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GPR3

Previous and Unofficial Names
GPCR3
ACCA
Gpcr21
Structural Information
class A G protein-coupled receptor
View phylogenetic tree in Ensembl
Species TM AA Chromosomal Location Gene Name Reference
Human 7 330 1p36.1-p35 GPR3
Rat 7 322 5q36 Gpr3
Mouse 7 330 4 D3 Gpr3
Contents:
Previous and Unofficial Names
Structural Information
Database Links
Agonists
Transduction Mechanisms
Tissue Distribution
Physiological Functions
Physiological Consequences of Altering Gene Expression
Biologically Significant Variants
Receptor Comments
Database Links
Ensembl ENSG00000181773 (Hs), ENSMUSG00000049649 (Mm), ENSRNOG00000009540 (Rn)
Entrez Gene 2827 (Hs), 14748 (Mm), 266769 (Rn)
GeneCards GPR3 (Hs)
HomoloGene 31303 (Hs)
OMIM 600241 (Hs)
PharmGKB Gene PA28872 (Hs)
Protein Ontology (PRO) PRO:000001643 (Hs)
RefSeq Nucleotide NM_005281 (Hs), NM_008154 (Mm), NM_153727 (Rn)
RefSeq Protein NP_005272 (Hs), NP_032180 (Mm), NP_714949 (Rn)
UniGene Hs. 66542 (Hs)
UniProt P46089 (Hs), P35413 (Mm)
Wikipedia GPR3
Search for 3D structures on the PDB
Search using keywords: Class A Orphans GPR3 Search using accession numbers: P46089 || P35413
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
Sphingosine 1-phosphate Hs Full agonist 7.1 – 7.7 pEC50 3
Agonist Comments
Proposed ligand (sphingosine 1-phosphate), supported by one publication [3], this result was not repeated in β-arrestin assay [4] and so the GPR3 is still recognised as an orphan.
Primary Transduction Mechanisms
Comments:  When expressed transiently in HEK293 cells, gpr3 confers constitutive activation of adenylate cyclase (AC) similar in amplitude to that seen with fully activated G(alpha)(s)-coupled receptors
References: 
Tissue Distribution
Tissue distribution of Gpr3
Species:  Mouse
Technique:  qPCR
References:  9
Physiological Functions
GPR3 is an antiproliferative mediator of cerebellar granule precursors (CGPs) in the postnatal development of murine cerebellum
Species:  Mouse
Tissue:  cerebellum
References:  10
Gs-linked receptor GPR3 maintains meiotic arrest in mammalian oocytes
Species:  Mouse
Tissue:  Oocytes
References:  7
Physiological Consequences of Altering Gene Expression
Premature termination of meiotic arrest in mammalian oocytes.
Species:  Mouse
Tissue: 
Technique:  Knockout mice
References:  7
Deletion of Gpr3 causes premature ovarian aging in mice
Species:  Mouse
Tissue: 
Technique:  Knockout mice
References:  8
Gpr3(-/-) mice display low basal intracellular cAMP levels and behavioural analyses of the mice revealed a high level of avoidance of novel and unfamiliar environments and increased stress.
Species:  Mouse
Tissue: 
Technique:  Knockout mice
References:  6
GPR3 is highly expressed in areas of the normal human brain implicated in Alzheimer's disease and is elevated in the sporadic Alzheimer's disease brain.
Species:  Human
Tissue: 
Technique:  immunoblot analysis and densitometric quantification
References:  5
Biologically Significant Variants
Variant
  • Type: NON_SYNONYMOUS_CODING
  • Alleles: T/G
  • Amino acids: V->G
  • Class: snp
  • dbSNP:rs34585631
Type:  SNP
Species:  Human
References: 
Variant
  • Type: FRAMESHIFT_CODING
  • Alleles: G/-
  • Amino acids: -
  • Class: deletion
  • dbSNP:rs34890664
Type:  SNP
Species:  Human
References: 
Variant
  • Type: NON_SYNONYMOUS_CODING
  • Alleles: G/A
  • Amino acids: R->H
  • Class: snp
  • dbSNP:rs734852
Type:  SNP
Species:  Human
References: 
Receptor Comments
Research has also shown that GPR3 modulates amyloid-beta peptide generation in neurons and maybe a potential therapeutic target [5] for the treatment of Alzheimer's disease OMIM:600241 . A further study suggests that GPR3 normal function is involved in the modulation of behavioral responses to stress [6].

REFERENCES

3. Uhlenbrock, K., Gassenhuber, H. and Kostenis, E.   (2002)
Sphingosine 1-phosphate is a ligand of the human gpr3, gpr6 and gpr12 family of constitutively active G protein-coupled receptors.
Cell Signal, 14. 941-953 [PMID: 12220620 ]
4. Yin, H., Chu, A., Li, W., Wang, B., Shelton, F., Otero, F., Nguyen, D.G., Caldwell, J.S. and Chen, Y.A.   (2009)
Lipid G protein-coupled receptor ligand identification using beta-arrestin PathHunter assay.
J Biol Chem, 284. 12328-12338 [PMID: 19286662 ]
5. Thathiah, A., Spittaels, K., Hoffmann, M., Staes, M., Cohen, A., Horré, K., Vanbrabant, M., Coun, F., Baekelandt, V., Delacourte, A., Fischer, D.F., Pollet, D., De Strooper, B. and Merchiers, P.   (2009)
The orphan G protein-coupled receptor 3 modulates amyloid-beta peptide generation in neurons.
Science, 323. 946-951 [PMID: 19213921 ]
6. Valverde, O., Célérier, E., Baranyi, M., Vanderhaeghen, P., Maldonado, R., Sperlágh, B., Vassart, G. and Ledent, C.   (2009)
GPR3 receptor, a novel actor in the emotional-like responses.
PLoS One., 4. 4704-4704 [PMID: 19259266 ]
7. Mehlmann, L.M., Saeki, Y., Tanaka, S., Brennan, T.J., Evsikov, A.V., Pendola, F.L., Knowles, B.B., Eppig, J.J. and Jaffe, L.A.   (2004)
The Gs-linked receptor GPR3 maintains meiotic arrest in mammalian oocytes.
Science, 306. 1947-1950 [PMID: 15591206 ]
8. Ledent, C., Demeestere, I., Blum, D., Petermans, J., Hämäläinen, T., Smits, G. and Vassart, G.   (2005)
Premature ovarian aging in mice deficient for Gpr3.
Proc Natl Acad Sci U S A, 102. 8922-8926 [PMID: 15956199 ]
9. Regard, J.B., Sato, I.T. and Coughlin, S.R.   (2008)
Anatomical profiling of G protein-coupled receptor expression.
Cell, 135. 561-571 [PMID: 18984166 ]
10. Tanaka, S., Shaikh, I.M., Chiocca, E.A. and Saeki, Y.   (2009)
The Gs-linked receptor GPR3 inhibits the proliferation of cerebellar granule cells during postnatal development.
PLoS One., 4. 5922-5922 [PMID: 19526062 ]

To cite this receptor data page, please use the following:

Class A Orphans: GPR3. Last modified on 2010-08-02. Accessed on 2010-09-09. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=83.


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