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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)DescriptionActionsGraphical viewLength
Topological domaini17 – 531ExtracellularSequence analysisAdd BLAST515
Transmembranei532 – 552HelicalSequence analysisAdd BLAST21
Topological domaini553 – 567CytoplasmicSequence analysisAdd BLAST15

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)DescriptionActionsGraphical viewLength
Signal peptidei1 – 16Sequence analysisAdd BLAST16
ChainiPRO_000003906517 – 345Hemagglutinin HA1 chainAdd BLAST329
ChainiPRO_0000039066347 – 567Hemagglutinin HA2 chainAdd BLAST221

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi24N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi25N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi31 ↔ 483Interchain (between HA1 and HA2 chains)By similarity
Glycosylationi39N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi55N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi69 ↔ 294By similarity
Glycosylationi80N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi81 ↔ 93By similarity
Disulfide bondi114 ↔ 156By similarity
Glycosylationi143N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi182N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi298 ↔ 322By similarity
Glycosylationi302N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi490 ↔ 494By similarity
Glycosylationi500N-linked (GlcNAc...); by hostSequence analysis1
Lipidationi556S-palmitoyl cysteine; by hostBy similarity1
Lipidationi563S-palmitoyl cysteine; by hostBy similarity1
Lipidationi566S-palmitoyl cysteine; by hostBy similarity1

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)DescriptionActionsGraphical viewLength
Sitei346 – 347Cleavage; by hostBy similarity2

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

1567
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi28 – 35Combined sources8
Beta strandi41 – 43Combined sources3
Beta strandi49 – 54Combined sources6
Beta strandi56 – 58Combined sources3
Beta strandi66 – 73Combined sources8
Beta strandi75 – 77Combined sources3
Helixi83 – 88Combined sources6
Helixi91 – 96Combined sources6
Beta strandi102 – 106Combined sources5
Helixi122 – 132Combined sources11
Beta strandi137 – 139Combined sources3
Beta strandi146 – 148Combined sources3
Beta strandi152 – 158Combined sources7
Beta strandi161 – 163Combined sources3
Beta strandi168 – 170Combined sources3
Beta strandi172 – 174Combined sources3
Beta strandi181 – 186Combined sources6
Beta strandi189 – 191Combined sources3
Beta strandi193 – 201Combined sources9
Helixi205 – 212Combined sources8
Beta strandi213 – 216Combined sources4
Beta strandi219 – 222Combined sources4
Beta strandi227 – 230Combined sources4
Beta strandi246 – 254Combined sources9
Beta strandi259 – 266Combined sources8
Beta strandi268 – 276Combined sources9
Beta strandi283 – 286Combined sources4
Beta strandi291 – 295Combined sources5
Beta strandi297 – 300Combined sources4
Beta strandi303 – 305Combined sources3
Beta strandi308 – 312Combined sources5
Beta strandi319 – 321Combined sources3
Beta strandi332 – 334Combined sources3
Turni353 – 355Combined sources3
Beta strandi367 – 374Combined sources8
Beta strandi377 – 382Combined sources6
Helixi384 – 401Combined sources18
Beta strandi406 – 408Combined sources3
Helixi422 – 472Combined sources51
Helixi473 – 475Combined sources3
Beta strandi476 – 478Combined sources3
Beta strandi480 – 486Combined sources7
Helixi492 – 500Combined sources9
Helixi505 – 516Combined sources12

3D structure databases

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

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: November 2, 2016
This is version 110 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.