RXFP1

Target id: 351

Nomenclature: RXFP1

Family: Relaxin family peptide receptors

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 RXFP1 in GtoImmuPdb

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 53
Mouse 7 758 3 E3 Rxfp1 relaxin/insulin-like family peptide receptor 1 91
Rat 7 758 2q32 Rxfp1 relaxin/insulin-like family peptide receptor 1 91
Previous and Unofficial Names
LGR7 [52-53] | RXFPR1 | relaxin receptor 1 | leucine-rich repeat-containing G-protein-coupled receptor 7 [52-53] | RX1
Database Links
Specialist databases
GPCRDB rxfp1_human (Hs), rxfp1_mouse (Mm), rxfp1_rat (Rn)
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
Natural/Endogenous Ligands
relaxin-1 {Sp: Human}
relaxin {Sp: Human}
relaxin-3 {Sp: Human}
Comments: Relaxin is the most potent endogenous agonist and is the cognate ligand for RXFP1. There is cross reactivity between relaxin family peptides and their receptors: relaxin binds to and activates RXFP1 and RXFP2 and is a biased agonist at RXFP3; relaxin-3 binds to and activates RXFP1, RXFP2, RXFP3 and RXFP4.
Potency order of endogenous ligands (Human)
relaxin (RLN2, P04090) = relaxin-1 (RLN1, P04808) > relaxin-3 (RLN3, Q8WXF3)  [97]

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
[33P]relaxin (human) Hs Full agonist 9.3 – 9.7 pKd 41,97
pKd 9.3 – 9.7 (Kd 5x10-10 – 2x10-10 M) [41,97]
relaxin {Sp: Rhesus macaque} Hs Full agonist 9.4 pKd 41
pKd 9.4 [41]
europium-labelled relaxin Hs Agonist 9.3 pKd 94
pKd 9.3 (Kd 5x10-10 M) [94]
relaxin {Sp: Pig} Hs Full agonist 9.1 pKd 41
pKd 9.1 [41]
europium-labelled relaxin Hs Full agonist 9.0 pKd 49
pKd 9.0 (Kd 1x10-9 M) [49]
relaxin {Sp: Rat} Hs Full agonist 7.3 pKd 41
pKd 7.3 [41]
A(4-24)(B7-24)H2 Hs Full agonist 7.0 pKd 48
pKd 7.0 [48]
relaxin {Sp: Human} Hs Full agonist 9.2 – 10.2 pKi 41,47,97
pKi 9.2 – 10.2 [41,47,97]
A(4-24)(F23A)H2 Hs Full agonist 9.2 pKi 17
pKi 9.2 [17]
relaxin-3 {Sp: Human} Hs Full agonist 7.5 – 8.0 pKi 41,97
pKi 7.5 – 8.0 [41,97]
INSL3 {Sp: Human} Hs Full agonist 5.7 pKi 10
pKi 5.7 [10]
(B7-33)H2 Hs Full agonist 5.5 pKi 46
pKi 5.5 [46]
relaxin {Sp: Human} Hs Full agonist 10.4 pEC50 47
pEC50 10.4 [47]
A(4-24)(F23A)H2 Hs Full agonist 9.8 pEC50 17
pEC50 9.8 [17]
relaxin-1 {Sp: Human} Hs Full agonist 8.8 pEC50 11
pEC50 8.8 [11]
A(4-24)(B7-24)H2 Hs Full agonist 8.2 pEC50 48
pEC50 8.2 [48]
[125I]relaxin (human) Hs Full agonist - -
Agonist Comments
Human relaxin and porcine relaxin activate RXFP1 and RXFP2 and are biased agonists at RXFP3 (untested at RXFP4).
Rat relaxin selectively activates RXFP1 not RXFP2 (untested at RXFP3 and RXFP4).
Human relaxin-3 activates RXFP1 but not RXFP2, is the cognate ligand for RXFP3 and also activates RXFP4.
Rhesus monkey relaxin activates RXFP1 and RXFP2 (untested at RXFP3 and RXFP4).
Affinity values were determined in HEK 293 cells expressing human RXFP1.

