Details of Drug Off-Target (DOT)

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

• DOT Name: Coiled-coil domain-containing protein 80 (CCDC80)
• Synonyms: Down-regulated by oncogenes protein 1; Up-regulated in BRS-3 deficient mouse homolog
• Gene Name: CCDC80
• Related Disease:
  Melanoma
  Adenocarcinoma
  Advanced cancer
  Arteriosclerosis
  Atherosclerosis
  Atopic dermatitis
  Bone osteosarcoma
  Colitis
  Colon cancer
  Colon carcinoma
  Colonic neoplasm
  Endometriosis
  Fatty liver disease
  Inflammatory bowel disease
  Metabolic disorder
  Neoplasm
  Obesity
  Osteosarcoma
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid gland undifferentiated (anaplastic) carcinoma
  Thyroid tumor
  Ovarian cancer
  Thyroid gland papillary carcinoma
• UniProt ID: CCD80_HUMAN
• Pfam ID: PF13778
• Sequence:
  MTWRMGPRFTMLLAMWLVCGSEPHPHATIRGSHGGRKVPLVSPDSSRPARFLRHTGRSRG
  IERSTLEEPNLQPLQRRRSVPVLRLARPTEPPARSDINGAAVRPEQRPAARGSPREMIRD
  EGSSARSRMLRFPSGSSSPNILASFAGKNRVWVISAPHASEGYYRLMMSLLKDDVYCELA
  ERHIQQIVLFHQAGEEGGKVRRITSEGQILEQPLDPSLIPKLMSFLKLEKGKFGMVLLKK
  TLQVEERYPYPVRLEAMYEVIDQGPIRRIEKIRQKGFVQKCKASGVEGQVVAEGNDGGGG
  AGRPSLGSEKKKEDPRRAQVPPTRESRVKVLRKLAATAPALPQPPSTPRATTLPPAPATT
  VTRSTSRAVTVAARPMTTTAFPTTQRPWTPSPSHRPPTTTEVITARRPSVSENLYPPSRK
  DQHRERPQTTRRPSKATSLESFTNAPPTTISEPSTRAAGPGRFRDNRMDRREHGHRDPNV
  VPGPPKPAKEKPPKKKAQDKILSNEYEEKYDLSRPTASQLEDELQVGNVPLKKAKESKKH
  EKLEKPEKEKKKKMKNENADKLLKSEKQMKKSEKKSKQEKEKSKKKKGGKTEQDGYQKPT
  NKHFTQSPKKSVADLLGSFEGKRRLLLITAPKAENNMYVQQRDEYLESFCKMATRKISVI
  TIFGPVNNSTMKIDHFQLDNEKPMRVVDDEDLVDQRLISELRKEYGMTYNDFFMVLTDVD
  LRVKQYYEVPITMKSVFDLIDTFQSRIKDMEKQKKEGIVCKEDKKQSLENFLSRFRWRRR
  LLVISAPNDEDWAYSQQLSALSGQACNFGLRHITILKLLGVGEEVGGVLELFPINGSSVV
  EREDVPAHLVKDIRNYFQVSPEYFSMLLVGKDGNVKSWYPSPMWSMVIVYDLIDSMQLRR
  QEMAIQQSLGMRCPEDEYAGYGYHSYHQGYQDGYQDDYRHHESYHHGYPY
• Function: Promotes cell adhesion and matrix assembly.
• Tissue Specificity: Expressed in dermal papilla and dermal fibroblasts (at protein level). Expressed in heart, thymus, placenta, pancreas, colon, epithelium, spleen and osteoblasts.

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Melanoma	DIS1RRCY	Definitive	Altered Expression	[1]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[4]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[4]
Atopic dermatitis	DISTCP41	Strong	Biomarker	[5]
Bone osteosarcoma	DIST1004	Strong	Genetic Variation	[6]
Colitis	DISAF7DD	Strong	Altered Expression	[2]
Colon cancer	DISVC52G	Strong	Biomarker	[2]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[2]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[2]
Endometriosis	DISX1AG8	Strong	Biomarker	[7]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[8]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[2]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Obesity	DIS47Y1K	Strong	Biomarker	[9]
Osteosarcoma	DISLQ7E2	Strong	Genetic Variation	[6]
Thyroid cancer	DIS3VLDH	Strong	Biomarker	[10]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[10]
Thyroid gland undifferentiated (anaplastic) carcinoma	DISYBB1W	Strong	Altered Expression	[3]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[10]
Ovarian cancer	DISZJHAP	moderate	Biomarker	[10]
Thyroid gland papillary carcinoma	DIS48YMM	moderate	Altered Expression	[10]

