LPAR1_MOUSE
ID LPAR1_MOUSE Reviewed; 364 AA.
AC P61793; A2AMJ2; O88584; P56487; P70420; Q61130;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2004, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Lysophosphatidic acid receptor 1 {ECO:0000305};
DE Short=LPA receptor 1 {ECO:0000305};
DE Short=LPA-1 {ECO:0000303|PubMed:9600933, ECO:0000303|PubMed:9721207};
DE AltName: Full=Lysophosphatidic acid receptor Edg-2 {ECO:0000303|PubMed:9600933};
DE AltName: Full=Rec1.3 {ECO:0000303|PubMed:9013780};
DE AltName: Full=VZG-1 {ECO:0000303|PubMed:8922387, ECO:0000303|PubMed:9600933};
GN Name=Lpar1;
GN Synonyms=Edg2, Gpcr26 {ECO:0000303|PubMed:9721207},
GN Lpa1 {ECO:0000303|PubMed:9600933, ECO:0000303|PubMed:9721207},
GN Vzg1 {ECO:0000303|PubMed:8922387, ECO:0000303|PubMed:9600933};
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] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ;
RX PubMed=8922387; DOI=10.1083/jcb.135.4.1071;
RA Hecht J.H., Weiner J.A., Post S.R., Chun J.;
RT "Ventricular zone gene-1 (vzg-1) encodes a lysophosphatidic acid receptor
RT expressed in neurogenic regions of the developing cerebral cortex.";
RL J. Cell Biol. 135:1071-1083(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=9013780; DOI=10.1016/s0169-328x(96)00128-3;
RA Macrae A.D., Premont R.T., Jaber M., Petersen A.S., Lefkowitz R.J.;
RT "Cloning, characterization, and chromosomal localization of rec1.3, a
RT member of the G-protein-coupled receptor family highly expressed in
RT brain.";
RL Brain Res. Mol. Brain Res. 42:245-254(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2).
RC STRAIN=129/SvJ;
RX PubMed=9721207; DOI=10.1006/geno.1998.5400;
RA Contos J.J.A., Chun J.;
RT "Complete cDNA sequence, genomic structure, and chromosomal localization of
RT the LPA receptor gene, lpA1/vzg-1/Gpcr26.";
RL Genomics 51:364-378(1998).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N-3;
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 FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=9600933; DOI=10.1073/pnas.95.11.6151;
RA Fukushima N., Kimura Y., Chun J.;
RT "A single receptor encoded by vzg-1/lpA1/edg-2 couples to G proteins and
RT mediates multiple cellular responses to lysophosphatidic acid.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:6151-6156(1998).
RN [7]
RP FUNCTION.
RX PubMed=11040035; DOI=10.1124/mol.58.5.895;
RA Ishii I., Contos J.J., Fukushima N., Chun J.;
RT "Functional comparisons of the lysophosphatidic acid receptors, LP(A1)/VZG-
RT 1/EDG-2, LP(A2)/EDG-4, and LP(A3)/EDG-7 in neuronal cell lines using a
RT retrovirus expression system.";
RL Mol. Pharmacol. 58:895-902(2000).
RN [8]
RP REVIEW.
RX PubMed=11093753; DOI=10.1124/mol.58.6.1188;
RA Contos J.J.A., Ishii I., Chun J.;
RT "Lysophosphatidic acid receptors.";
RL Mol. Pharmacol. 58:1188-1196(2000).
RN [9]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=11087877; DOI=10.1073/pnas.97.24.13384;
RA Contos J.J., Fukushima N., Weiner J.A., Kaushal D., Chun J.;
RT "Requirement for the lpA1 lysophosphatidic acid receptor gene in normal
RT suckling behavior.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:13384-13389(2000).
RN [10]
RP FUNCTION.
RX PubMed=12181339; DOI=10.1091/mbc.01-09-0465;
RA Fukushima N., Ishii I., Habara Y., Allen C.B., Chun J.;
RT "Dual regulation of actin rearrangement through lysophosphatidic acid
RT receptor in neuroblast cell lines: actin depolymerization by Ca(2+)-alpha-
RT actinin and polymerization by rho.";
RL Mol. Biol. Cell 13:2692-2705(2002).
