HLA-A

Gene Information
 
Gene Symbol
HLA-A
 
Aliases
HLAA
 
Entrez Gene ID
 
Gene Name
Major histocompatibility complex, class I, A
 
Chromosomal Location
6p22.1
 
HGNC ID
 
Summary
HLA-A belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. Class I molecules play a central role in the immune system by presenting peptides derived from the endoplasmic reticulum lumen. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon 1 encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exons 6 and 7 encode the cytoplasmic tail. Polymorphisms within exon 2 and exon 3 are responsible for the peptide binding specificity of each class one molecule. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. Hundreds of HLA-A alleles have been described. [provided by RefSeq, Jul 2008]
 
RefSeq DNA
 
RefSeq mRNA
  e!Ensembl
Gene
Transcript  
Protein

Gene Ontology (GO)

GO ID Ontology Function Evidence Reference
GO:0001916 Biological process Positive regulation of T cell mediated cytotoxicity IBA 21873635
GO:0002476 Biological process Antigen processing and presentation of endogenous peptide antigen via MHC class Ib IBA 21873635
GO:0002486 Biological process Antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent IBA 21873635
GO:0006955 Biological process Immune response IBA 21873635
GO:0005615 Cellular component Extracellular space IBA 21873635
Protein Information
 
Protein Name
HLA class I histocompatibility antigen, A alpha chain, HLA class I histocompatibility antigen, A-1 alpha chain, MHC class I antigen HLA-A heavy chain, leukocyte antigen class I-A
 
Function
Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells for recognition by alpha-beta T cell receptor (TCR) on HLA-A-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected or transformed cells. May also present self-peptides derived from the signal sequence of secreted or membrane proteins, although T cells specific for these peptides are usually inactivated to prevent autoreactivity. Both the peptide and the MHC molecule are recognized by TCR, the peptide is responsible for the fine specificity of antigen recognition and MHC residues account for the MHC restriction of T cells. Typically presents intracellular peptide antigens of 8 to 13 amino acids that arise from cytosolic proteolysis via IFNG-induced immunoproteasome or via endopeptidase IDE/insulin-degrading enzyme. Can bind different peptides containing allele-specific binding motifs, which are mainly defined by anchor residues at position 2 and 9. Allele A*01:01: Presents a restricted peptide repertoire including viral epitopes derived from IAV NP/nucleoprotein (CTELKLSDY), IAV PB1/polymerase basic protein 1 (VSDGGPNLY), HAdV-11 capsid L3/hexon protein (LTDLGQNLLY) as well as tumor peptide antigens including MAGE1 (EADPTGHSY), MAGEA3 (EVDPIGHLY) and WT1 (TSEKRPFMCAY), all having in common a canonical motif with a negatively charged Asp or Glu residue at position 3 and a Tyr anchor residue at the C-terminus. A number of HLA-A*01:01-restricted peptides carry a post-translational modification with oxidation and N-terminal acetylation being the most frequent. Fails to present highly immunogenic peptides from the EBV latent antigens. Allele A*02:01: A major allele in human populations, presents immunodominant viral epitopes derived from IAV M/matrix protein 1 (GILGFVFTL), HIV-1 env (TLTSCNTSV), HIV-1 gag-pol (ILKEPVHGV), HTLV-1 Tax (LLFGYPVYV), HBV C/core antigen (FLPSDFFPS), HCMV UL83/pp65 (NLVPMVATV) as well as tumor peptide antigens including MAGEA4 (GVYDGREHTV), WT1 (RMFPNAPYL) and CTAG1A/NY-ESO-1 (SLLMWITQC), all having in common hydrophobic amino acids at position 2 and at the C-terminal anchors. Allele A*03:01: Presents viral epitopes derived from IAV NP (ILRGSVAHK), HIV-1 nef (QVPLRPMTYK), HIV-1 gag-pol (AIFQSSMTK) as well as tumor peptide antigens including PMEL (LIYRRRLMK), NODAL (HAYIQSLLK), TRP-2 (RMYNMVPFF), all having in common hydrophobic amino acids at position 2 and Lys or Arg anchor residues at the C-terminus. May also display spliced peptides resulting from the ligation of two separate proteasomal cleavage products that are not contiguous in the parental protein. Allele A*11:01: Presents several immunodominant epitopes derived from HIV-1 gag-pol and HHV-4 EBNA4, containing the peptide motif with Val, Ile, Thr, Leu, Tyr or Phe at position 2 and Lys anchor residue at the C-terminus. Important in the control of HIV-1, EBV and HBV infections. .; Allele A*23:01: Interacts with natural killer (NK) cell receptor KIR3DL1 and may contribute to functional maturation of NK cells and self-nonself discrimination during innate immune response. .; Allele A*24:02: Presents viral epitopes derived from HIV-1 nef (RYPLTFGWCF), EBV lytic- and latent-cycle antigens BRLF1 (TYPVLEEMF), BMLF1 (DYNFVKQLF) and LMP2 (IYVLVMLVL), SARS-CoV nucleocapsid/N (QFKDNVILL), as well as tumor peptide antigens including PRAME (LYVDSLFFL), all sharing a common signature motif, namely an aromatic residue Tyr or Phe at position 2 and a nonhydrophobic anchor residue Phe, Leu or Iso at the C-terminus. Interacts with natural killer (NK) cell receptor KIR3DL1 and may contribute to functional maturation of NK cells and self-nonself discrimination during innate immune response. Allele A*26:01: Presents several epitopes derived from HIV-1 gag-pol (EVIPMFSAL, ETKLGKAGY) and env (LVSDGGPNLY), carrying as anchor residues preferentially Glu at position 1, Val or Thr at position 2 and Tyr at the C-terminus. Allele A*29:02: Presents peptides having a common motif, namely a Glu residue at position 2 and Tyr or Leu anchor residues at the C-terminus. Allele A*32:01: Interacts with natural killer (NK) cell receptor KIR3DL1 and may contribute to functional maturation of NK cells and self-nonself discrimination during innate immune response. Allele A*68:01: Presents viral epitopes derived from IAV NP (KTGGPIYKR) and HIV-1 tat (ITKGLGISYGR), having a common signature motif namely, Val or Thr at position 2 and positively charged residues Arg or Lys at the C-terminal anchor. Allele A*74:01: Presents immunodominant HIV-1 epitopes derived from gag-pol (GQMVHQAISPR, QIYPGIKVR) and rev (RQIHSISER), carrying an aliphatic residue at position 2 and Arg anchor residue at the C-terminus. May contribute to viral load control in chronic HIV-1 infection
 
