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Protein

Hemagglutinin

Gene

HA

Organism
Influenza A virus (strain A/Swine/Wisconsin/1/1961 H1N1)
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 either through clathrin-dependent endocytosis or through 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.UniRule annotation

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.Curated

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHemagglutinin
Biological processClathrin- 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:
HemagglutininUniRule annotation
Cleaved into the following 2 chains:
Hemagglutinin HA1 chainUniRule annotation
Hemagglutinin HA2 chainUniRule annotation
Gene namesi
Name:HAUniRule annotation
OrganismiInfluenza A virus (strain A/Swine/Wisconsin/1/1961 H1N1)
Taxonomic identifieri383533 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]
Proteomesi
  • UP000007769 Componenti: Genome

Subcellular locationi

  • Virion membrane UniRule annotation; Single-pass type I membrane protein UniRule annotation
  • Host apical cell membrane UniRule annotation; Single-pass type I membrane protein UniRule annotation

  • 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.UniRule annotation

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini18 – 529ExtracellularUniRule annotationAdd BLAST512
Transmembranei530 – 550HelicalUniRule annotationAdd BLAST21
Topological domaini551 – 566CytoplasmicUniRule annotationAdd BLAST16

GO - Cellular componenti

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 17UniRule annotationAdd BLAST17
ChainiPRO_000044039718 – 566HemagglutininUniRule annotationAdd BLAST549
ChainiPRO_500005515018 – 343Hemagglutinin HA1 chainUniRule annotationAdd BLAST326
ChainiPRO_5000055151345 – 566Hemagglutinin HA2 chainUniRule annotationAdd BLAST222

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi21 ↔ 481Interchain (between HA1 and HA2 chains)UniRule annotation
Glycosylationi27N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi28N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi40N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi59 ↔ 292UniRule annotation
Disulfide bondi72 ↔ 84UniRule annotation
Glycosylationi104N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi107 ↔ 153UniRule annotation
Disulfide bondi296 ↔ 320UniRule annotation
Glycosylationi304N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi488 ↔ 492UniRule annotation
Glycosylationi498N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Lipidationi555S-palmitoyl cysteine; by hostUniRule annotation1
Lipidationi562S-palmitoyl cysteine; by hostUniRule annotation1
Lipidationi565S-palmitoyl cysteine; by hostUniRule annotation1

Post-translational modificationi

Palmitoylated.UniRule annotation
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.UniRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei344 – 345Cleavage; by hostUniRule annotation2

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Interactioni

Subunit structurei

Homotrimer of disulfide-linked HA1-HA2.UniRule annotation

GO - Molecular functioni

Structurei

3D structure databases

ProteinModelPortaliQ9WCD8.
SMRiQ9WCD8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the influenza viruses hemagglutinin family.UniRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

OrthoDBiVOG090000DU.

Family and domain databases

Gene3Di3.90.209.20. 1 hit.
HAMAPiMF_04072. INFV_HEMA. 1 hit.
InterProiView protein in InterPro
IPR008980. Capsid_hemagglutn.
IPR013828. Hemagglutn_HA1_a/b_dom.
IPR000149. Hemagglutn_influenz_A.
IPR001364. Hemagglutn_influenz_A/B.
PfamiView protein in Pfam
PF00509. Hemagglutinin. 1 hit.
PRINTSiPR00330. HEMAGGLUTN1.
PR00329. HEMAGGLUTN12.
SUPFAMiSSF49818. SSF49818. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9WCD8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKAILLVLLC AFAATNADTL CIGYHANNST DTVDTVLEKN VTVTHSVNLL
60 70 80 90 100
EDRHNGKLCK LGGIAPLHLG KCNIAGWLLG NPECELLLTV SSWSYIVETS
110 120 130 140 150
NSDNGTCYPG DFINYEELRE QLSSVSSFER FEIFPKTSSW PNHETNRGVT
160 170 180 190 200
AACPYAGANS FYRNLIWLVK KESSYPKLSK SYVNNKGKEV LVLWGIHHPP
210 220 230 240 250
TSTDQQSLYQ NADAYVFVGS SKYNRKFKPE IAARPKVRGQ AGRMNYYWTL
260 270 280 290 300
IEPGDTITFE ATGNLVVPRY AFAMNRGSGS GIIISDAPVH DCNTKCQTPK
310 320 330 340 350
GAINTSLPFQ NIHPVTIGEC PKYVKSTKLR MATGLRNIPS IQSRGLFGAI
360 370 380 390 400
AGFIEGGWTG MIDGWYGYHH QNGQGSGYAA DQKSTQNAID GITNKVNSVI
410 420 430 440 450
EKMNMQFTAV GKEFNNLEKR IENLNKKVDD GFLDVWTYNA ELLVLLENER
460 470 480 490 500
TLDFHDSNVK NLYEKVRSQL RNNAKEIGNG CFEFYHKCDD TCMESVKNGT
510 520 530 540 550
YDYPKYSEES KLNREEIDGV KLESTRVYQI LAIYSTVASS LVLLVSLGAI
560
SFWMCSNGSL QCRICI
Length:566
Mass (Da):63,083
Last modified:November 1, 1999 - v1
Checksum:i1CC621E7A3B45111
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti172E → G. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF091307 mRNA. Translation: AAD25302.1.
CY032213 Viral cRNA. Translation: ACD85154.1.

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.

Entry informationi

Entry nameiHEMA_I61A1
AccessioniPrimary (citable) accession number: Q9WCD8
Secondary accession number(s): B3EUQ6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 6, 2007
Last sequence update: November 1, 1999
Last modified: June 7, 2017
This is version 93 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families