RN [11]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=12215548; DOI=10.1128/mcb.22.19.6921-6929.2002;
RA Contos J.J., Ishii I., Fukushima N., Kingsbury M.A., Ye X., Kawamura S.,
RA Brown J.H., Chun J.;
RT "Characterization of lpa(2) (Edg4) and lpa(1)/lpa(2) (Edg2/Edg4)
RT lysophosphatidic acid receptor knockout mice: signaling deficits without
RT obvious phenotypic abnormality attributable to lpa(2).";
RL Mol. Cell. Biol. 22:6921-6929(2002).
RN [12]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15195086; DOI=10.1038/nm1060;
RA Inoue M., Rashid M.H., Fujita R., Contos J.J., Chun J., Ueda H.;
RT "Initiation of neuropathic pain requires lysophosphatidic acid receptor
RT signaling.";
RL Nat. Med. 10:712-718(2004).
RN [13]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18157949; DOI=10.1016/j.bbamcr.2007.11.013;
RA Shano S., Hatanaka K., Ninose S., Moriyama R., Tsujiuchi T., Fukushima N.;
RT "A lysophosphatidic acid receptor lacking the PDZ-binding domain is
RT constitutively active and stimulates cell proliferation.";
RL Biochim. Biophys. Acta 1783:748-759(2008).
RN [14]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=17656621; DOI=10.1093/cercor/bhm132;
RA Estivill-Torrus G., Llebrez-Zayas P., Matas-Rico E., Santin L., Pedraza C.,
RA De Diego I., Del Arco I., Fernandez-Llebrez P., Chun J., De Fonseca F.R.;
RT "Absence of LPA1 signaling results in defective cortical development.";
RL Cereb. Cortex 18:938-950(2008).
RN [15]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17692995; DOI=10.1016/j.neuint.2007.07.004;
RA Shano S., Moriyama R., Chun J., Fukushima N.;
RT "Lysophosphatidic acid stimulates astrocyte proliferation through LPA1.";
RL Neurochem. Int. 52:216-220(2008).
RN [16]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=18708146; DOI=10.1016/j.mcn.2008.07.014;
RA Matas-Rico E., Garcia-Diaz B., Llebrez-Zayas P., Lopez-Barroso D.,
RA Santin L., Pedraza C., Smith-Fernandez A., Fernandez-Llebrez P., Tellez T.,
RA Redondo M., Chun J., De Fonseca F.R., Estivill-Torrus G.;
RT "Deletion of lysophosphatidic acid receptor LPA1 reduces neurogenesis in
RT the mouse dentate gyrus.";
RL Mol. Cell. Neurosci. 39:342-355(2008).
RN [17]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=18066075; DOI=10.1038/nm1685;
RA Tager A.M., LaCamera P., Shea B.S., Campanella G.S., Selman M., Zhao Z.,
RA Polosukhin V., Wain J., Karimi-Shah B.A., Kim N.D., Hart W.K., Pardo A.,
RA Blackwell T.S., Xu Y., Chun J., Luster A.D.;
RT "The lysophosphatidic acid receptor LPA1 links pulmonary fibrosis to lung
RT injury by mediating fibroblast recruitment and vascular leak.";
RL Nat. Med. 14:45-54(2008).
RN [18]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=19689455; DOI=10.1111/j.1601-183x.2009.00524.x;
RA Santin L.J., Bilbao A., Pedraza C., Matas-Rico E., Lopez-Barroso D.,
RA Castilla-Ortega E., Sanchez-Lopez J., Riquelme R., Varela-Nieto I.,
RA de la Villa P., Suardiaz M., Chun J., De Fonseca F.R., Estivill-Torrus G.;
RT "Behavioral phenotype of maLPA1-null mice: increased anxiety-like behavior
RT and spatial memory deficits.";
RL Genes Brain Behav. 8:772-784(2009).
RN [19]
RP DISRUPTION PHENOTYPE.
