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Gene and Protein Information | ||||||
class B G protein-coupled receptor | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 7 | 423 | 7p14.3 | GHRHR | growth hormone releasing hormone receptor | 12,22 |
Mouse | 7 | 423 | 6 27.38 cM | Ghrhr | growth hormone releasing hormone receptor | 20,23 |
Rat | 7 | 464 | 4q24 | Ghrhr | growth hormone releasing hormone receptor | 20 |
Previous and Unofficial Names |
GRF receptor | GRFR | growth hormone-releasing factor receptor | Ghrfr |
Database Links | |
Specialist databases | |
GPCRdb | ghrhr_human (Hs), ghrhr_mouse (Mm), ghrhr_rat (Rn) |
Other databases | |
Alphafold | Q02643 (Hs), P32082 (Mm), Q02644 (Rn) |
CATH/Gene3D | 4.10.1240.10 |
ChEMBL Target | CHEMBL2032 (Hs), CHEMBL3709 (Rn) |
DrugBank Target | Q02643 (Hs) |
Ensembl Gene | ENSG00000106128 (Hs), ENSMUSG00000004654 (Mm), ENSRNOG00000011808 (Rn) |
Entrez Gene | 2692 (Hs), 14602 (Mm), 25321 (Rn) |
Human Protein Atlas | ENSG00000106128 (Hs) |
KEGG Gene | hsa:2692 (Hs), mmu:14602 (Mm), rno:25321 (Rn) |
OMIM | 139191 (Hs) |
Orphanet | ORPHA122097 (Hs) |
Pharos | Q02643 (Hs) |
RefSeq Nucleotide | NM_000823 (Hs), NM_001003685 (Mm), NM_012850 (Rn) |
RefSeq Protein | NP_000814 (Hs), NP_001003685 (Mm), NP_036982 (Rn) |
UniProtKB | Q02643 (Hs), P32082 (Mm), Q02644 (Rn) |
Wikipedia | GHRHR (Hs) |
Natural/Endogenous Ligands |
GHRH {Sp: Human} , GHRH {Sp: Mouse} , GHRH {Sp: Rat} |
Download all structure-activity data for this target as a CSV file
Agonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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View species-specific agonist tables |
Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | Click column headers to sort | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Primary Transduction Mechanisms | |
Transducer | Effector/Response |
Gs family |
Adenylyl cyclase stimulation Calcium channel |
References: 18 |
Tissue Distribution | ||||||||
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Expression Datasets | |
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Functional Assays | ||||||||||
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Physiological Functions | ||||||||
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Phenotypes, Alleles and Disease Models | Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Clinically-Relevant Mutations and Pathophysiology | ||||||||||
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Biologically Significant Variants | ||||||||||
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Biologically Significant Variant Comments | ||||||||||
GHRH-R splice variant 1 (SV1) is a hypoxia-driven promoter of tumour progression [31]. |
1. Adams EF, Symowski H, Buchfelder M, Poyner DR. (2000) A polymorphism in the growth hormone (GH)-releasing hormone (GHRH) receptor gene is associated with elevated response to GHRH by human pituitary somatotrophinomas in vitro. Biochem Biophys Res Commun, 275 (1): 33-6. [PMID:10944436]
2. Barinaga M, Yamonoto G, Rivier C, Vale W, Evans R, Rosenfeld MG. (1983) Transcriptional regulation of growth hormone gene expression by growth hormone-releasing factor. Nature, 306 (5938): 84-5. [PMID:6415487]
3. Billestrup N, Vale W. (1986) Growth hormone-releasing factor stimulates proliferation of somatotrophsin vitro. Proc Natl Acad Sci USA, 83: 6854-6857. [PMID:3018748]
4. Boisvert C, Paré C, Veyrat-Durebex C, Robert A, Dubuisson S, Morel G, Gaudreau P. (2002) Localization and regulation of a functional GHRH receptor in the rat renal medulla. Endocrinology, 143 (4): 1475-84. [PMID:11897706]
