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Protein

Hemagglutinin

Gene

HA

Organism
Influenza A virus (strain A/Singapore/1/1957 H2N2)
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 (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/Singapore/1/1957 H2N2)
Taxonomic identifieri382781 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000008218 Componenti: Genome

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini16 – 525ExtracellularSequence analysisAdd BLAST510
Transmembranei526 – 546HelicalSequence analysisAdd BLAST21
Topological domaini547 – 562CytoplasmicSequence 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 – 15Sequence analysisAdd BLAST15
ChainiPRO_000028020116 – 339Hemagglutinin HA1 chainAdd BLAST324
ChainiPRO_0000280202341 – 562Hemagglutinin HA2 chainAdd BLAST222

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi19 ↔ 477Interchain (between HA1 and HA2 chains)By similarity
Glycosylationi25N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi26N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi38N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi57 ↔ 288By similarity
Disulfide bondi70 ↔ 82By similarity
Disulfide bondi105 ↔ 149By similarity
Glycosylationi179N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi180N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi292 ↔ 316By similarity
Glycosylationi300N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi484 ↔ 488By similarity
Glycosylationi494N-linked (GlcNAc...); by hostSequence analysis1
Lipidationi551S-palmitoyl cysteine; by hostBy similarity1
Lipidationi558S-palmitoyl cysteine; by hostBy similarity1
Lipidationi561S-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
Sitei340 – 341Cleavage; by hostBy similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Interactioni

Subunit structurei

Homotrimer of disulfide-linked HA1-HA2.By similarity

Structurei

Secondary structure

1562
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi17 – 19Combined sources3
Beta strandi21 – 23Combined sources3
Beta strandi37 – 42Combined sources6
Beta strandi44 – 46Combined sources3
Beta strandi56 – 59Combined sources4
Helixi72 – 77Combined sources6
Helixi80 – 82Combined sources3
Beta strandi91 – 96Combined sources6
Beta strandi101 – 103Combined sources3
Beta strandi108 – 110Combined sources3
Helixi113 – 120Combined sources8
Beta strandi122 – 132Combined sources11
Helixi134 – 136Combined sources3
Beta strandi146 – 151Combined sources6
Beta strandi154 – 156Combined sources3
Beta strandi161 – 163Combined sources3
Beta strandi167 – 169Combined sources3
Beta strandi174 – 179Combined sources6
Beta strandi182 – 194Combined sources13
Helixi198 – 205Combined sources8
Beta strandi212 – 215Combined sources4
Beta strandi220 – 223Combined sources4
Beta strandi239 – 247Combined sources9
Beta strandi252 – 259Combined sources8
Beta strandi261 – 271Combined sources11
Beta strandi278 – 280Combined sources3
Beta strandi285 – 294Combined sources10
Beta strandi304 – 306Combined sources3
Beta strandi313 – 315Combined sources3
Beta strandi326 – 328Combined sources3
Turni347 – 349Combined sources3
Beta strandi361 – 364Combined sources4
Helixi378 – 397Combined sources20
Helixi412 – 414Combined sources3
Helixi415 – 466Combined sources52
Helixi467 – 469Combined sources3
Beta strandi470 – 472Combined sources3
Beta strandi474 – 476Combined sources3
Beta strandi478 – 482Combined sources5
Helixi486 – 494Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2WR7X-ray2.50A/B/C1-506[»]
2WRBX-ray3.10A/B/C1-506[»]
2WRCX-ray2.71A/B/C1-506[»]
ProteinModelPortaliQ67333.
SMRiQ67333.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ67333.

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.

Q67333-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAIIYLILLF TAVRGDQICI GYHANNSTEK VDTILERNVT VTHAKDILEK
60 70 80 90 100
THNGKLCKLN GIPPLELGDC SIAGWLLGNP ECDRLLSVPE WSYIMEKENP
110 120 130 140 150
RDGLCYPGSF NDYEELKHLL SSVKHFEKVK ILPKDRWTQH TTTGGSRACA
160 170 180 190 200
VSGNPSFFRN MVWLTEKGSN YPVAKGSYNN TSGEQMLIIW GVHHPNDEKE
210 220 230 240 250
QRTLYQNVGT YVSVGTSTLN KRSTPDIATR PKVNGLGSRM EFSWTLLDMW
260 270 280 290 300
DTINFESTGN LIAPEYGFKI SKRGSSGIMK TEGTLENCET KCQTPLGAIN
310 320 330 340 350
TTLPFHNVHP LTIGECPKYV KSEKLVLATG LRNVPQIESR GLFGAIAGFI
360 370 380 390 400
EGGWQGMIDG WYGYHHSNDQ GSGYAADKES TQKAFDGITN KVNSVIEKMN
410 420 430 440 450
TQFEAVGKEF SNLERRLENL NKKMEDGFLD VWTYNAELLV LMENERTLDF
460 470 480 490 500
HDSNVKNLYD KVRMQLRDNV KELGNGCFEF YHKCDDECMN SVKNGTYDYP
510 520 530 540 550
KYEEESKLNR NEIKGVKLSS MGVYQILAIY ATVAGSLSLA IMMAGISFWM
560
CSNGSLQCRI CI
Length:562
Mass (Da):63,162
Last modified:November 1, 1996 - v1
Checksum:i5178496D4EDF5172
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L11142 Genomic RNA. Translation: AAA43678.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L11142 Genomic RNA. Translation: AAA43678.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2WR7X-ray2.50A/B/C1-506[»]
2WRBX-ray3.10A/B/C1-506[»]
2WRCX-ray2.71A/B/C1-506[»]
ProteinModelPortaliQ67333.
SMRiQ67333.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Miscellaneous databases

EvolutionaryTraceiQ67333.

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_I57A5
AccessioniPrimary (citable) accession number: Q67333
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 6, 2007
Last sequence update: November 1, 1996
Last modified: November 2, 2016
This is version 92 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, Complete proteome

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.