RX PubMed=20358347; DOI=10.1007/bf03185929;
RA Dusaulcy R., Daviaud D., Pradere J.P., Gres S., Valet P.,
RA Saulnier-Blache J.S.;
RT "Altered food consumption in mice lacking lysophosphatidic acid receptor-
RT 1.";
RL J. Physiol. Biochem. 65:345-350(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-351, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [21]
RP DISRUPTION PHENOTYPE, FUNCTION, INTERACTION WITH CD14, SUBCELLULAR
RP LOCATION, INDUCTION BY BACTERIAL LIPOPOLYSACCHARIDE, AND TISSUE
RP SPECIFICITY.
RX PubMed=21821728; DOI=10.1152/ajplung.00058.2011;
RA Zhao J., He D., Su Y., Berdyshev E., Chun J., Natarajan V., Zhao Y.;
RT "Lysophosphatidic acid receptor 1 modulates lipopolysaccharide-induced
RT inflammation in alveolar epithelial cells and murine lungs.";
RL Am. J. Physiol. 301:L547-L556(2011).
RN [22]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=21569876; DOI=10.1016/j.bone.2011.04.018;
RA Gennero I., Laurencin-Dalicieux S., Conte-Auriol F., Briand-Mesange F.,
RA Laurencin D., Rue J., Beton N., Malet N., Mus M., Tokumura A., Bourin P.,
RA Vico L., Brunel G., Oreffo R.O., Chun J., Salles J.P.;
RT "Absence of the lysophosphatidic acid receptor LPA1 results in abnormal
RT bone development and decreased bone mass.";
RL Bone 49:395-403(2011).
RN [23]
RP DISRUPTION PHENOTYPE, FUNCTION, AND INTERACTION WITH GNAQ AND GNA13.
RX PubMed=23478264; DOI=10.1128/mcb.00038-13;
RA Lee S.J., Leoni G., Neumann P.A., Chun J., Nusrat A., Yun C.C.;
RT "Distinct phospholipase C-beta isozymes mediate lysophosphatidic acid
RT receptor 1 effects on intestinal epithelial homeostasis and wound
RT closure.";
RL Mol. Cell. Biol. 33:2016-2028(2013).
RN [24]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=25226845; DOI=10.1007/s00429-014-0885-7;
RA Garcia-Diaz B., Riquelme R., Varela-Nieto I., Jimenez A.J., de Diego I.,
RA Gomez-Conde A.L., Matas-Rico E., Aguirre J.A., Chun J., Pedraza C.,
RA Santin L.J., Fernandez O., Rodriguez de Fonseca F., Estivill-Torrus G.;
RT "Loss of lysophosphatidic acid receptor LPA1 alters oligodendrocyte
RT differentiation and myelination in the mouse cerebral cortex.";
RL Brain Struct. Funct. 220:3701-3720(2015).
RN [25]
RP REVIEW.
RX PubMed=25732591; DOI=10.1007/s00018-015-1872-8;
RA Fukushima N., Ishii S., Tsujiuchi T., Kagawa N., Katoh K.;
RT "Comparative analyses of lysophosphatidic acid receptor-mediated
RT signaling.";
RL Cell. Mol. Life Sci. 72:2377-2394(2015).
CC -!- FUNCTION: Receptor for lysophosphatidic acid (LPA) (PubMed:11087877,
CC PubMed:18066075). Plays a role in the reorganization of the actin
CC cytoskeleton, cell migration, differentiation and proliferation, and
CC thereby contributes to the responses to tissue damage and infectious
CC agents. Activates downstream signaling cascades via the G(i)/G(o),
CC G(12)/G(13), and G(q) families of heteromeric G proteins
CC (PubMed:8922387, PubMed:9600933, PubMed:11040035, PubMed:18157949,
CC PubMed:18066075, PubMed:23478264). Signaling inhibits adenylyl cyclase
CC activity and decreases cellular cAMP levels (PubMed:11040035,
CC PubMed:12215548). Signaling triggers an increase of cytoplasmic Ca(2+)
CC levels (PubMed:12215548). Activates RALA; this leads to the activation
CC of phospholipase C (PLC) and the formation of inositol 1,4,5-
CC trisphosphate (PubMed:11040035, PubMed:12215548, PubMed:23478264).
