ID GPR3_MOUSE Reviewed; 330 AA. AC P35413; Q3USD4; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1994, sequence version 1. DT 24-JAN-2024, entry version 161. DE RecName: Full=G-protein coupled receptor 3; DE AltName: Full=GPCR21; GN Name=Gpr3; Synonyms=Gpcr3; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC STRAIN=BALB/cJ; TISSUE=Brain; RX PubMed=8262253; DOI=10.1016/0014-5793(93)80828-i; RA Saeki Y., Ueno S., Mizuno R., Nishimura T., Fujimura H., Nagai Y., RA Yanagihara T.; RT "Molecular cloning of a novel putative G protein-coupled receptor (GPCR21) RT which is expressed predominantly in mouse central nervous system."; RL FEBS Lett. 336:317-322(1993). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; RC TISSUE=Corpora quadrigemina, Medulla oblongata, and Visual cortex; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=15956199; DOI=10.1073/pnas.0503840102; RA Ledent C., Demeestere I., Blum D., Petermans J., Hamalainen T., Smits G., RA Vassart G.; RT "Premature ovarian aging in mice deficient for Gpr3."; RL Proc. Natl. Acad. Sci. U.S.A. 102:8922-8926(2005). RN [7] RP TISSUE SPECIFICITY, AND FUNCTION. RX PubMed=19259266; DOI=10.1371/journal.pone.0004704; RA Valverde O., Celerier E., Baranyi M., Vanderhaeghen P., Maldonado R., RA Sperlagh B., Vassart G., Ledent C.; RT "GPR3 receptor, a novel actor in the emotional-like responses."; RL PLoS ONE 4:E4704-E4704(2009). RN [8] RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY. RX PubMed=26455425; DOI=10.1038/srep14953; RA Godlewski G., Jourdan T., Szanda G., Tam J., Cinar R., Harvey-White J., RA Liu J., Mukhopadhyay B., Pacher P., Ming Mo F., Osei-Hyiaman D., Kunos G.; RT "Mice lacking GPR3 receptors display late-onset obese phenotype due to RT impaired thermogenic function in brown adipose tissue."; RL Sci. Rep. 5:14953-14953(2015). RN [9] RP FUNCTION. RX PubMed=34048700; DOI=10.1016/j.cell.2021.04.037; RA Sveidahl Johansen O., Ma T., Hansen J.B., Markussen L.K., Schreiber R., RA Reverte-Salisa L., Dong H., Christensen D.P., Sun W., Gnad T., RA Karavaeva I., Nielsen T.S., Kooijman S., Cero C., Dmytriyeva O., Shen Y., RA Razzoli M., O'Brien S.L., Kuipers E.N., Nielsen C.H., Orchard W., RA Willemsen N., Jespersen N.Z., Lundh M., Sustarsic E.G., Hallgren C.M., RA Frost M., McGonigle S., Isidor M.S., Broholm C., Pedersen O., Hansen J.B., RA Grarup N., Hansen T., Kjaer A., Granneman J.G., Babu M.M., Calebiro D., RA Nielsen S., Ryden M., Soccio R., Rensen P.C.N., Treebak J.T., RA Schwartz T.W., Emanuelli B., Bartolomucci A., Pfeifer A., Zechner R., RA Scheele C., Mandrup S., Gerhart-Hines Z.; RT "Lipolysis drives expression of the constitutively active receptor GPR3 to RT induce adipose thermogenesis."; RL Cell 184:3502-3518(2021). RN [10] RP FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP ASP-133 AND ARG-134. RX PubMed=34871769; DOI=10.1016/j.mcn.2021.103691; RA Tanaka S., Shimada N., Shiraki H., Miyagi T., Harada K., Hide I., Sakai N.; RT "GPR3 accelerates neurite outgrowth and neuronal polarity formation via PI3 RT kinase-mediating signaling pathway in cultured primary neurons."; RL Mol. Cell. Neurosci. 118:103691-103691(2022). CC -!