15 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 Coiled-coil domain-containing protein 80 (CCDC80).	[11]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Coiled-coil domain-containing protein 80 (CCDC80).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Coiled-coil domain-containing protein 80 (CCDC80).	[13]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Coiled-coil domain-containing protein 80 (CCDC80).	[14]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Coiled-coil domain-containing protein 80 (CCDC80).	[15]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Coiled-coil domain-containing protein 80 (CCDC80).	[16]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Coiled-coil domain-containing protein 80 (CCDC80).	[11]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Coiled-coil domain-containing protein 80 (CCDC80).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Coiled-coil domain-containing protein 80 (CCDC80).	[18]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Coiled-coil domain-containing protein 80 (CCDC80).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Coiled-coil domain-containing protein 80 (CCDC80).	[21]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Coiled-coil domain-containing protein 80 (CCDC80).	[22]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Coiled-coil domain-containing protein 80 (CCDC80).	[23]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Coiled-coil domain-containing protein 80 (CCDC80).	[24]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the expression of Coiled-coil domain-containing protein 80 (CCDC80).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Coiled-coil domain-containing protein 80 (CCDC80).	[20]

References

• [1] The function of FAK/CCDC80/E-cadherin pathway in the regulation of B16F10 cell migration.Oncol Lett. 2018 Oct;16(4):4761-4767. doi: 10.3892/ol.2018.9159. Epub 2018 Jul 17.
• [2] Dro1/Ccdc80 inactivation promotes AOM/DSS-induced colorectal carcinogenesis and aggravates colitis by DSS in mice.Carcinogenesis. 2018 Sep 21;39(9):1176-1184. doi: 10.1093/carcin/bgy077.
• [3] Tumor suppressor role of the CL2/DRO1/CCDC80 gene in thyroid carcinogenesis.J Clin Endocrinol Metab. 2013 Jul;98(7):2834-43. doi: 10.1210/jc.2012-2926. Epub 2013 May 10.
• [4] Coiled-coil domain-containing 80 accelerates atherosclerosis development through decreasing lipoprotein lipase expression via ERK1/2 phosphorylation and TET2 expression.Eur J Pharmacol. 2019 Jan 15;843:177-189. doi: 10.1016/j.ejphar.2018.11.009. Epub 2018 Nov 12.
• [5] Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population.Nat Genet. 2012 Nov;44(11):1222-6. doi: 10.1038/ng.2438. Epub 2012 Oct 7.
• [6] Clinical impact of the methotrexate resistance-associated genes C-MYC and dihydrofolate reductase (DHFR) in high-grade osteosarcoma.Ann Oncol. 2008 Aug;19(8):1500-1508. doi: 10.1093/annonc/mdn148. Epub 2008 Apr 2.
• [7] Identification of LINC01279 as a cell cycleassociated long noncoding RNA in endometriosis with GBA analysis.Mol Med Rep. 2018 Oct;18(4):3850-3858. doi: 10.3892/mmr.2018.9387. Epub 2018 Aug 14.
• [8] Adipose tissue and serum CCDC80 in obesity and its association with related metabolic disease.Mol Med. 2017 Oct;23:225-234. doi: 10.2119/molmed.2017.00067. Epub 2017 Aug 23.
• [9] Loss of DRO1/CCDC80 results in obesity and promotes adipocyte differentiation.Mol Cell Endocrinol. 2017 Jan 5;439:286-296. doi: 10.1016/j.mce.2016.09.014. Epub 2016 Sep 16.
• [10] The cl2/dro1/ccdc80 null mice develop thyroid and ovarian neoplasias.Cancer Lett. 2015 Feb 28;357(2):535-41. doi: 10.1016/j.canlet.2014.12.010. Epub 2014 Dec 9.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [15] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [16] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [17] A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer. Toxicol Appl Pharmacol. 2015 Jun 1;285(2):79-88.
• [18] Gene expression profiling of A549 cells exposed to Milan PM2.5. Toxicol Lett. 2012 Mar 7;209(2):136-45.
• [19] 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.
• [20] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [21] 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.
• [22] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [23] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [24] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [25] Global changes in gene regulation demonstrate that unconjugated bilirubin is able to upregulate and activate select components of the endoplasmic reticulum stress response pathway. J Biochem Mol Toxicol. 2010 Mar-Apr;24(2):73-88.