Protein: Leucine-rich repeat-containing G-protein coupled receptor 4 (G-protein coupled receptor 48) (Q9BXB1)
Organism: Homo sapiens (Human)
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 pro-inflammatory cytokine production. Plays an important role in regulating the circadian rhythms of plasma lipids, partially through regulating the rhythmic expression of MTTP (By similarity). Required for proper development of GnRH neurons (gonadotropin-releasing hormone expressing neurons) that control the release of reproductive hormones from the pituitary gland (By similarity).
Subcellular location: Cell membrane {ECO:0000269|PubMed:21693646, ECO:0000269|PubMed:22815884}; Multi-pass membrane protein {ECO:0000269|PubMed:21693646, ECO:0000269|PubMed:22815884}.
Sequence: MPGPLGLLCFLALGLLGSAGPSGAAPPLCAAPCSCDGDRRVDCSGKGLTAVPEGLSAFTQALDISMNNITQLPEDAFKNFPFLEELQLAGNDLSFIHPKALSGLKELKVLTLQNNQLKTVPSEAIRGLSALQSLRLDANHITSVPEDSFEGLVQLRHLWLDDNSLTEVPVHPLSNLPTLQALTLALNKISSIPDFAFTNLSSLVVLHLHNNKIRSLSQHCFDGLDNLETLDLNYNNLGEFPQAIKALPSLKELGFHSNSISVIPDGAFDGNPLLRTIHLYDNPLSFVGNSAFHNLSDLHSLVIRGASMVQQFPNLTGTVHLESLTLTGTKISSIPNNLCQEQKMLRTLDLSYNNIRDLPSFNGCHALEEISLQRNQIYQIKEGTFQGLISLRILDLSRNLIHEIHSRAFATLGPITNLDVSFNELTSFPTEGLNGLNQLKLVGNFKLKEALAAKDFVNLRSLSVPYAYQCCAFWGCDSYANLNTEDNSLQDHSVAQEKGTADAANVTSTLENEEHSQIIIHCTPSTGAFKPCEYLLGSWMIRLTVWFIFLVALFFNLLVILTTFASCTSLPSSKLFIGLISVSNLFMGIYTGILTFLDAVSWGRFAEFGIWWETGSGCKVAGFLAVFSSESAIFLLMLATVERSLSAKDIMKNGKSNHLKQFRVAALLAFLGATVAGCFPLFHRGEYSASPLCLPFPTGETPSLGFTVTLVLLNSLAFLLMAVIYTKLYCNLEKEDLSENSQSSMIKHVAWLIFTNCIFFCPVAFFSFAPLITAISISPEIMKSVTLIFFPLPACLNPVLYVFFNPKFKEDWKLLKRRVTKKSGSVSVSISSQGGCLEQDFYYDCGMYSHLQGNLTVCDCCESFLLTKPVSCKHLIKSHSCPALAVASCQRPEGYWSDCGTQSAHSDYADEEDSFVSDSSDQVQACGRACFYQSRGFPLVRYAYNLPRVKD
InterPro domains: - IPR032675: Leucine-rich repeat domain superfamily (homologous_superfamily) [27-474]
- IPR017452: GPCR, rhodopsin-like, 7TM (domain) [555-801]
- IPR000276: G protein-coupled receptor, rhodopsin-like (family) [540-809]
- IPR000372: Leucine-rich repeat N-terminal domain (domain) [28-61]
- IPR003591: Leucine-rich repeat, typical subtype (repeat) [55-435]
- IPR001611: Leucine-rich repeat (repeat) [106-425]
- IPR002131: Glycoprotein hormone receptor family (family) [529-759]
Interaction partners: - E3 ubiquitin-protein ligase ZNRF3
- R-spondin-3
- R-spondin-1
- R-spondin-2
- R-spondin-4
- E3 ubiquitin-protein ligase RNF43
- Leucine-rich repeat-containing G-protein coupled receptor 5
- Norrin
- Leucine-rich repeat-containing G-protein coupled receptor 6
- Tumor necrosis factor ligand superfamily member 11
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0060089 (molecular transducer activity), GO:0038023 (signaling receptor activity), GO:0005515 (protein binding), GO:0004888 (transmembrane signaling receptor activity), GO:0004930 (G protein-coupled receptor activity)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0009987 (cellular process), GO:0023052 (signaling), GO:0048518 (positive regulation of biological process), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0048583 (regulation of response to stimulus), GO:0051716 (cellular response to stimulus), GO:0023051 (regulation of signaling), GO:0023056 (positive regulation of signaling), GO:0048584 (positive regulation of response to stimulus), GO:0007154 (cell communication), GO:0007165 (signal transduction), GO:0050794 (regulation of cellular process), GO:0048522 (positive regulation of cellular process), GO:0009967 (positive regulation of signal transduction), GO:0010647 (positive regulation of cell communication), GO:0009966 (regulation of signal transduction), GO:0010646 (regulation of cell communication), GO:0007186 (G protein-coupled receptor signaling pathway), GO:0030111 (regulation of Wnt signaling pathway), GO:0030177 (positive regulation of Wnt signaling pathway), GO:0060828 (regulation of canonical Wnt signaling pathway), GO:0090263 (positive regulation of canonical Wnt signaling pathway)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0043226 (organelle), GO:0071944 (cell periphery), GO:0016020 (membrane), GO:0043227 (membrane-bounded organelle), GO:0005886 (plasma membrane), GO:0031982 (vesicle)