- FUNCTION: Constitutively active G-protein coupled receptor that CC maintains high 3'-5'-cyclic adenosine monophosphate (cAMP) levels that CC a plays a role in serveral processes including meiotic arrest in CC oocytes or neuronal development via activation of numerous CC intracellular signaling pathways (PubMed:15956199, PubMed:19259266). CC Acts as an essential activator of thermogenic adipocytes and drives CC thermogenesis via its intrinsic G(s)-coupling activity without the CC requirement of a ligand (PubMed:26455425, PubMed:34048700). Has a CC potential role in modulating a number of brain functions, including CC behavioral responses to stress, amyloid-beta peptide generation in CC neurons. Stimulates neurite outgrowth in cerebellar granular neurons CC modulated via PKA, ERK, and most strongly PI3K-mediated signaling CC pathways (PubMed:34871769). {ECO:0000269|PubMed:15956199, CC ECO:0000269|PubMed:19259266, ECO:0000269|PubMed:26455425, CC ECO:0000269|PubMed:34048700, ECO:0000269|PubMed:34871769}. CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein CC {ECO:0000269|PubMed:34871769}. CC -!- TISSUE SPECIFICITY: Expressed in both the forebrain and hindbrain, with CC the highest level in habenula (PubMed:8262253). Lower level expression CC in the testis. Expressed in several metabolically active peripheral CC tissues, although at lower levels than in the central nervous system CC (CNS) (PubMed:26455425). {ECO:0000269|PubMed:19259266, CC ECO:0000269|PubMed:26455425, ECO:0000269|PubMed:8262253}. CC -!- DISRUPTION PHENOTYPE: Mice are fertile but display progressive CC reduction in litter size despite a stable age-independent alteration of CC the meiotic pause, characterized by premature resumption of meiosis in CC about one-third of antral follicles in mutant females regardless of CC age. Aging mutant mice had severe reduction of fertility, manifested by CC an increasing number of nondeveloping early embryos upon spontaneous CC ovulation and massive amounts of fragmented oocytes after CC superovulation (PubMed:15956199). Older mice have also reduced total CC energy expenditure, Hippocampal neurons show delayed polarity formation CC with an increased DPYSL2 phosphorylation at the neurite tips CC (PubMed:34871769). {ECO:0000269|PubMed:15956199, CC ECO:0000269|PubMed:34871769}. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. CC {ECO:0000255|PROSITE-ProRule:PRU00521}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D21062; BAA04641.1; -; mRNA. DR EMBL; AK140302; BAE24325.1; -; mRNA. DR EMBL; AK140464; BAE24399.1; -; mRNA. DR EMBL; AK158917; BAE34727.1; -; mRNA. DR EMBL; AL671858; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH466552; EDL30077.1; -; Genomic_DNA. DR EMBL; BC138248; AAI38249.1; -; mRNA. DR EMBL; BC138250; AAI38251.1; -; mRNA. DR CCDS; CCDS18743.1; -. DR PIR; S40454; S40454. DR RefSeq; NP_032180.1; NM_008154.3. DR AlphaFoldDB; P35413; -. DR SMR; P35413; -. DR STRING; 10090.ENSMUSP00000101531; -. DR GlyCosmos; P35413; 1 site, No reported glycans. DR GlyGen; P35413; 1 site. DR PhosphoSitePlus; P35413; -. DR PaxDb; 10090-ENSMUSP00000101531; -. DR Antibodypedia; 3339; 390 antibodies from 39 providers. DR DNASU; 14748; -. DR Ensembl; ENSMUST00000052090.9; ENSMUSP00000062083.9; ENSMUSG00000049649.9. DR Ensembl; ENSMUST00000105911.2; ENSMUSP00000101531.2; ENSMUSG00000049649.9. DR GeneID; 14748; -. DR KEGG; mmu:14748; -. DR UCSC; uc008vci.1; mouse. DR AGR; MGI:101908; -. DR CTD; 2827; -. DR MGI; MGI:101908; Gpr3. DR VEuPathDB; HostDB:ENSMUSG00000049649; -. DR eggNOG; KOG3656; Eukaryota. DR GeneTree; ENSGT01060000248564; -. DR HOGENOM; CLU_065071_0_0_1; -. DR InParanoid; P35413; -. DR OMA; IQKVLWT; -. DR OrthoDB; 5397365at2759; -. DR PhylomeDB; P35413; -. DR TreeFam; TF330052; -. DR BioGRID-ORCS; 14748; 2 hits in 80 CRISPR screens. DR PRO; PR:P35413; -. DR