LGR4_MOUSE
ID LGR4_MOUSE Reviewed; 951 AA.
AC A2ARI4; A2ARI3; Q6PHA3; Q80T31; Q8BXS9;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Leucine-rich repeat-containing G-protein coupled receptor 4;
DE AltName: Full=G-protein coupled receptor 48;
DE Flags: Precursor;
GN Name=Lgr4; Synonyms=Gpr48;
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 [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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 63-196.
RX PubMed=12679517; DOI=10.1073/pnas.0230374100;
RA Vassilatis D.K., Hohmann J.G., Zeng H., Li F., Ranchalis J.E.,
RA Mortrud M.T., Brown A., Rodriguez S.S., Weller J.R., Wright A.C.,
RA Bergmann J.E., Gaitanaris G.A.;
RT "The G protein-coupled receptor repertoires of human and mouse.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:4903-4908(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 74-951.
RC STRAIN=C57BL/6J; TISSUE=Retina;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 464-951.
RC STRAIN=Czech II; TISSUE=Mammary tumor;
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 [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=15192078; DOI=10.1210/me.2004-0133;
RA Mazerbourg S., Bouley D.M., Sudo S., Klein C.A., Zhang J.V., Kawamura K.,
RA Goodrich L.V., Rayburn H., Tessier-Lavigne M., Hsueh A.J.;
RT "Leucine-rich repeat-containing, G protein-coupled receptor 4 null mice
RT exhibit intrauterine growth retardation associated with embryonic and
RT perinatal lethality.";
RL Mol. Endocrinol. 18:2241-2254(2004).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=16406039; DOI=10.1016/j.ydbio.2005.11.043;
RA Mendive F., Laurent P., Van Schoore G., Skarnes W., Pochet R., Vassart G.;
RT "Defective postnatal development of the male reproductive tract in LGR4
RT knockout mice.";
RL Dev. Biol. 290:421-434(2006).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=16785743; DOI=10.1159/000093999;
RA Kato S., Matsubara M., Matsuo T., Mohri Y., Kazama I., Hatano R.,
RA Umezawa A., Nishimori K.;
RT "Leucine-rich repeat-containing G protein-coupled receptor-4 (LGR4, Gpr48)
RT is essential for renal development in mice.";
RL Nephron Exp. Nephrol. 104:E63-E75(2006).
RN [8]
RP DISRUPTION PHENOTYPE.
RX PubMed=17079737; DOI=10.1095/biolreprod.106.054619;
RA Hoshii T., Takeo T., Nakagata N., Takeya M., Araki K., Yamamura K.;
RT "LGR4 regulates the postnatal development and integrity of male
RT reproductive tracts in mice.";
RL Biol. Reprod. 76:303-313(2007).
RN [9]
RP DISRUPTION PHENOTYPE.
RX PubMed=17850793; DOI=10.1016/j.febslet.2007.08.064;
RA Kato S., Mohri Y., Matsuo T., Ogawa E., Umezawa A., Okuyama R.,
RA Nishimori K.;
RT "Eye-open at birth phenotype with reduced keratinocyte motility in LGR4
RT null mice.";
RL FEBS Lett. 581:4685-4690(2007).
RN [10]
RP DISRUPTION PHENOTYPE.
RX PubMed=18651655; DOI=10.1002/dvdy.21639;
RA Mohri Y., Kato S., Umezawa A., Okuyama R., Nishimori K.;
RT "Impaired hair placode formation with reduced expression of hair follicle-
RT related genes in mice lacking Lgr4.";
RL Dev. Dyn. 237:2235-2242(2008).
RN [11]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18955481; DOI=10.1074/jbc.m800721200;
RA Song H., Luo J., Luo W., Weng J., Wang Z., Li B., Li D., Liu M.;
RT "Inactivation of G-protein-coupled receptor 48 (Gpr48/Lgr4) impairs
RT definitive erythropoiesis at midgestation through down-regulation of the
RT ATF4 signaling pathway.";
RL J. Biol. Chem. 283:36687-36697(2008).
RN [12]
RP DISRUPTION PHENOTYPE.
RX PubMed=18424556; DOI=10.1073/pnas.0708257105;
RA Weng J., Luo J., Cheng X., Jin C., Zhou X., Qu J., Tu L., Ai D., Li D.,
RA Wang J., Martin J.F., Amendt B.A., Liu M.;
RT "Deletion of G protein-coupled receptor 48 leads to ocular anterior segment
RT dysgenesis (ASD) through down-regulation of Pitx2.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:6081-6086(2008).
