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Protein

Hemagglutinin

Gene

HA

Organism
Influenza A virus (strain A/Aichi/2/1968 H3N2)
Status
Reviewed-Annotation score: Annotation score: 5 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/Aichi/2/1968 H3N2)
Taxonomic identifieri387139 [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 – 530ExtracellularSequence analysisAdd BLAST514
Transmembranei531 – 551HelicalSequence analysisAdd BLAST21
Topological domaini552 – 566CytoplasmicSequence analysisAdd BLAST15

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL1932897.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 16Sequence analysisAdd BLAST16
ChainiPRO_000003888517 – 344Hemagglutinin HA1 chainAdd BLAST328
ChainiPRO_0000038886346 – 566Hemagglutinin HA2 chainAdd BLAST221

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi24N-linked (GlcNAc...); by host1
Disulfide bondi30 ↔ 482Interchain (between HA1 and HA2 chains)
Glycosylationi38N-linked (GlcNAc...); by host1
Glycosylationi54N-linked (GlcNAc...); by host1
Disulfide bondi68 ↔ 293
Disulfide bondi80 ↔ 92
Glycosylationi97N-linked (GlcNAc...); by host1
Disulfide bondi113 ↔ 155
Glycosylationi181N-linked (GlcNAc...); by host1
Disulfide bondi297 ↔ 321
Glycosylationi301N-linked (GlcNAc...); by host1
Disulfide bondi489 ↔ 493
Glycosylationi499N-linked (GlcNAc...); by host1
Lipidationi555S-palmitoyl cysteine; by hostBy similarity1
Lipidationi562S-palmitoyl cysteine; by hostBy similarity1
Lipidationi565S-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.1 Publication
Palmitoylated.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei345 – 346Cleavage; by host2

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Interactioni

Subunit structurei

Homotrimer of disulfide-linked HA1-HA2.

Protein-protein interaction databases

DIPiDIP-45342N.
IntActiP03437. 1 interactor.

Chemistry databases

BindingDBiP03437.

Structurei

Secondary structure

1566
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi27 – 35Combined sources9
Beta strandi40 – 42Combined sources3
Beta strandi50 – 53Combined sources4
Beta strandi55 – 57Combined sources3
Beta strandi65 – 72Combined sources8
Beta strandi74 – 76Combined sources3
Helixi82 – 87Combined sources6
Helixi90 – 95Combined sources6
Beta strandi101 – 105Combined sources5
Helixi121 – 131Combined sources11
Beta strandi136 – 138Combined sources3
Turni144 – 146Combined sources3
Beta strandi152 – 157Combined sources6
Beta strandi160 – 162Combined sources3
Beta strandi167 – 169Combined sources3
Beta strandi171 – 173Combined sources3
Beta strandi180 – 185Combined sources6
Beta strandi188 – 190Combined sources3
Beta strandi192 – 200Combined sources9
Helixi204 – 211Combined sources8
Beta strandi212 – 215Combined sources4
Beta strandi217 – 221Combined sources5
Beta strandi226 – 229Combined sources4
Beta strandi245 – 253Combined sources9
Beta strandi258 – 265Combined sources8
Beta strandi267 – 270Combined sources4
Beta strandi272 – 275Combined sources4
Beta strandi282 – 285Combined sources4
Beta strandi290 – 294Combined sources5
Beta strandi296 – 299Combined sources4
Beta strandi302 – 304Combined sources3
Beta strandi307 – 311Combined sources5
Beta strandi318 – 320Combined sources3
Beta strandi331 – 333Combined sources3
Beta strandi337 – 339Combined sources3
Turni352 – 354Combined sources3
Beta strandi366 – 373Combined sources8
Beta strandi376 – 382Combined sources7
Helixi383 – 449Combined sources67
Beta strandi455 – 457Combined sources3
Helixi458 – 470Combined sources13
Helixi472 – 474Combined sources3
Beta strandi475 – 479Combined sources5
Beta strandi485 – 487Combined sources3
Helixi491 – 499Combined sources9
Helixi504 – 515Combined sources12
Turni516 – 519Combined sources4
Beta strandi524 – 526Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
1KENX-ray3.50B/D/F346-520[»]
1QFUX-ray2.80B346-520[»]
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[»]
4C56X-ray2.90F/L322-334[»]
4HMGX-ray3.00A/C/E17-344[»]
B/D/F346-520[»]
5HMGX-ray3.20A/C/E17-344[»]
B/D/F346-520[»]
ProteinModelPortaliP03437.
SMRiP03437.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP03437.

