Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHA8ESR)

DOT Name	Chemerin-like receptor 1 (CMKLR1)
Synonyms	Chemokine-like receptor 1; G-protein coupled receptor ChemR23; G-protein coupled receptor DEZ
Gene Name	CMKLR1
UniProt ID	CML1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	7YKD; 8SG1
Pfam ID	PF00001
Sequence	MRMEDEDYNTSISYGDEYPDYLDSIVVLEDLSPLEARVTRIFLVVVYSIVCFLGILGNGL VIIIATFKMKKTVNMVWFLNLAVADFLFNVFLPIHITYAAMDYHWVFGTAMCKISNFLLI HNMFTSVFLLTIISSDRCISVLLPVWSQNHRSVRLAYMACMVIWVLAFFLSSPSLVFRDT ANLHGKISCFNNFSLSTPGSSSWPTHSQMDPVGYSRHMVVTVTRFLCGFLVPVLIITACY LTIVCKLQRNRLAKTKKPFKIIVTIIITFFLCWCPYHTLNLLELHHTAMPGSVFSLGLPL ATALAIANSCMNPILYVFMGQDFKKFKVALFSRLVNALSEDTGHSSYPSHRSFTKMSSMN ERTSMNERETGML
Function	Receptor for the chemoattractant adipokine chemerin/RARRES2 and for the omega-3 fatty acid derived molecule resolvin E1. Interaction with RARRES2 initiates activation of G proteins G(i)/G(o) and beta-arrestin pathways inducing cellular responses via second messenger pathways such as intracellular calcium mobilization, phosphorylation of MAP kinases MAPK1/MAPK3 (ERK1/2), TYRO3, MAPK14/P38MAPK and PI3K leading to multifunctional effects, like reduction of immune responses, enhancing of adipogenesis and angionesis. Resolvin E1 down-regulates cytokine production in macrophages by reducing the activation of MAPK1/3 (ERK1/2) and NF-kappa-B. Positively regulates adipogenesis and adipocyte metabolism; (Microbial infection) Acts as a coreceptor for several SIV strains (SIVMAC316, SIVMAC239, SIVMACL7E-FR and SIVSM62A), as well as a primary HIV-1 strain (92UG024-2).
Tissue Specificity	Prominently expressed in developing osseous and cartilaginous tissue. Also found in adult parathyroid glands. Expressed in cardiovascular system, brain, kidney, gastrointestinal tissues and myeloid tissues. Expressed in a broad array of tissues associated with hematopoietic and immune function including, spleen, thymus, appendix, lymph node, bone marrow and fetal liver. Among leukocyte populations abundant expression in monocyte-derived macrophage and immature dendritic cells (DCs). High expression in blood monocytes and low levels in polymorphonuclear cells and T-cells. Expressed on endothelial cells. Highly expressed in differentiating adipocytes.
Reactome Pathway	Class A/1 (Rhodopsin-like receptors) (R-HSA-373076 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA)

MIA Detail

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6 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Chemerin-like receptor 1 (CMKLR1).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Chemerin-like receptor 1 (CMKLR1).	[2]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Chemerin-like receptor 1 (CMKLR1).	[3]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Chemerin-like receptor 1 (CMKLR1).	[4]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Chemerin-like receptor 1 (CMKLR1).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Chemerin-like receptor 1 (CMKLR1).	[6]
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⏷ Show the Full List of 6 Drug(s)

2 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 affects the methylation of Chemerin-like receptor 1 (CMKLR1).	[7]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Chemerin-like receptor 1 (CMKLR1).	[8]
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References

1	Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
2	Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
3	Endoplasmic reticulum stress contributes to arsenic trioxide-induced intrinsic apoptosis in human umbilical and bone marrow mesenchymal stem cells. Environ Toxicol. 2016 Mar;31(3):314-28.
4	Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
5	Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
6	The MT1G Gene in LUHMES Neurons Is a Sensitive Biomarker of Neurotoxicity. Neurotox Res. 2020 Dec;38(4):967-978. doi: 10.1007/s12640-020-00272-3. Epub 2020 Sep 1.
7	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.
8	Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.