General Information of Drug Off-Target (DOT) (ID: OTJNJQPF)

DOT Name Lysophosphatidic acid receptor 1 (LPAR1)
Synonyms LPA receptor 1; LPA-1; Lysophosphatidic acid receptor Edg-2
Gene Name LPAR1
UniProt ID
LPAR1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
4Z34; 4Z35; 4Z36; 7TD0; 7TD1; 7TD2; 7YU3; 7YU4; 7YU5; 7YU6; 7YU7; 7YU8
Pfam ID
PF00001
Sequence
MAAISTSIPVISQPQFTAMNEPQCFYNESIAFFYNRSGKHLATEWNTVSKLVMGLGITVC
IFIMLANLLVMVAIYVNRRFHFPIYYLMANLAAADFFAGLAYFYLMFNTGPNTRRLTVST
WLLRQGLIDTSLTASVANLLAIAIERHITVFRMQLHTRMSNRRVVVVIVVIWTMAIVMGA
IPSVGWNCICDIENCSNMAPLYSDSYLVFWAIFNLVTFVVMVVLYAHIFGYVRQRTMRMS
RHSSGPRRNRDTMMSLLKTVVIVLGAFIICWTPGLVLLLLDVCCPQCDVLAYEKFFLLLA
EFNSAMNPIIYSYRDKEMSATFRQILCCQRSENPTGPTEGSDRSASSLNHTILAGVHSND
HSVV
Function
Receptor for lysophosphatidic acid (LPA). Plays a role in the reorganization of the actin cytoskeleton, cell migration, differentiation and proliferation, and thereby contributes to the responses to tissue damage and infectious agents. Activates downstream signaling cascades via the G(i)/G(o), G(12)/G(13), and G(q) families of heteromeric G proteins. Signaling inhibits adenylyl cyclase activity and decreases cellular cAMP levels. Signaling triggers an increase of cytoplasmic Ca(2+) levels. Activates RALA; this leads to the activation of phospholipase C (PLC) and the formation of inositol 1,4,5-trisphosphate. Signaling mediates activation of down-stream MAP kinases. Contributes to the regulation of cell shape. Promotes Rho-dependent reorganization of the actin cytoskeleton in neuronal cells and neurite retraction. Promotes the activation of Rho and the formation of actin stress fibers. Promotes formation of lamellipodia at the leading edge of migrating cells via activation of RAC1. Through its function as LPA receptor, plays a role in chemotaxis and cell migration, including responses to injury and wounding. Plays a role in triggering inflammation in response to bacterial lipopolysaccharide (LPS) via its interaction with CD14. Promotes cell proliferation in response to LPA. Inhibits the intracellular ciliogenesis pathway in response to LPA and through AKT1 activation. Required for normal skeleton development. May play a role in osteoblast differentiation. Required for normal brain development. Required for normal proliferation, survival and maturation of newly formed neurons in the adult dentate gyrus. Plays a role in pain perception and in the initiation of neuropathic pain.
Tissue Specificity
Expressed in many adult organs, including brain, heart, colon, small intestine, placenta, prostate, ovary, pancreas, testes, spleen, skeletal muscle, and kidney. Little or no expression in liver, lung, thymus, or peripheral blood leukocytes . Detected in lung fibroblasts from bronchoalveolar fluid from patients with idiopathic pulmonary fibrosis . Detected in bone marrow-derived mesenchymal stem cells .
KEGG Pathway
Rap1 sig.ling pathway (hsa04015 )
Phospholipase D sig.ling pathway (hsa04072 )
Neuroactive ligand-receptor interaction (hsa04080 )
PI3K-Akt sig.ling pathway (hsa04151 )
Gap junction (hsa04540 )
Regulation of actin cytoskeleton (hsa04810 )
Pathogenic Escherichia coli infection (hsa05130 )
Pathways in cancer (hsa05200 )
Reactome Pathway
G alpha (i) signalling events (R-HSA-418594 )
Lysosphingolipid and LPA receptors (R-HSA-419408 )
G alpha (q) signalling events (R-HSA-416476 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 4 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Lysophosphatidic acid receptor 1 (LPAR1) affects the response to substance of Doxorubicin. [14]
Methotrexate DM2TEOL Approved Lysophosphatidic acid receptor 1 (LPAR1) affects the response to substance of Methotrexate. [14]
Vinblastine DM5TVS3 Approved Lysophosphatidic acid receptor 1 (LPAR1) affects the response to substance of Vinblastine. [14]
LPA DMI5XR1 Investigative Lysophosphatidic acid receptor 1 (LPAR1) increases the response to substance of LPA. [15]
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13 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Lysophosphatidic acid receptor 1 (LPAR1). [1]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Lysophosphatidic acid receptor 1 (LPAR1). [2]
Estradiol DMUNTE3 Approved Estradiol affects the expression of Lysophosphatidic acid receptor 1 (LPAR1). [3]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Lysophosphatidic acid receptor 1 (LPAR1). [4]
Triclosan DMZUR4N Approved Triclosan increases the expression of Lysophosphatidic acid receptor 1 (LPAR1). [5]
Selenium DM25CGV Approved Selenium increases the expression of Lysophosphatidic acid receptor 1 (LPAR1). [6]
Cocaine DMSOX7I Approved Cocaine decreases the expression of Lysophosphatidic acid receptor 1 (LPAR1). [7]
Curcumin DMQPH29 Phase 3 Curcumin decreases the expression of Lysophosphatidic acid receptor 1 (LPAR1). [8]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of Lysophosphatidic acid receptor 1 (LPAR1). [6]
Belinostat DM6OC53 Phase 2 Belinostat decreases the expression of Lysophosphatidic acid receptor 1 (LPAR1). [9]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Lysophosphatidic acid receptor 1 (LPAR1). [11]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Lysophosphatidic acid receptor 1 (LPAR1). [12]
Z-Pro-Prolinal DM43O2U Investigative Z-Pro-Prolinal decreases the expression of Lysophosphatidic acid receptor 1 (LPAR1). [13]
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⏷ Show the Full List of 13 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Lysophosphatidic acid receptor 1 (LPAR1). [10]
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References

1 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
2 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
3 Estradiol and selective estrogen receptor modulators differentially regulate target genes with estrogen receptors alpha and beta. Mol Biol Cell. 2004 Mar;15(3):1262-72. doi: 10.1091/mbc.e03-06-0360. Epub 2003 Dec 29.
4 Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
5 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
6 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
7 Gene expression profile of the nucleus accumbens of human cocaine abusers: evidence for dysregulation of myelin. J Neurochem. 2004 Mar;88(5):1211-9. doi: 10.1046/j.1471-4159.2003.02247.x.
8 Curcumin downregulates the inflammatory cytokines CXCL1 and -2 in breast cancer cells via NFkappaB. Carcinogenesis. 2008 Apr;29(4):779-89.
9 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
10 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
11 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
12 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
13 Prolyl endopeptidase is involved in cellular signalling in human neuroblastoma SH-SY5Y cells. Neurosignals. 2011;19(2):97-109. doi: 10.1159/000326342. Epub 2011 Apr 10.
14 Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
15 Expression and function of lysophosphatidic acid LPA1 receptor in prostate cancer cells. Endocrinology. 2006 Oct;147(10):4883-92. doi: 10.1210/en.2005-1635. Epub 2006 Jun 29.