LPAR2_HUMAN
ID LPAR2_HUMAN Reviewed; 348 AA.
AC Q9HBW0; O00543; O43431;
DT 06-DEC-2002, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 3.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Lysophosphatidic acid receptor 2 {ECO:0000305};
DE Short=LPA receptor 2;
DE Short=LPA-2;
DE AltName: Full=Lysophosphatidic acid receptor Edg-4;
GN Name=LPAR2 {ECO:0000312|HGNC:HGNC:3168}; Synonyms=EDG4, LPA2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Ovarian carcinoma;
RX PubMed=9525886; DOI=10.1074/jbc.273.14.7906;
RA An S., Bleu T., Hallmark O.G., Goetzl E.J.;
RT "Characterization of a novel subtype of human G protein-coupled receptor
RT for lysophosphatidic acid.";
RL J. Biol. Chem. 273:7906-7910(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10922489; DOI=10.1016/s0014-5793(00)01827-5;
RA Bandoh K., Aoki J., Taira A., Tsujimoto M., Arai H., Inoue K.;
RT "Lysophosphatidic acid (LPA) receptors of the EDG family are differentially
RT activated by LPA species. Structure-activity relationship of cloned LPA
RT receptors.";
RL FEBS Lett. 478:159-165(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Colon cancer;
RA An S.;
RT "Human Edg4 lysophosphatidic acid receptor cDNA encoding a putative protein
RT with COOH-terminus different from the previously-reported Edg4.";
RL Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kopatz S.A., King M.M., Cismowski M.J., Aronstam R.S., Sharma S.V.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [7]
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 [8]
RP IDENTIFICATION OF A PROBABLE FRAMESHIFT MUTATION.
RX PubMed=10729222; DOI=10.1006/geno.2000.6122;
RA Contos J.J.A., Chun J.;
RT "Genomic characterization of the lysophosphatidic acid receptor gene,
RT lp(A2)/Edg4, and identification of a frameshift mutation in a previously
RT characterized cDNA.";
RL Genomics 64:155-169(2000).
RN [9]
RP FUNCTION, AND INTERACTION WITH SLC9A3R2/NHERF2 AND PLCB3.
RX PubMed=15143197; DOI=10.1128/mcb.24.11.5069-5079.2004;
RA Oh Y.-S., Jo N.W., Choi J.W., Kim H.S., Seo S.-W., Kang K.-O., Hwang J.-I.,
RA Heo K., Kim S.-H., Kim Y.-H., Kim I.-H., Kim J.H., Banno Y., Ryu S.H.,
RA Suh P.-G.;
RT "NHERF2 specifically interacts with LPA2 receptor and defines the
RT specificity and efficiency of receptor-mediated phospholipase C-beta3
RT activation.";
RL Mol. Cell. Biol. 24:5069-5079(2004).
RN [10]
RP INTERACTION WITH MAGI3, AND MUTAGENESIS OF ASP-345; SER-346; THR-347 AND
RP LEU-348.
RX PubMed=16904289; DOI=10.1016/j.cellsig.2006.06.008;
RA Zhang H., Wang D., Sun H., Hall R.A., Yun C.C.;
RT "MAGI-3 regulates LPA-induced activation of Erk and RhoA.";
RL Cell. Signal. 19:261-268(2007).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH RALA AND GRK2.
RX PubMed=19306925; DOI=10.1016/j.cellsig.2009.03.011;
RA Aziziyeh A.I., Li T.T., Pape C., Pampillo M., Chidiac P., Possmayer F.,
RA Babwah A.V., Bhattacharya M.;
RT "Dual regulation of lysophosphatidic acid (LPA1) receptor signalling by Ral
RT and GRK.";
RL Cell. Signal. 21:1207-1217(2009).
CC -!- FUNCTION: Receptor for lysophosphatidic acid (LPA), a mediator of
CC diverse cellular activities. Seems to be coupled to the G(i)/G(o),
CC G(12)/G(13), and G(q) families of heteromeric G proteins. Plays a key
CC role in phospholipase C-beta (PLC-beta) signaling pathway. Stimulates
CC phospholipase C (PLC) activity in a manner that is independent of RALA
CC activation. {ECO:0000269|PubMed:15143197, ECO:0000269|PubMed:19306925}.
