InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: LGR4

Summary

InnateDB Protein

IDBP-36647.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

LGR4

Protein Name

leucine-rich repeat containing G protein-coupled receptor 4

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000368516

InnateDB Gene

IDBG-36645 (LGR4)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:21693646, ECO:0000269PubMed:21727895, ECO:0000269PubMed:21909076, ECO:0000269PubMed:22815884, ECO:0000269PubMed:23444378, ECO:0000269PubMed:23756652}.

Subcellular Localization

Cell membrane {ECO:0000269PubMed:21693646, ECO:0000269PubMed:22815884}; Multi-pass membrane protein {ECO:0000269PubMed:21693646, ECO:0000269PubMed:22815884}.

Disease Associations

Osteoporosis (OSTEOP) [MIM:166710]: 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. {ECO:0000269PubMed:23644456}. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry. A LGR4 nonsense mutation creating a stop codon after position 126 (c.376C>T) is strongly associated with low bone mineral density and osteoporotic fractures (PubMed:23644456). This mutation probably causes degradation of the transcript by nonsense-mediated decay (NMD). The c.376C>T mutation is also associated with electrolyte imbalance, late onset of menarche and reduced testosterone levels, as well as an increased risk of squamous cell carcinoma of the skin and biliary tract cancer (PubMed:23644456). {ECO:0000269PubMed:23644456}.

Tissue Specificity

Expressed in multiple steroidogenic tissues: placenta, ovary, testis and adrenal. Expressed also in spinal cord, thyroid, stomach, trachea, heart, pancreas, kidney, prostate and spleen.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 200 experimentally validated interaction(s) in this database.

Experimentally validated
Total	200 [view]
Protein-Protein	199 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004888	transmembrane signaling receptor activity
GO:0004930	G-protein coupled receptor activity
GO:0005515	protein binding

Biological Process

GO:0001649	osteoblast differentiation
GO:0007186	G-protein coupled receptor signaling pathway
GO:0007283	spermatogenesis
GO:0030282	bone mineralization
GO:0030539	male genitalia development
GO:0034122	negative regulation of toll-like receptor signaling pathway
GO:0035239	tube morphogenesis
GO:0045087	innate immune response
GO:0045892	negative regulation of transcription, DNA-templated
GO:0045893	positive regulation of transcription, DNA-templated
GO:0046849	bone remodeling
GO:0050673	epithelial cell proliferation
GO:0050710	negative regulation of cytokine secretion
GO:0061290	canonical Wnt signaling pathway involved in metanephric kidney development
GO:0072202	cell differentiation involved in metanephros development
GO:0072224	metanephric glomerulus development
GO:0072282	metanephric nephron tubule morphogenesis
GO:0090190	positive regulation of branching involved in ureteric bud morphogenesis
GO:0090263	positive regulation of canonical Wnt signaling pathway

Cellular Component

GO:0005887	integral component of plasma membrane
GO:0016021	integral component of membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000276 G protein-coupled receptor, rhodopsin-like
IPR000372 Leucine-rich repeat-containing N-terminal
IPR001611 Leucine-rich repeat
IPR002131 Glycoprotein hormone receptor family
IPR003591 Leucine-rich repeat, typical subtype
IPR017452 GPCR, rhodopsin-like, 7TM

PFAM

PF00001
PF01462
PF00560
PF13504
PF13855

PRINTS

PR00237
PR00373

PIRSF

SMART

SM00013
SM00369

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt