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RXFP1 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
Physiological Consequences of Altering Gene Expression
Phenotypes, Alleles and Disease Models
Biologically Significant Variants
General Comments
References
Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 757 4q32.1 RXFP1 relaxin/insulin-like family peptide receptor 1 15
Mouse 7 758 3 E3 Rxfp1 relaxin/insulin-like family peptide receptor 1 27
Rat 7 758 2q32 Rxfp1 relaxin/insulin-like family peptide receptor 1 27
Previous and Unofficial Names
Names References
RX1 receptor
LGR7 14-15
Leucine-rich repeat-containing G-protein-coupled receptor 7 14-15
Relaxin receptor
leucine-rich repeat-containing G protein-coupled receptor 7
RX1
RXFPR1
leucine-rich repeat-containing G-protein coupled receptor 7
relaxin family peptide receptor 1
relaxin receptor 1
relaxin/insulin-like family peptide receptor 1
LOC381489
Gm1018
Database Links
Ensembl
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProt
Wikipedia
Search for 3D structures on the PDB
Search by keyword: Relaxin family peptide receptors RXFP1 receptor
Natural/Endogenous Ligand(s)
H1 relaxin {Sp: Human}
H2 relaxin {Sp: Human}
H3 relaxin {Sp: Human}
INSL3 {Sp: Human}
Rank order of potency (Human)
Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[33P]H2 relaxin Hs Full agonist 9.3 – 9.7 pKd 11,29
relaxin {Sp: Rhesus macaque} Hs Full agonist 9.4 pKd 11
relaxin {Sp: Pig} Hs Full agonist 9.1 pKd 11
europium-labelled H2 relaxin Hs Full agonist 9.0 pKd 12
relaxin {Sp: Rat} Hs Full agonist 7.3 pKd 11
H2 relaxin {Sp: Human} Hs Full agonist 9.4 – 10.2 pKi 11,29
H3 relaxin {Sp: Human} Hs Full agonist 7.5 – 8.0 pKi 11,29
H1 relaxin {Sp: Human} Hs Full agonist 8.8 pEC50 4
Agonist Comments
H2 relaxin and porcine relaxin activate both RXFP1 and RXFP2.
Rat relaxin selectively activates RXFP1.
H3 relaxin activates RXFP1 but is the cognate ligand for RXFP3 and also activates RXFP4.
Rhesus monkey relaxin is relatively selective for RXFP1.
Affinity values were determined in HEK 293 cells expressing human RXFP1.
Antagonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
B-R13/17K H2 relaxin Hs Antagonist 6.7 pEC50 13
Antagonist Comments
RXFP1-truncate is a naturally occurring splice variant of the receptor that includes the LDLa region that acts as a functional antagonist of the RXFP1 receptor. It has been identified in mouse, rat and pig and in rodents levels rise in late pregnancy suggesting that it may have a physiological role in antagonising the actions of relaxin.
Primary Transduction Mechanisms
Transducer Effector/Response
Gs family
Gi/Go family
Adenylate cyclase stimulation
Adenylate cyclase inhibition
Comments:  RXFP1 displays complex cAMP signalling. There is evidence that increases in cAMP involve both Gs and pertussis toxin-sensitive Gi/Go.
References:  9-10,15,23,29
Secondary Transduction Mechanisms
Transducer Effector/Response
Gs family Guanylate cyclase stimulation
Comments:  Guanylate cyclase stimulation occurs secondary to increased NOSII expression and sustained increases in cAMP levels.
References:  24
Tissue Distribution
Uterus, cervix, vagina, nipple, breast.
Species:  Human
Technique:  immunocytochemistry.
References:  19,22
Uterus, cervix, vagina, placenta, nipple, testes, prostate, brain, heart, lung, intestine, skin.
Species:  Human
Technique:  RT-PCR.
References:  15-16
Ovary.
Species:  Mouse
Technique:  Receptor autoradiography.
References:  33
Oviduct, uterus, cervix, vagina, testes, brain, pituitary.
Species:  Mouse
Technique:  Receptor gene assay.
References:  20
Uterus, cervix, vagina, nipple, mammary gland.
Species:  Rat
Technique:  immunocytochemistry.
References:  15,21
Uterus, cervix, vagina, nipple, mammary gland, brain, heart adrenal.
Species:  Rat
Technique:  Receptor autoradiography.
References:  25,32
Ovary, oviduct, uterus, testes, brain, kidney, heart, intestine, colon, adrenal.
Species:  Rat
Technique:  Northern blotting.
References:  14,27
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
Relaxation of pre-contracted rat uterus.
Species:  Rat
Tissue:  Uterus.
Response measured:  Relaxation.
References:  6-7,31
Positive inotropic effect in rat isolated atrium.
Species:  Rat
Tissue:  Left atrium.
Response measured:  Increase in developed tension.
References:  17,31
Positive chronotropic effect in rat isolated atrium.
Species:  Rat
Tissue:  Right atrium.
Response measured:  Increase in rate of spontaneous beating.
