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RXFP3 receptor

Family: Relaxin family peptide receptors

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Agonists
Antagonists
Transduction Mechanisms
Tissue Distribution
Expression Datasets
Functional Assays
Physiological Functions
References
Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 469 5p15.1-p14 RXFP3 relaxin/insulin-like family peptide receptor 3 7
Mouse 7 472 15 A1 Rxfp3 relaxin family peptide receptor 3 8
Rat 7 476 2q16 Rxfp3 relaxin/insulin-like family peptide receptor 3
Previous and Unofficial Names
GPCR135
SALPR
RLN3R1
Relaxin 3 receptor
somatostatin and angiotensin-like peptide receptor SALPR
RX3
RXFPR3
relaxin 3 receptor 1
relaxin family peptide receptor 3
LOC294807_predicted
RGD1311550
RGD1311550_predicted
G-protein coupled receptor SALPR
relaxin-3 receptor 1
relaxin-3/INSL7 receptor 1
relaxin/insulin-like family peptide receptor 3
similar to Somatostatin- and angiogenin-like peptide receptor (G-protein coupled receptor SALPR)
similar to Somatostatin- and angiogenin-like peptide receptor (G-protein coupled receptor SALPR) (predicted)
BC053073
Database Links
Ensembl ENSG00000182631 (Hs), ENSMUSG00000060735 (Mm), ENSRNOG00000023126 (Rn)
Entrez Gene 51289 (Hs), 239336 (Mm), 294807 (Rn)
GeneCards RXFP3 (Hs)
GenitoUrinary Development Molecular Anatomy Project Rxfp3 (Mm)
HomoloGene 9568 (Hs)
Human Protein Reference Database 17979 (Hs)
InterPro Q9NSD7 (Hs), Q8BGE9 (Mm), Q5Y986 (Rn)
KEGG Gene hsa:51289 (Hs), mmu:239336 (Mm), rno:294807 (Rn)
OMIM 609445 (Hs)
PharmGKB Gene PA134868535 (Hs)
PhosphoSitePlus Q9NSD7 (Hs), Q8BGE9 (Mm)
Protein Ontology (PRO) PRO:000001552 (Hs)
RefSeq Nucleotide NM_016568 (Hs), NM_178717 (Mm), NM_001008310 (Rn)
RefSeq Protein NP_057652 (Hs), NP_848832 (Mm), NP_001008311 (Rn)
TreeFam ENSG00000182631 (Hs), ENSMUSG00000060735 (Mm), ENSRNOG00000023126 (Rn)
UniGene Hs. 170146 (Hs)
UniProt Q9NSD7 (Hs), Q8BGE9 (Mm), Q5Y986 (Rn)
Wikipedia RXFP3 receptor
Relaxin family peptide receptors
Search for 3D structures on the PDB
Search by keyword: Relaxin family peptide receptors RXFP3 receptor Search by accession number: Q5Y986, Q9NSD7, Q8BGE9
Natural/Endogenous Ligand(s)
H2 relaxin {Sp: Human}
H3 relaxin {Sp: Human}
H3 relaxin (B chain) {Sp: Human}
Comments: H3 relaxin is the most potent endogenous agonist
Rank order of potency (Human)
H3 relaxin > H3 relaxin (B chain)  [5]
Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[125I]H3 relaxin Hs Full agonist 9.5 pKd 5
[125I]H3-B/INSL5 A chimera Hs Agonist 9.3 pKd 4
H3 relaxin {Sp: Human} Hs Full agonist 9.4 – 9.6 pIC50 1,5
H3 relaxin/INSL5 chimera Hs Full agonist 9.3 pIC50 4
H3 relaxin (B chain) {Sp: Human} Hs Full agonist 6.9 pIC50 5
Agonist Comments
H3 relaxin activates RXFP3 but also RXFP4 and RXFP1. Relaxin-3 is highly conserved across species and is believed to be the ancestral relaxin.
Affinity values were determined in COS-7 cells transiently expressing human RXFP3 labelled using [125I]H3 relaxin.
Antagonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
R3-B1-22R Hs Antagonist 7.4 pKi 2
R3(BΔ23-27)R/I5 chimeric peptide Hs Antagonist 9.2 pIC50 3
INSL5 {Sp: Human} Hs Antagonist 6.3 pIC50 6
Antagonist Comments
Affinity values were determined in COS-7 cells transiently expressing human RXFP3 labelled using [125I] H3 relaxin.
Produces parallel rightward shifts of c/r curve to H3 relaxin induced inhibition of forskolin stimulated cAMP accumulation in SK-N-MC cells expressing human RXFP3 receptors.
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
References:  1,4-6
Tissue Distribution
Brain, testis, thymus, adrenal gland.
Species:  Human
Technique:  RT-PCR.
References:  5
Hypothalamus, supraoptic nucleus, periaqueductal gray, nucleus incertus, brainstem, olfactory bulb, sensory cortex, amygdala, thalamus, paraventricular nucleus, inferior and superior colliculus.
Species:  Human
Technique:  in situ hybridisation.
References:  5,9
Brain, testis.
Species:  Mouse
Technique:  RT-PCR.
References:  1
Olfactory bulb, sensory cortex, amygdala, thalamus, paraventricular nucleus, supraoptic nucleus, inferior and superior colliculus.
Species:  Rat
Technique:  Autoradiography.
References:  4,9
Brain, testis.
Species:  Rat
Technique:  RT-PCR.
References:  1
Expression Datasets

