Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZN8Z4A)

• DOT Name: C-Maf-inducing protein (CMIP)
• Synonyms: c-Mip; Truncated c-Maf-inducing protein; Tc-Mip
• Gene Name: CMIP
• Related Disease:
  Advanced cancer
  Cardiovascular disease
  Glioma
  HIV infectious disease
  Idiopathic nephrotic syndrome
  Language disorder
  Metastatic prostate carcinoma
  Nephropathy
  Nephrotic syndrome
  Obesity
  Ovarian neoplasm
  Specific language impairment
  Vibrio cholerae infection
  Wilms tumor
  Lupus nephritis
  Small-cell lung cancer
  Acute myelogenous leukaemia
  Angioimmunoblastic T-cell Lymphoma
  Autism spectrum disorder
  Gastric cancer
  Non-insulin dependent diabetes
  Pervasive developmental disorder
  Prostate cancer
  Prostate carcinoma
  Stomach cancer
• UniProt ID: CMIP_HUMAN
• Sequence:
  MDVTSSSGGGGDPRQIEETKPLLGGDVSAPEGTKMGAVPCRRALLLCNGMRYKLLQEGDI
  QVCVIRHPRTFLSKILTSKFLRRWEPHHLTLADNSLASATPTGYMENSVSYSAIEDVQLL
  SWENAPKYCLQLTIPGGTVLLQAANSYLRDQWFHSLQWKKKIYKYKKVLSNPSRWEVVLK
  EIRTLVDMALTSPLQDDSINQAPLEIVSKLLSENTNLTTQEHENIIVAIAPLLENNHPPP
  DLCEFFCKHCRERPRSMVVIEVFTPVVQRILKHNMDFGKCPRLRLFTQEYILALNELNAG
  MEVVKKFIQSMHGPTGHCPHPRVLPNLVAVCLAAIYSCYEEFINSRDNSPSLKEIRNGCQ
  QPCDRKPTLPLRLLHPSPDLVSQEATLSEARLKSVVVASSEIHVEVERTSTAKPALTASA
  GNDSEPNLIDCLMVSPACSTMSIELGPQADRTLGCYVEILKLLSDYDDWRPSLASLLQPI
  PFPKEALAHEKFTKELKYVIQRFAEDPRQEVHSCLLSVRAGKDGWFQLYSPGGVACDDDG
  ELFASMVHILMGSCYKTKKFLLSLAENKLGPCMLLALRGNQTMVEILCLMLEYNIIDNND
  TQLQIISTLESTDVGKRMYEQLCDRQRELKELQRKGGPTRLTLPSKSTDADLARLLSSGS
  FGNLENLSLAFTNVTSACAEHLIKLPSLKQLNLWSTQFGDAGLRLLSEHLTMLQVLNLCE
  TPVTDAGLLALSSMKSLCSLNMNSTKLSADTYEDLKAKLPNLKEVDVRYTEAW
• Function: Plays a role in T-cell signaling pathway. Isoform 2 may play a role in T-helper 2 (Th2) signaling pathway and seems to represent the first proximal signaling protein that links T-cell receptor-mediated signal to the activation of c-Maf Th2 specific factor.
• Tissue Specificity: Isoform 1 is expressed in peripheral blood mononuclear cells and kidney. Lower expression in brain and liver. Expression is down-regulated in activated cells. Isoform 2 is expressed in lymphocyte precursors, however, expression shuts down during maturation and differentiation in thymus and fetal liver.

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[2]
Glioma	DIS5RPEH	Strong	Biomarker	[3]
HIV infectious disease	DISO97HC	Strong	Altered Expression	[4]
Idiopathic nephrotic syndrome	DISV4XYG	Strong	Biomarker	[5]
Language disorder	DISTLKP7	Strong	Genetic Variation	[6]
Metastatic prostate carcinoma	DISVBEZ9	Strong	Biomarker	[7]
Nephropathy	DISXWP4P	Strong	Altered Expression	[8]
Nephrotic syndrome	DISSPSC2	Strong	Biomarker	[9]
Obesity	DIS47Y1K	Strong	Genetic Variation	[10]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[11]
Specific language impairment	DISEKRML	Strong	Genetic Variation	[12]
Vibrio cholerae infection	DISW7E3U	Strong	Biomarker	[13]
Wilms tumor	DISB6T16	Strong	Altered Expression	[14]
Lupus nephritis	DISCVGPZ	moderate	Biomarker	[15]
Small-cell lung cancer	DISK3LZD	moderate	Biomarker	[9]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[16]
Angioimmunoblastic T-cell Lymphoma	DISZPFTL	Limited	Altered Expression	[17]
Autism spectrum disorder	DISXK8NV	Limited	Biomarker	[12]
Gastric cancer	DISXGOUK	Limited	Biomarker	[18]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[19]
Pervasive developmental disorder	DIS51975	Limited	Biomarker	[12]
Prostate cancer	DISF190Y	Limited	Biomarker	[20]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[20]
Stomach cancer	DISKIJSX	Limited	Biomarker	[18]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Daunorubicin	DMQUSBT	Approved	C-Maf-inducing protein (CMIP) affects the response to substance of Daunorubicin.	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of C-Maf-inducing protein (CMIP).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of C-Maf-inducing protein (CMIP).	[31]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of C-Maf-inducing protein (CMIP).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of C-Maf-inducing protein (CMIP).	[34]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of C-Maf-inducing protein (CMIP).	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of C-Maf-inducing protein (CMIP).	[22]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of C-Maf-inducing protein (CMIP).	[23]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of C-Maf-inducing protein (CMIP).	[24]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of C-Maf-inducing protein (CMIP).	[25]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of C-Maf-inducing protein (CMIP).	[26]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of C-Maf-inducing protein (CMIP).	[27]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of C-Maf-inducing protein (CMIP).	[28]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of C-Maf-inducing protein (CMIP).	[29]
Menadione	DMSJDTY	Approved	Menadione affects the expression of C-Maf-inducing protein (CMIP).	[30]
Vitamin C	DMXJ7O8	Approved	Vitamin C increases the expression of C-Maf-inducing protein (CMIP).	[27]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of C-Maf-inducing protein (CMIP).	[32]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of C-Maf-inducing protein (CMIP).	[35]