References:  17,31
Measurement of cAMP levels in HEK 293T cells transfected with the human RXFP1 receptor.
Species:  Human
Tissue:  HEK 293T cells.
Response measured:  cAMP accumulation.
References:  10-11,15,29
Measurement of cAMP levels in the monocyte cell line, THP-1, endogenously expressing RXFP1 receptors.
Species:  Human
Tissue:  THP-1 cells.
Response measured:  cAMP accumulation (in the presence of a low concentration of forskolin).
References:  1,26
Measurement of cAMP levels in human endometrial stromal cells.
Species:  Human
Tissue:  Human endometrial stromal cells.
Response measured:  cAMP accumulation.
References:  1-2,8
Physiological Functions
Growth of interpubic ligament.
Species:  Mouse
Tissue:  Pubic symphysis.
References:  3
Increase in size and softening of the cervix.
Species:  Mouse
Tissue:  Cervix.
References:  3
Relaxation of the uterus.
Species:  Rat
Tissue:  Uterus.
References:  31
Growth and development of the uterus. (Rodent studies tend to show less of an effect, pig studies are very clear).
Species:  Rat
Tissue:  Uterus.
References:  3
Growth of the vagina.
Species:  Rat
Tissue:  Vagina.
References:  3
Plasma osmolarity regulation.
Species:  Rat
Tissue:  Subfornical organ; organum vasculosum of the lamina terminalis.
References:  30
Increased renal glomerular filtration rate and plasma flow, and decreased vascular resistance.
Species:  Rat
Tissue:  Kidney.
References:  3,5
Vasodilatation.
Species:  Rat
Tissue:  Blood vessels.
References:  24
Inotropic and chronotropic effects in the heart.
Species:  Rat
Tissue:  Right and left atria.
References:  17,31
Nipple and mammary gland growth and development.
Species:  Rat
Tissue:  Nipple and mammary gland.
References:  3
Implantation.
Species:  Human
Tissue:  Uterine endometrium.
References:  3
Inhibition of collagen synthesis and promotion of collagen breakdown.
Species:  Mouse
Tissue:  Fibroblasts.
References:  3
Wound healing.
Species:  Rat
Tissue:  Wounds.
References:  3
Cardiac protection.
Species:  Rat
Tissue:  Heart.
References:  3
Physiological Consequences of Altering Gene Expression
Female mice lacking the the RXFP1 receptor show normal fertility and parturition but 15% of pups die soon after birth and 100% within 24-48 hours due to maternal failure of nipple and mammary gland development.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  20
Male mice lacking the RXFP1 receptor show reduced fertility due to disrupted spermatogenesis associated with increased apoptosis of meiotic spermatocytes.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  20
Mice lacking the RXFP1 receptor show an increase in tissue collagen.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  18
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Rxfp1tm1Jgo Rxfp1tm1Jgo/Rxfp1tm1Jgo
involves: 129S5/SvEvBrd * C57BL/6
MGI:2682211  MP:0001119 abnormal female reproductive system morphology PMID: 14701741 
Rxfp1tm1Aia|Tg(Ins2-Insl3)4Imad Rxfp1tm1Aia/Rxfp1tm1Aia,Tg(Ins2-Insl3)4Imad/0
involves: 129S7/SvEvBrd * C57BL/6J
MGI:2682211  MGI:3054959  MP:0005149 abnormal gubernaculum morphology PMID: 15256493 
Rxfp1tm1Aia Rxfp1tm1Aia/Rxfp1tm1Aia
involves: 129S7/SvEvBrd * C57BL/6J
MGI:2682211  MP:0001882 abnormal lactation PMID: 15256493 
Rxfp1tm1Aia|Rxfp2tm1Aia Rxfp1tm1Aia/Rxfp1tm1Aia,Rxfp2tm1Aia/Rxfp2tm1Aia
involves: 129S7/SvEvBrd * C57BL/6J
MGI:2153463  MGI:2682211  MP:0001882 abnormal lactation PMID: 15256493 
Rxfp1tm1Aia|Tg(Ins2-Insl3)4Imad Rxfp1tm1Aia/Rxfp1tm1Aia,Tg(Ins2-Insl3)4Imad/0
involves: 129S7/SvEvBrd * C57BL/6J
MGI:2682211  MGI:3054959  MP:0001882 abnormal lactation PMID: 15256493 
Rxfp1tm1Jgo Rxfp1tm1Jgo/Rxfp1tm1Jgo
