Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL1K0OB)

• DOT Name: C2 domain-containing protein 2 (C2CD2)
• Synonyms: Transmembrane protein 24-like
• Gene Name: C2CD2
• Related Disease: Tuberculosis
• UniProt ID: C2CD2_HUMAN
• Pfam ID: PF00168 ; PF18696
• Sequence:
  MAMARLGSWLGEAQWLALVSLFVAALATVGLYLAQWALARARPQPQRRAVEPGEGPRPGS
  DALLSWILTLGSWRSQWQAAWVTALNEEAERKGGPPFLSFEEDPRQQALELVVQEVSSVL
  RSAEEKVVVCHVVGQAIQFLVSETPALGAGCRLYDMRLSPFHLQLEFHMKEKREDLQISW
  SFISVPEMAVNIQPKALGEDQVAETSAMSDVLKDILKHLAGSASPSVVLITKPTTVKEAQ
  NLQCAASTAQESCPPKPPRAHELKLLVRNIHVLLLSEPGASGHINAVCVVQLNDPVQRFS
  STLTKNTPDLMWEEEFTFELNAKSKELHLQISEAGRSSEGLLATATVPLDLFKKQPSGPQ
  SFTLTSGSACGSSVLGSVTAEFSYMEPGELKSWPIPPPVPAAKIEKDRTVMPCGTVVTTV
  TAVKTKPRVDVGRASPLSSDSPVKTPIKVKVIEKDISVQAIACRSAPVSKTLSSSDTELL
  VLNGSDPVAEVAIRQLSESSKLKLKSPRKKSTIIISGISKTSLSQDHDAALMQGYTASVD
  STHQEDAPSHPERAAASAPPEEAESAQASLAPKPQEDELDSWDLEKEPQAAAWSSQVLLD
  PDGDELSESSMSVLEPGTAKKHKGGILRKGAKLFFRRRHQQKDPGMSQSHNDLVFLEQPE
  GSRRKGITLTRILNKKLLSRHRNKNTMNGAPVEPCT

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Tuberculosis	DIS2YIMD	Definitive	Genetic Variation	[1]

11 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 C2 domain-containing protein 2 (C2CD2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of C2 domain-containing protein 2 (C2CD2).	[3]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of C2 domain-containing protein 2 (C2CD2).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of C2 domain-containing protein 2 (C2CD2).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of C2 domain-containing protein 2 (C2CD2).	[6]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of C2 domain-containing protein 2 (C2CD2).	[7]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of C2 domain-containing protein 2 (C2CD2).	[8]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of C2 domain-containing protein 2 (C2CD2).	[9]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of C2 domain-containing protein 2 (C2CD2).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of C2 domain-containing protein 2 (C2CD2).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of C2 domain-containing protein 2 (C2CD2).	[15]

4 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 increases the methylation of C2 domain-containing protein 2 (C2CD2).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of C2 domain-containing protein 2 (C2CD2).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of C2 domain-containing protein 2 (C2CD2).	[13]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of C2 domain-containing protein 2 (C2CD2).	[12]

References

• [1] Genome-wide association study of ancestry-specific TB risk in the South African Coloured population.Hum Mol Genet. 2014 Feb 1;23(3):796-809. doi: 10.1093/hmg/ddt462. Epub 2013 Sep 20.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] Estradiol and selective estrogen receptor modulators differentially regulate target genes with estrogen receptors alpha and beta. Mol Biol Cell. 2004 Mar;15(3):1262-72. doi: 10.1091/mbc.e03-06-0360. Epub 2003 Dec 29.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] 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.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] 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.
• [9] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [10] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [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] 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.
• [13] 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.
• [14] 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.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.