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Protein

Hemagglutinin

Gene

HA

Organism
Influenza A virus (strain A/Chicken/Hong Kong/220/1997 H5N1 genotype Gs/Gd)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Protein inferred from homologyi

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 (By similarity).By similarity

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/Chicken/Hong Kong/220/1997 H5N1 genotype Gs/Gd)
Taxonomic identifieri100834 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Felis catus (Cat) (Felis silvestris catus) [TaxID: 9685]
Homo sapiens (Human) [TaxID: 9606]
Panthera pardus (Leopard) (Felis pardus) [TaxID: 9691]
Panthera tigris (Tiger) [TaxID: 9694]
Sus scrofa (Pig) [TaxID: 9823]

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini17 – 531ExtracellularSequence analysisAdd BLAST515
Transmembranei532 – 552HelicalSequence analysisAdd BLAST21
Topological domaini553 – 568CytoplasmicSequence 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 – 16Sequence analysisAdd BLAST16
ChainiPRO_000028018317 – 338Hemagglutinin HA1 chainAdd BLAST322
PropeptideiPRO_0000392213339 – 346Connecting peptide8
ChainiPRO_0000280184347 – 568Hemagglutinin HA2 chainAdd BLAST222

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi20 ↔ 483Interchain (between HA1 and HA2 chains)By similarity
Glycosylationi26N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi27N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi39N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi58 ↔ 290By similarity
Disulfide bondi71 ↔ 83By similarity
Disulfide bondi106 ↔ 151By similarity
Glycosylationi170N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi181N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi294 ↔ 318By similarity
Glycosylationi302N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi490 ↔ 494By similarity
Glycosylationi500N-linked (GlcNAc...); by hostSequence analysis1
Lipidationi557S-palmitoyl cysteine; by hostBy similarity1
Lipidationi564S-palmitoyl cysteine; by hostBy similarity1
Lipidationi567S-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

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Interactioni

Subunit structurei

Homotrimer of disulfide-linked HA1-HA2.By similarity

Structurei

3D structure databases

ProteinModelPortaliO89746.
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.

O89746-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEKIVLLLAT VSLVKSDQIC IGYHANNSTE QVDTIMEKNV TVTHAQDILE
60 70 80 90 100
RTHNGKLCDL NGVKPLILRD CSVAGWLLGN PMCDEFINVP EWSYIVEKAS
110 120 130 140 150
PANDLCYPGN FNDYEELKHL LSRINHFEKI QIIPKSSWSN HDASSGVSSA
160 170 180 190 200
CPYLGRSSFF RNVVWLIKKN STYPTIKRSY NNTNQEDLLV LWGIHHPNDA
210 220 230 240 250
AEQTKLYQNP TTYISVGTST LNQRLVPEIA TRPKVNGQSG RMEFFWTILK
260 270 280 290 300
PNDAINFESN GNFIAPEYAY KIVKKGDSTI MKSELEYGNC NTKCQTPMGA
310 320 330 340 350
INSSMPFHNI HPLTIGECPK YVKSNRLVLA TGLRNTPQRE RRRKKRGLFG
360 370 380 390 400
AIAGFIEGGW QGMVDGWYGY HHSNEQGSGY AADQESTQKA IDGVTNKVNS
410 420 430 440 450
IINKMNTQFE AVGREFNNLE RRIENLNKKM EDGFLDVWTY NTELLVLMEN
460 470 480 490 500
ERTLDFHDSN VKNLYDKVRL QLRDNAKELG NGCFEFYHKC DNECMESVKN
510 520 530 540 550
GTYDYPQYSE EARLNREEIS GVKLESMGTY QILSIYSTVA SSLALAIMVA
560
GLSLWMCSNG SLQCRICI
Length:568
Mass (Da):64,349
Last modified:November 1, 1998 - v1
Checksum:i97A04110F2093E01
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF046080 Genomic RNA. Translation: AAC32078.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF046080 Genomic RNA. Translation: AAC32078.1.

3D structure databases

ProteinModelPortaliO89746.
ModBaseiSearch...
MobiDBiSearch...

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_I97A0
AccessioniPrimary (citable) accession number: O89746
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 6, 2007
Last sequence update: November 1, 1998
Last modified: November 2, 2016
This is version 91 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.

Documents

  1. 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.