Gene Summary: This gene encodes a member of the G protein-coupled receptor family. The protein contains 7 transmembrane domains and a mucin-like domain in the N-terminal region. The gene is implicated in the regulation of brain cortical patterning. The protein binds specifically to transglutaminase 2 in the extracellular space. Expression of this gene is downregulated in melanoma cell lines, and overexpression of this gene can suppress tumor growth and metastasis. Mutations in this gene result in bilateral frontoparietal polymicrogyria. Multiple transcript variants encoding different isoforms have been found for this gene.General information above from NCBI
Enzyme regulation: GPR56 NT is proposed to inhibit receptor signaling; its interactions with extracellular ligands and /or homophilic GPR56 NT interactions may relieve the inhibition.
Subunit structure: Predominantly non-covalently linked heterodimer of the N- terminal and the C-terminal fragment. GPR56 NT self-associates in a trans-trans manner; the homophilic interaction enhances receptor signaling. GPR56 CT interacts with ARRB2; the interaction is impaired by GPR56 NT. Interacts with TGM2; TGM2 probably is not a GPR56 ligand and the interaction is reported conflictingly (PubMed:16757564, PubMed:21349848). Part of a GPCR-tetraspanin complex at least consisting of GPR56, CD81, eventually CD9, and GNA11 in which CD81 is enhancing the association of GPR56 with GNA11.
Tissue specificity: Widely distributed with highest levels found in thyroid gland, brain and heart. Expressed in a great number of tumor cells. Expression is down-regulated in different tumors from highly metastatic cells.
Induction: By glucose and lovastain. Up-regulation is prevented by mevalonic acid, farnesol, and geranylgeraniol. Up-regulated by E2F1.
Post-translational: Autoproteolytically cleaved into 2 fragments; the large extracellular N-terminal fragment and the membrane-bound C- terminal fragment predominantly remain associated and non- covalently linked. Shedding to yield the secreted GPR56 N-terminal fragment seems to involve metalloprotease(s). N-glycosylated. Contains sialic acid residues. Ubiquitinated. Undergoes polyubiquitination upon activation.
Involvement in disease: Polymicrogyria, bilateral frontoparietal (BFPP) [MIM:606854]: A malformation of the cortex in which the brain surface is irregular and characterized by an excessive number of small gyri with abnormal lamination, most severe in the frontoparietal regions. BFPP clinical manifestations include developmental and psychomotor delay, cerebellar and pyramidal signs, truncal ataxia, seizures, hyperreflexia. Polymicrogyria is a heterogeneous disorder, considered to be the result of postmigratory abnormal cortical organization. Note=The disease is caused by mutations affecting the gene represented in this entry.
Sequence similarity: Belongs to the G-protein coupled receptor 2 family. LN-TM7 subfamily. Contains 1 GPS domain.