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Protein

Hemagglutinin

Gene

HA

Organism
Influenza A virus (strain A/Duck/Alberta/35/1976 H1N1)
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/Duck/Alberta/35/1976 H1N1)
Taxonomic identifieri352520 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini18 – 529ExtracellularSequence analysisAdd BLAST512
Transmembranei530 – 550HelicalSequence analysisAdd BLAST21
Topological domaini551 – 566CytoplasmicSequence analysisAdd BLAST16

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 – 17Sequence analysisAdd BLAST17
ChainiPRO_000003891018 – 343Hemagglutinin HA1 chainAdd BLAST326
ChainiPRO_0000038911345 – 566Hemagglutinin HA2 chainAdd BLAST222

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi21 ↔ 481Interchain (between HA1 and HA2 chains)By similarity
Glycosylationi27N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi28N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi40N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi59 ↔ 292By similarity
Disulfide bondi72 ↔ 84By similarity
Glycosylationi104N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi107 ↔ 153By similarity
Disulfide bondi296 ↔ 320By similarity
Glycosylationi304N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi488 ↔ 492By similarity
Glycosylationi498N-linked (GlcNAc...); by hostSequence analysis1
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 (By similarity).By similarity
Palmitoylated.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei344 – 345Cleavage; by hostBy similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Interactioni

Subunit structurei

Homotrimer of disulfide-linked HA1-HA2.

Structurei

Secondary structure

1566
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi19 – 25Combined sources7
Beta strandi39 – 44Combined sources6
Beta strandi46 – 48Combined sources3
Beta strandi56 – 61Combined sources6
Helixi74 – 79Combined sources6
Helixi82 – 84Combined sources3
Turni85 – 87Combined sources3
Beta strandi96 – 98Combined sources3
Helixi115 – 121Combined sources7
Beta strandi123 – 134Combined sources12
Helixi136 – 139Combined sources4
Beta strandi150 – 155Combined sources6
Beta strandi158 – 160Combined sources3
Beta strandi163 – 167Combined sources5
Beta strandi170 – 173Combined sources4
Beta strandi178 – 183Combined sources6
Beta strandi186 – 198Combined sources13
Helixi202 – 209Combined sources8
Beta strandi216 – 220Combined sources5
Beta strandi223 – 227Combined sources5
Beta strandi242 – 251Combined sources10
Beta strandi256 – 263Combined sources8
Beta strandi265 – 276Combined sources12
Beta strandi282 – 284Combined sources3
Beta strandi289 – 293Combined sources5
Beta strandi295 – 297Combined sources3
Beta strandi307 – 310Combined sources4
Beta strandi317 – 319Combined sources3
Beta strandi330 – 332Combined sources3
Turni351 – 353Combined sources3
Beta strandi365 – 368Combined sources4
Helixi382 – 401Combined sources20
Helixi419 – 470Combined sources52
Helixi471 – 473Combined sources3
Beta strandi474 – 478Combined sources5
Beta strandi481 – 486Combined sources6
Helixi490 – 498Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2WRHX-ray3.00H/J/L18-343[»]
I/K/M345-566[»]
ProteinModelPortaliP26562.
SMRiP26562.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP26562.

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.

P26562-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEAKLFVLFC TFTVLKADTI CVGYHANNST DTVDTVLEKN VTVTHSVNLL
60 70 80 90 100
EDSHNGKLCS LNGIAPLQLG KCNVAGWLLG NPECDLLLTA NSWSYIIETS
110 120 130 140 150
NSENGTCYPG EFIDYEELRE QLSSISSFEK FEIFPKASSW PNHETTKGVT
160 170 180 190 200
AACSYSGASS FYRNLLWITK KGTSYPKLSK SYTNNKGKEV LVLWGVHHPP
210 220 230 240 250
SVSEQQSLYQ NADAYVSVGS SKYNRRFAPE IAARPEVRGQ AGRMNYYWTL
260 270 280 290 300
LDQGDTITFE ATGNLIAPWY AFALNKGSDS GIITSDAPVH NCDTRCQTPH
310 320 330 340 350
GALNSSLPFQ NVHPITIGEC PKYVKSTKLR MATGLRNVPS IQSRGLFGAI
360 370 380 390 400
AGFIEGGWTG MIDGWYGYHH QNEQGSGYAA DQKSTQNAID GITSKVNSVI
410 420 430 440 450
EKMNTQFTAV GKEFNNLERR IENLNKKVDD GFLDVWTYNA ELLVLLENER
460 470 480 490 500
TLDFHDSNVR NLYEKVKSQL RNNAKEIGNG CFEFYHKCDD ECMESVKNGT
510 520 530 540 550
YDYPKYSEES KLNREEIDGV KLESMGVYQI LAIYSTVASS LVLLVSWGAI
560
SFWMCSNGSL QCRICI
Length:566
Mass (Da):63,072
Last modified:February 1, 1996 - v2
Checksum:i9B7ADCA0E9BCA819
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti65A → P in AAB52910 (PubMed:8892928).Curated1
Sequence conflicti125I → V in AAB52910 (PubMed:8892928).Curated1
Sequence conflicti236E → K in AAB52910 (PubMed:8892928).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D10477 Genomic RNA. Translation: BAA01280.1.
U47310 mRNA. Translation: AAB52910.1.
PIRiA36257. HMIVD1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D10477 Genomic RNA. Translation: BAA01280.1.
U47310 mRNA. Translation: AAB52910.1.
PIRiA36257. HMIVD1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2WRHX-ray3.00H/J/L18-343[»]
I/K/M345-566[»]
ProteinModelPortaliP26562.
SMRiP26562.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Miscellaneous databases

EvolutionaryTraceiP26562.

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_I76A4
AccessioniPrimary (citable) accession number: P26562
Secondary accession number(s): O09652
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: February 1, 1996
Last modified: November 2, 2016
This is version 104 of the entry and version 2 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.