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P03454

- HEMA_I33A0

UniProt

P03454 - HEMA_I33A0

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Protein
Hemagglutinin
Gene
HA
Organism
Influenza A virus (strain A/Wilson-Smith/1933 H1N1) (Influenza A virus (strain A/WS/1933 H1N1))
Status
Reviewed - Annotation score: 5 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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei343 – 3442Cleavage; 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/Wilson-Smith/1933 H1N1) (Influenza A virus (strain A/WS/1933 H1N1))
Taxonomic identifieri381518 [NCBI]
Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]
ProteomesiUP000000834: 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.1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini18 – 528511Extracellular Reviewed prediction
Add
BLAST
Transmembranei529 – 54921Helical; Reviewed prediction
Add
BLAST
Topological domaini550 – 56516Cytoplasmic Reviewed prediction
Add
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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi561 – 5611C → Y: 60% of proteins are targeted to the basolateral membrane in polarized epithelial cells. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1717 Reviewed prediction
Add
BLAST
Chaini18 – 342325Hemagglutinin HA1 chain
PRO_0000039069Add
BLAST
Chaini344 – 565222Hemagglutinin HA2 chain
PRO_0000039070Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi21 ↔ 480Interchain (between HA1 and HA2 chains) By similarity
Glycosylationi27 – 271N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi28 – 281N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi59 ↔ 291 By similarity
Disulfide bondi72 ↔ 84 By similarity
Glycosylationi73 – 731N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi107 ↔ 152 By similarity
Glycosylationi142 – 1421N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi285 – 2851N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi295 ↔ 319 By similarity
Disulfide bondi487 ↔ 491 By similarity
Glycosylationi497 – 4971N-linked (GlcNAc...); by host Reviewed prediction
Lipidationi554 – 5541S-palmitoyl cysteine; by host By similarity
Lipidationi561 – 5611S-palmitoyl cysteine; by host By similarity
Lipidationi564 – 5641S-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

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Interactioni

Subunit structurei

Homotrimer of disulfide-linked HA1-HA2.

Structurei

3D structure databases

ProteinModelPortaliP03454.
SMRiP03454. Positions 18-339, 344-518.

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.

P03454-1 [UniParc]FASTAAdd to Basket

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MKAKLLVLLY AFVATDADTI CIGYHANNST DTVDTIFEKN VAVTHSVNLL    50
EDRHNGKLCK LKGIAPLQLG KCNITGWLLG NPECDSLLPA RSWSYIVETP 100
NSENGACYPG DFIDYEELRE QLSSVSSLER FEIFPKESSW PNHTFNGVTV 150
SCSHRGKSSF YRNLLWLTKK GDSYPKLTNS YVNNKGKEVL VLWGVHHPSS 200
SDEQQSLYSN GNAYVSVASS NYNRRFTPEI AARPKVKDQH GRMNYYWTLL 250
EPGDTIIFEA TGNLIAPWYA FALSRGFESG IITSNASMHE CNTKCQTPQG 300
SINSNLPFQN IHPVTIGECP KYVRSTKLRM VTGLRNIPSI QYRGLFGAIA 350
GFIEGGWTGM IDGWYGYHHQ NEQGSGYAAD QKSTQNAING ITNKVNSVIE 400
KMNTQFTAVG KEFNNLEKRM ENLNKKVDDG FLDIWTYNAE LLVLLENERT 450
LDFHDLNVKN LYEKVKSQLK NNAKEIGNGC FEFYHKCDNE CMESVRNGTY 500
DYPKYSEESK LNREKIDGVK LESMGVYQIL AIYSTVASSL VLLVSLGAIS 550
FWMCSNGSLQ CRICI 565
Length:565
Mass (Da):63,525
Last modified:July 21, 1986 - v1
Checksum:i1BFF292E4A709299
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
J02176 Genomic RNA. Translation: AAA43209.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
J02176 Genomic RNA. Translation: AAA43209.1 .

3D structure databases

ProteinModelPortali P03454.
SMRi P03454. Positions 18-339, 344-518.
ModBasei 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. "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].
  2. "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.
  3. "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.

Entry informationi

Entry nameiHEMA_I33A0
AccessioniPrimary (citable) accession number: P03454
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: February 19, 2014
This is version 97 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

Complete proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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