Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTZNV6Y)

• DOT Name: Cysteine-rich motor neuron 1 protein (CRIM1)
• Synonyms: CRIM-1; Cysteine-rich repeat-containing protein S52
• Gene Name: CRIM1
• Related Disease:
  Cardiovascular disease
  Lung adenocarcinoma
  Asthma
  Colobomatous macrophthalmia-microcornea syndrome
  Advanced cancer
  Microphthalmia
  Prostate cancer
  Prostate carcinoma
• UniProt ID: CRIM1_HUMAN
• Pfam ID: PF02822 ; PF19442 ; PF00219 ; PF00093
• Sequence:
  MYLVAGDRGLAGCGHLLVSLLGLLLLLARSGTRALVCLPCDESKCEEPRNCPGSIVQGVC
  GCCYTCASQRNESCGGTFGIYGTCDRGLRCVIRPPLNGDSLTEYEAGVCEDENWTDDQLL
  GFKPCNENLIAGCNIINGKCECNTIRTCSNPFEFPSQDMCLSALKRIEEEKPDCSKARCE
  VQFSPRCPEDSVLIEGYAPPGECCPLPSRCVCNPAGCLRKVCQPGNLNILVSKASGKPGE
  CCDLYECKPVFGVDCRTVECPPVQQTACPPDSYETQVRLTADGCCTLPTRCECLSGLCGF
  PVCEVGSTPRIVSRGDGTPGKCCDVFECVNDTKPACVFNNVEYYDGDMFRMDNCRFCRCQ
  GGVAICFTAQCGEINCERYYVPEGECCPVCEDPVYPFNNPAGCYANGLILAHGDRWREDD
  CTFCQCVNGERHCVATVCGQTCTNPVKVPGECCPVCEEPTIITVDPPACGELSNCTLTGK
  DCINGFKRDHNGCRTCQCINTEELCSERKQGCTLNCPFGFLTDAQNCEICECRPRPKKCR
  PIICDKYCPLGLLKNKHGCDICRCKKCPELSCSKICPLGFQQDSHGCLICKCREASASAG
  PPILSGTCLTVDGHHHKNEESWHDGCRECYCLNGREMCALITCPVPACGNPTIHPGQCCP
  SCADDFVVQKPELSTPSICHAPGGEYFVEGETWNIDSCTQCTCHSGRVLCETEVCPPLLC
  QNPSRTQDSCCPQCTDQPFRPSLSRNNSVPNYCKNDEGDIFLAAESWKPDVCTSCICIDS
  VISCFSESCPSVSCERPVLRKGQCCPYCIEDTIPKKVVCHFSGKAYADEERWDLDSCTHC
  YCLQGQTLCSTVSCPPLPCVEPINVEGSCCPMCPEMYVPEPTNIPIEKTNHRGEVDLEVP
  LWPTPSENDIVHLPRDMGHLQVDYRDNRLHPSEDSSLDSIASVVVPIIICLSIIIAFLFI
  NQKKQWIPLLCWYRTPTKPSSLNNQLVSVDCKKGTRVQVDSSQRMLRIAEPDARFSGFYS
  MQKQNHLQADNFYQTV
• Function: May play a role in CNS development by interacting with growth factors implicated in motor neuron differentiation and survival. May play a role in capillary formation and maintenance during angiogenesis. Modulates BMP activity by affecting its processing and delivery to the cell surface.
• Tissue Specificity: Expressed in pancreas, kidney, skeletal muscle, lung, placenta, brain, heart, spleen, liver and small intestine. Expressed in blood vessels (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[1]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[2]
Asthma	DISW9QNS	moderate	Genetic Variation	[3]
Colobomatous macrophthalmia-microcornea syndrome	DISFXRK4	Supportive	Autosomal dominant	[4]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[5]
Microphthalmia	DISGEBES	Limited	Altered Expression	[6]
Prostate cancer	DISF190Y	Limited	Altered Expression	[5]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[5]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Cysteine-rich motor neuron 1 protein (CRIM1).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Cysteine-rich motor neuron 1 protein (CRIM1).	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cysteine-rich motor neuron 1 protein (CRIM1).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cysteine-rich motor neuron 1 protein (CRIM1).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cysteine-rich motor neuron 1 protein (CRIM1).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cysteine-rich motor neuron 1 protein (CRIM1).	[11]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cysteine-rich motor neuron 1 protein (CRIM1).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cysteine-rich motor neuron 1 protein (CRIM1).	[13]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Cysteine-rich motor neuron 1 protein (CRIM1).	[14]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Cysteine-rich motor neuron 1 protein (CRIM1).	[15]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Cysteine-rich motor neuron 1 protein (CRIM1).	[16]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Cysteine-rich motor neuron 1 protein (CRIM1).	[17]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cysteine-rich motor neuron 1 protein (CRIM1).	[18]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Cysteine-rich motor neuron 1 protein (CRIM1).	[19]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Cysteine-rich motor neuron 1 protein (CRIM1).	[20]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Cysteine-rich motor neuron 1 protein (CRIM1).	[21]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Cysteine-rich motor neuron 1 protein (CRIM1).	[22]
Lindane	DMB8CNL	Approved	Lindane increases the expression of Cysteine-rich motor neuron 1 protein (CRIM1).	[23]
Prednisolone	DMQ8FR2	Approved	Prednisolone increases the expression of Cysteine-rich motor neuron 1 protein (CRIM1).	[23]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Cysteine-rich motor neuron 1 protein (CRIM1).	[24]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Cysteine-rich motor neuron 1 protein (CRIM1).	[25]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Cysteine-rich motor neuron 1 protein (CRIM1).	[26]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cysteine-rich motor neuron 1 protein (CRIM1).	[28]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Cysteine-rich motor neuron 1 protein (CRIM1).	[29]