References

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• [2] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [3] CMIP Promotes Proliferation and Metastasis in Human Glioma.Biomed Res Int. 2017;2017:5340160. doi: 10.1155/2017/5340160. Epub 2017 Jul 4.
• [4] Minimal change nephrotic syndrome in patients infected with human immunodeficiency virus: a retrospective study of 8 cases.BMC Nephrol. 2018 Nov 20;19(1):331. doi: 10.1186/s12882-018-1132-x.
• [5] Upregulation of c-mip is closely related to podocyte dysfunction in membranous nephropathy.Kidney Int. 2013 Mar;83(3):414-25. doi: 10.1038/ki.2012.426. Epub 2013 Jan 9.
• [6] Decoding the genetics of speech and language.Curr Opin Neurobiol. 2013 Feb;23(1):43-51. doi: 10.1016/j.conb.2012.11.006. Epub 2012 Dec 7.
• [7] Assessment of Treatment Response by 99mTc-MIP-1404 SPECT/CT: A Pilot Study in Patients With Metastatic Prostate Cancer.Clin Nucl Med. 2018 Aug;43(8):e250-e258. doi: 10.1097/RLU.0000000000002162.
• [8] cMaf inducing protein inhibits cofilin? activity and alters podocyte cytoskeleton organization.Mol Med Rep. 2017 Oct;16(4):4955-4963. doi: 10.3892/mmr.2017.7156. Epub 2017 Aug 3.
• [9] Nephrotic Syndrome in Small Cell Lung Cancer and Induction of C-Mip in Podocytes.Am J Kidney Dis. 2017 Mar;69(3):477-480. doi: 10.1053/j.ajkd.2016.09.026. Epub 2017 Jan 4.
• [10] Opposite Genetic Effects of CMIP Polymorphisms on the Risk of Type 2 Diabetes and Obesity: A Family-Based Study in China.Int J Mol Sci. 2018 Mar 28;19(4):1011. doi: 10.3390/ijms19041011.
• [11] Genome-wide association studies identify susceptibility loci for epithelial ovarian cancer in east Asian women.Gynecol Oncol. 2019 May;153(2):343-355. doi: 10.1016/j.ygyno.2019.02.023. Epub 2019 Mar 19.
• [12] CMIP haploinsufficiency in two patients with autism spectrum disorder and co-occurring gastrointestinal issues.Am J Med Genet A. 2017 Aug;173(8):2101-2107. doi: 10.1002/ajmg.a.38277. Epub 2017 May 15.
• [13] CMIP is a negative regulator of T cell signaling.Cell Mol Immunol. 2020 Oct;17(10):1026-1041. doi: 10.1038/s41423-019-0266-5. Epub 2019 Aug 8.
• [14] Repression of CMIP transcription by WT1 is relevant to podocyte health.Kidney Int. 2016 Dec;90(6):1298-1311. doi: 10.1016/j.kint.2016.07.016. Epub 2016 Sep 17.
• [15] Expression of CMIP in podocytes is restricted to specific classes of lupus nephritis.PLoS One. 2018 Nov 15;13(11):e0207066. doi: 10.1371/journal.pone.0207066. eCollection 2018.
• [16] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [17] CMIP is oncogenic in human gastric cancer cells.Mol Med Rep. 2017 Nov;16(5):7277-7286. doi: 10.3892/mmr.2017.7541. Epub 2017 Sep 20.
• [18] CMIP promotes Herceptin resistance of HER2 positive gastric cancer cells.Pathol Res Pract. 2020 Feb;216(2):152776. doi: 10.1016/j.prp.2019.152776. Epub 2019 Dec 2.
• [19] East Asian Genome-wide association study derived loci in relation to type 2 diabetes in the Han Chinese population.Acta Biochim Pol. 2019 May 30;66(2):679-686. doi: 10.18388/abp.2020_5563.
• [20] PSMA SPECT/CT with (99m)Tc-MIP-1404 in biochemical recurrence of prostate cancer: predictive factors and efficacy for the detection of PSMA-positive lesions at low and very-low PSA levels.Ann Nucl Med. 2019 Dec;33(12):891-898. doi: 10.1007/s12149-019-01400-6. Epub 2019 Sep 9.
• [21] 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.
• [22] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [23] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [24] 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.
• [25] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [26] 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.
• [27] Synergistic effects of arsenic trioxide combined with ascorbic acid in human osteosarcoma MG-63 cells: a systems biology analysis. Eur Rev Med Pharmacol Sci. 2014;18(24):3877-88.
• [28] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [29] 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.
• [30] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [31] 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.
• [32] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [33] 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.
• [34] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [35] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [36] Mapping genes that contribute to daunorubicin-induced cytotoxicity. Cancer Res. 2007 Jun 1;67(11):5425-33. doi: 10.1158/0008-5472.CAN-06-4431.