CC -!- SUBUNIT: Interacts with SLC9A3R2/NHERF2, MAGI3 and PLCB3. Interacts
CC with RALA and GRK2. {ECO:0000269|PubMed:15143197,
CC ECO:0000269|PubMed:16904289, ECO:0000269|PubMed:19306925}.
CC -!- INTERACTION:
CC Q9HBW0; P13569: CFTR; NbExp=4; IntAct=EBI-765995, EBI-349854;
CC Q9HBW0; Q15599: SLC9A3R2; NbExp=2; IntAct=EBI-765995, EBI-1149760;
CC -!- SUBCELLULAR LOCATION: Cell surface {ECO:0000269|PubMed:19306925}. Cell
CC membrane {ECO:0000269|PubMed:19306925}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:19306925}. Note=Prior to LPA treatment found
CC predominantly at the cell surface but in the presence of LPA
CC colocalizes with RALA in the endocytic vesicles.
CC -!- TISSUE SPECIFICITY: Expressed most abundantly in testes and peripheral
CC blood leukocytes with less expression in pancreas, spleen, thymus and
CC prostate. Little or no expression in heart, brain, placenta, lung,
CC liver, skeletal muscle, kidney, ovary, small intestine, or colon.
CC -!- MISCELLANEOUS: PubMed:9525886 cDNA clone has a guanine nucleotide
CC deletion that causes a frameshift near its C-terminal coding region.
CC This likely reflects a somatic mutation in the ovary tumor cells from
CC which the cDNA was isolated and may have altered the function of the
CC encoded receptor, and contributed to transformation of the original
CC ovary cells that formed a tumor.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB61528.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAC27728.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAC27728.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAF43409.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAG28521.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH25695.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAP84361.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/LPAR2ID40406ch19p13.html";
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DR EMBL; AF011466; AAC27728.1; ALT_SEQ; mRNA.
DR EMBL; AF233092; AAF43409.1; ALT_INIT; mRNA.
DR EMBL; AF197929; AAG28521.1; ALT_INIT; mRNA.
DR EMBL; AY322548; AAP84361.1; ALT_INIT; mRNA.
DR EMBL; AC002306; AAB61528.1; ALT_INIT; Genomic_DNA.
DR EMBL; BC025695; AAH25695.1; ALT_INIT; mRNA.
DR CCDS; CCDS12407.1; -.
DR RefSeq; NP_004711.2; NM_004720.5.
DR RefSeq; XP_011526723.1; XM_011528421.2.
DR RefSeq; XP_016882957.1; XM_017027468.1.
DR RefSeq; XP_016882958.1; XM_017027469.1.
DR PDB; 4P0C; X-ray; 1.34 A; A=344-348.
DR PDBsum; 4P0C; -.
DR AlphaFoldDB; Q9HBW0; -.
DR BioGRID; 114611; 134.
DR CORUM; Q9HBW0; -.
DR IntAct; Q9HBW0; 7.
DR STRING; 9606.ENSP00000443256; -.
DR BindingDB; Q9HBW0; -.
DR ChEMBL; CHEMBL3724; -.
DR GuidetoPHARMACOLOGY; 273; -.
DR SwissLipids; SLP:000001569; -.
DR TCDB; 9.A.14.2.5; the g-protein-coupled receptor (gpcr) family.
DR GlyGen; Q9HBW0; 2 sites.
DR iPTMnet; Q9HBW0; -.
DR PhosphoSitePlus; Q9HBW0; -.
DR BioMuta; LPAR2; -.
DR DMDM; 26393399; -.
DR EPD; Q9HBW0; -.
DR jPOST; Q9HBW0; -.
DR MassIVE; Q9HBW0; -.
DR MaxQB; Q9HBW0; -.
DR PaxDb; Q9HBW0; -.
DR PeptideAtlas; Q9HBW0; -.
DR PRIDE; Q9HBW0; -.
DR ProteomicsDB; 81600; -.
DR Antibodypedia; 15391; 347 antibodies from 32 providers.
DR DNASU; 9170; -.
DR Ensembl; ENST00000407877.8; ENSP00000384665.2; ENSG00000064547.14.
DR Ensembl; ENST00000542587.5; ENSP00000443256.1; ENSG00000064547.14.
DR Ensembl; ENST00000586703.1; ENSP00000465280.1; ENSG00000064547.14.
DR GeneID; 9170; -.
DR UCSC; uc002nna.6; human.
DR CTD; 9170; -.
