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GLP-2 receptor

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Target not currently curated in GtoImmuPdb

Target id: 250

Nomenclature: GLP-2 receptor

Family: Glucagon receptor family

Gene and Protein Information Click here for help
class B G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 553 17p13.3 GLP2R glucagon like peptide 2 receptor 10
Mouse 7 512 11 B3 Glp2r glucagon-like peptide 2 receptor
Rat 7 550 10q24 Glp2r glucagon-like peptide 2 receptor 10
Previous and Unofficial Names Click here for help
GLP-2R
Database Links Click here for help
Specialist databases
GPCRDB glp2r_human (Hs), glp2r_mouse (Mm), glp2r_rat (Rn)
Other databases
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands Click here for help
glucagon-like peptide 2 {Sp: Human}
glucagon-like peptide 2-(3-33) {Sp: Human}
glucagon-like peptide 2 {Sp: Mouse}
glucagon-like peptide 2-(3-33) {Sp: Mouse}
glucagon-like peptide 2-(2-33) {Sp: Rat}
glucagon-like peptide 2 {Sp: Rat}
glucagon-like peptide 2-(3-33) {Sp: Rat}

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
glucagon-like peptide 2 {Sp: Rat} Peptide Ligand is endogenous in the given species Rn Full agonist 10.2 pKi 10
pKi 10.2 [10]
GLP-2-(1-29) (rat) Peptide Rn Partial agonist 9.5 pKi 10
pKi 9.5 [10]
[Tyr34]GLP-2 (human) Peptide Rn Full agonist 9.2 pKi 10
pKi 9.2 [10]
glucagon-like peptide 2 {Sp: Human} Peptide Rn Full agonist 8.8 pKi 10
pKi 8.8 [10]
glucagon-like peptide 2-(3-33) {Sp: Rat} Peptide Ligand is endogenous in the given species Rn Partial agonist 6.6 pKi 10
pKi 6.6 [10]
glucagon-like peptide 2-(2-33) {Sp: Rat} Peptide Ligand is endogenous in the given species Rn Partial agonist 6.1 pKi 10
pKi 6.1 [10]
GLP-2 analogue 10 Peptide Immunopharmacology Ligand Hs Agonist 10.6 pEC50 16
pEC50 10.6 (EC50 2.8x10-11 M) [16]
Description: Determined in a reporter assay using HEK293 cells stably overexpressing a cAMP response element (CRE) driven luciferase reporter and human GLP-2R.
apraglutide Peptide Hs Agonist 10.5 pEC50 7,11
pEC50 10.5 (EC50 3x10-11 M) [7,11]
glucagon-like peptide 2 {Sp: Human} Peptide Ligand is endogenous in the given species Hs Full agonist 8.5 pIC50 12
pIC50 8.5 [12]
glucagon-like peptide 2-(3-33) {Sp: Human} Peptide Ligand is endogenous in the given species Hs Partial agonist 7.4 pIC50 12
pIC50 7.4 [12]
teduglutide Peptide Approved drug Primary target of this compound Immunopharmacology Ligand Hs Agonist - - 9
[9]
View species-specific agonist tables
Agonist Comments
Glepaglutide, elsiglutide, and FE 203799 [15] are three additional DPP4-resistant GLP-2 analogues that are in clinical development:
Glepaglutide (ZP1848)- completed Phase 2 for short bowel syndrome and Phase 1 for Crohn's disease.
Elsiglutide (ZP1846)- completed Phase 2 proof-of-concept study as a preventative agent to combat chemotherapy-induced diarrhea.
Phase 1/2 FE 203799 trials for short bowel syndrome and non-Hodgkin's lymphoma (to help manage GI mucositis in patients receiving myeloablative chemotherapy) are planned but are not yet recruiting subjects (April 2018).
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
References: 
Tissue Distribution Click here for help
Isolated rat small intestine mucosal cells.
Species:  Rat
Technique:  RT-PCR.
References:  14
Highest levels found in the jejunum.
Also found in duodenum, ileum, colon and stomach.
Undetectable in the brain, heart, kidney, liver, lung, muscle and spleen.
Species:  Rat
Technique:  RNase protection assay.
References:  10
Fetal, neonatal, weaned and adult stomach.
Small and large intestines.
Jejunum, ileum and colon (higher in fetal tissues than adult).
Species:  Rat
Technique:  RT-PCR.
References:  8
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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Functional Assays Click here for help
Measurement of cAMP levels in isolated rat small intestinal mucosal cells expressing GLP-2 receptors.