Proteomes; UP000000589; Chromosome 4. DR RNAct; P35413; Protein. DR Bgee; ENSMUSG00000049649; Expressed in animal zygote and 49 other cell types or tissues. DR ExpressionAtlas; P35413; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central. DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central. DR GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; ISO:MGI. DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IMP:YuBioLab. DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; ISO:MGI. DR GO; GO:0040020; P:regulation of meiotic nuclear division; IMP:MGI. DR GO; GO:0019222; P:regulation of metabolic process; IBA:GO_Central. DR CDD; cd15963; 7tmA_GPR3; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR InterPro; IPR000984; GPR3. DR InterPro; IPR000723; GPR_3/6/12_orphan. DR PANTHER; PTHR22750; G-PROTEIN COUPLED RECEPTOR; 1. DR PANTHER; PTHR22750:SF39; G-PROTEIN COUPLED RECEPTOR 3; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR00237; GPCRRHODOPSN. DR PRINTS; PR00648; GPR3ORPHANR. DR PRINTS; PR00644; GPRORPHANR. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1. DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1. DR Genevisible; P35413; MM. PE 1: Evidence at protein level; KW Cell membrane; G-protein coupled receptor; Glycoprotein; Lipoprotein; KW Membrane; Palmitate; Phosphoprotein; Receptor; Reference proteome; KW Transducer; Transmembrane; Transmembrane helix. FT CHAIN 1..330 FT /note="G-protein coupled receptor 3" FT /id="PRO_0000069511" FT TOPO_DOM 1..42 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 43..62 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 63..74 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 75..98 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 99..110 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 111..132 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 133..153 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 154..173 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TOPO_DOM 174..198 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 199..217 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TOPO_DOM 218..245 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 246..272 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT TOPO_DOM 273..277 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 278..299 FT /note="Helical; Name=7" FT /evidence="ECO:0000255" FT TOPO_DOM 300..330 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT MOD_RES 324 FT /note="Phosphoserine" FT /evidence="ECO:0000255" FT MOD_RES 326 FT /note="Phosphoserine" FT /evidence="ECO:0000255" FT MOD_RES 328 FT /note="Phosphoserine" FT /evidence="ECO:0000255" FT LIPID 313 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250" FT CARBOHYD 20 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT MUTAGEN 133 FT /note="D->A: Loss of plasma membrane localization; when FT associated with A-134." FT /evidence="ECO:0000269|PubMed:34871769" FT MUTAGEN 134 FT /note="R->A: Loss of plasma membrane localization; when FT associated with A-133." FT /evidence="ECO:0000269|PubMed:34871769" SQ SEQUENCE 330 AA; 35453 MW; 89122C57945482B3 CRC64; MMWGAGSSMA WFSAGSGSVN VSSVDPVEEP TGPATLLPSP RAWDVVLCIS GTLVSCENAL VVAIIVGTPA FRAPMFLLVG SLAVADLLAG LGLVLHFAAD FCIGSPEMSL MLVGVLAMAF TASIGSLLAI TVDRYLSLYN ALTYYSETTV TRTYVMLALV WVGALGLGLV PVLAWNCRDG LTTCGVVYPL SKNHLVVLAI AFFMVFGIML QLYAQICRIV CRHAQQIALQ RHLLPASHYV ATRKGIATLA VVLGAFAACW LPFTVYCLLG DADSPRLYTY LTLLPATYNS MINPVIYAFR NQDVQKVLWA ICCCCSTSKI PFRSRSPSDV //