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LGR5

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Target id: 148

Nomenclature: LGR5

Family: LGR4, LGR5, LGR6

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 907 12q21.1 LGR5 leucine rich repeat containing G protein-coupled receptor 5
Mouse 7 907 10 D2 Lgr5 leucine rich repeat containing G protein coupled receptor 5
Rat 7 907 7q22 Lgr5 leucine rich repeat containing G protein coupled receptor 5
Previous and Unofficial Names Click here for help
GPR49 | FEX | GPR67 | orphan G protein-coupled receptor HG38 | leucine-rich repeat-containing G protein-coupled receptor 5 | leucine-rich repeat containing G protein-coupled receptor 5
Database Links Click here for help
Specialist databases
GPCRdb lgr5_human (Hs), lgr5_mouse (Mm)
Other databases
Alphafold O75473 (Hs), Q9Z1P4 (Mm)
CATH/Gene3D 3.80.10.10
Ensembl Gene ENSG00000139292 (Hs), ENSMUSG00000020140 (Mm), ENSRNOG00000004221 (Rn)
Entrez Gene 8549 (Hs), 14160 (Mm), 299802 (Rn)
Human Protein Atlas ENSG00000139292 (Hs)
KEGG Gene hsa:8549 (Hs), mmu:14160 (Mm), rno:299802 (Rn)
OMIM 606667 (Hs)
Pharos O75473 (Hs)
RefSeq Nucleotide NM_003667 (Hs), NM_010195 (Mm), NM_001106784 (Rn)
RefSeq Protein NP_003658 (Hs), NP_034325 (Mm), NP_001100254 (Rn)
UniProtKB O75473 (Hs), Q9Z1P4 (Mm)
Wikipedia LGR5 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human LGR5-RSPO1-RNF43
PDB Id:  4KNG
Ligand:  R-spondin-1
Resolution:  2.5Å
Species:  Human
References:  2
Natural/Endogenous Ligands Click here for help
R-spondin-1 {Sp: Human}
R-spondin-2 {Sp: Human}
R-spondin-3 {Sp: Human}
R-spondin-4 {Sp: Human}