Click here to show/hide data

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
Inhibition of forskolin stimulated cAMP responses in CHO-K1 cells stably transfected with human RXFP3 receptors.
Species:  Human
Tissue:  CHO-K1 cells.
Response measured:  cAMP accumulation.
References:  1,4-6
[35S] GTPγS incorporation in CHO-K1 cells stably transfected with human RXFP3 receptors.
Species:  Human
Tissue:  CHO-K1 cells.
Response measured:  [35S] GTPγS incorporation.
References:  1,5
Reporter gene assay in SK-N-MC/β-gal cells stably transfected with human RXFP3 receptors.
Species:  Human
Tissue:  SK-N-MC cells.
Response measured:  Increased β-galactosidase expression.
References:  4,6
Ca2+ mobilisation assay in HEK 293 cells transiently expressing human RXFP3 receptors and Gα16.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Ca2+ dye Fluo-3 fluorescence.
References:  4,6
Extracellular acidification rate response of CHO-K1 cells stably expressing human RXFP3 receptors in the cytosensor microphysiometer.
Species:  Human
Tissue:  CHO-K1 cells.
Response measured:  Increased extracellular acidification rate.
References:  10
Physiological Functions
Sensory processing particularly under stressful conditions.
Species:  Rat
Tissue:  Brain.
References:  9

REFERENCES

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1. Chen, J., Kuei, C., Sutton, S. W., Bonaventure, P., Nepomuceno, D., Eriste, E., Sillard, R., Lovenberg, T. W. and Liu, C. (2005) Pharmacological characterization of relaxin-3/INSL7 receptors GPCR135 and GPCR142 from different mammalian species. J Pharmacol Exp Ther, 312: 83-95. [PMID:15367576]

2. Haugaard-Kedström, LM; Shabanpoor, F; Hossain, MA; Clark, RJ; Ryan, PJ; Craik, DJ; Gundlach, AL; Wade, JD; Bathgate, RA; Rosengren, KJ. (2011) Design, synthesis, and characterization of a single-chain peptide antagonist for the relaxin-3 receptor RXFP3. J. Am. Chem. Soc., 133 (13): 4965-74. [PMID:21384867]

3. Kuei, C; Sutton, S; Bonaventure, P; Pudiak, C; Shelton, J; Zhu, J; Nepomuceno, D; Wu, J; Chen, J; Kamme, F; et al.. (2007) R3(BDelta23 27)R/I5 chimeric peptide, a selective antagonist for GPCR135 and GPCR142 over relaxin receptor LGR7: in vitro and in vivo characterization. J. Biol. Chem., 282 (35): 25425-35. [PMID:17606621]

4. Liu, C., Chen, J., Kuei, C., Sutton, S., Nepomuceno, D., Bonaventure, P. and Lovenberg, T. W. (2005) Relaxin-3/insulin-like peptide 5 chimeric peptide, a selective ligand for G protein-coupled receptor (GPCR)135 and GPCR142 over leucine-rich repeat-containing G protein-coupled receptor 7. Mol Pharmacol, 67: 231-240. [PMID:15465925]

5. Liu, C., Eriste, E., Sutton, S., Chen, J., Roland, B., Kuei, C., Farmer, N., Jörnvall, H., Sillard, R. and Lovenberg, T. W. (2003) Identification of relaxin-3/INSL7 as an endogenous ligand for the orphan G-protein-coupled receptor GPCR135. J Biol Chem, 278: 50754-50764. [PMID:14522968]

6. Liu, C., Kuei, C., Sutton, S., Chen, J., Bonaventure, P., Wu, J., Nepomuceno, D., Kamme, F., Tran, D. T., Zhu, J., Wilkinson, T., Bathgate, R., Eriste, E., Sillard, R. and Lovenberg, T. W. (2005) INSL5 is a high affinity specific agonist for GPCR142 (GPR100). J Biol Chem, 280: 292-300. [PMID:15525639]

7. Matsumoto, M., Kamohara, M., Sugimoto, T., Hidaka, K., Takasaki, J., Saito, T., Okada, M., Yamaguchi, T. and Furuichi, K. (2000) The novel G-protein coupled receptor SALPR shares sequence similarity with somatostatin and angiotensin receptors. Gene, 248: 183-189. [PMID:10806363]

8. Strausberg, R. L., Feingold, E. A., Grouse, L. H., Derge, J. G. et al.. (2002) Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proc Natl Acad Sci U S A, 99: 16899-16903. [PMID:12477932]

9. Sutton, S. W., Bonaventure, P., Kuei, C., Roland, B., Chen, J., Nepomuceno, D., Lovenberg, T. W. and Liu, C. (2004) Distribution of G-protein-coupled receptor (GPCR)135 binding sites and receptor mRNA in the rat brain suggests a role for relaxin-3 in neuroendocrine and sensory processing. Neuroendocrinology, 80: 298-307. [PMID:15677880]

10. Van der Westhuizen, E. T., Sexton, P. M., Bathgate, R. A. and Summers, R. J. (2005) Responses of GPCR135 to human gene 3 (H3) relaxin in CHO-K1 cells determined by microphysiometry. Ann N Y Acad Sci, 1041: 332-337. [PMID:15956730]

To cite this database page, please use the following:

Ross Bathgate, Richard Ivell, Barbara Sanborn, David Sherwood, Roger Summers.
Relaxin family peptide receptors: RXFP3 receptor. Last modified on 13/03/2013. Accessed on 19/06/2013. IUPHAR database (IUPHAR-DB), http://iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=3530.


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