RN [13]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19605502; DOI=10.1242/dev.033571;
RA Luo J., Zhou W., Zhou X., Li D., Weng J., Yi Z., Cho S.G., Li C., Yi T.,
RA Wu X., Li X.Y., de Crombrugghe B., Hook M., Liu M.;
RT "Regulation of bone formation and remodeling by G-protein-coupled receptor
RT 48.";
RL Development 136:2747-2756(2009).
RN [14]
RP DISRUPTION PHENOTYPE.
RX PubMed=20638054; DOI=10.1016/j.fertnstert.2010.05.050;
RA Mohri Y., Umezu T., Hidema S., Tomisawa H., Akamatsu A., Kato S., Nawa A.,
RA Nishimori K.;
RT "Reduced fertility with impairment of early-stage embryos observed in mice
RT lacking Lgr4 in epithelial tissues.";
RL Fertil. Steril. 94:2878-2881(2010).
RN [15]
RP DISRUPTION PHENOTYPE.
RX PubMed=21523854; DOI=10.1002/dvdy.22651;
RA Mohri Y., Oyama K., Akamatsu A., Kato S., Nishimori K.;
RT "Lgr4-deficient mice showed premature differentiation of ureteric bud with
RT reduced expression of Wnt effector Lef1 and Gata3.";
RL Dev. Dyn. 240:1626-1634(2011).
RN [16]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21508962; DOI=10.1038/embor.2011.52;
RA Mustata R.C., Van Loy T., Lefort A., Libert F., Strollo S., Vassart G.,
RA Garcia M.I.;
RT "Lgr4 is required for Paneth cell differentiation and maintenance of
RT intestinal stem cells ex vivo.";
RL EMBO Rep. 12:558-564(2011).
RN [17]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21727895; DOI=10.1038/nature10337;
RA de Lau W., Barker N., Low T.Y., Koo B.K., Li V.S., Teunissen H., Kujala P.,
RA Haegebarth A., Peters P.J., van de Wetering M., Stange D.E., van Es J.E.,
RA Guardavaccaro D., Schasfoort R.B., Mohri Y., Nishimori K., Mohammed S.,
RA Heck A.J., Clevers H.;
RT "Lgr5 homologues associate with Wnt receptors and mediate R-spondin
RT signalling.";
RL Nature 476:293-297(2011).
RN [18]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH RSPO1; RSPO2; RSPO3
RP AND RSPO4.
RX PubMed=21693646; DOI=10.1073/pnas.1106083108;
RA Carmon K.S., Gong X., Lin Q., Thomas A., Liu Q.;
RT "R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to
RT regulate Wnt/beta-catenin signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:11452-11457(2011).
RN [19]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23533175; DOI=10.1242/dev.093641;
RA Qian Y., Liu S., Guan Y., Pan H., Guan X., Qiu Z., Li L., Gao N., Zhao Y.,
RA Li X., Lu Y., Liu M., Li D.;
RT "Lgr4-mediated Wnt/beta-catenin signaling in peritubular myoid cells is
RT essential for spermatogenesis.";
RL Development 140:1751-1761(2013).
RN [20]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23393138; DOI=10.1074/jbc.m112.436204;
RA Liu S., Qian Y., Li L., Wei G., Guan Y., Pan H., Guan X., Zhang L., Lu X.,
RA Zhao Y., Liu M., Li D.;
RT "Lgr4 gene deficiency increases susceptibility and severity of dextran
RT sodium sulfate-induced inflammatory bowel disease in mice.";
RL J. Biol. Chem. 288:8794-8803(2013).
RN [21]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF THR-755.
RX PubMed=23589304; DOI=10.1074/jbc.m113.455535;
RA Du B., Luo W., Li R., Tan B., Han H., Lu X., Li D., Qian M., Zhang D.,
RA Zhao Y., Liu M.;
RT "Lgr4/Gpr48 negatively regulates TLR2/4 associated pattern recognition and
RT innate immunity by targeting CD14 expression.";
RL J. Biol. Chem. 288:15131-15141(2013).
RN [22]
RP FUNCTION.
RX PubMed=23444378; DOI=10.1242/jcs.123471;
RA Deng C., Reddy P., Cheng Y., Luo C.W., Hsiao C.L., Hsueh A.J.;
RT "Multi-functional norrin is a ligand for the LGR4 receptor.";
RL J. Cell Sci. 126:2060-2068(2013).