CC Signaling mediates activation of down-stream MAP kinases
CC (PubMed:11040035). Contributes to the regulation of cell shape
CC (PubMed:8922387, PubMed:9600933, PubMed:11040035, PubMed:11087877).
CC Promotes Rho-dependent reorganization of the actin cytoskeleton in
CC neuronal cells and neurite retraction (PubMed:9600933, PubMed:11040035,
CC PubMed:12181339). Promotes the activation of Rho and the formation of
CC actin stress fibers (PubMed:9600933, PubMed:12215548). Promotes
CC formation of lamellipodia at the leading edge of migrating cells via
CC activation of RAC1 (PubMed:23478264). Through its function as
CC lysophosphatidic acid receptor, plays a role in chemotaxis and cell
CC migration, including responses to injury and wounding (PubMed:11087877,
CC PubMed:18066075, PubMed:23478264). Plays a role in triggering
CC inflammation in response to bacterial lipopolysaccharide (LPS) via its
CC interaction with CD14 (PubMed:21821728). Promotes cell proliferation in
CC response to lysophosphatidic acid (PubMed:9600933, PubMed:11087877,
CC PubMed:12215548, PubMed:18157949, PubMed:17692995, PubMed:23478264).
CC Required for normal skeleton development (PubMed:21569876). May play a
CC role in osteoblast differentiation (PubMed:21569876). Required for
CC normal brain development (PubMed:17656621, PubMed:18708146). Required
CC for normal proliferation, survival and maturation of newly formed
CC neurons in the adult dentate gyrus (PubMed:18708146). Plays a role in
CC pain perception and in the initiation of neuropathic pain
CC (PubMed:15195086, PubMed:19689455). {ECO:0000269|PubMed:11040035,
CC ECO:0000269|PubMed:11087877, ECO:0000269|PubMed:12181339,
CC ECO:0000269|PubMed:12215548, ECO:0000269|PubMed:15195086,
CC ECO:0000269|PubMed:17656621, ECO:0000269|PubMed:17692995,
CC ECO:0000269|PubMed:18066075, ECO:0000269|PubMed:18157949,
CC ECO:0000269|PubMed:18708146, ECO:0000269|PubMed:19689455,
CC ECO:0000269|PubMed:21569876, ECO:0000269|PubMed:23478264,
CC ECO:0000269|PubMed:8922387, ECO:0000269|PubMed:9600933}.
CC -!- SUBUNIT: Interacts with RALA and GRK2 (By similarity). Interacts with
CC GNAQ and GNA13 (PubMed:23478264). Interacts with CD14; the interaction
CC is enhanced by exposure to bacterial lipopolysaccharide (LPS)
CC (PubMed:21821728). {ECO:0000250|UniProtKB:Q92633,
CC ECO:0000269|PubMed:21821728, ECO:0000269|PubMed:23478264}.
CC -!- INTERACTION:
CC P61793; Q9NZN5: ARHGEF12; Xeno; NbExp=3; IntAct=EBI-7512335, EBI-821440;
CC -!- SUBCELLULAR LOCATION: Cell surface {ECO:0000269|PubMed:8922387}. Cell
CC membrane {ECO:0000269|PubMed:18157949, ECO:0000269|PubMed:21821728,
CC ECO:0000269|PubMed:9600933, ECO:0000305|PubMed:8922387}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:Q92633}. Endosome
CC {ECO:0000250|UniProtKB:Q92633, ECO:0000305|PubMed:18157949}. Note=Prior
CC to LPA treatment found predominantly at the cell surface. Internalized
CC after LPA treatment (PubMed:18157949). Colocalizes with RALA in
CC endocytic vesicles after LPA treatment. {ECO:0000250|UniProtKB:Q92633,
CC ECO:0000269|PubMed:18157949}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P61793-1, Q61130-1;
CC Sequence=Displayed;
CC Name=2;
CC IsoId=P61793-2, Q61130-2;
CC Sequence=VSP_001986;
CC -!- TISSUE SPECIFICITY: Detected in lung (PubMed:21821728). Detected in
CC oligodendrocytes in corpus callosum in brain cortex (at protein level)
CC (PubMed:25226845). Expressed within the embryonic cerebral cortex,
CC where it is enriched in the ventricular zone (PubMed:8922387). In the
CC adult brain, also expressed in oligodendrocytes, as well as Schwann
CC cells of the peripheral nervous system (PubMed:9013780,
CC PubMed:25226845). Expressed in many other tissues, including lung,
CC heart, intestine, spleen, thymus, and stomach. No expression in liver
CC (PubMed:9013780). Detected in kidney and testis (PubMed:9013780,
CC PubMed:12215548). Detected in embryonic fibroblasts (PubMed:12215548).
