACIGSIRN
510 520 530 540 550
GTYDHDVYRD EALNNRFQIK GVELKSGYKD WILWISFAIS CFLLCVVLLG
560
FIMWACQKGN IRCNICI
Length:567
Mass (Da):63,423
Last modified:July 21, 1986 - v1
Checksum:i824D98A880EC5DEF
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
V01098 Genomic RNA. Translation: CAA24281.1.
V01086 Genomic RNA. Translation: CAA24270.1.
PIRiA90794. HMIVV.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
V01098 Genomic RNA. Translation: CAA24281.1.
V01086 Genomic RNA. Translation: CAA24270.1.
PIRiA90794. HMIVV.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4GMSX-ray2.95A/C/E28-346[»]
B/D/F347-522[»]
4O58X-ray2.75A28-346[»]
B347-522[»]
ProteinModelPortaliP03435.
SMRiP03435. Positions 26-519.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-60078N.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Family and domain databases

Gene3Di2.10.77.10. 1 hit.
3.90.20.10. 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.
IPR013829. Hemagglutn_stalk.
[Graphical view]
PfamiPF00509. Hemagglutinin. 1 hit.
[Graphical view]
PRINTSiPR00330. HEMAGGLUTN1.
PR00329. HEMAGGLUTN12.
SUPFAMiSSF49818. SSF49818. 1 hit.
ProtoNetiSearch...

Publicationsi

  1. "Complete structure of the hemagglutinin gene from the human influenza A/Victoria/3/75 (H3N2) strain as determined from cloned DNA."
    Min Jou W., Verhoeyen M., Devos R., Saman E., Fang R., Huylebroeck D., Fiers W., Threlfall G., Barber C., Carey N., Emtage S.
    Cell 19:683-696(1980) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. "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].

Entry informationi

Entry nameiHEMA_I75A3
AccessioniPrimary (citable) accession number: P03435
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: October 14, 2015
This is version 108 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.