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O56140

- HEMA_I97A1

UniProt

O56140 - HEMA_I97A1

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Protein

Hemagglutinin

Gene
HA
Organism
Influenza A virus (strain A/Hong Kong/156/1997 H5N1 genotype Gs/Gd)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript 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 speptide. Several trimers are required to form a competent fusion pore.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei346 – 3472Cleavage; by host

GO - Biological processi

  1. clathrin-mediated endocytosis of virus by host cell Source: UniProtKB-KW
  2. fusion of virus membrane with host endosome membrane Source: UniProtKB-KW
  3. fusion of virus membrane with host plasma membrane Source: InterPro
  4. virion attachment to host cell Source: UniProtKB-KW
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/Hong Kong/156/1997 H5N1 genotype Gs/Gd)
Taxonomic identifieri130763 [NCBI]
Taxonomic lineageiVirusesssRNA 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]
ProteomesiUP000008587: Genome

Subcellular locationi

Virion membrane; Single-pass type I membrane protein Reviewed prediction. Host apical cell membrane; Single-pass type I membrane protein
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.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini17 – 531515Extracellular Reviewed predictionAdd
BLAST
Transmembranei532 – 55221Helical; Reviewed predictionAdd
BLAST
Topological domaini553 – 56816Cytoplasmic Reviewed predictionAdd
BLAST

GO - Cellular componenti

  1. host cell plasma membrane Source: UniProtKB-SubCell
  2. integral component of membrane Source: UniProtKB-KW
  3. viral envelope Source: UniProtKB-KW
  4. virion membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1616 Reviewed predictionAdd
BLAST
Chaini17 – 338322Hemagglutinin HA1 chainPRO_0000043412Add
BLAST
Propeptidei339 – 3468Connecting peptidePRO_0000392214
Chaini347 – 568222Hemagglutinin HA2 chainPRO_0000043413Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi20 ↔ 483Interchain (between HA1 and HA2 chains) By similarity
Glycosylationi26 – 261N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi27 – 271N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi39 – 391N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi58 ↔ 290 By similarity
Disulfide bondi71 ↔ 83 By similarity
Disulfide bondi106 ↔ 151 By similarity
Glycosylationi181 – 1811N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi294 ↔ 318 By similarity
Glycosylationi302 – 3021N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi490 ↔ 494 By similarity
Glycosylationi500 – 5001N-linked (GlcNAc...); by host Reviewed prediction
Lipidationi557 – 5571S-palmitoyl cysteine; by host By similarity
Lipidationi564 – 5641S-palmitoyl cysteine; by host By similarity
Lipidationi567 – 5671S-palmitoyl cysteine; by host By similarity

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.
Palmitoylated By similarity.

Keywords - PTMi

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

Interactioni

Subunit structurei

Homotrimer of disulfide-linked HA1-HA2.

Structurei

3D structure databases

ProteinModelPortaliO56140.
SMRiO56140. Positions 17-337, 347-520.

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.

O56140-1 [UniParc]FASTAAdd to Basket

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MEKTVLLLAT VSLVKSDQIC IGYHANNSTE QVDTIMEKNV TVTHAQDILE    50
RTHNGKLCDL NGVKPLILRD CSVAGWLLGN PMCDEFINVP EWSYIVEKAS 100
PANDLCYPGN FNDYEELKHL LSRINHFEKI QIIPKSSWSN HDASSGVSSA 150
CPYLGRSSFF RNVVWLIKKN SAYPTIKRSY NNTNQEDLLV LWGIHHPNDA 200
AEQTKLYQNP TTYISVGTST LNQRLVPEIA TRPKVNGQSG RMEFFWTILK 250
PNDAINFESN GNFIAPEYAY KIVKKGDSTI MKSELEYGNC NTKCQTPMGA 300
INSSMPFHNI HPLTIGECPK YVKSNRLVLA TGLRNTPQRE RRRKKRGLFG 350
AIAGFIEGGW QGMVDGWYGY HHSNEQGSGY AADKESTQKA IDGVTNKVNS 400
IINKMNTQFE AVGREFNNLE RRIENLNKKM EDGFLDVWTY NAELLVLMEN 450
ERTLDFHDSN VKNLYDKVRL QLRDNAKELG NGCFEFYHKC DNECMESVKN 500
GTYDYPQYSE EARLNREEIS GVKLESMGTY QILSIYSTVA SSLALAIMVA 550
GLSLWMCSNG SLQCRICI 568
Length:568
Mass (Da):64,277
Last modified:January 24, 2006 - v2
Checksum:iD99BD1729B730A40
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti3 – 31K → R in AAC40508. 1 Publication
Sequence conflicti194 – 1941I → V in AAC40508. 1 Publication
Sequence conflicti379 – 3813GYA → CYS in AAC40508. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF028709 mRNA. Translation: AAC40508.1.
AF046088 Genomic RNA. Translation: AAC32088.1.
AF036356 Genomic RNA. Translation: AAC34263.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF028709 mRNA. Translation: AAC40508.1 .
AF046088 Genomic RNA. Translation: AAC32088.1 .
AF036356 Genomic RNA. Translation: AAC34263.1 .

3D structure databases

ProteinModelPortali O56140.
SMRi O56140. Positions 17-337, 347-520.
ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Family and domain databases

Gene3Di 2.10.77.10. 1 hit.
3.90.20.10. 1 hit.
3.90.209.20. 1 hit.
InterProi IPR008980. 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 ]
Pfami PF00509. Hemagglutinin. 1 hit.
[Graphical view ]
PRINTSi PR00330. HEMAGGLUTN1.
PR00329. HEMAGGLUTN12.
SUPFAMi SSF49818. SSF49818. 1 hit.
ProtoNeti Search...

Publicationsi

  1. "Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus."
    Claas E.C.J., Osterhaus A.D., van Beek R., De Jong J.C., Rimmelzwaan G.F., Senne D.A., Krauss S., Shortridge K.F., Webster R.G.
    Lancet 351:472-477(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Comparisons of highly virulent H5N1 influenza A viruses isolated from humans and chickens from Hong Kong."
    Suarez D.L., Perdue M.L., Cox N., Rowe T., Bender C., Huang J., Swayne D.E.
    J. Virol. 72:6678-6688(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  3. "Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness."
    Subbarao K., Klimov A., Katz J., Regnery H., Lim W., Hall H., Perdue M., Swayne D., Bender C., Huang J., Hemphill M., Rowe T., Shaw M., Xu X., Fukuda K., Cox N.
    Science 279:393-396(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 17-568.

Entry informationi

Entry nameiHEMA_I97A1
AccessioniPrimary (citable) accession number: O56140
Secondary accession number(s): O56262, Q9WAA0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: January 24, 2006
Last modified: February 19, 2014
This is version 89 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

Complete proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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