CC Detected in adult lung fibroblasts and lung endothelial cells
CC (PubMed:18066075). Detected in dorsal root ganglion and dorsal root
CC (PubMed:15195086). Detected in astrocytes (PubMed:17692995). Detected
CC in bone (PubMed:21569876). {ECO:0000269|PubMed:12215548,
CC ECO:0000269|PubMed:15195086, ECO:0000269|PubMed:18066075,
CC ECO:0000269|PubMed:21569876, ECO:0000269|PubMed:25226845,
CC ECO:0000269|PubMed:8922387, ECO:0000269|PubMed:9013780}.
CC -!- INDUCTION: Up-regulated by bacterial lipopolysaccharide (LPS) (at
CC protein level). Up-regulated by bacterial lipopolysaccharide (LPS).
CC {ECO:0000269|PubMed:21821728}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q92633}.
CC -!- DISRUPTION PHENOTYPE: Mutant embryos are detected at the expected
CC Mendelian rate, but there is about 50% perinatal lethality. This is
CC mostly due to suckling defects, possibly because the neonates cannot
CC find a nipple. Surviving mice are smaller, and they have shorter snouts
CC and more widely spaced eyes than wild-type. A small percentage of the
CC embryos and neonates display frontal hematomas. Besides, a small
CC percentage of the embryos display exencephaly (PubMed:11087877). These
CC mice display also deformity of the rib cage with sterno-distal rib
CC fusions, shorter, crooked sternebrae, delayed vertebral calcification
CC and closure of the thoracic spine (PubMed:21569876). Their small size
CC is due to growth defects of limbs and vertebrae (PubMed:21569876).
CC Mutant mice display decreased bone mass, as well as defects in
CC proliferation and osteoblastic differentiation of bone marrow
CC mesenchymal stem cells (PubMed:21569876). A spontaneous variant (the
CC Malaga variant) that appeared among the descendants of the original
CC knockout mice shows almost complete perinatal viability, but the mice
CC still present small size, shorter snouts, wider-spaced eyes and reduced
CC brain volume (PubMed:17656621). Compared to wild-type, the Malaga
CC variants display smaller olfactory bulbs, and generally a smaller brain
CC with slightly decreased thickness of the brain cortex and subtle
CC defects in cortex development (PubMed:17656621). The hippocampus
CC appears normal at birth, but displays a reduced number of cell
CC divisions in adult dentate gyrus, both under normal conditions and when
CC mice are exposed to a stimulating environment that promotes
CC neurogenesis (PubMed:18708146). Compared to wild-type, the newly formed
CC hippocampus cells show reduced survival (PubMed:18708146). Newly formed
CC granule cells display defects in their maturation (PubMed:18708146).
CC Mutant mice present subtle myelination defects in the brain cortex
CC (PubMed:25226845). Mutant mice display minor defects in somesthesis,
CC olfaction, grasping and keeping their equilibrium, and show decreased
CC sensitivity to pain caused by heat (PubMed:19689455). Mutant mice do
CC not display allodynia and hyperalgesia after nerve injury and are
CC protected against demyelination after nerve injury (PubMed:15195086).