RN [23]
RP FUNCTION, AND INDUCTION.
RX PubMed=24353284; DOI=10.1530/jme-13-0042;
RA Wang F., Zhang X., Wang J., Chen M., Fan N., Ma Q., Liu R., Wang R., Li X.,
RA Liu M., Ning G.;
RT "LGR4 acts as a link between the peripheral circadian clock and lipid
RT metabolism in liver.";
RL J. Mol. Endocrinol. 52:133-143(2014).
RN [24]
RP DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=29769720; DOI=10.1038/s41586-018-0118-y;
RA Szenker-Ravi E., Altunoglu U., Leushacke M., Bosso-Lefevre C., Khatoo M.,
RA Thi Tran H., Naert T., Noelanders R., Hajamohideen A., Beneteau C.,
RA de Sousa S.B., Karaman B., Latypova X., Basaran S., Yuecel E.B., Tan T.T.,
RA Vlaminck L., Nayak S.S., Shukla A., Girisha K.M., Le Caignec C.,
RA Soshnikova N., Uyguner Z.O., Vleminckx K., Barker N., Kayserili H.,
RA Reversade B.;
RT "RSPO2 inhibition of RNF43 and ZNRF3 governs limb development independently
RT of LGR4/5/6.";
RL Nature 557:564-569(2018).
RN [25]
RP FUNCTION.
RX PubMed=32493844; DOI=10.1172/jci.insight.133434;
RA Mancini A., Howard S.R., Marelli F., Cabrera C.P., Barnes M.R.,
RA Sternberg M.J., Leprovots M., Hadjidemetriou I., Monti E., David A.,
RA Wehkalampi K., Oleari R., Lettieri A., Vezzoli V., Vassart G., Cariboni A.,
RA Bonomi M., Garcia M.I., Guasti L., Dunkel L.;
RT "LGR4 deficiency results in delayed puberty through impaired Wnt/beta-
RT catenin signaling.";
RL JCI Insight 5:0-0(2020).
CC -!- FUNCTION: Receptor for R-spondins that potentiates the canonical Wnt
CC signaling pathway and is involved in the formation of various organs.
CC Upon binding to R-spondins (RSPO1, RSPO2, RSPO3 or RSPO4), associates
CC with phosphorylated LRP6 and frizzled receptors that are activated by
CC extracellular Wnt receptors, triggering the canonical Wnt signaling
CC pathway to increase expression of target genes. In contrast to
CC classical G-protein coupled receptors, does not activate heterotrimeric
CC G-proteins to transduce the signal. Its function as activator of the
CC Wnt signaling pathway is required for the development of various
CC organs, including liver, kidney, intestine, bone, reproductive tract
CC and eye. May also act as a receptor for norrin (NDP), such results
CC however require additional confirmation in vivo. Required during
CC spermatogenesis to activate the Wnt signaling pathway in peritubular
CC myoid cells. Required for the maintenance of intestinal stem cells and
CC Paneth cell differentiation in postnatal intestinal crypts. Acts as a
CC regulator of bone formation and remodeling. Involved in kidney
CC development; required for maintaining the ureteric bud in an
CC undifferentiated state. Involved in the development of the anterior
CC segment of the eye. Required during erythropoiesis. Also acts as a
CC negative regulator of innate immunity by inhibiting TLR2/TLR4
CC associated pattern-recognition and pro-inflammatory cytokine
CC production. Plays an important role in regulating the circadian rhythms
CC of plasma lipids, partially through regulating the rhythmic expression
CC of MTTP (PubMed:24353284). Required for proper development of GnRH
CC neurons (gonadotropin-releasing hormone expressing neurons) that
CC control the release of reproductive hormones from the pituitary gland
CC (PubMed:32493844). {ECO:0000269|PubMed:18955481,
CC ECO:0000269|PubMed:19605502, ECO:0000269|PubMed:21508962,
CC ECO:0000269|PubMed:21693646, ECO:0000269|PubMed:21727895,
CC ECO:0000269|PubMed:23393138, ECO:0000269|PubMed:23444378,
CC ECO:0000269|PubMed:23533175, ECO:0000269|PubMed:23589304,
CC ECO:0000269|PubMed:24353284, ECO:0000269|PubMed:32493844}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21693646};
CC Multi-pass membrane protein {ECO:0000269|PubMed:21693646}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=A2ARI4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A2ARI4-2; Sequence=VSP_047137;
CC -!- DEVELOPMENTAL STAGE: During limb development, at 14.5 dpc, expressed in
CC the mesenchyme, but not in the overlying ectoderm of the limb bud. In
CC developing lungs, at 14.5 dpc, expressed at low levels in both the
CC epithelium and mesenchyme lineages. {ECO:0000269|PubMed:29769720}.