5. Boulanger L, Girard N, Strecko J, Gaudreau P. (2002) Characterization of a growth hormone-releasing hormone binding site in the rat renal medulla. Peptides, 23 (1): 43-50. [PMID:11814616]
6. Buchholz S, Schally AV, Engel JB, Hohla F, Heinrich E, Koester F, Varga JL, Halmos G. (2007) Potentiation of mammary cancer inhibition by combination of antagonists of growth hormone-releasing hormone with docetaxel. Proc Natl Acad Sci USA, 104 (6): 1943-6. [PMID:17261802]
7. Busto R, Schally AV, Braczkowski R, Plonowski A, Krupa M, Groot K, Armatis P, Varga JL. (2002) Expression of mRNA for growth hormone-releasing hormone and splice variants of GHRH receptors in human malignant bone tumors. Regul Pept, 108 (2-3): 47-53. [PMID:12220726]
8. Cai R, Schally AV, Cui T, Szalontay L, Halmos G, Sha W, Kovacs M, Jaszberenyi M, He J, Rick FG et al.. (2014) Synthesis of new potent agonistic analogs of growth hormone-releasing hormone (GHRH) and evaluation of their endocrine and cardiac activities. Peptides, 52: 104-12. [PMID:24373935]
9. Carakushansky M, Whatmore AJ, Clayton PE, Shalet SM, Gleeson HK, Price DA, Levine MA, Salvatori R. (2003) A new missense mutation in the growth hormone-releasing hormone receptor gene in familial isolated GH deficiency. Eur J Endocrinol, 148 (1): 25-30. [PMID:12534354]
10. Coy DH, Jiang NY, Fuselier J, Murphy WA. (1996) Structural simplification of potent growth hormone-releasing hormone analogs: implications for other members of the VIP/GHRH/PACAP family. Ann N Y Acad Sci, 805: 149-58. [PMID:8993400]
11. Gaudreau P, Boulanger L, Abribat T. (1992) Affinity of human growth hormone-releasing factor (1-29)NH2 analogues for GRF binding sites in rat adenopituitary. J Med Chem, 35 (10): 1864-9. [PMID:1534126]
12. Gaylinn BD, Harrison JK, Zysk JR, Lyons CE, Lynch KR, Thorner MO. (1993) Molecular cloning and expression of a human anterior pituitary receptor for growth hormone-releasing hormone. Mol Endocrinol, 7 (1): 77-84. [PMID:7680413]
13. Gick GG, Zeytin FN, Brazeau P, Ling NC, Esch FS, Bancroft C. (1984) Growth hormone-releasing factor regulates growth hormone mRNA in primary cultures of rat pituitary cells. Proc Natl Acad Sci USA, 81 (5): 1553-5. [PMID:6424119]
14. Guillemin R, Brazeau P, Böhlen P, Esch F, Ling N, Wehrenberg WB. (1982) Growth hormone-releasing factor from a human pancreatic tumor that caused acromegaly. Science, 218 (4572): 585-7. [PMID:6812220]
15. Hashimoto K, Koga M, Motomura T, Kasayama S, Kouhara H, Ohnishi T, Arita N, Hayakawa T, Sato B, Kishimoto T. (1995) Identification of alternatively spliced messenger ribonucleic acid encoding truncated growth hormone-releasing hormone receptor in human pituitary adenomas. J Clin Endocrinol Metab, 80 (10): 2933-9. [PMID:7559877]
16. Horváth JE, Zarándi M, Groot K, Schally AV. (1995) Effect of long-acting antagonists of growth hormone (GH)-releasing hormone on GH and cyclic adenosine 3',5'-monophosphate release in superfused rat pituitary cells. Endocrinology, 136 (9): 3849-55. [PMID:7649091]
17. Kanashiro-Takeuchi RM, Tziomalos K, Takeuchi LM, Treuer AV, Lamirault G, Dulce R, Hurtado M, Song Y, Block NL, Rick F et al.. (2010) Cardioprotective effects of growth hormone-releasing hormone agonist after myocardial infarction. Proc Natl Acad Sci USA, 107 (6): 2604-9. [PMID:20133784]
18. Kostic TS, Tomić M, Andric SA, Stojilkovic SS. (2002) Calcium-independent and cAMP-dependent modulation of soluble guanylyl cyclase activity by G protein-coupled receptors in pituitary cells. J Biol Chem, 277 (19): 16412-8. [PMID:11867632]
