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Protein

Hemagglutinin

Gene

HA

Organism
Influenza A virus (strain A/Korea/426/1968 H2N2)
Status
Reviewed-Annotation score: 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 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/Korea/426/1968 H2N2)
Taxonomic identifieri488241 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000146661 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 domaini16 – 525ExtracellularUniRule annotationAdd BLAST510
Transmembranei526 – 546HelicalUniRule annotationAdd BLAST21
Topological domaini547 – 562CytoplasmicUniRule 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 – 15UniRule annotationAdd BLAST15
ChainiPRO_000044041616 – 562HemagglutininUniRule annotationAdd BLAST547
ChainiPRO_000028019516 – 339Hemagglutinin HA1 chainUniRule annotationAdd BLAST324
ChainiPRO_0000280196341 – 562Hemagglutinin HA2 chainUniRule annotationAdd BLAST222

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi19 ↔ 477Interchain (between HA1 and HA2 chains)UniRule annotation
Glycosylationi25N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi26N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi38N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi57 ↔ 288UniRule annotation
Disulfide bondi70 ↔ 82UniRule annotation
Disulfide bondi105 ↔ 149UniRule annotation
Glycosylationi179N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi180N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi292 ↔ 316UniRule annotation
Glycosylationi300N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi484 ↔ 488UniRule annotation
Glycosylationi494N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Lipidationi551S-palmitoyl cysteine; by hostUniRule annotation1
Lipidationi558S-palmitoyl cysteine; by hostUniRule annotation1
Lipidationi561S-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
Sitei340 – 341Cleavage; 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

ProteinModelPortaliQ67143.
SMRiQ67143.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the influenza viruses hemagglutinin family.UniRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

KOiK19251.

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.

Q67143-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAIIYLILLF TAVRGDQICI GYHANNSTEK VDTILERNVT VTHAKDILEK
60 70 80 90 100
THNGKLCKLN GIPPLELGDC SIAGWLLGNP ECDRLLSVPE WSYIMEKENP
110 120 130 140 150
RYSLCYPGSF NDYEELKHLL SSVKHFEKVK ILPKDRWTQH TTTGGSWACA
160 170 180 190 200
VSGKPSFFRN MVWLTRKGSN YPVAKGSYNN TSGEQMLIIW GVHHPNDEAE
210 220 230 240 250
QRALYQNVGT YVSVATSTLY KRSIPEIAAR PKVNGLGRRM EFSWTLLDMW
260 270 280 290 300
DTINFESTGN LVAPEYGFKI SKRGSSGIMK TEGTLENCET KCQTPLGAIN
310 320 330 340 350
TTLPFHNVHP LTIGECPKYV KSEKLVLATG LRNVPQIESR GLFGAIAGFI
360 370 380 390 400
EGGWQGMVDG WYGYHHSNDQ GSGYAADKES TQKAFNGITN KVNSVIEKMN
410 420 430 440 450
TQFEAVGKEF SNLEKRLENL NKKMEDGFLD VWTYNAELLV LMENERTLDF
460 470 480 490 500
HDSNVKNLYD KVRMQLRDNV KELGNGCFEF YHKCDNECMD SVKNGTYDYP
510 520 530 540 550
KYEEESKLNR NEIKGVKLSS MGVYQILAIY ATVAGSLSLA IMMAGISFWM
560
CSNGSLQCRI CI
Length:562
Mass (Da):63,295
Last modified:November 1, 1996 - v1
Checksum:i427AFDA3BF5E6696
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L11133 Genomic RNA. Translation: AAA43247.1.
RefSeqiYP_308850.1. NC_007374.1.

Genome annotation databases

GeneIDi3655103.
KEGGivg:3655103.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L11133 Genomic RNA. Translation: AAA43247.1.
RefSeqiYP_308850.1. NC_007374.1.

3D structure databases

ProteinModelPortaliQ67143.
SMRiQ67143.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi3655103.
KEGGivg:3655103.

Phylogenomic databases

KOiK19251.

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.
ProtoNetiSearch...

Entry informationi

Entry nameiHEMA_I68A5
AccessioniPrimary (citable) accession number: Q67143
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 6, 2007
Last sequence update: November 1, 1996
Last modified: June 7, 2017
This is version 98 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

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.