DR DisGeNET; 9170; -.
DR GeneCards; LPAR2; -.
DR HGNC; HGNC:3168; LPAR2.
DR HPA; ENSG00000064547; Tissue enhanced (lymphoid).
DR MIM; 605110; gene.
DR neXtProt; NX_Q9HBW0; -.
DR PharmGKB; PA162394202; -.
DR VEuPathDB; HostDB:ENSG00000064547; -.
DR eggNOG; KOG3656; Eukaryota.
DR HOGENOM; CLU_047979_0_0_1; -.
DR InParanoid; Q9HBW0; -.
DR OMA; TRMSKHT; -.
DR OrthoDB; 1366218at2759; -.
DR PhylomeDB; Q9HBW0; -.
DR PathwayCommons; Q9HBW0; -.
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR Reactome; R-HSA-419408; Lysosphingolipid and LPA receptors.
DR SignaLink; Q9HBW0; -.
DR SIGNOR; Q9HBW0; -.
DR BioGRID-ORCS; 9170; 39 hits in 1084 CRISPR screens.
DR ChiTaRS; LPAR2; human.
DR GeneWiki; LPAR2; -.
DR GenomeRNAi; 9170; -.
DR Pharos; Q9HBW0; Tchem.
DR PRO; PR:Q9HBW0; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9HBW0; protein.
DR Bgee; ENSG00000064547; Expressed in ganglionic eminence and 140 other tissues.
DR ExpressionAtlas; Q9HBW0; baseline and differential.
DR Genevisible; Q9HBW0; HS.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
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:0008289; F:lipid binding; TAS:ProtInc.
DR GO; GO:0070915; F:lysophosphatidic acid receptor activity; IEA:InterPro.
DR GO; GO:0007202; P:activation of phospholipase C activity; TAS:ProtInc.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; TAS:ProtInc.
DR GO; GO:0019222; P:regulation of metabolic process; IBA:GO_Central.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR004065; LPA_rcpt.
DR InterPro; IPR004066; LPA_rcpt_EDG4.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR01528; EDG4RECEPTOR.
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 3D-structure; Cell membrane; G-protein coupled receptor; Glycoprotein;
KW Lipoprotein; Membrane; Palmitate; Receptor; Reference proteome; Transducer;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..348
FT /note="Lysophosphatidic acid receptor 2"
FT /id="PRO_0000069424"
FT TOPO_DOM 1..30
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 31..51
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 52..66
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 67..87
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 88..100
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 101..123
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 124..143
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 144..164
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 165..185
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 186..206
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 207..239
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 240..260
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 261..276
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 277..294
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 295..348
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOTIF 345..348
FT /note="PDZ-binding"
FT LIPID 308
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 7
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 15
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 345
FT /note="D->A: Abolishes interaction with MAGI3."
FT /evidence="ECO:0000269|PubMed:16904289"
FT MUTAGEN 346
FT /note="S->A: Abolishes interaction with MAGI3."
FT /evidence="ECO:0000269|PubMed:16904289"
FT MUTAGEN 347
FT /note="T->A: Does not affect interaction with MAGI3."
FT /evidence="ECO:0000269|PubMed:16904289"
FT MUTAGEN 348
FT /note="L->A: Abolishes interaction with MAGI3."
FT /evidence="ECO:0000269|PubMed:16904289"
FT CONFLICT 218
FT /note="R -> S (in Ref. 3; AAG28521)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 348 AA; 38741 MW; D9AD934104B80167 CRC64;
MGQCYYNETI GFFYNNSGKE LSSHWRPKDV VVVALGLTVS VLVLLTNLLV IAAIASNRRF
HQPIYYLLGN LAAADLFAGV AYLFLMFHTG PRTARLSLEG WFLRQGLLDT SLTASVATLL
AIAVERHRSV MAVQLHSRLP RGRVVMLIVG VWVAALGLGL LPAHSWHCLC ALDRCSRMAP
LLSRSYLAVW ALSSLLVFLL MVAVYTRIFF YVRRRVQRMA EHVSCHPRYR ETTLSLVKTV
VIILGAFVVC WTPGQVVLLL DGLGCESCNV LAVEKYFLLL AEANSLVNAA VYSCRDAEMR
RTFRRLLCCA CLRQSTRESV HYTSSAQGGA STRIMLPENG HPLMDSTL