19. Kovacs M, Schally AV, Lee EJ, Busto R, Armatis P, Groot K, Varga JL. (2002) Inhibitory effects of antagonistic analogs of GHRH on GH3 pituitary cells overexpressing the human GHRH receptor. J Endocrinol, 175 (2): 425-34. [PMID:12429040]
20. Lin C, Lin SC, Chang CP, Rosenfeld MG. (1992) Pit-1-dependent expression of the receptor for growth hormone releasing factor mediates pituitary cell growth. Nature, 360 (6406): 765-8. [PMID:1334535]
21. Matsubara S, Sato M, Mizobuchi M, Niimi M, Takahara J. (1995) Differential gene expression of growth hormone (GH)-releasing hormone (GRH) and GRH receptor in various rat tissues. Endocrinology, 136 (9): 4147-50. [PMID:7649123]
22. Mayo KE. (1992) Molecular cloning and expression of a pituitary-specific receptor for growth hormone-releasing hormone. Mol Endocrinol, 6 (10): 1734-44. [PMID:1333056]
23. Miller TL, Godfrey PA, Dealmeida VI, Mayo KE. (1999) The rat growth hormone-releasing hormone receptor gene: structure, regulation, and generation of receptor isoforms with different signaling properties. Endocrinology, 140 (9): 4152-65. [PMID:10465288]
24. Motomura T, Hashimoto K, Koga M, Arita N, Hayakawa T, Kishimoto T, Kasayama S. (1998) Inhibition of signal transduction by a splice variant of the growth hormone-releasing hormone receptor expressed in human pituitary adenomas. Metab Clin Exp, 47 (7): 804-8. [PMID:9667225]
25. Rivier J, Vale W. (1982) Characterization of a growth hormone-releasing factor from a human pancreatic islet tumour. Nature, 300: 276-278. [PMID:6292724]
26. Schally AV, Varga JL. (1999) Antagonistic Analogs of Growth Hormone-releasing Hormone: New Potential Antitumor Agents. Trends Endocrinol Metab, 10 (10): 383-391. [PMID:10542394]
27. Takano K, Takei T, Teramoto A, Yamashita N. (1996) GHRH activates a nonselective cation current in human GH-secreting adenoma cells. Am J Physiol, 270 (6 Pt 1): E1050-7. [PMID:8764191]
28. Tang J, Lagacé G, Castagné J, Collu R. (1995) Identification of human growth hormone-releasing hormone receptor splicing variants. J Clin Endocrinol Metab, 80 (8): 2381-7. [PMID:7629234]
29. Varga JL, Schally AV, Csernus VJ, Zarándi M, Halmos G, Groot K, Rékási Z. (1999) Synthesis and biological evaluation of antagonists of growth hormone-releasing hormone with high and protracted in vivo activities. Proc Natl Acad Sci USA, 96 (2): 692-7. [PMID:9892695]
30. Varga JL, Schally AV, Horvath JE, Kovacs M, Halmos G, Groot K, Toller GL, Rekasi Z, Zarandi M. (2004) Increased activity of antagonists of growth hormone-releasing hormone substituted at positions 8, 9, and 10. Proc Natl Acad Sci USA, 101 (6): 1708-13. [PMID:14755056]
31. Xiong X, Ke X, Wang L, Yao Z, Guo Y, Zhang X, Chen Y, Pang CP, Schally AV, Zhang H. (2020) Splice variant of growth hormone-releasing hormone receptor drives esophageal squamous cell carcinoma conferring a therapeutic target. Proc Natl Acad Sci USA, 117 (12): 6726-6732. [PMID:32156725]
32. Zarandi M, Horvath JE, Halmos G, Pinski J, Nagy A, Groot K, Rekasi Z, Schally AV. (1994) Synthesis and biological activities of highly potent antagonists of growth hormone-releasing hormone. Proc Natl Acad Sci USA, 91 (25): 12298-302. [PMID:7991622]
33. Zarandi M, Kovacs M, Horvath JE, Toth K, Halmos G, Groot K, Nagy A, Kele Z, Schally AV. (1997) Synthesis and in vitro evaluation of new potent antagonists of growth hormone-releasing hormone (GH-RH). Peptides, 18: 423-430. [PMID:9145431]
34. Zeitler P, Stevens P, Siriwardana G. (1998) Functional GHRH receptor carboxyl terminal isoforms in normal and dwarf (dw) rats. J Mol Endocrinol, 21 (3): 363-71. [PMID:9845677]