UniProtKB - P03437 (HEMA_I68A0)
Protein
Hemagglutinin
Gene
HA
Organism
Influenza A virus (strain A/Aichi/2/1968 H3N2)
Status
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.
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 either through clathrin-dependent endocytosis or through 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.UniRule annotation
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.Curated
GO - Molecular functioni
- host cell surface receptor binding Source: UniProtKB-UniRule
GO - Biological processi
- clathrin-dependent endocytosis of virus by host cell Source: UniProtKB-UniRule
- fusion of virus membrane with host endosome membrane Source: UniProtKB-UniRule
- fusion of virus membrane with host plasma membrane Source: InterPro
- viral budding from plasma membrane Source: UniProtKB-UniRule
- virion attachment to host cell Source: UniProtKB-KW
Keywordsi
Protein family/group databases
UniLectini | P03437 |
Names & Taxonomyi
Protein namesi | Recommended name: HemagglutininUniRule annotationCleaved into the following 2 chains: Hemagglutinin HA1 chainUniRule annotation Hemagglutinin HA2 chainUniRule annotation |
Gene namesi | Name:HAUniRule annotation |
Organismi | Influenza A virus (strain A/Aichi/2/1968 H3N2) |
Taxonomic identifieri | 387139 [NCBI] |
Taxonomic lineagei | Viruses › Riboviria › Negarnaviricota › Polyploviricotina › Insthoviricetes › Articulavirales › Orthomyxoviridae › Alphainfluenzavirus › |
Virus hosti | Aves [TaxID: 8782] Cetacea (whales) [TaxID: 9721] Homo sapiens (Human) [TaxID: 9606] Phocidae (true seals) [TaxID: 9709] Sus scrofa (Pig) [TaxID: 9823] |
Proteomesi |
|
Subcellular locationi
- Virion membrane UniRule annotation; Single-pass type I membrane protein UniRule annotation
- Host apical cell membrane UniRule annotation; Single-pass type I membrane protein UniRule annotation 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.UniRule annotation
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 17 – 530 | ExtracellularUniRule annotationAdd BLAST | 514 | |
Transmembranei | 531 – 551 | HelicalUniRule annotationAdd BLAST | 21 | |
Topological domaini | 552 – 566 | CytoplasmicUniRule annotationAdd BLAST | 15 |
GO - Cellular componenti
- host cell plasma membrane Source: UniProtKB-SubCell
- integral component of membrane Source: UniProtKB-UniRule
- viral envelope Source: UniProtKB-UniRule
- virion membrane Source: UniProtKB-SubCell
Keywords - Cellular componenti
Host cell membrane, Host membrane, Membrane, Viral envelope protein, VirionPathology & Biotechi
Chemistry databases
ChEMBLi | CHEMBL1932897 |
DrugBanki | DB07726 2-tert-butylbenzene-1,4-diol |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 16 | UniRule annotationAdd BLAST | 16 | |
ChainiPRO_0000440411 | 17 – 566 | HemagglutininUniRule annotationAdd BLAST | 550 | |
ChainiPRO_0000038885 | 17 – 344 | Hemagglutinin HA1 chainAdd BLAST | 328 | |
ChainiPRO_0000038886 | 346 – 566 | Hemagglutinin HA2 chainUniRule annotationAdd BLAST | 221 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 24 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation | 1 | |
Disulfide bondi | 30 ↔ 482 | Interchain (between HA1 and HA2 chains)UniRule annotation | ||
Glycosylationi | 38 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation | 1 | |
Glycosylationi | 54 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation | 1 | |
Disulfide bondi | 68 ↔ 293 | UniRule annotation | ||
Disulfide bondi | 80 ↔ 92 | UniRule annotation | ||
Glycosylationi | 97 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation | 1 | |
Disulfide bondi | 113 ↔ 155 | UniRule annotation | ||
Glycosylationi | 181 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation | 1 | |
Disulfide bondi | 297 ↔ 321 | UniRule annotation | ||
Glycosylationi | 301 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation | 1 | |
Disulfide bondi | 489 ↔ 493 | UniRule annotation | ||
Glycosylationi | 499 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation | 1 | |
Lipidationi | 555 | S-palmitoyl cysteine; by hostUniRule annotation | 1 | |
Lipidationi | 562 | S-palmitoyl cysteine; by hostUniRule annotation | 1 | |
Lipidationi | 565 | S-palmitoyl cysteine; by hostUniRule annotation | 1 |
Post-translational modificationi
Palmitoylated.UniRule annotation
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.UniRule annotation1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 345 – 346 | Cleavage; by hostUniRule annotation | 2 |
Keywords - PTMi
Disulfide bond, Glycoprotein, Lipoprotein, PalmitateInteractioni
Subunit structurei
Homotrimer of disulfide-linked HA1-HA2.