Species:  Rat
Tissue:  Small intestinal mucosal cells.
Response measured:  Stimulation of cAMP production.
References:  14
Measurement of cAMP levels in COS cells transfected with the GLP-2 receptor.
Species:  Human
Tissue:  COS cells.
Response measured:  Increase in cAMP production.
References:  10
Measurement of cAMP levels in the stable GLP-2 receptor episomal expression line, rG2R.
Species:  Rat
Tissue:  rG2R episomal cell line.
Response measured:  Stimulation of cAMP production.
References:  10
Measurement of the activity of a cAMP-dependent reporter gene, CRE-β-galactosidase, in BHK cells endogenously expressing the GLP-2 receptor.
Species:  Rat
Tissue:  BHK fibroblast cells.
Response measured:  Increased activity of the reporter gene.
References:  17
Measurement of AP-1 luciferase reporter gene activity in BHK fibroblast cells endogenously expressing the GLP-2 receptor.
Species:  Rat
Tissue:  BHK fibroblast cells.
Response measured:  Induction of AP-1 luciferase activity.
References:  17
Physiological Functions Click here for help
Promotes growth of the small intestine.
Species:  Mouse
Tissue:  Small intestine.
References:  5,13
Small bowel crypt cell proliferation.
Species:  Mouse
Tissue:  Small intestine.
References:  6
h[Gly2]GLP-2-treated mice show increased epithelial repair and reduced cell death in the crypt compartment.
Species:  Mouse
Tissue:  Small intestine.
References:  1
GLP-2 receptor activation maintains small bowel mucosal epithelium in perenteral nutrition fed rats.
Species:  Rat
Tissue:  Small intestine.
References:  3
Upregulation of small bowel hexose transport.
Species:  Rat
Tissue:  Jejunum.
References:  4
The GLP-2 receptor-mediated small bowel growth results in an increase in nutrient digestion and absorption.
Species:  Mouse
Tissue:  In vivo.
References:  2
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
Apc+|ApcMin|Glp2r+|Glp2rtm1Ddr ApcMin/Apc+,Glp2rtm1Ddr/Glp2r+
involves: C57BL/6J
MGI:2136733  MGI:88039  MP:0000490 abnormal crypts of Lieberkuhn morphology PMID: 18829546 
Apc+|ApcMin|Glp2rtm1Ddr ApcMin/Apc+,Glp2rtm1Ddr/Glp2rtm1Ddr
involves: C57BL/6J
MGI:2136733  MGI:88039  MP:0000490 abnormal crypts of Lieberkuhn morphology PMID: 18829546 
Apc+|ApcMin|Glp2r+|Glp2rtm1Ddr ApcMin/Apc+,Glp2rtm1Ddr/Glp2r+
involves: C57BL/6J
MGI:2136733  MGI:88039  MP:0000488 abnormal intestinal epithelium morphology PMID: 18829546 
Apc+|ApcMin|Glp2rtm1Ddr ApcMin/Apc+,Glp2rtm1Ddr/Glp2rtm1Ddr
involves: C57BL/6J
MGI:2136733  MGI:88039  MP:0000488 abnormal intestinal epithelium morphology PMID: 18829546 
Apc+|ApcMin|Glp2r+|Glp2rtm1Ddr ApcMin/Apc+,Glp2rtm1Ddr/Glp2r+
involves: C57BL/6J
MGI:2136733  MGI:88039  MP:0003448 altered tumor morphology PMID: 18829546 
Apc+|ApcMin|Glp2rtm1Ddr ApcMin/Apc+,Glp2rtm1Ddr/Glp2rtm1Ddr
involves: C57BL/6J
MGI:2136733  MGI:88039  MP:0003448 altered tumor morphology PMID: 18829546 
Apc+|ApcMin|Glp2r+|Glp2rtm1Ddr ApcMin/Apc+,Glp2rtm1Ddr/Glp2r+
involves: C57BL/6J
MGI:2136733  MGI:88039  MP:0002404 increased intestinal adenoma incidence PMID: 18829546 
Apc+|ApcMin|Glp2rtm1Ddr ApcMin/Apc+,Glp2rtm1Ddr/Glp2rtm1Ddr
involves: C57BL/6J
MGI:2136733  MGI:88039  MP:0002404 increased intestinal adenoma incidence PMID: 18829546 
Apc+|ApcMin|Glp2r+|Glp2rtm1Ddr ApcMin/Apc+,Glp2rtm1Ddr/Glp2r+
involves: C57BL/6J
MGI:2136733  MGI:88039  MP:0008011 intestine polyps PMID: 18829546 
Apc+|ApcMin|Glp2rtm1Ddr ApcMin/Apc+,Glp2rtm1Ddr/Glp2rtm1Ddr
involves: C57BL/6J
MGI:2136733  MGI:88039  MP:0008011 intestine polyps PMID: 18829546 

References

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1. Boushey RP, Yusta B, Drucker DJ. (1999) Glucagon-like peptide 2 decreases mortality and reduces the severity of indomethacin-induced murine enteritis. Am. J. Physiol., 277 (5): E937-47. [PMID:10567023]

2. Brubaker PL, Izzo A, Hill M, Drucker DJ. (1997) Intestinal function in mice with small bowel growth induced by glucagon-like peptide-2. Am. J. Physiol., 272 (6 Pt 1): E1050-8. [PMID:9227451]