A(4-24)(B7-24)H2 is a synthetic peptide comprising the minimal active core of relaxin, with improved selectivity over RXFP2. A(4-24)(F23A)H2 has a minimised A-chain including an F23A mutation, generating improved selectivity for RXFP1 over RXFP2. A single chain derivative of relaxin, B7-33 is a functionally selective agonist at RXFP1 that preferentially activates ERK1/2 over cAMP. B7-33 has anti-fibrotic properties like relaxin but unlike relaxin does not promote tumour growth in vivo [46]. Short linear peptides derived from a naturally occurring protein containing a collagen-like repeat, have been reported to act at RXFP1 [95]. Although the effects produced by the peptides CGEN-25009 and CGEN-25010 in several systems were extremely variable and the effects of human relaxin in these systems unusual [95], there is some evidence to suggest relaxin-like activity of these peptides in THP-1 cells and in a fibrosis model [84]. In the latter study, CGEN-25009 and human relaxin increased cAMP, cGMP and nitrite, decreased collagen deposition and increased MMP2 activity in human dermal fibroblasts [84]. More recent studies with these peptides and the precursor protein C1q-tumor necrosis factor-related protein 8 (CTRP8) demonstrated activation of RXFP1 [37] with cAMP production and a PI3K mediated pro-migratory phenotype in glioblastoma cell lines and primary cells. Co-immunoprecipitation studies demonstrated a direct interaction between human CTRP8 and RXFP1. Although these studies suggest that CTRP8 or peptide fragments are able to activate RXFP1, it remains to be seen whether they are native ligands.
Antagonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
B-R13/17K H2 relaxin Hs Antagonist 5.0 – 6.3 pKi 50,74
pKi 5.0 – 6.3 [50,74]
B-R13/17K H2 relaxin Hs Antagonist 5.7 – 6.7 pEC50 50,74
pEC50 5.7 – 6.7 [50,74]
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 RXFP1 [92]. 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. B-R13/17K H2 is also referred to as AT-001, and has mutations R13K and R17K within the relaxin binding motif. B-R13/17K H2 is a partial agonist in recombinant systems with high RXFP1 expression and an antagonist in physiological systems with lower receptor expression.
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
ML290 Hs Agonist 7.0 pEC50 109-110
pEC50 7.0 (EC50 9.4x10-8 M) [109-110]
Allosteric Modulator Comments
The actions of ML290 are species-specific being confined to the human RXFP1 with no agonist action at the mouse receptor. Mutation studies demonstrate that ML290 interacts with ECL3 of the human receptor and chimeras with the mouse receptor have identified the residues G659 and T660 as essential for activation [110].
Primary Transduction Mechanisms
Transducer Effector/Response
Gs family
Gi/Go family
Adenylate cyclase stimulation
Adenylate cyclase inhibition
Comments:  RXFP1 displays complex cAMP signalling. RXFP1 couples to Gs to increase cAMP, an effect that is negatively modulated by coupling to GoB. RXFP1 also couples to Gi3 to activate a delayed surge of cAMP accumulation via a Gβγ-PI3K-PKCζ pathway that activates AC5. cAMP accumulation may also occur in response to relaxin by a G protein-independent mechanism, and in some cells may be downstream of tyrosine kinase inhibition of phosphodiesterase activity. A constitutive RXFP1-dependent cAMP response occurs in single rat cardiac fibroblasts, HeLa cells, and HEK293 cells expressing RXFP1. The response is dependent upon a protein complex, or signalosome, linked to the relaxin receptor, and the signalosome is highly sensitive to attomolar concentrations of relaxin.
References:  3,8,39-40,42-44,52-53,65,75-77
Secondary Transduction Mechanisms
Transducer Effector/Response
Gs family
Gi/Go family
Guanylate cyclase stimulation
Other - See Comments
Comments:  Responses also include kinase activation and other signalling pathways. Guanylate cyclase stimulation occurs secondary to increased NOS activity. Depending on the cell type under investigation, relaxin may activate endothelial nitric oxide synthase (eNOS) and neuronal NOS (nNOS) or stimulate the expression of inducible NOS (iNOS). In rat isolated lungs, the relaxin-mediated iNOS upregulation depends on a subtle balance between stimulatory ERK1/2 activation and counter-regulatory PI3K stimulation.
