LGR4

G protein-coupled receptors (GPCRs) play key roles in a variety of physiologic functions. Members of the leucine-rich GPCR (LGR) family, such as GPR48, have multiple N-terminal leucine-rich repeats (LRRs) and a 7-transmembrane domain (Weng et al., 2008 [PubMed 18424556]).[supplied by OMIM

Full Name

leucine-rich repeat-containing G protein-coupled receptor 4

Function

Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and is involved in the formation of various organs. Upon binding to R-spondins (RSPO1, RSPO2, RSPO3 or RSPO4), associates with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. In contrast to classical G-protein coupled receptors, does not activate heterotrimeric G-proteins to transduce the signal. Its function as activator of the Wnt signaling pathway is required for the development of various organs, including liver, kidney, intestine, bone, reproductive tract and eye. May also act as a receptor for norrin (NDP), such results however require additional confirmation in vivo. Required during spermatogenesis to activate the Wnt signaling pathway in peritubular myoid cells. Required for the maintenance of intestinal stem cells and Paneth cell differentiation in postnatal intestinal crypts. Acts as a regulator of bone formation and remodeling. Involved in kidney development; required for maintaining the ureteric bud in an undifferentiated state. Involved in the development of the anterior segment of the eye. Required during erythropoiesis. Also acts as a negative regulator of innate immunity by inhibiting TLR2/TLR4 associated pattern-recognition and proinflammatory cytokine production. Plays an important role in regulating the circadian rhythms of plasma lipids, partially through regulating the rhythmic expression of MTTP (By similarity).

Biological Process

Activation of adenylate cyclase activityManual Assertion Based On ExperimentIBA:GO_Central
Adenylate cyclase-activating G protein-coupled receptor signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Bone mineralizationISS:UniProtKB
Bone remodelingISS:UniProtKB
Canonical Wnt signaling pathway involved in metanephric kidney developmentIEA:Ensembl
Cell differentiation involved in metanephros developmentIEA:Ensembl
Circadian regulation of gene expressionISS:UniProtKB
Digestive tract developmentIEA:Ensembl
Epithelial cell proliferation involved in renal tubule morphogenesisIEA:Ensembl
Hair follicle developmentIEA:Ensembl
Hormone-mediated signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Innate immune responseIEA:UniProtKB-KW
Intestinal stem cell homeostasisIEA:Ensembl
Male genitalia developmentIEA:Ensembl
Metanephric glomerulus developmentIEA:Ensembl
Metanephric nephron tubule morphogenesisIEA:Ensembl
Negative regulation of cold-induced thermogenesisBy SimilarityISS:YuBioLab
Negative regulation of cytokine productionISS:UniProtKB
Negative regulation of toll-like receptor signaling pathwayISS:UniProtKB
Negative regulation of transcription, DNA-templatedIEA:Ensembl
Osteoblast differentiationISS:UniProtKB
Positive regulation of branching involved in ureteric bud morphogenesisIEA:Ensembl
Positive regulation of canonical Wnt signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of transcription, DNA-templatedIEA:Ensembl
SpermatogenesisISS:UniProtKB

Cellular Location

Cell membrane

Involvement in disease

Osteoporosis (OSTEOP):
A systemic skeletal disorder characterized by decreased bone mass and deterioration of bone microarchitecture without alteration in the composition of bone. The result is fragile bones and an increased risk of fractures, even after minimal trauma. Osteoporosis is a chronic condition of multifactorial etiology and is usually clinically silent until a fracture occurs.

Topology

Extracellular: 25-544
Helical: 545-565
Cytoplasmic: 566-575
Helical: 576-596
Extracellular: 597-620
Helical: 621-641
Cytoplasmic: 642-661
Helical: 662-682
Extracellular: 683-703
Helical: 704-724
Cytoplasmic: 725-756
Helical: 757-777
Extracellular: 778-783
Helical: 784-804
Cytoplasmic: 805-951