involves: 129S5/SvEvBrd * C57BL/6
MGI:2682211  MP:0001145 abnormal male reproductive system morphology PMID: 14701741 
Rxfp1tm1Jgo Rxfp1tm1Jgo/Rxfp1tm1Jgo
involves: 129S5/SvEvBrd * C57BL/6
MGI:2682211  MP:0006078 abnormal nipple morphology PMID: 14701741 
Rxfp1tm1Aia Rxfp1tm1Aia/Rxfp1tm1Aia
involves: 129S7/SvEvBrd * C57BL/6J
MGI:2682211  MP:0006078 abnormal nipple morphology PMID: 15256493 
Rxfp1tm1Aia|Rxfp2tm1Aia Rxfp1tm1Aia/Rxfp1tm1Aia,Rxfp2tm1Aia/Rxfp2tm1Aia
involves: 129S7/SvEvBrd * C57BL/6J
MGI:2153463  MGI:2682211  MP:0006078 abnormal nipple morphology PMID: 15256493 
Rxfp1tm1Aia|Tg(Ins2-Insl3)4Imad Rxfp1tm1Aia/Rxfp1tm1Aia,Tg(Ins2-Insl3)4Imad/0
involves: 129S7/SvEvBrd * C57BL/6J
MGI:2682211  MGI:3054959  MP:0006078 abnormal nipple morphology PMID: 15256493 
Rxfp1tm1Aia|Tg(Ins2-Insl3)4Imad Rxfp1tm1Aia/Rxfp1tm1Aia,Tg(Ins2-Insl3)4Imad/0
involves: 129S7/SvEvBrd * C57BL/6J
MGI:2682211  MGI:3054959  MP:0001126 abnormal ovary morphology PMID: 15256493 
Rxfp1tm1Jgo Rxfp1tm1Jgo/Rxfp1tm1Jgo
involves: 129S5/SvEvBrd * C57BL/6
MGI:2682211  MP:0002907 abnormal parturition PMID: 14701741 
Rxfp1tm1Aia Rxfp1tm1Aia/Rxfp1tm1Aia
involves: 129S7/SvEvBrd * C57BL/6J
MGI:2682211  MP:0002907 abnormal parturition PMID: 15256493 
Rxfp1tm1Jgo Rxfp1tm1Jgo/Rxfp1tm1Jgo
involves: 129S5/SvEvBrd * C57BL/6
MGI:2682211  MP:0001156 abnormal spermatogenesis PMID: 14701741 
Rxfp1tm1Jgo Rxfp1tm1Jgo/Rxfp1tm1Jgo
involves: 129S5/SvEvBrd * C57BL/6
MGI:2682211  MP:0005159 azoospermia PMID: 14701741 
Rxfp1tm1Aia|Rxfp2tm1Aia Rxfp1tm1Aia/Rxfp1tm1Aia,Rxfp2tm1Aia/Rxfp2tm1Aia
involves: 129S7/SvEvBrd * C57BL/6J
MGI:2153463  MGI:2682211  MP:0002286 cryptorchism PMID: 15256493 
Rxfp1tm1Jgo Rxfp1tm1Jgo/Rxfp1tm1Jgo
involves: 129S5/SvEvBrd * C57BL/6
MGI:2682211  MP:0004929 decreased epididymis weight PMID: 14701741 
Rxfp1tm1Jgo Rxfp1tm1Jgo/Rxfp1tm1Jgo
involves: 129S5/SvEvBrd * C57BL/6
MGI:2682211  MP:0004852 decreased testis weight PMID: 14701741 
Rxfp1tm1Aia Rxfp1tm1Aia/Rxfp1tm1Aia
involves: 129S7/SvEvBrd * C57BL/6J
MGI:2682211  MP:0006050 pulmonary fibrosis PMID: 15256493 
Rxfp1tm1Jgo Rxfp1tm1Jgo/Rxfp1tm1Jgo
involves: 129S5/SvEvBrd * C57BL/6
MGI:2682211  MP:0001923 reduced female fertility PMID: 14701741 
Rxfp1tm1Jgo Rxfp1tm1Jgo/Rxfp1tm1Jgo
involves: 129S5/SvEvBrd * C57BL/6
MGI:2682211  MP:0001921 reduced fertility PMID: 14701741 
Rxfp1tm1Jgo Rxfp1tm1Jgo/Rxfp1tm1Jgo
involves: 129S5/SvEvBrd * C57BL/6
MGI:2682211  MP:0001922 reduced male fertility PMID: 14701741 
Biologically Significant Variants
An exon-4 deleted transcript of the RXFP1 receptor is expressed in the endometrium, myometrium, uterus and cervix/vagina of pregnant female mice and rats. It has been suggested that this RXFP1 receptor splice variant (RXFP1-truncate) acts as a functional antagonist of relaxin in late pregnancy.
Type:  Splice variant.
Species:  Mouse
References:  28
General Comments
Many studies has examined RXFP1 receptor tissue expression using a range of techniques. Most provide complimentary data but RT-PCR studies are subject to the usual caveats regarding the extent of amplification of physiologically relevant copy numbers of mRNA. Receptor autoradiography has also been used to provide quantitative data on properties of RXFP1 receptors in particular tissue locations which is in good agreement with other methods.

REFERENCES

To cite this database page, please use the following:

Ross Bathgate, Richard Ivell, Barbara Sanborn, David Sherwood, Roger Summers.
Relaxin family peptide receptors: RXFP1 receptor. Last modified on 13/03/2013. Accessed on 21/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=351.


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