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
R-spondin-2 {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 12.0 pEC50 1
⤷ pEC50 12.0 (EC50 1x10-12 M) [1]
R-spondin-1 {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 11.1 pEC50 1
⤷ pEC50 11.1 (EC50 8x10-12 M) [1]
R-spondin-3 {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 11.0 pEC50 1
⤷ pEC50 11.0 (EC50 1x10-11 M) [1]
R-spondin-4 {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 9.4 pEC50 1
⤷ pEC50 9.4 (EC50 4x10-10 M) [1]
Agonist Comments
The four R-spondins can bind to LGR4, LGR5, and LGR6, which specifically associate with Frizzled and LRPs—proteins that are activated by extracellular Wnt molecules- and then trigger canonical Wnt signalling to increase gene expression [3].
Tissue Distribution Click here for help
Tongue- base of folate taste papillae (strong expression), basal area of taste buds (weak expression)
Species:  Mouse
Technique:  RT-PCR and immunohistochemistry
References:  6
Hair follicles
Species:  Mouse
Technique:  LacZ insertion
References:  5
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Lgr5tm1Ah Lgr5tm1Ah/Lgr5tm1Ah
involves: 129S5/SvEvBrd * C57BL/6		 MGI:1341817  MP:0001436 abnormal suckling behavior PMID: 15509778 
Lgr5tm1Ah Lgr5tm1Ah/Lgr5tm1Ah
involves: 129S5/SvEvBrd		 MGI:1341817  MP:0001436 abnormal suckling behavior PMID: 17934449 
Lgr5tm1Ah Lgr5tm1Ah/Lgr5tm1Ah
involves: 129S5/SvEvBrd * C57BL/6		 MGI:1341817  MP:0000762 abnormal tongue morphology PMID: 15509778 
Lgr5tm1Ah Lgr5tm1Ah/Lgr5tm1Ah
involves: 129S5/SvEvBrd		 MGI:1341817  MP:0000762 abnormal tongue morphology PMID: 17934449 
Lgr5tm1Ah Lgr5tm1Ah/Lgr5tm1Ah
involves: 129S5/SvEvBrd * C57BL/6		 MGI:1341817  MP:0001575 cyanosis PMID: 15509778 
Lgr5tm1Ah Lgr5tm1Ah/Lgr5tm1Ah
involves: 129S5/SvEvBrd		 MGI:1341817  MP:0001575 cyanosis PMID: 17934449 
Lgr5tm1Ah Lgr5tm1Ah/Lgr5tm1Ah
involves: 129S5/SvEvBrd * C57BL/6		 MGI:1341817  MP:0001270 distended abdomen PMID: 15509778 
Lgr5tm1Ah Lgr5tm1Ah/Lgr5tm1Ah
involves: 129S5/SvEvBrd		 MGI:1341817  MP:0001270 distended abdomen PMID: 17934449 
Lgr5tm1Ah Lgr5tm1Ah/Lgr5tm1Ah
involves: 129S5/SvEvBrd * C57BL/6		 MGI:1341817  MP:0002058 neonatal lethality PMID: 15509778 
Lgr5tm1Ah Lgr5tm1Ah/Lgr5tm1Ah
involves: 129S5/SvEvBrd		 MGI:1341817  MP:0002058 neonatal lethality PMID: 17934449 
Lgr5tm1Ah Lgr5tm1Ah/Lgr5tm1Ah
involves: 129S5/SvEvBrd * C57BL/6		 MGI:1341817  MP:0001953 respiratory failure PMID: 15509778 
Lgr5tm1Ah Lgr5tm1Ah/Lgr5tm1Ah
involves: 129S5/SvEvBrd		 MGI:1341817  MP:0001953 respiratory failure PMID: 17934449 
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  V666A
Global MAF (%):  6
Subpopulation MAF (%):  AFR|AMR|EUR: 11|7|6
Minor allele count:  C=0.059/130
SNP accession:  VAR_049412, rs17109924
Validation:  1000 Genomes, HapMap, Cited, Frequency, Multiple observations
References:  4
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  H383R
Global MAF (%):  <1
Subpopulation MAF (%):  AFR: 1
Minor allele count:  G=0.003/6
Comment on frequency:  Low frequency (<10% in all tested populations)
SNP accession:  VAR_049411, rs12303775
Validation:  HapMap, Frequency, Multiple observations
Type:  Naturally occurring SNP
Species:  Human
Amino acid change:  F482L
Comment on frequency:  Low frequency (<10% in all tested populations)
SNP accession:  rs76115696

References

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1. Carmon KS, Gong X, Lin Q, Thomas A, Liu Q. (2011) R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/beta-catenin signaling. Proc Natl Acad Sci USA, 108 (28): 11452-7. [PMID:21693646]

2. Chen PH, Chen X, Lin Z, Fang D, He X. (2013) The structural basis of R-spondin recognition by LGR5 and RNF43. Genes Dev, 27 (12): 1345-50. [PMID:23756651]

3. de Lau W, Barker N, Low TY, Koo BK, Li VS, Teunissen H, Kujala P, Haegebarth A, Peters PJ, van de Wetering M et al.. (2011) Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling. Nature, 476 (7360): 293-7. [PMID:21727895]

4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P et al.. (2004) The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res, 14 (10B): 2121-7. [PMID:15489334]

5. Jaks V, Barker N, Kasper M, van Es JH, Snippert HJ, Clevers H, Toftgård R. (2008) Lgr5 marks cycling, yet long-lived, hair follicle stem cells. Nat Genet, 40 (11): 1291-9. [PMID:18849992]

6. Yee KK, Li Y, Redding KM, Iwatsuki K, Margolskee RF, Jiang P. (2013) Lgr5-EGFP marks taste bud stem/progenitor cells in posterior tongue. Stem Cells, 31 (5): 992-1000. [PMID:23377989]

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