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P03453

- HEMA_I77AB

UniProt

P03453 - HEMA_I77AB

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Protein

Hemagglutinin

Gene

HA

Organism
Influenza A virus (strain A/USSR/90/1977 H1N1)
Status
Reviewed - Annotation score: 4 out of 5- Protein inferred from homologyi

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
Sitei344 – 3452Cleavage; by hostBy similarity

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/USSR/90/1977 H1N1)
Taxonomic identifieri381516 [NCBI]
Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]
ProteomesiUP000007793: Genome

Subcellular locationi

Virion membrane Curated; Single-pass type I membrane protein Curated. 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.

GO - Cellular componenti

  1. host cell plasma membrane Source: UniProtKB-KW
  2. integral component of membrane Source: UniProtKB-KW
  3. viral envelope Source: UniProtKB-KW
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 – 1717Sequence AnalysisAdd
BLAST
Chaini18 – 343326Hemagglutinin HA1 chainPRO_0000039063Add
BLAST
Chaini345 – 566222Hemagglutinin HA2 chainPRO_0000039064Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi21 ↔ 481Interchain (between HA1 and HA2 chains)By similarity
Glycosylationi27 – 271N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi28 – 281N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi40 – 401N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi59 ↔ 292By similarity
Disulfide bondi72 ↔ 84By similarity
Glycosylationi104 – 1041N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi144 – 1441N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi172 – 1721N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi177 – 1771N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi286 – 2861N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi296 ↔ 320By similarity
Glycosylationi304 – 3041N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi488 ↔ 492By similarity
Glycosylationi498 – 4981N-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

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Interactioni

Subunit structurei

Homotrimer of disulfide-linked HA1-HA2.

Structurei

3D structure databases

ProteinModelPortaliP03453.
SMRiP03453. Positions 18-340, 345-519.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini18 – 529512ExtracellularSequence AnalysisAdd
BLAST
Topological domaini551 – 56616CytoplasmicSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei530 – 55021HelicalSequence AnalysisAdd
BLAST

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.

P03453-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MKAKLLVLLC ALSATDADTI CIGYHANNST DTVDTVLEKN VTVTHSVNLL
60 70 80 90 100
EDSHNGKLCR LKGIAPLQLG KCNIAGWILG NPECESLFSK KSWSYIAETP
110 120 130 140 150
NSENGTCYPG YFADYEELRE QLSSVSSFER FEIFPKERSW PKHNVTRGVT
160 170 180 190 200
ASCSHKGKSS FYRNLLWLTE KNGSYPNLSK SYVNNKEKEV LVLWGVHHPS
210 220 230 240 250
NIEDQKTIYR KENAYVSVVS SNYNRRFTPE IAERPKVRGQ AGRINYYWTL
260 270 280 290 300
LEPGDTIIFE ANGNLIAPWH AFALNRGFGS GIITSNASMD ECDTKCQTPQ
310 320 330 340 350
GAINSSLPFQ NIHPVTIGEC PKYVRSTKLR MVTGLRNIPS IQSRGLFGAI
360 370 380 390 400
AGFIEGGWTG MIDGWYGYHH QNEQGSGYAA DQKSTQNAIN GITNKVNSVI
410 420 430 440 450
EKMNTQFTAV GKEFNKLEKR MENLNKKVDD GFLDIWTYNA ELLVLLENER
460 470 480 490 500
TLDFHDSNVK NLYEKVKSQL KNNAKEIGNG CFEFYHKCNN ECMESVKNGT
510 520 530 540 550
YDYPKYSEES KLNREKIDGV KLESMGVYQI LAIYSTVASS LVLLVSLGAI
560
SFWMCSNGSL QCRICI
Length:566
Mass (Da):63,587
Last modified:April 17, 2007 - v2
Checksum:iD23D848AB2A6793B
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti13 – 131S → A in AAA43206. (PubMed:6690716)Curated
Sequence conflicti180 – 1801K → S in AAA43206. (PubMed:6690716)Curated
Sequence conflicti296 – 2961Missing in AAA43240. (PubMed:6196912)Curated
Sequence conflicti458 – 4581N → S in AAA43206. (PubMed:6690716)Curated
Sequence conflicti462 – 4621L → A in AAA43206. (PubMed:6690716)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
K01330 Genomic RNA. Translation: AAA43206.1.
CY010372 Genomic RNA. Translation: ABD95350.1.
DQ508897 Genomic RNA. Translation: ABF21277.1.
K01331 Genomic RNA. Translation: AAA43240.1.
PIRiA04064. HMIVUR.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
K01330 Genomic RNA. Translation: AAA43206.1 .
CY010372 Genomic RNA. Translation: ABD95350.1 .
DQ508897 Genomic RNA. Translation: ABF21277.1 .
K01331 Genomic RNA. Translation: AAA43240.1 .
PIRi A04064. HMIVUR.

3D structure databases

ProteinModelPortali P03453.
SMRi P03453. Positions 18-340, 345-519.
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. "Nucleotide sequence of the influenza virus A/USSR/90/77 hemagglutinin gene."
    Concannon P., Cummings I.W., Salser W.A.
    J. Virol. 49:276-278(1984) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  3. "Complete genome sequencing and analysis of selected influenza virus vaccine strains spanning six decades (1933-1999)."
    Mbawuike I.N., Zhang Y., Yamada R.E., Nino D., Bui H.-H., Sette A., Couch R.B.
    Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  4. "Identification of the binding sites to monoclonal antibodies on A/USSR/90/77 (H1N1) hemagglutinin and their involvement in antigenic drift in H1N1 influenza viruses."
    Nakajima S., Nakajima K., Kendal A.P.
    Virology 131:116-127(1983) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-343.

Entry informationi

Entry nameiHEMA_I77AB
AccessioniPrimary (citable) accession number: P03453
Secondary accession number(s): Q1WP09
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: April 17, 2007
Last modified: October 29, 2014
This is version 100 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