LGR5

Target id: 148

Nomenclature: LGR5

Family: Class A Orphans

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for LGR5 in GtoImmuPdb

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 907 12q22-q23 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
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
Specialist databases
GPCRDB lgr5_human (Hs), lgr5_mouse (Mm)
Other databases
CATH/Gene3D
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
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

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
R-spondin-2 {Sp: Human} Hs Full agonist 12.0 pEC50 1
pEC50 12.0 (EC50 1x10-12 M) [1]
R-spondin-1 {Sp: Human} Hs Full agonist 11.1 pEC50 1
pEC50 11.1 (EC50 8x10-12 M) [1]
R-spondin-3 {Sp: Human} Hs Full agonist 11.0 pEC50 1
pEC50 11.0 (EC50 1x10-11 M) [1]
R-spondin-4 {Sp: Human} 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
Hair follicles
Species:  Mouse
Technique:  LacZ insertion
References:  5
Tongue- base of folate taste papillae (strong expression), basal area of taste buds (weak expression)
Species:  Mouse
Technique:  RT-PCR and immunohistochemistry
References:  6
Expression Datasets

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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 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
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: 
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: 
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: 

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. U.S.A.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. Nature476 (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 Cells31 (5): 992-1000. [PMID:23377989]

Contributors

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How to cite this page

Anthony P. Davenport, Stephen Alexander, Joanna L. Sharman, Adam J. Pawson, Helen E. Benson, Amy E. Monaghan, Wen Chiy Liew, Chido Mpamhanga, Jim Battey, Richard V. Benya, Robert T. Jensen, Sadashiva Karnik, Evi Kostenis, Eliot Spindel, Laura Storjohann, Kalyan Tirupula, Tom I. Bonner, Richard Neubig, Jean-Philippe Pin, Michael Spedding, Anthony Harmar.
Class A Orphans: LGR5. Last modified on 23/05/2017. Accessed on 11/12/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=148.