Refseq Proteins
 
UniProt
 
PDB
Pathways
 
KEGG
 
Reactome
 

Endocytosis
Phagosome
Cellular senescence
Cell adhesion molecules (CAMs)
Antigen processing and presentation
Natural killer cell mediated cytotoxicity
Type I diabetes mellitus
Human cytomegalovirus infection
Human papillomavirus infection
Human T-cell leukemia virus 1 infection
Kaposi sarcoma-associated herpesvirus infection
Herpes simplex virus 1 infection
Epstein-Barr virus infection
Human immunodeficiency virus 1 infection
Viral carcinogenesis
Autoimmune thyroid disease
Allograft rejection
Graft-versus-host disease
Viral myocarditis

 

ER-Phagosome pathway
Endosomal/Vacuolar pathway
Nef mediated downregulation of MHC class I complex cell surface expression
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
Neutrophil degranulation
Interferon gamma signaling
E3 ubiquitin ligases ubiquitinate target proteins
Interferon alpha/beta signaling
Antigen Presentation: Folding, assembly and peptide loading of class I MHC

Interactions
 
STRING MINT IntAct
ENSP00000312673 P01241
    View interactions
     

Associated Diseases

Disease groupDisease NameReferences
Digestive System Diseases
Hepatitis
Liver Diseases
Ear Or Mastoid Diseases
Meniere Disease
Endocrine System Diseases
Diabetes Mellitus
PCOS
References
 

Association of polycystic ovarian syndrome with human leukocyte antigen polymorphism in Korean women.

Kim Jin Ju, Hwang Kyu Ri, Shin Sue, Yoon Jong Hyun, Kim Byoung Jae, Choi Young Min, Roh Eun Youn
Department of Obstetrics and Gynecology, Healthcare System Gangnam Center, Seoul National University College of Medicine, Korea.
APMIS. 2011 Sep;119(9):618-25. doi: 10.1111/j.1600-0463.2011.02779.x. Epub 2011

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