HLA-G gene

major histocompatibility complex, class I, G

The information on this page was automatically extracted from online scientific databases.

From NCBI Gene:

HLA-G 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. HLA-G is expressed on fetal derived placental cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domain, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exon 6 encodes the cytoplasmic tail. [provided by RefSeq, Jul 2008]

From UniProt:

Isoform 4: Negatively regulates NK cell- and CD8+ T cell-mediated cytotoxicity (PubMed:11290782). Likely do not bind B2M and present peptides.

Isoform 6: Physiological function remains unknown. Likely do not bind B2M and present peptides.

Isoform 1: Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface (PubMed:23184984, PubMed:29262349, PubMed:19304799). In complex with B2M/beta-2 microglobulin binds a limited repertoire of nonamer self-peptides derived from intracellular proteins including histones and ribosomal proteins (PubMed:7584149, PubMed:8805247). Peptide-bound HLA-G-B2M complex acts as a ligand for inhibitory/activating KIR2DL4, LILRB1 and LILRB2 receptors on uterine immune cells to promote fetal development while maintaining maternal-fetal tolerance (PubMed:23184984, PubMed:29262349, PubMed:16366734, PubMed:19304799, PubMed:20448110, PubMed:27859042). Upon interaction with KIR2DL4 and LILRB1 receptors on decidual NK cells, it triggers NK cell senescence-associated secretory phenotype as a molecular switch to promote vascular remodeling and fetal growth in early pregnancy (PubMed:23184984, PubMed:29262349, PubMed:16366734, PubMed:19304799). Through interaction with KIR2DL4 receptor on decidual macrophages induces proinflammatory cytokine production mainly associated with tissue remodeling (PubMed:19304799). Through interaction with LILRB2 receptor triggers differentiation of type 1 regulatory T cells and myeloid-derived suppressor cells, both of which actively maintain maternal-fetal tolerance (PubMed:20448110, PubMed:27859042). May play a role in balancing tolerance and antiviral-immunity at maternal-fetal interface by keeping in check the effector functions of NK, CD8+ T cells and B cells (PubMed:10190900, PubMed:11290782, PubMed:24453251). Reprograms B cells toward an immune suppressive phenotype via LILRB1 (PubMed:24453251). May induce immune activation/suppression via intercellular membrane transfer (trogocytosis), likely enabling interaction with KIR2DL4, which resides mostly in endosomes (PubMed:20179272, PubMed:26460007). Through interaction with the inhibitory receptor CD160 on endothelial cells may control angiogenesis in immune privileged sites (PubMed:16809620).

Isoform 3: Negatively regulates NK cell- and CD8+ T cell-mediated cytotoxicity (PubMed:11290782). Likely do not bind B2M and present peptides.

Isoform 5: Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface (PubMed:23184984, PubMed:29262349, PubMed:19304799). In complex with B2M/beta-2 microglobulin binds a limited repertoire of nonamer self-peptides derived from intracellular proteins including histones and ribosomal proteins (PubMed:7584149, PubMed:8805247). Peptide-bound HLA-G-B2M complex acts as a ligand for inhibitory/activating KIR2DL4, LILRB1 and LILRB2 receptors on uterine immune cells to promote fetal development while maintaining maternal-fetal tolerance (PubMed:23184984, PubMed:29262349, PubMed:16366734, PubMed:19304799, PubMed:20448110). Upon interaction with KIR2DL4 and LILRB1 receptors on decidual NK cells, it triggers NK cell senescence-associated secretory phenotype as a molecular switch to promote vascular remodeling and fetal growth in early pregnancy (PubMed:23184984, PubMed:29262349, PubMed:16366734, PubMed:19304799). Through interaction with KIR2DL4 receptor on decidual macrophages induces proinflammatory cytokine production mainly associated with tissue remodeling (PubMed:19304799). Through interaction with LILRB2 receptor triggers differentiation of type 1 regulatory T cells and myeloid-derived suppressor cells, both of which actively maintain maternal-fetal tolerance (PubMed:20448110). Reprograms B cells toward an immune suppressive phenotype via LILRB1 (PubMed:24453251).

Isoform 7: Physiological function remains unknown. Likely do not bind B2M and present peptides.

Isoform 2: Negatively regulates NK cell- and CD8+ T cell-mediated cytotoxicity (PubMed:11290782). Likely do not bind B2M and present peptides.

Cytogenetic Location: 6p22.1, which is the short (p) arm of chromosome 6 at position 22.1

Molecular Location: base pairs 29,826,967 to 29,831,130 on chromosome 6 (Homo sapiens Annotation Release 109, GRCh38.p12) (NCBI)

Cytogenetic Location: 6p22.1, which is the short (p) arm of chromosome 6 at position 22.1