The reference OMIM entry for this protein is 142800

Major histocompatibility complex, class i, a; hla-a
Hla-a histocompatibility type major histocompatibility complex, class i, h pseudogene, included; hla-h, included
Major histocompatibility complex, class i, j pseudogene, included; hla-j, include

DESCRIPTION

The human major histocompatibility complex (MHC) has been divided into 3 regions on chromosome 6p21.3: class II (centromeric), class III, and class I (telomeric), with extended class I and class II regions on either side. The MHC encodes highly polymorphic proteins, many of which are associated with the immune system. The products of classical polymorphic class I genes, human leukocyte antigen-A (HLA-A), HLA-B (142830), and HLA-C (142840), interact with T-cell receptor (TCR; see 186880) molecules, as well as killer immunoglobulin-like receptors (KIRs; see 604936) expressed on natural killer cells and some T cells (review by Trowsdale, 2001). Evidence from amino acid sequences suggests an evolutionary relatedness of transplantation antigens, immunoglobulins and beta-2-microglobins (Tragardh et al., 1979). Both the class I MHC antigens (A, B, and C) and the class II antigens DR and DC1 are polymorphic 2-chain cell surface glycoproteins; they are recognized by different subsets of T cells and have different functions, tissue distributions, and structures. The light chain of class I antigens is beta-2-microglobulin (B2M; 109700), which is coded by chromosome 15. The heavy chain, coded by chromosome 6, has a molecular mass of 44,000 and is made up of 3 N-terminal extracellular domains of 90 amino acids each, a small hydrophobic membrane-spanning segment and a small hydrophilic intracellular C-terminal domain. The 2 N-terminal domains are polymorphic, bear the carbohydrate and have no sequence homology with immunoglobulin. The third domain, closest to the membrane, and the 11.6-kD B2M light chain are highly conserved and have strong sequence homology with immunoglobulin.

GENE STRUCTURE

The sequence of a human class I gene was determined by Malissen et al. (1982). As in mouse, the domain organization of the HLA protein is reflected precisely in the exon-intron structure of the gene: separate exons encode the signal peptide, each of the 3 external domains and the transmembrane region, and 3 exons encode the small cytoplasmic domain. (See Hood et al., 1982.)

MAPPING

Studying a family with a pericentric inversion, Lamm et al. (1974) confirmed assignment of the HLA complex to chromosome 6. In a familial 6-21 translocation (Borgaonkar et al., 1973), Borgaonkar and Bias (1974) could show that HLA is proximal to 6p22. Francke and Pellegrino (1977) concluded that HLA is distal to 6p21. Thus, rather precise localization is possible. Kompf et al. (1978) and Schunter et al. (1978) presented evidence suggesting that PGM3 (172100) is on the HLA-A side of MHC rather than on the HLA-B side, as had previously been thought. From study of a 3-generation family segregating for variation of the centromeric heterochromatic region of chromosome 6p11 (6ph), Bakker et al. (1979) concluded that the HLA cluster and 6ph are about 6 cM apart (with peak lod score of 3.466 at a recombination fraction of 0.0588; 95% confidence limits 0-0.18), that GLO is on the centromeric side of HLA, that PGM-3 is not on the short arm, and that HLA-B is closer to the centromere than HLA-A. In a child partially trisomic for chromosome 6, Berger et al. (1979) discovered 3 haplotypes for HLA-A, -B and -C from the mother. The patient had only 2 HLA-DR specificities. The region was assigned to 6p2105. By in situ hybridization, Morton et al. (1984) showed that class I HLA determinants (HLA-A, -B, -C) are located in 6p21.3 and class II determinants in ... More on the omim web site

Subscribe to this protein entry history

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 142800 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).