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.

P03437-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKTIIALSYI FCLALGQDLP GNDNSTATLC LGHHAVPNGT LVKTITDDQI
60 70 80 90 100
EVTNATELVQ SSSTGKICNN PHRILDGIDC TLIDALLGDP HCDVFQNETW
110 120 130 140 150
DLFVERSKAF SNCYPYDVPD YASLRSLVAS SGTLEFITEG FTWTGVTQNG
160 170 180 190 200
GSNACKRGPG SGFFSRLNWL TKSGSTYPVL NVTMPNNDNF DKLYIWGIHH
210 220 230 240 250
PSTNQEQTSL YVQASGRVTV STRRSQQTII PNIGSRPWVR GLSSRISIYW
260 270 280 290 300
TIVKPGDVLV INSNGNLIAP RGYFKMRTGK SSIMRSDAPI DTCISECITP
310 320 330 340 350
NGSIPNDKPF QNVNKITYGA CPKYVKQNTL KLATGMRNVP EKQTRGLFGA
360 370 380 390 400
IAGFIENGWE GMIDGWYGFR HQNSEGTGQA ADLKSTQAAI DQINGKLNRV
410 420 430 440 450
IEKTNEKFHQ IEKEFSEVEG RIQDLEKYVE DTKIDLWSYN AELLVALENQ
460 470 480 490 500
HTIDLTDSEM NKLFEKTRRQ LRENAEEMGN GCFKIYHKCD NACIESIRNG
510 520 530 540 550
TYDHDVYRDE ALNNRFQIKG VELKSGYKDW ILWISFAISC FLLCVVLLGF
560
IMWACQRGNI RCNICI
Length:566
Mass (Da):63,416
Last modified:July 21, 1986 - v1
Checksum:iE395659C23CAFECA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti14A → P in AAA43239 (Ref. 2) Curated1
Sequence conflicti15L → I in BAF37221 (PubMed:15331693).Curated1
Sequence conflicti160G → S in BAF37221 (PubMed:15331693).Curated1
Sequence conflicti198I → V in BAF37221 (PubMed:15331693).Curated1
Sequence conflicti240R → G in BAF37221 (PubMed:15331693).Curated1
Sequence conflicti477E → D in BAF37221 (PubMed:15331693).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J02090 Genomic RNA. Translation: AAA43178.1.
V01085 Genomic RNA. Translation: CAA24269.1.
M55059 Genomic RNA. Translation: AAA43239.1.
AB284320 Genomic RNA. Translation: BAF37221.1.
PIRiA93231. HMIVHA.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J02090 Genomic RNA. Translation: AAA43178.1.
V01085 Genomic RNA. Translation: CAA24269.1.
M55059 Genomic RNA. Translation: AAA43239.1.
AB284320 Genomic RNA. Translation: BAF37221.1.
PIRiA93231. HMIVHA.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
1KENX-ray3.50B/D/F346-520[»]
1QFUX-ray2.80B346-520[»]
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[»]
4C56X-ray2.90F/L322-334[»]
4HMGX-ray3.00A/C/E17-344[»]
B/D/F346-520[»]
5HMGX-ray3.20A/C/E17-344[»]
B/D/F346-520[»]
ProteinModelPortaliP03437.
SMRiP03437.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-45342N.
IntActiP03437. 1 interactor.

Chemistry databases

BindingDBiP03437.
ChEMBLiCHEMBL1932897.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Miscellaneous databases

EvolutionaryTraceiP03437.

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_I68A0
AccessioniPrimary (citable) accession number: P03437
Secondary accession number(s): A0PC85, Q67132
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: November 2, 2016
This is version 131 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.