When stimulated by relaxin, RXFP1 activates a number of MAP kinases (including MEK, ERK1/2, Akt and p38), depending on the cell type in question. Activation of ERK1/2 is dependent on G protein coupling in rat renal myofibroblasts. The allosteric agonist ML-290 stimulates many of the pathways activated by relaxin but does not cause ERK1/2 activation.
Activation of PI3K and NOS-NO-cGMP signalling pathways by RXFP1 leads to inhibition of TGF-β1 signalling, and this is responsible for the anti-fibrotic effects of relaxin.
Relaxin activates the glucocorticoid receptor, a nuclear receptor that acts as a ligand-dependent transcription factor. The activation, and the subsequent changes in gene transcription, may account for the many effects of relaxin upon the expression levels of a variety of proteins, including those involved in connective tissue metabolism.
References:  1-2,4,6-7,19,27-30,73,78,90,112
Tissue Distribution
Uterus, endometrium, cervix, vagina, nipple, breast.
Species:  Human
Technique:  Immunocytochemistry.
References:  54,60,66-67
Oviduct, endometrium
Species:  Human
Technique:  Receptor autoradiography
References:  14,101
Ovary, uterus, endometrium, cervix, vagina, placenta, nipple, testes, prostate, brain, heart, kidney, adrenal, lung, intestine, skin.
Species:  Human
Technique:  RT-PCR.
References:  53-54,66-67,70-71
Ovary, uterus, brain.
Species:  Mouse
Technique:  Receptor autoradiography.
References:  111
Oviduct, uterus, cervix, vagina, nipple, testes, brain, pituitary, heart.
Species:  Mouse
Technique:  Receptor gene assay.
References:  38,62,83
Uterus, cerebral cortex, ventricle, atria, lung, nipple, gut spleen, skin, endometrium, myometrium, uterus, cervix, vagina, placenta, testes, prostate.
Species:  Mouse
Technique:  RT-PCR
References:  55,86,91,96
Cervix, vagina, brain
Species:  Mouse
Technique:  Northern blot
References:  91
Uterine smooth muscle, endometrium, cervix, vagina
Species:  Mouse
Technique:  Immunohistochemistry
References:  53
Brain
Species:  Mouse
Technique:  In situ hybridisation
References:  38,83
Uterine smooth muscle, endometrium, brain, testes, heart, prostate
Species:  Rat
Technique:  RT-PCR
References:  16,35,61,63,85,106-108
Uterus, cervix, vagina, nipple, mammary gland, testes.
Species:  Rat
Technique:  Immunocytochemistry.
References:  35,53,64,106-107
Uterus, cervix, vagina, nipple, mammary gland, brain, heart, adrenal.
Species:  Rat
Technique:  Receptor autoradiography.
References:  69,80,100
Ovary, oviduct, uterus, testes, brain, kidney, heart, intestine, colon, adrenal.
Species:  Rat
Technique:  Northern blotting.
References:  52,91
Brain
Species:  Rat
Technique:  In situ hybridisation
References:  69
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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Functional Assays
Activation of ERK1/2
Species:  Rat
Tissue:  Renal myofibroblasts
Response measured:  Increased phosphorylation of ERK1/2
References:  73
Activation of ERK1/2
Species:  Mouse
Tissue:  Fibrochondrocytes
Response measured:  Increased phosphorylation of ERK1/2
References:  1
Positive inotropic effect in rat isolated atrium.
Species:  Rat
Tissue:  Left atrium.
Response measured:  Increase in developed tension.
References:  57,99
Positive chronotropic effect in rat isolated atrium.
Species:  Rat
Tissue:  Right atrium.
Response measured:  Increase in rate of spontaneous beating.
References:  57,99
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:  40-41,43,53,97
Measurement of cAMP levels in cells/tissues endogenously expressing RXFP1 receptors.
Species:  Human
Tissue:  THP-1 cells, MCF7 cells, endometrial cells, endometrial glandular epithelial cells, myometrial cells, umbilical vein endothelial cells (HUVEC), artery and vein smooth muscle cells (HUASMC, HUVSMC)
Response measured:  cAMP accumulation
References:  3,8-9,13,18,32,44,65,76-77,81,88-89
Nitric oxide formation and increased cGMP
Species:  Rat
Tissue:  Aortic rings, renal myofibroblasts, lung
Response measured:  Increased NOS expression
References:  2,30,73
Activation of ERK1/2
Species:  Human