CC -!- INDUCTION: Expressed in a circadian manner in the liver.
CC {ECO:0000269|PubMed:24353284}.
CC -!- DISRUPTION PHENOTYPE: Strong variations in phenotypes, probably
CC depending on the strain background used in the different experiments.
CC According to a first report done in a C57BL/6 background, mice show
CC intra-uterine growth retardation leading to embryonic and perinatal
CC lethality (PubMed:15192078). A lethal phenotype was confirmed by other
CC groups. In some cases however, few mice survive until adulthood. Mice
CC that survive show wide spectrum of anterior segment dysgenesis
CC phenotypes, including microphthalmia, iris hypoplasia, irdiocorneal
CC angle malformation, cornea dysgenesis and cataract (PubMed:18424556).
CC Defects in osteoblast differentiation and mineralization during
CC embryonic bone formation are also observed. Postnatal mice that survive
CC show defects in bone remodeling (PubMed:19605502). According to other
CC reports done in other strain backgrounds, mice do not die and display
CC defects in the male reproductive tract during the postnatal period
CC (PubMed:16406039, PubMed:17079737, PubMed:23533175). Mice also show
CC small kidneys, in which the total number and density of the glomeruli
CC are decreased (PubMed:16785743). The use of conditional knockouts,
CC leads to defects in hair placode formation, possibly due to reduced
CC keratinocyte migration (PubMed:17079737, PubMed:17850793). Decrease in
CC epithelial cell proliferation and strong reduction in terminal
CC differentiation of Paneth cells in postnatal intestinal crypts
CC (PubMed:21508962, PubMed:23393138). Fetuses display transient anemia
CC during midgestation and abnormal definitive erythropoiesis
CC (PubMed:18955481). Mice are also more susceptible and have much higher
CC mortality to lipopolysaccharide (LPS) stimulation due to over-activated
CC innate immune response (PubMed:23589304). Conditional knockout of both
CC Lgr4 and Lgr5 in the gut results in Wnt signaling inhibition and
CC results in the rapid demise of intestinal crypts (PubMed:21727895).
CC Simultaneous knockdown of LGR4, LGR5 and LGR6 results in developmental
CC phenotypes, such as cleft palate and ankyloglossia, but not in tetra-
CC amelia with lung agenesis (PubMed:29769720).
CC {ECO:0000269|PubMed:15192078, ECO:0000269|PubMed:16406039,
CC ECO:0000269|PubMed:16785743, ECO:0000269|PubMed:17079737,
CC ECO:0000269|PubMed:17850793, ECO:0000269|PubMed:18424556,
CC ECO:0000269|PubMed:18651655, ECO:0000269|PubMed:18955481,
CC ECO:0000269|PubMed:19605502, ECO:0000269|PubMed:20638054,
CC ECO:0000269|PubMed:21508962, ECO:0000269|PubMed:21523854,
CC ECO:0000269|PubMed:21727895, ECO:0000269|PubMed:23393138,
CC ECO:0000269|PubMed:23533175, ECO:0000269|PubMed:23589304,
CC ECO:0000269|PubMed:29769720}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AL845423; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL928922; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX294391; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AY255619; AAO85131.1; -; mRNA.
DR EMBL; AK044357; BAC31882.1; -; mRNA.
DR EMBL; BC056637; AAH56637.1; -; mRNA.
DR CCDS; CCDS38195.1; -. [A2ARI4-1]
DR RefSeq; NP_766259.2; NM_172671.2. [A2ARI4-1]
DR AlphaFoldDB; A2ARI4; -.
DR SMR; A2ARI4; -.
DR STRING; 10090.ENSMUSP00000047325; -.
DR GlyGen; A2ARI4; 5 sites.
DR iPTMnet; A2ARI4; -.
DR PhosphoSitePlus; A2ARI4; -.
DR MaxQB; A2ARI4; -.
DR PaxDb; A2ARI4; -.
DR PeptideAtlas; A2ARI4; -.
DR PRIDE; A2ARI4; -.
DR ProteomicsDB; 290023; -. [A2ARI4-1]
DR ProteomicsDB; 290024; -. [A2ARI4-2]
DR Antibodypedia; 12720; 434 antibodies from 33 providers.