CC Mutant mice display increased Schwann cell apoptosis in sciatic nerve,
CC but this still leaves the majority of Schwann cells intact and does not
CC cause any visible effect on movement (PubMed:11087877). Mutant mice
CC display decreased exploration in the open field and increased anxiety-
CC like responses to novelty; they also show subtle deficits in spatial
CC learning and memory (PubMed:19689455). Mutant mice show blunted
CC responses to bacterial lipopolysaccharide (LPS) and show reduced acute
CC inflammation in response to LPS (PubMed:21821728). Mutant mice show
CC decreased migration of fibroblasts to sites of lung injury, decreased
CC injury-induced vascular leak, and are protected against the development
CC of lung fibrosis after bleomycin treatment (PubMed:18066075). Mutant
CC mice have reduced levels of proliferating epithelial cells in their
CC intestinal crypts, and the cells do not migrate normally from the
CC bottom of the crypts up into the villi (PubMed:23478264). Mutant mice
CC show impaired repair after wounding of the intestinal mucosa
CC (PubMed:23478264).Mutant mice have less body weight, but increased
CC brown and white adipose tissue (PubMed:20358347). Contrary to wild-
CC type, mutant mice do not increase their food consumption on a high fat
CC diet and do not gain weight on a high fat diet (PubMed:20358347). Mice
CC deficient in both Lpar1 and Lpar2 have the same phenotype as mice
CC lacking Lpar1, excepting a higher incidence of frontal hematomas and
CC slightly higher perinatal lethality (PubMed:12215548).
CC {ECO:0000269|PubMed:11087877, ECO:0000269|PubMed:12215548,
CC ECO:0000269|PubMed:15195086, ECO:0000269|PubMed:17656621,
CC ECO:0000269|PubMed:18066075, ECO:0000269|PubMed:18708146,
CC ECO:0000269|PubMed:19689455, ECO:0000269|PubMed:20358347,
CC ECO:0000269|PubMed:21569876, ECO:0000269|PubMed:21821728,
CC ECO:0000269|PubMed:25226845}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; U70622; AAC52923.1; -; mRNA.
DR EMBL; U48235; AAC53035.1; -; mRNA.
DR EMBL; AF075456; AAC34301.1; -; Genomic_DNA.
DR EMBL; AF075453; AAC34301.1; JOINED; Genomic_DNA.
DR EMBL; AF075455; AAC34301.1; JOINED; Genomic_DNA.
DR EMBL; AF075456; AAC34302.1; -; Genomic_DNA.
DR EMBL; AF075455; AAC34302.1; JOINED; Genomic_DNA.
DR EMBL; AL807748; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC025425; AAH25425.1; -; mRNA.
DR CCDS; CCDS18212.1; -.
DR CCDS; CCDS71391.1; -. [P61793-2]
DR RefSeq; NP_001277415.1; NM_001290486.1. [P61793-2]
DR RefSeq; NP_034466.2; NM_010336.2. [P61793-1]
DR RefSeq; NP_766577.1; NM_172989.1. [P61793-1]
DR RefSeq; XP_011248230.1; XM_011249928.2. [P61793-1]
DR RefSeq; XP_011248231.1; XM_011249929.2. [P61793-1]
DR RefSeq; XP_011248232.1; XM_011249930.2. [P61793-1]
DR RefSeq; XP_011248233.1; XM_011249931.2. [P61793-1]
DR RefSeq; XP_011248234.1; XM_011249932.2. [P61793-1]
DR RefSeq; XP_011248235.1; XM_011249933.2. [P61793-1]
DR RefSeq; XP_011248236.1; XM_011249934.2. [P61793-1]
DR RefSeq; XP_011248237.1; XM_011249935.2. [P61793-1]
DR AlphaFoldDB; P61793; -.
DR SMR; P61793; -.
DR BioGRID; 200018; 3.
DR DIP; DIP-42214N; -.
DR IntAct; P61793; 4.
DR MINT; P61793; -.
DR STRING; 10090.ENSMUSP00000052581; -.
DR ChEMBL; CHEMBL3621025; -.
DR GuidetoPHARMACOLOGY; 272; -.
DR GlyGen; P61793; 2 sites.
DR iPTMnet; P61793; -.
DR PhosphoSitePlus; P61793; -.
DR SwissPalm; P61793; -.
DR jPOST; P61793; -.
DR MaxQB; P61793; -.
DR PaxDb; P61793; -.
DR PeptideAtlas; P61793; -.
DR PRIDE; P61793; -.