Tissue:  Endometrial stromal cells, THP-1 cells, cononary artery cells, pulmonary artery smooth muscle cells, HeLa cells, umbilical vein endothelial cells (HUVECs), umbilical artery and vein smooth muscle cells (HUASMC, HUVSMC), cardiac fibroblasts (HCF).
Response measured:  Increased phosphorylation of ERK1/2
References:  26-27,88-89,112
Nitric oxide formation and increased cGMP
Species:  Mouse
Tissue:  Ileum, gastric fundus
Response measured:  Increased NOS expression
References:  5-6
Measurement of cAMP levels in cells/tissues endogenously expressing RXFP1 receptors
Species:  Mouse
Tissue:  Pubic symphysis
Response measured:  cAMP accumulation
References:  15
Measurement of cAMP levels in cells/tissues endogenously expressing RXFP1 receptors
Species:  Rat
Tissue:  Uterine strips and uterine longitudional muscle from oestrogen-primed rats, myometrial cells, anterior pituitary cells, left atria, skeletal muscle
Response measured:  cAMP accumulation
References:  22,51,61,65,79,87
Relaxation of pre-contracted rat uterus.
Species:  Rat
Tissue:  Uterus.
Response measured:  Relaxation.
References:  23-24,99
Measurement of cGMP levels in cells endogenously expressing RXFP1 receptors
Species:  Human
Tissue:  Umbilical vein endothelial cells (HUVEC), umbilical artery and vein smooth muscle cells (HUASMC, HUVSMC), cardiac fibroblasts (HCF), coronary artery endothelial cells
Response measured:  cGMP accumulation
References:  88-89
Physiological Functions
Relaxation of the uterus.
Species:  Rat
Tissue:  Uterus.
References:  99
Growth of interpubic ligament.
Species:  Mouse
Tissue:  Pubic symphysis.
References:  12
Increase in size and softening of the cervix.
Species:  Mouse
Tissue:  Cervix.
References:  12
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:  12
Growth of the vagina.
Species:  Rat
Tissue:  Vagina.
References:  12
Plasma osmolarity regulation.
Species:  Rat
Tissue:  Subfornical organ; organum vasculosum of the lamina terminalis.
References:  98
Increased renal glomerular filtration rate and plasma flow, and decreased vascular resistance.
Species:  Rat
Tissue:  Kidney.
References:  12,21
Inotropic and chronotropic effects in the heart.
Species:  Rat
Tissue:  Right and left atria.
References:  57,99
Nipple and mammary gland growth and development.
Species:  Rat
Tissue:  Nipple and mammary gland.
References:  12
Implantation.
Species:  Human
Tissue:  Uterine endometrium.
References:  12
Inhibition of collagen synthesis and promotion of collagen breakdown.
Species:  Mouse
Tissue:  Fibroblasts.
References:  12
Wound healing.
Species:  Rat
Tissue:  Wounds.
References:  12
Cardiac protection.
Species:  Rat
Tissue:  Heart.
References:  12
Vasodilatation.
Species:  Rat
Tissue:  Blood vessels- vasodilator effects in gluteal resistance or subcutaneous arteries but little or no effect in pulmonary, myometrial or placental vessels.
References:  20,27,56,72,78
Formation and growth of tumours
Species:  Human
Tissue:  Endometrial, mammary, thyroid, prostate tumours; oesteosarcoma, glioblastoma
References:  33-34,37,45,58,68,102,105
Vasodilatation– vasodilator effects in gluteal resistance or subcutaneous arteries but little or no effect in pulmonary, myometrial or placental vessels
Species:  Mouse
Tissue:  Blood vessels
References:  20,72
Vasodilatation– vasodilator effects in gluteal resistance or subcutaneous arteries but little or no effect in pulmonary, myometrial or placental vessels
Species:  Human
Tissue:  Blood vessels
References:  20,36,72,82
Inotropic effects in the heart.
Species:  Human
Tissue:  Atria
References:  25
Cardiac protection
Species:  Human
Tissue:  Heart
References:  31,103-104
Physiological Consequences of Altering Gene Expression
Mice lacking the RXFP1 receptor show an increase in tissue collagen.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  59
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:  62
Female mice lacking 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:  62
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
Type:  Splice variant
Species:  Mouse
Description:  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.
References:  93
General Comments
Many studies have examined RXFP1 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 in particular tissue locations which is in good agreement with other methods.

