P03454 (HEMA_I33A0) Reviewed, UniProtKB/Swiss-Prot
Last modified October 16, 2013. Version 95. History...
Names and origin
|Protein names||Recommended name:|
|Organism||Influenza A virus (strain A/Wilson-Smith/1933 H1N1) (Influenza A virus (strain A/WS/1933 H1N1)) [Complete proteome]|
|Taxonomic identifier||381518 [NCBI]|
|Taxonomic lineage||Viruses › ssRNA negative-strand viruses › Orthomyxoviridae › Influenzavirus A ›|
|Virus host||Aves [TaxID: 8782]|
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]
|Sequence length||565 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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.
Homotrimer of disulfide-linked HA1-HA2.
Virion membrane; Single-pass type I membrane protein Potential. 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. Ref.2
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.
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.
Belongs to the influenza viruses hemagglutinin family.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Signal peptide||1 – 17||17||Potential|
|Chain||18 – 342||325||Hemagglutinin HA1 chain||PRO_0000039069|
|Chain||344 – 565||222||Hemagglutinin HA2 chain||PRO_0000039070|
|Topological domain||18 – 528||511||Extracellular Potential|
|Transmembrane||529 – 549||21||Helical; Potential|
|Topological domain||550 – 565||16||Cytoplasmic Potential|
|Site||343 – 344||2||Cleavage; by host|
Amino acid modifications
|Lipidation||554||1||S-palmitoyl cysteine; by host By similarity|
|Lipidation||561||1||S-palmitoyl cysteine; by host By similarity|
|Lipidation||564||1||S-palmitoyl cysteine; by host By similarity|
|Glycosylation||27||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||28||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||73||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||142||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||285||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||497||1||N-linked (GlcNAc...); by host Potential|
|Disulfide bond||21 ↔ 480||Interchain (between HA1 and HA2 chains) By similarity|
|Disulfide bond||59 ↔ 291||By similarity|
|Disulfide bond||72 ↔ 84||By similarity|
|Disulfide bond||107 ↔ 152||By similarity|
|Disulfide bond||295 ↔ 319||By similarity|
|Disulfide bond||487 ↔ 491||By similarity|
|Mutagenesis||561||1||C → Y: 60% of proteins are targeted to the basolateral membrane in polarized epithelial cells. Ref.3|
|||"Complete sequence analysis shows that the hemagglutinins of the H0 and H2 subtypes of human influenza virus are closely related."|
Hiti A.L., Davis A.R., Nayak D.P.
Virology 111:113-124(1981) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
|||"Analysis of the transmembrane domain of influenza virus neuraminidase, a type II transmembrane glycoprotein, for apical sorting and raft association."|
Barman S., Nayak D.P.
J. Virol. 74:6538-6545(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
|||"Influenza A virus hemagglutinin containing basolateral localization signal does not alter the apical budding of a recombinant influenza A virus in polarized MDCK cells."|
Barman S., Adhikary L., Kawaoka Y., Nayak D.P.
Virology 305:138-152(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF CYS-561.
|J02176 Genomic RNA. Translation: AAA43209.1.|
3D structure databases
|SMR||P03454. Positions 18-339, 344-518. |
Protocols and materials databases
Family and domain databases
|Gene3D||220.127.116.11. 1 hit. |
18.104.22.168. 1 hit.
22.214.171.124. 1 hit.
|InterPro||IPR008980. Capsid_hemagglutn. |
|Pfam||PF00509. Hemagglutinin. 1 hit. |
|PRINTS||PR00330. HEMAGGLUTN1. |
|SUPFAM||SSF49818. SSF49818. 1 hit. |
|Accession||Primary (citable) accession number: P03454|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|
Index of protein domains and families