DR ProteomicsDB; 290140; -.
DR ProteomicsDB; 290141; -. [P61793-2]
DR Antibodypedia; 15104; 406 antibodies from 35 providers.
DR DNASU; 14745; -.
DR Ensembl; ENSMUST00000055018; ENSMUSP00000052581; ENSMUSG00000038668. [P61793-1]
DR Ensembl; ENSMUST00000107570; ENSMUSP00000103196; ENSMUSG00000038668. [P61793-2]
DR Ensembl; ENSMUST00000107571; ENSMUSP00000103197; ENSMUSG00000038668. [P61793-1]
DR Ensembl; ENSMUST00000107574; ENSMUSP00000103200; ENSMUSG00000038668. [P61793-1]
DR Ensembl; ENSMUST00000107575; ENSMUSP00000103201; ENSMUSG00000038668. [P61793-1]
DR GeneID; 14745; -.
DR KEGG; mmu:14745; -.
DR UCSC; uc008szb.3; mouse.
DR CTD; 1902; -.
DR MGI; MGI:108429; Lpar1.
DR VEuPathDB; HostDB:ENSMUSG00000038668; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01050000244941; -.
DR HOGENOM; CLU_047979_0_0_1; -.
DR InParanoid; P61793; -.
DR OMA; TNCSNMA; -.
DR PhylomeDB; P61793; -.
DR TreeFam; TF330052; -.
DR Reactome; R-MMU-416476; G alpha (q) signalling events.
DR Reactome; R-MMU-418594; G alpha (i) signalling events.
DR Reactome; R-MMU-419408; Lysosphingolipid and LPA receptors.
DR BioGRID-ORCS; 14745; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Lpar1; mouse.
DR PRO; PR:P61793; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; P61793; protein.
DR Bgee; ENSMUSG00000038668; Expressed in 1st arch maxillary component and 276 other tissues.
DR ExpressionAtlas; P61793; baseline and differential.
DR Genevisible; P61793; MM.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0043198; C:dendritic shaft; ISO:MGI.
DR GO; GO:0043197; C:dendritic spine; ISO:MGI.
DR GO; GO:0030139; C:endocytic vesicle; ISO:MGI.
DR GO; GO:0005768; C:endosome; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0001965; F:G-protein alpha-subunit binding; ISO:MGI.
DR GO; GO:0035727; F:lysophosphatidic acid binding; ISO:MGI.
DR GO; GO:0070915; F:lysophosphatidic acid receptor activity; IDA:UniProtKB.
DR GO; GO:0030165; F:PDZ domain binding; IPI:MGI.
DR GO; GO:0005543; F:phospholipid binding; ISO:MGI.
DR GO; GO:0007202; P:activation of phospholipase C activity; IDA:UniProtKB.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0032060; P:bleb assembly; IGI:MGI.
DR GO; GO:0060326; P:cell chemotaxis; ISO:MGI.
DR GO; GO:1904566; P:cellular response to 1-oleoyl-sn-glycerol 3-phosphate; ISO:MGI.
DR GO; GO:0071453; P:cellular response to oxygen levels; IEA:Ensembl.
DR GO; GO:0021549; P:cerebellum development; IEA:Ensembl.
DR GO; GO:0022038; P:corpus callosum development; IEA:Ensembl.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0042552; P:myelination; IEA:Ensembl.
DR GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; ISO:MGI.
DR GO; GO:0010977; P:negative regulation of neuron projection development; IDA:UniProtKB.
DR GO; GO:0022008; P:neurogenesis; IBA:GO_Central.
DR GO; GO:0014003; P:oligodendrocyte development; IEA:Ensembl.
DR GO; GO:0021554; P:optic nerve development; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0010942; P:positive regulation of cell death; ISO:MGI.
DR GO; GO:0051482; P:positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway; ISO:MGI.
DR GO; GO:0060999; P:positive regulation of dendritic spine development; ISO:MGI.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:UniProtKB.
DR GO; GO:0035025; P:positive regulation of Rho protein signal transduction; IDA:UniProtKB.
DR GO; GO:0071673; P:positive regulation of smooth muscle cell chemotaxis; ISO:MGI.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; IDA:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; IDA:UniProtKB.
