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Protein

Hemagglutinin

Gene

HA

Organism
Influenza A virus (strain A/Beijing/353/1989 H3N2)
Status
Reviewed-Annotation score: Annotation score: 4 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 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/Beijing/353/1989 H3N2)
Taxonomic identifieri380949 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Cetacea (whales) [TaxID: 9721]
Homo sapiens (Human) [TaxID: 9606]
Phocidae (true seals) [TaxID: 9709]
Sus scrofa (Pig) [TaxID: 9823]

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini17 – 530514ExtracellularSequence analysisAdd
BLAST
Transmembranei531 – 55121HelicalSequence analysisAdd
BLAST
Topological domaini552 – 56615CytoplasmicSequence analysisAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1616Sequence analysisAdd
BLAST
Chaini17 – 344328Hemagglutinin HA1 chainPRO_0000280181Add
BLAST
Chaini346 – 566221Hemagglutinin HA2 chainPRO_0000280182Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi24 – 241N-linked (GlcNAc...); by hostSequence analysis
Disulfide bondi30 ↔ 482Interchain (between HA1 and HA2 chains)By similarity
Glycosylationi38 – 381N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi54 – 541N-linked (GlcNAc...); by hostSequence analysis
Disulfide bondi68 ↔ 293By similarity
Glycosylationi79 – 791N-linked (GlcNAc...); by hostSequence analysis
Disulfide bondi80 ↔ 92By similarity
Disulfide bondi113 ↔ 155By similarity
Glycosylationi142 – 1421N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi181 – 1811N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi262 – 2621N-linked (GlcNAc...); by hostSequence analysis
Disulfide bondi297 ↔ 321By similarity
Glycosylationi301 – 3011N-linked (GlcNAc...); by hostSequence analysis
Disulfide bondi489 ↔ 493By similarity
Glycosylationi499 – 4991N-linked (GlcNAc...); by hostSequence analysis
Lipidationi555 – 5551S-palmitoyl cysteine; by hostBy similarity
Lipidationi562 – 5621S-palmitoyl cysteine; by hostBy similarity
Lipidationi565 – 5651S-palmitoyl cysteine; by hostBy 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).By similarity
Palmitoylated.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei345 – 3462Cleavage; by hostBy similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Interactioni

Subunit structurei

Homotrimer of disulfide-linked HA1-HA2.By similarity

Structurei

3D structure databases

ProteinModelPortaliO11283.
SMRiO11283. Positions 25-518.
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.

O11283-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKTIIALSYI LCLVFAQKLP GNDNSTATLC LGHHAVPNGT LVKTITNDQI
60 70 80 90 100
EVTNATELVQ SSSTGRICDS PHRILDGKNC TLIDALLGDP HCDGFQNKEW
110 120 130 140 150
DLFVERSKAY SNCYPYDVPD YASLRSLVAS SGTLEFINED FNWTGVAQSG
160 170 180 190 200
ESYACKRGSV KSFFSRLNWL HESEYKYPAL NVTMPNNGKF DKLYIWGVHH
210 220 230 240 250
PSTDREQTNL YVRASGRVTV STKRSQQTVI PNIGSRPWVR GLSSRISIYW
260 270 280 290 300
TIVKPGDILL INSTGNLIAP RGYFKIRTGK SSIMRSDAPI GTCSSECITP
310 320 330 340 350
NGSIPNDKPF QNVNRITYGA CPRYVKQNTL KLATGMRNVP EKQTRGIFGA
360 370 380 390 400
IAGFIENGWE GMVNGWYGFR HQNSEGTGQA ADLKSTQAAI DQINGKLNRL
410 420 430 440 450
IEKTNEKFHQ IEKEFSEVEG RIQDLEKYVE DTKIDLWSYN AELLVALENQ
460 470 480 490 500
HTIDLTDSEM NKLFEKTRKQ LRENAEDMGN GCFKIYHKCD NACIGSIRNG
510 520 530 540 550
TYDHDVYRDE ALNNRFQIKG VELKSGYKDW ILWISFAISC FLLCVVLLGF
560
IMWACQKGNI RCNICI
Length:566
Mass (Da):63,732
Last modified:March 6, 2007 - v2
Checksum:i2AAF326A5D341213
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti202 – 2021S → I in AAB66751 (PubMed:9223253).Curated
Sequence conflicti209 – 2091N → K in AAB58297 (Ref. 1) Curated
Sequence conflicti364 – 3641N → D in AAT64741 (PubMed:15218094).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U97740 mRNA. Translation: AAB58297.1.
AY661066 Genomic DNA. Translation: AAT64741.1.
AF008684 Genomic RNA. Translation: AAB66751.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U97740 mRNA. Translation: AAB58297.1.
AY661066 Genomic DNA. Translation: AAT64741.1.
AF008684 Genomic RNA. Translation: AAB66751.1.

3D structure databases

ProteinModelPortaliO11283.
SMRiO11283. Positions 25-518.
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...

Publicationsi

  1. "Nucleotide sequence of the complete HA of influenza virus A/Beijing/353/89 (H3 subtype)."
    Reading P.C., Sahasrabudhe A.
    Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-562.
  3. "Long term trends in the evolution of H(3) HA1 human influenza type A."
    Fitch W.M., Bush R.M., Bender C.A., Cox N.J.
    Proc. Natl. Acad. Sci. U.S.A. 94:7712-7718(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 17-345.

Entry informationi

Entry nameiHEMA_I89A2
AccessioniPrimary (citable) accession number: O11283
Secondary accession number(s): O40676, Q6DME6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 6, 2007
Last sequence update: March 6, 2007
Last modified: December 9, 2015
This is version 91 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.

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.