DR DNASU; 107515; -.
DR Ensembl; ENSMUST00000046548; ENSMUSP00000047325; ENSMUSG00000050199. [A2ARI4-1]
DR Ensembl; ENSMUST00000111037; ENSMUSP00000106666; ENSMUSG00000050199. [A2ARI4-2]
DR GeneID; 107515; -.
DR KEGG; mmu:107515; -.
DR UCSC; uc008lmq.1; mouse. [A2ARI4-1]
DR CTD; 55366; -.
DR MGI; MGI:1891468; Lgr4.
DR VEuPathDB; HostDB:ENSMUSG00000050199; -.
DR eggNOG; KOG0619; Eukaryota.
DR eggNOG; KOG2087; Eukaryota.
DR GeneTree; ENSGT00940000157925; -.
DR HOGENOM; CLU_006843_0_0_1; -.
DR InParanoid; A2ARI4; -.
DR OMA; DLFWMCL; -.
DR PhylomeDB; A2ARI4; -.
DR TreeFam; TF316814; -.
DR BioGRID-ORCS; 107515; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Lgr4; mouse.
DR PRO; PR:A2ARI4; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; A2ARI4; protein.
DR Bgee; ENSMUSG00000050199; Expressed in indifferent gonad and 229 other tissues.
DR Genevisible; A2ARI4; MM.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0008201; F:heparin binding; IBA:GO_Central.
DR GO; GO:0016500; F:protein-hormone receptor activity; IEA:InterPro.
DR GO; GO:0048495; F:Roundabout binding; IBA:GO_Central.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IDA:UniProtKB.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0030282; P:bone mineralization; IMP:UniProtKB.
DR GO; GO:0046849; P:bone remodeling; IMP:UniProtKB.
DR GO; GO:0061290; P:canonical Wnt signaling pathway involved in metanephric kidney development; IMP:UniProtKB.
DR GO; GO:0072202; P:cell differentiation involved in metanephros development; IMP:UniProtKB.
DR GO; GO:0032922; P:circadian regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; IEP:UniProtKB.
DR GO; GO:0048565; P:digestive tract development; IMP:MGI.
DR GO; GO:0050673; P:epithelial cell proliferation; IMP:MGI.
DR GO; GO:2001013; P:epithelial cell proliferation involved in renal tubule morphogenesis; IGI:MGI.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0001942; P:hair follicle development; IMP:MGI.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0036335; P:intestinal stem cell homeostasis; IMP:MGI.
DR GO; GO:0030539; P:male genitalia development; IMP:MGI.
DR GO; GO:0072224; P:metanephric glomerulus development; IMP:UniProtKB.
DR GO; GO:0072282; P:metanephric nephron tubule morphogenesis; IMP:UniProtKB.
DR GO; GO:0050919; P:negative chemotaxis; IBA:GO_Central.
DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR GO; GO:0001818; P:negative regulation of cytokine production; IMP:UniProtKB.
DR GO; GO:0034122; P:negative regulation of toll-like receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0001649; P:osteoblast differentiation; IMP:UniProtKB.
DR GO; GO:0090190; P:positive regulation of branching involved in ureteric bud morphogenesis; IMP:UniProtKB.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IMP:UniProtKB.
DR GO; GO:0035239; P:tube morphogenesis; IMP:MGI.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR002131; Gphrmn_rcpt_fam.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR000372; LRRNT.
DR Pfam; PF00001; 7tm_1; 1.
DR Pfam; PF13855; LRR_8; 4.
DR Pfam; PF01462; LRRNT; 1.
DR PRINTS; PR00373; GLYCHORMONER.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR SMART; SM00369; LRR_TYP; 15.
DR SMART; SM00013; LRRNT; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
DR PROSITE; PS51450; LRR; 15.