References

• [1] CRIM1 is necessary for coronary vascular endothelial cell development and homeostasis.J Mol Histol. 2017 Feb;48(1):53-61. doi: 10.1007/s10735-016-9702-3. Epub 2016 Nov 1.
• [2] Circular RNA circCRIM1 inhibits invasion and metastasis in lung adenocarcinoma through the microRNA (miR)-182/miR-93-leukemia inhibitory factor receptor pathway.Cancer Sci. 2019 Sep;110(9):2960-2972. doi: 10.1111/cas.14131. Epub 2019 Aug 14.
• [3] A genome-wide association study of total serum and mite-specific IgEs in asthma patients.PLoS One. 2013 Aug 13;8(8):e71958. doi: 10.1371/journal.pone.0071958. eCollection 2013.
• [4] CRIM1 haploinsufficiency causes defects in eye development in human and mouse. Hum Mol Genet. 2015 Apr 15;24(8):2267-73. doi: 10.1093/hmg/ddu744. Epub 2015 Jan 5.
• [5] SOST Inhibits Prostate Cancer Invasion.PLoS One. 2015 Nov 6;10(11):e0142058. doi: 10.1371/journal.pone.0142058. eCollection 2015.
• [6] Crim1 is required for maintenance of the ocular lens epithelium.Exp Eye Res. 2018 May;170:58-66. doi: 10.1016/j.exer.2018.02.012. Epub 2018 Feb 16.
• [7] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [8] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [9] 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.
• [10] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
• [13] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [14] Prenatal arsenic exposure and shifts in the newborn proteome: interindividual differences in tumor necrosis factor (TNF)-responsive signaling. Toxicol Sci. 2014 Jun;139(2):328-37. doi: 10.1093/toxsci/kfu053. Epub 2014 Mar 27.
• [15] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [16] Changes in gene expression profiles of multiple myeloma cells induced by arsenic trioxide (ATO): possible mechanisms to explain ATO resistance in vivo. Br J Haematol. 2005 Mar;128(5):636-44.
• [17] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [18] 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.
• [19] Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 2006 Mar 1;66(5):2765-77.
• [20] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [21] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [22] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [23] Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
• [24] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [25] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [26] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [27] 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.
• [28] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [29] Comparative DNA microarray analysis of human monocyte derived dendritic cells and MUTZ-3 cells exposed to the moderate skin sensitizer cinnamaldehyde. Toxicol Appl Pharmacol. 2009 Sep 15;239(3):273-83.