Tbio HLA-G HLA class I histocompatibility antigen, alpha chain G

Protein Summary

Description

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 2: Negatively regulates NK cell- and CD8+ T cell-mediated cytotoxicity (PubMed:11290782). Likely do not bind B2M and present peptides (Probable). Isoform 3: Negatively regulates NK cell- and CD8+ T cell-mediated cytotoxicity (PubMed:11290782). Likely do not bind B2M and present peptides (Probable). Isoform 4: Negatively regulates NK cell- and CD8+ T cell-mediated cytotoxicity (PubMed:11290782). Likely do not bind B2M and present peptides (Probable). 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 6: Physiological function remains unknown. Likely do not bind B2M and present peptides. Isoform 7: Physiological function remains unknown. Likely do not bind B2M and present peptides. 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]

Uniprot Accession IDs

• P17693

Gene Name

• HLA-G

Ensembl ID

• ENST00000360323
• ENSP00000353472
• ENSG00000204632
• ENST00000376815
• ENSP00000366011
• ENST00000383621
• ENSP00000373116
• ENSG00000206506
• ENST00000383622
• ENSP00000373117
• ENST00000415687
• ENSP00000389969
• ENSG00000237216
• ENST00000423011
• ENSP00000389522
• ENSG00000233095
• ENST00000423373
• ENSP00000405238
• ENSG00000235346
• ENST00000428701
• ENSP00000412927
• ENST00000428952
• ENSP00000388176
• ENSG00000235680
• ENST00000429890
• ENSP00000401326
• ENST00000444098
• ENSP00000398200
• ENSG00000230413
• ENST00000445373
• ENSP00000416408
• ENST00000448306
• ENSP00000413926
• ENST00000449127
• ENSP00000408773
• ENST00000457132
• ENSP00000410247
• ENST00000546545
• ENSP00000447762
• ENST00000546634
• ENSP00000447780
• ENST00000547241
• ENSP00000448085
• ENST00000547931
• ENSP00000448363
• ENST00000550897
• ENSP00000449903
• ENST00000553052
• ENSP00000449291
• ENST00000622601
• ENSP00000479399
• ENSG00000276051

Symbol

• HLA-6.0
• HLAG
• MHC-G

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological term	1
virus perturbation	1
protein domain	0.97
cellular component	0.94
disease	0.91

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1370.34   (req: < 5)

Gene RIFs: 779   (req: <= 3)

Antibodies: 1368   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1370.34   (req: >= 5)

Gene RIFs: 779   (req: > 3)

Antibodies: 1368   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 22

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0