3. Chance WT, Foley-Nelson T, Thomas I, Balasubramaniam A. (1997) Prevention of parenteral nutrition-induced gut hypoplasia by coinfusion of glucagon-like peptide-2. Am. J. Physiol., 273 (2 Pt 1): G559-63. [PMID:9277438]

4. Cheeseman CI, Tsang R. (1996) The effect of GIP and glucagon-like peptides on intestinal basolateral membrane hexose transport. Am. J. Physiol., 271 (3 Pt 1): G477-82. [PMID:8843773]

5. Drucker DJ, Brubaker PL. (1996) Induction of intestinal epithelial proliferation by glucagon-like peptide 2. Proc. Natl. Acad. Sci. U.S.A., 93: 7911-7916. [PMID:8755576]

6. Drucker DJ, DeForest L, Brubaker PL. (1997) Intestinal response to growth factors administered alone or in combination with human [Gly2]glucagon-like peptide 2. Am. J. Physiol., 273 (6): G1252-62. [PMID:9435550]

7. Hargrove DM, Alagarsamy S, Croston G, Laporte R, Qi S, Srinivasan K, Sueiras-Diaz J, Wiśniewski K, Hartwig J, Lu M et al.. (2020) Pharmacological Characterization of Apraglutide, a Novel Long-Acting Peptidic Glucagon-Like Peptide-2 Agonist, for the Treatment of Short Bowel Syndrome. J. Pharmacol. Exp. Ther., 373 (2): 193-203. [PMID:32075870]

8. Lovshin J, Yusta B, Iliopoulos I, Migirdicyan A, Dableh L, Brubaker PL, Drucker DJ. (2000) Ontogeny of the glucagon-like peptide-2 receptor axis in the developing rat intestine. Endocrinology, 141 (11): 4194-201. [PMID:11089553]

9. McKeage K. (2015) Teduglutide: a guide to its use in short bowel syndrome. Clin Drug Investig, 35 (5): 335-40. [PMID:25859983]

10. Munroe DG, Gupta AK, Kooshesh F, Vyas TB, Rizkalla G, Wang H, Demchyshyn L, Yang ZJ, Kamboj RK, Chen H et al.. (1999) Prototypic G protein-coupled receptor for the intestinotrophic factor glucagon-like peptide 2. Proc. Natl. Acad. Sci. U.S.A., 96 (4): 1569-73. [PMID:9990065]

11. Slim GM, Lansing M, Wizzard P, Nation PN, Wheeler SE, Brubaker PL, Jeppesen PB, Wales PW, Turner JM. (2019) Novel Long-Acting GLP-2 Analogue, FE 203799 (Apraglutide), Enhances Adaptation and Linear Intestinal Growth in a Neonatal Piglet Model of Short Bowel Syndrome with Total Resection of the Ileum. JPEN J Parenter Enteral Nutr, 43 (7): 891-898. [PMID:30614011]

12. Thulesen J, Knudsen LB, Hartmann B, Hastrup S, Kissow H, Jeppesen PB, Ørskov C, Holst JJ, Poulsen SS. (2002) The truncated metabolite GLP-2 (3-33) interacts with the GLP-2 receptor as a partial agonist. Regul. Pept., 103 (1): 9-15. [PMID:11738243]

13. Tsai CH, Hill M, Asa SL, Brubaker PL, Drucker DJ. (1997) Intestinal growth-promoting properties of glucagon-like peptide-2 in mice. Am. J. Physiol., 273 (1 Pt 1): E77-84. [PMID:9252482]

14. Walsh NA, Yusta B, DaCambra MP, Anini Y, Drucker DJ, Brubaker PL. (2003) Glucagon-like peptide-2 receptor activation in the rat intestinal mucosa. Endocrinology, 144 (10): 4385-92. [PMID:12960094]

15. Wiśniewski K, Sueiras-Diaz J, Jiang G, Galyean R, Lu M, Thompson D, Wang YC, Croston G, Posch A, Hargrove DM et al.. (2016) Synthesis and Pharmacological Characterization of Novel Glucagon-like Peptide-2 (GLP-2) Analogues with Low Systemic Clearance. J. Med. Chem., 59 (7): 3129-39. [PMID:26986178]

16. Yang PY, Zou H, Lee C, Muppidi A, Chao E, Fu Q, Luo X, Wang D, Schultz PG, Shen W. (2018) Stapled, Long-Acting Glucagon-like Peptide 2 Analog with Efficacy in Dextran Sodium Sulfate Induced Mouse Colitis Models. J. Med. Chem., 61 (7): 3218-3223. [PMID:29528634]

17. Yusta B, Somwar R, Wang F, Munroe D, Grinstein S, Klip A, Drucker DJ. (1999) Identification of glucagon-like peptide-2 (GLP-2)-activated signaling pathways in baby hamster kidney fibroblasts expressing the rat GLP-2 receptor. J. Biol. Chem., 274 (43): 30459-67. [PMID:10521425]

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