PE 1: Evidence at protein level;
KW Alternative splicing; Biological rhythms; Cell membrane;
KW Developmental protein; Differentiation; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Immunity; Innate immunity;
KW Leucine-rich repeat; Membrane; Phosphoprotein; Receptor;
KW Reference proteome; Repeat; Signal; Spermatogenesis; Transducer;
KW Transmembrane; Transmembrane helix; Wnt signaling pathway.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..951
FT /note="Leucine-rich repeat-containing G-protein coupled
FT receptor 4"
FT /id="PRO_0000303240"
FT TOPO_DOM 25..544
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 545..565
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 566..575
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 576..596
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 597..619
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 620..640
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 641..661
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 662..682
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 683..703
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 704..724
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 725..756
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 757..777
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 778..783
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 784..804
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 805..951
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 25..57
FT /note="LRRNT"
FT REPEAT 58..79
FT /note="LRR 1"
FT REPEAT 82..103
FT /note="LRR 2"
FT REPEAT 106..127
FT /note="LRR 3"
FT REPEAT 130..151
FT /note="LRR 4"
FT REPEAT 154..177
FT /note="LRR 5"
FT REPEAT 178..199
FT /note="LRR 6"
FT REPEAT 202..223
FT /note="LRR 7"
FT REPEAT 226..247
FT /note="LRR 8"
FT REPEAT 249..270
FT /note="LRR 9"
FT REPEAT 273..294
FT /note="LRR 10"
FT REPEAT 320..341
FT /note="LRR 11"
FT REPEAT 344..365
FT /note="LRR 12"
FT REPEAT 366..387
FT /note="LRR 13"
FT REPEAT 390..411
FT /note="LRR 14"
FT REPEAT 414..435
FT /note="LRR 15"
FT REGION 487..512
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 920
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BXB1"
FT CARBOHYD 68
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 188
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 199
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 294
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 505
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 29..35
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 33..43
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 339..364
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 470..522
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 471..476
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 618..693
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VAR_SEQ 62..85
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_047137"
FT MUTAGEN 755
FT /note="T->I: Confers constitutive activity."
FT /evidence="ECO:0000269|PubMed:23589304"
FT CONFLICT 668
FT /note="V -> L (in Ref. 4; AAH56637)"
FT /evidence="ECO:0000305"
FT CONFLICT 684
FT /note="G -> R (in Ref. 4; AAH56637)"
FT /evidence="ECO:0000305"
FT CONFLICT 730
FT /note="C -> F (in Ref. 3; BAC31882)"
FT /evidence="ECO:0000305"
FT CONFLICT 928
FT /note="R -> P (in Ref. 4; AAH56637)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 951 AA; 104150 MW; AD41C68730A19C6B CRC64;
MPGPLRLLCF FALGLLGSAG PSGAAPPLCA APCSCDGDRR VDCSGKGLTA VPEGLSAFTQ
ALDISMNNIT QLPEDAFKNF PFLEELQLAG NDLSFIHPKA LSGLKELKVL TLQNNQLKTV
PSEAIRGLSA LQSLRLDANH ITSVPEDSFE GLVQLRHLWL DDNILTEVPV RPLSNLPTLQ
ALTLALNNIS SIPDFAFTNL SSLVVLHLHN NKIKSLSQHC FDGLDNLETL DLNYNNLDEF
PQAIKALPSL KELGFHSNSI SVIPDGAFAG NPLLRTIHLY DNPLSFVGNS AFHNLSDLHS
LVIRGASLVQ WFPNLAGTVH LESLTLTGTK ISSIPDDLCQ NQKMLRTLDL SYNDIRDLPS
FNGCRALEEI SLQRNQISLI KETTFQGLTS LRILDLSRNL IREIHSGAFA KLGTITNLDV
SFNELTSFPT EGLNGLNQLK LVGNFQLKDA LAARDFANLR SLSVPYAYQC CAFWGCDSYA
NLNTEDNSPQ DHSVTKEKGA TDAANATSTA ESEEHSQIII HCTPSTGAFK PCEYLLGSWM
IRLTVWFIFL VALLFNLLVI LTVFASCSSL PASKLFIGLI SVSNLLMGIY TGILTFLDAV
SWGRFAEFGI WWETGSGCKV AGSLAVFSSE SAVFLLTLAA VERSVFAKDV MKNGKSSHLR
QFQVAALVAL LGAAIAGCFP LFHGGQYSAS PLCLPFPTGE TPSLGFTVTL VLLNSLAFLL
MAIIYTKLYC NLEKEDPSEN SQSSMIKHVA WLIFTNCIFF CPVAFFSFAP LITAISISPE
IMKSVTLIFF PLPACLNPVL YVFFNPKFKD DWKLLKRRVT RKHGSVSVSI SSQGGCGEQD
FYYDCGMYSH LQGNLTVCDC CESFLLTKPV SCKHLIKSHS CPVLTVASCQ RPEAYWSDCG
TQSAHSDYAD EEDSFVSDSS DQVQACGRAC FYQSRGFPLV RYAYNLPRVR D
