Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1PAIN0)

• DOT Name: Calcium-binding and coiled-coil domain-containing protein 1 (CALCOCO1)
• Synonyms: Calphoglin; Coiled-coil coactivator protein; Sarcoma antigen NY-SAR-3
• Gene Name: CALCOCO1
• Related Disease:
  Colorectal carcinoma
  Panic disorder
• UniProt ID: CACO1_HUMAN
• Pfam ID: PF07888 ; PF17751 ; PF18112
• Sequence:
  MEESPLSRAPSRGGVNFLNVARTYIPNTKVECHYTLPPGTMPSASDWIGIFKVEAACVRD
  YHTFVWSSVPESTTDGSPIHTSVQFQASYLPKPGAQLYQFRYVNRQGQVCGQSPPFQFRE
  PRPMDELVTLEEADGGSDILLVVPKATVLQNQLDESQQERNDLMQLKLQLEGQVTELRSR
  VQELERALATARQEHTELMEQYKGISRSHGEITEERDILSRQQGDHVARILELEDDIQTI
  SEKVLTKEVELDRLRDTVKALTREQEKLLGQLKEVQADKEQSEAELQVAQQENHHLNLDL
  KEAKSWQEEQSAQAQRLKDKVAQMKDTLGQAQQRVAELEPLKEQLRGAQELAASSQQKAT
  LLGEELASAAAARDRTIAELHRSRLEVAEVNGRLAELGLHLKEEKCQWSKERAGLLQSVE
  AEKDKILKLSAEILRLEKAVQEERTQNQVFKTELAREKDSSLVQLSESKRELTELRSALR
  VLQKEKEQLQEEKQELLEYMRKLEARLEKVADEKWNEDATTEDEEAAVGLSCPAALTDSE
  DESPEDMRLPPYGLCERGDPGSSPAGPREASPLVVISQPAPISPHLSGPAEDSSSDSEAE
  DEKSVLMAAVQSGGEEANLLLPELGSAFYDMASGFTVGTLSETSTGGPATPTWKECPICK
  ERFPAESDKDALEDHMDGHFFFSTQDPFTFE
• Function: Functions as a coactivator for aryl hydrocarbon and nuclear receptors (NR). Recruited to promoters through its contact with the N-terminal basic helix-loop-helix-Per-Arnt-Sim (PAS) domain of transcription factors or coactivators, such as NCOA2. During ER-activation acts synergistically in combination with other NCOA2-binding proteins, such as EP300, CREBBP and CARM1. Involved in the transcriptional activation of target genes in the Wnt/CTNNB1 pathway. Functions as a secondary coactivator in LEF1-mediated transcriptional activation via its interaction with CTNNB1. Coactivator function for nuclear receptors and LEF1/CTNNB1 involves differential utilization of two different activation regions. In association with CCAR1 enhances GATA1- and MED1-mediated transcriptional activation from the gamma-globin promoter during erythroid differentiation of K562 erythroleukemia cells ; Seems to enhance inorganic pyrophosphatase thus activating phosphogluomutase (PMG). Probably functions as a component of the calphoglin complex, which is involved in linking cellular metabolism (phosphate and glucose metabolism) with other core functions including protein synthesis and degradation, calcium signaling and cell growth.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[1]
Panic disorder	DISD3VNY	Strong	Genetic Variation	[2]

13 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 Calcium-binding and coiled-coil domain-containing protein 1 (CALCOCO1).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Calcium-binding and coiled-coil domain-containing protein 1 (CALCOCO1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Calcium-binding and coiled-coil domain-containing protein 1 (CALCOCO1).	[5]
Selenium	DM25CGV	Approved	Selenium increases the expression of Calcium-binding and coiled-coil domain-containing protein 1 (CALCOCO1).	[6]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Calcium-binding and coiled-coil domain-containing protein 1 (CALCOCO1).	[7]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Calcium-binding and coiled-coil domain-containing protein 1 (CALCOCO1).	[8]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Calcium-binding and coiled-coil domain-containing protein 1 (CALCOCO1).	[9]
PEITC	DMOMN31	Phase 2	PEITC increases the expression of Calcium-binding and coiled-coil domain-containing protein 1 (CALCOCO1).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Calcium-binding and coiled-coil domain-containing protein 1 (CALCOCO1).	[12]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Calcium-binding and coiled-coil domain-containing protein 1 (CALCOCO1).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Calcium-binding and coiled-coil domain-containing protein 1 (CALCOCO1).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Calcium-binding and coiled-coil domain-containing protein 1 (CALCOCO1).	[15]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Calcium-binding and coiled-coil domain-containing protein 1 (CALCOCO1).	[16]

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 affects the methylation of Calcium-binding and coiled-coil domain-containing protein 1 (CALCOCO1).	[11]

References

• [1] Long noncoding RNA LINC00052 inhibits colorectal cancer metastasis by sponging microRNA-574-5p to modulate CALCOCO1 expression.J Cell Biochem. 2019 Oct;120(10):17258-17272. doi: 10.1002/jcb.28988. Epub 2019 May 19.
• [2] Genome-wide association study of panic disorder in the Japanese population.J Hum Genet. 2009 Feb;54(2):122-6. doi: 10.1038/jhg.2008.17. Epub 2009 Jan 23.
• [3] 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.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [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] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [8] Toxicoproteomics reveals an effect of clozapine on autophagy in human liver spheroids. Toxicol Mech Methods. 2023 Jun;33(5):401-410. doi: 10.1080/15376516.2022.2156005. Epub 2022 Dec 19.
• [9] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [10] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [11] 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.
• [12] BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011 Sep 16;146(6):904-17.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] 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.
• [15] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [16] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.