References

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1. Ahmad N, Wang W, Nair R, Kapila S. (2012) Relaxin induces matrix-metalloproteinases-9 and -13 via RXFP1: induction of MMP-9 involves the PI3K, ERK, Akt and PKC-ζ pathways. Mol. Cell. Endocrinol.363 (1-2): 46-61. [PMID:22835547]

2. Alexiou K, Wilbring M, Matschke K, Dschietzig T. (2013) Relaxin protects rat lungs from ischemia-reperfusion injury via inducible NO synthase: role of ERK-1/2, PI3K, and forkhead transcription factor FKHRL1. PLoS ONE8 (9): e75592. [PMID:24098703]

3. Anand-Ivell R, Heng K, Bartsch O, Ivell R. (2007) Relaxin signalling in THP-1 cells uses a novel phosphotyrosine-dependent pathway. Mol. Cell. Endocrinol.272 (1-2): 1-13. [PMID:17509748]

4. Baccari MC, Bani D, Bigazzi M, Calamai F. (2004) Influence of relaxin on the neurally induced relaxant responses of the mouse gastric fundus. Biol. Reprod.71 (4): 1325-9. [PMID:15215200]

5. Baccari MC, Nistri S, Quattrone S, Bigazzi M, Bani Sacchi T, Calamai F, Bani D. (2004) Depression by relaxin of neurally induced contractile responses in the mouse gastric fundus. Biol. Reprod.70 (1): 222-8. [PMID:14522837]

6. Baccari MC, Nistri S, Vannucchi MG, Calamai F, Bani D. (2007) Reversal by relaxin of altered ileal spontaneous contractions in dystrophic (mdx) mice through a nitric oxide-mediated mechanism. Am. J. Physiol. Regul. Integr. Comp. Physiol.293 (2): R662-8. [PMID:17522128]

7. Bani D, Failli P, Bello MG, Thiemermann C, Bani Sacchi T, Bigazzi M, Masini E. (1998) Relaxin activates the L-arginine-nitric oxide pathway in vascular smooth muscle cells in culture. Hypertension31 (6): 1240-7. [PMID:9622136]

8. Bartsch O, Bartlick B, Ivell R. (2001) Relaxin signalling links tyrosine phosphorylation to phosphodiesterase and adenylyl cyclase activity. Mol Hum Reprod7: 799-809. [PMID:11517286]

9. Bartsch O, Bartlick B, Ivell R. (2004) Phosphodiesterase 4 inhibition synergizes with relaxin signaling to promote decidualization of human endometrial stromal cells. J Clin Endocrinol Metab89: 324-334. [PMID:14715868]

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Roger Summers, Michelle Halls, Ross Bathgate, Thomas Dschietzig, Andrew L. Gundlach.
Relaxin family peptide receptors: RXFP1. Last modified on 23/02/2017. Accessed on 18/12/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=351.