Protein: HLA class I histocompatibility antigen, alpha chain G (HLA G antigen) (MHC class I antigen G) [Cleaved into: Soluble HLA class I histocompatibility antigen, alpha chain G (sHLA-G)] (P17693)
Organism: Homo sapiens (Human)
Function: Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface. In complex with B2M/beta-2 microglobulin binds a limited repertoire of nonamer self-peptides derived from intracellular proteins including histones and ribosomal proteins. 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. 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. Through interaction with KIR2DL4 receptor on decidual macrophages induces pro-inflammatory cytokine production mainly associated with tissue remodeling. 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. 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. Reprograms B cells toward an immune suppressive phenotype via LILRB1. May induce immune activation/suppression via intercellular membrane transfer (trogocytosis), likely enabling interaction with KIR2DL4, which resides mostly in endosomes. Through interaction with the inhibitory receptor CD160 on endothelial cells may control angiogenesis in immune privileged sites.
Subcellular location: [Isoform 1]: Cell membrane {ECO:0000269|PubMed:20448110, ECO:0000269|PubMed:7584149}; Single-pass type I membrane protein {ECO:0000255}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:11520457}. Early endosome membrane {ECO:0000269|PubMed:16366734}.; SUBCELLULAR LOCATION: [Soluble HLA class I histocompatibility antigen, alpha chain G]: Secreted {ECO:0000269|PubMed:23737137}.; SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane {ECO:0000269|PubMed:11290782}; Single-pass type I membrane protein {ECO:0000255}.; SUBCELLULAR LOCATION: [Isoform 3]: Cell membrane {ECO:0000269|PubMed:11290782}; Single-pass type I membrane protein {ECO:0000255}.; SUBCELLULAR LOCATION: [Isoform 4]: Cell membrane {ECO:0000269|PubMed:11290782}; Single-pass type I membrane protein {ECO:0000255}.; SUBCELLULAR LOCATION: [Isoform 5]: Secreted {ECO:0000269|PubMed:11137219, ECO:0000269|PubMed:7558941, ECO:0000269|PubMed:7584149, ECO:0000269|PubMed:7989753}. Early endosome {ECO:0000269|PubMed:16366734}.; SUBCELLULAR LOCATION: [Isoform 6]: Secreted {ECO:0000269|PubMed:7989753}.; SUBCELLULAR LOCATION: [Isoform 7]: Secreted {ECO:0000269|PubMed:11137219}.; SUBCELLULAR LOCATION: Cell projection, filopodium membrane {ECO:0000269|PubMed:26460007}. Note=HLA-G trogocytosis from extravillous trophoblast's filopodia occurs in the majority of decidual NK cells. {ECO:0000269|PubMed:26460007}.
Interaction partners:
- Leukocyte immunoglobulin-like receptor subfamily B member 2
- Leukocyte immunoglobulin-like receptor subfamily B member 1
- Beta-2-microglobulin
- Natural killer cells antigen CD94
- Killer cell immunoglobulin-like receptor 2DL4
- NKG2-A/NKG2-B type II integral membrane protein
- T-cell surface glycoprotein CD8 alpha chain
- SH3 and cysteine-rich domain-containing protein
- CD160 antigen
- HLA class I histocompatibility antigen, alpha chain E
Sequence:
MVVMAPRTLFLLLSGALTLTETWAGSHSMRYFSAAVSRPGRGEPRFIAMGYVDDTQFVRFDSDSACPRMEPRAPWVEQEGPEYWEEETRNTKAHAQTDRMNLQTLRGYYNQSEASSHTLQWMIGCDLGSDGRLLRGYEQYAYDGKDYLALNEDLRSWTAADTAAQISKRKCEAANVAEQRRAYLEGTCVEWLHRYLENGKEMLQRADPPKTHVTHHPVFDYEATLRCWALGFYPAEIILTWQRDGEDQTQDVELVETRPAGDGTFQKWAAVVVPSGEEQRYTCHVQHEGLPEPLMLRWKQSSLPTIPIMGIVAGLVVLAAVVTGAAVAAVLWRKKSSD