DR GO; GO:0019222; P:regulation of metabolic process; IBA:GO_Central.
DR CDD; cd15344; 7tmA_LPAR1_Edg2; 1.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR004065; LPA_rcpt.
DR InterPro; IPR002277; LPA_rcpt_EDG2.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR01148; EDG2RECEPTOR.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01527; LPARECEPTOR.
DR SMART; SM01381; 7TM_GPCR_Srsx; 1.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disulfide bond; Endosome;
KW G-protein coupled receptor; Glycoprotein; Membrane; Phosphoprotein;
KW Receptor; Reference proteome; Transducer; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..364
FT /note="Lysophosphatidic acid receptor 1"
FT /id="PRO_0000069418"
FT TOPO_DOM 1..50
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q92633"
FT TRANSMEM 51..75
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:Q92633"
FT TOPO_DOM 76..83
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q92633"
FT TRANSMEM 84..107
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:Q92633"
FT TOPO_DOM 108..121
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q92633"
FT TRANSMEM 122..144
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:Q92633"
FT TOPO_DOM 145..163
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q92633"
FT TRANSMEM 164..184
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:Q92633"
FT TOPO_DOM 185..204
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q92633"
FT TRANSMEM 205..225
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:Q92633"
FT TOPO_DOM 226..255
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q92633"
FT TRANSMEM 256..280
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:Q92633"
FT TOPO_DOM 281..294
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q92633"
FT TRANSMEM 295..315
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:Q92633"
FT TOPO_DOM 316..364
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q92633"
FT BINDING 39
FT /ligand="a 1-acyl-sn-glycero-3-phosphate"
FT /ligand_id="ChEBI:CHEBI:57970"
FT /evidence="ECO:0000250|UniProtKB:Q92633"
FT BINDING 124..129
FT /ligand="a 1-acyl-sn-glycero-3-phosphate"
FT /ligand_id="ChEBI:CHEBI:57970"
FT /evidence="ECO:0000250|UniProtKB:Q92633"
FT BINDING 210
FT /ligand="a 1-acyl-sn-glycero-3-phosphate"
FT /ligand_id="ChEBI:CHEBI:57970"
FT /evidence="ECO:0000250|UniProtKB:Q92633"
FT MOD_RES 341
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92633"
FT MOD_RES 351
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 27
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 35
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 24..190
FT /evidence="ECO:0000250|UniProtKB:Q92633"
FT DISULFID 188..195
FT /evidence="ECO:0000250|UniProtKB:Q92633"
FT DISULFID 284..287
FT /evidence="ECO:0000250|UniProtKB:Q92633"
FT VAR_SEQ 1..18
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9013780"
FT /id="VSP_001986"
FT CONFLICT 119
FT /note="S -> N (in Ref. 3; AAC34301/AAC34302)"
FT /evidence="ECO:0000305"
FT CONFLICT 181..183
FT /note="IPS -> MPT (in Ref. 3; AAC34301/AAC34302)"
FT /evidence="ECO:0000305"
FT CONFLICT 225
FT /note="Y -> S (in Ref. 2; AAC53035)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 364 AA; 41119 MW; B0FA6265AA6688B7 CRC64;
MAAASTSSPV ISQPQFTAMN EQQCFYNESI AFFYNRSGKY LATEWNTVSK LVMGLGITVC
VFIMLANLLV MVAIYVNRRF HFPIYYLMAN LAAADFFAGL AYFYLMFNTG PNTRRLTVST
WLLRQGLIDT SLTASVANLL AIAIERHITV FRMQLHTRMS NRRVVVVIVV IWTMAIVMGA
IPSVGWNCIC DIDHCSNMAP LYSDSYLVFW AIFNLVTFVV MVVLYAHIFG YVRQRTMRMS
RHSSGPRRNR DTMMSLLKTV VIVLGAFIVC WTPGLVLLLL DVCCPQCDVL AYEKFFLLLA
EFNSAMNPII YSYRDKEMSA TFRQILCCQR NENPNGPTEG SDRSASSLNH TILAGVHSND
HSVV