UniRule annotationProtein-protein interaction databases
DIPi | DIP-45342N |
IntActi | P03437, 1 interactor |
Chemistry databases
BindingDBi | P03437 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P03437 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P03437 |
Family & Domainsi
Sequence similaritiesi
Belongs to the influenza viruses hemagglutinin family.UniRule annotation
Keywords - Domaini
Signal, Transmembrane, Transmembrane helixFamily and domain databases
Gene3Di | 3.90.209.20, 1 hit |
HAMAPi | MF_04072 INFV_HEMA, 1 hit |
InterProi | View protein in InterPro IPR008980 Capsid_hemagglutn IPR013828 Hemagglutn_HA1_a/b_dom_sf IPR000149 Hemagglutn_influenz_A IPR001364 Hemagglutn_influenz_A/B |
Pfami | View protein in Pfam PF00509 Hemagglutinin, 1 hit |
PRINTSi | PR00330 HEMAGGLUTN1 PR00329 HEMAGGLUTN12 |
SUPFAMi | SSF49818 SSF49818, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
P03437-1 [UniParc]FASTAAdd to basket
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 14 | A → P in AAA43239 (Ref. 2) Curated | 1 | |
Sequence conflicti | 15 | L → I in BAF37221 (PubMed:15331693).Curated | 1 | |
Sequence conflicti | 160 | G → S in BAF37221 (PubMed:15331693).Curated | 1 | |
Sequence conflicti | 198 | I → V in BAF37221 (PubMed:15331693).Curated | 1 | |
Sequence conflicti | 240 | R → G in BAF37221 (PubMed:15331693).Curated | 1 | |
Sequence conflicti | 477 | E → D in BAF37221 (PubMed:15331693).Curated | 1 |
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 |
PIRi | A93231 HMIVHA |
Similar proteinsi
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 |
PIRi | A93231 HMIVHA |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1EO8 | X-ray | 2.80 | A | 17-344 | [»] | |
B | 346-520 | [»] | ||||
1FYT | X-ray | 2.60 | C | 322-334 | [»] | |
1HA0 | X-ray | 2.80 | A | 25-518 | [»] | |
1HGG | X-ray | 2.90 | A/C/E | 17-344 | [»] | |
B/D/F | 346-520 | [»] | ||||
1HTM | X-ray | 2.50 | A/C/E | 17-43 | [»] | |
B/D/F | 383-520 | [»] | ||||
1J8H | X-ray | 2.40 | C | 322-334 | [»] | |
1KEN | X-ray | 3.50 | B/D/F | 346-520 | [»] | |
1KG0 | X-ray | 2.65 | D | 322-334 | [»] | |
1PYW | X-ray | 2.10 | C | 324-332 | [»] | |
1QFU | X-ray | 2.80 | B | 346-520 | [»] | |
1QU1 | X-ray | 1.90 | A/B/C/D/E/F | 376-530 | [»] | |
2HMG | X-ray | 3.00 | A/C/E | 17-344 | [»] | |
B/D/F | 346-520 | [»] | ||||
2VIR | X-ray | 3.25 | C | 44-325 | [»] | |
2VIS | X-ray | 3.25 | C | 44-325 | [»] | |
2VIT | X-ray | 3.25 | C | 44-325 | [»] | |
2VIU | X-ray | 2.50 | A | 17-344 | [»] | |
B | 346-520 | [»] | ||||
2YPG | X-ray | 2.85 | A/C/E | 17-344 | [»] | |
B/D/F | 346-520 | [»] | ||||
3EYM | X-ray | 2.80 | A/C/E | 25-345 | [»] | |
B/D/F | 346-517 | [»] | ||||
3HMG | X-ray | 2.90 | A/C/E | 17-344 | [»] | |
B/D/F | 346-520 | [»] | ||||
3S4S | X-ray | 2.40 | C/F | 322-334 | [»] | |
3S5L | X-ray | 2.10 | C/F | 322-334 | [»] | |
3VUN | X-ray | 3.00 | A/C/E | 17-345 | [»] | |
B/D/F | 346-520 | [»] | ||||
4C56 | X-ray | 2.90 | F/L | 322-334 | [»] | |
4HMG | X-ray | 3.00 | A/C/E | 17-344 | [»] | |
B/D/F | 346-520 | [»] | ||||
5HMG | X-ray | 3.20 | A/C/E | 17-344 | [»] | |
B/D/F | 346-520 | [»] | ||||
6E56 | X-ray | 2.00 | A/D | 53-335 | [»] | |
6N5D | X-ray | 3.00 | A/B/K | 53-334 | [»] | |
6N5E | X-ray | 3.00 | A/B/C | 53-334 | [»] | |
SMRi | P03437 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
DIPi | DIP-45342N |
IntActi | P03437, 1 interactor |
Chemistry databases
BindingDBi | P03437 |
ChEMBLi | CHEMBL1932897 |
DrugBanki | DB07726 2-tert-butylbenzene-1,4-diol |
Protein family/group databases
UniLectini | P03437 |
Protocols and materials databases
ABCDi | P03437 |
Miscellaneous databases
EvolutionaryTracei | P03437 |
Family and domain databases
Gene3Di | 3.90.209.20, 1 hit |
HAMAPi | MF_04072 INFV_HEMA, 1 hit |
InterProi | View protein in InterPro IPR008980 Capsid_hemagglutn IPR013828 Hemagglutn_HA1_a/b_dom_sf IPR000149 Hemagglutn_influenz_A IPR001364 Hemagglutn_influenz_A/B |
Pfami | View protein in Pfam PF00509 Hemagglutinin, 1 hit |
PRINTSi | PR00330 HEMAGGLUTN1 PR00329 HEMAGGLUTN12 |
SUPFAMi | SSF49818 SSF49818, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | HEMA_I68A0 | |
Accessioni | P03437Primary (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: | September 18, 2019 | |
This is version 146 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Viral Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Complete proteomeDocuments
- SIMILARITY comments
Index of protein domains and families - PDB cross-references
Index of Protein Data Bank (PDB) cross-references