Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN9UZHR)

• DOT Name: Coiled-coil domain-containing protein 144A (CCDC144A)
• Gene Name: CCDC144A
• Related Disease: Acute myelogenous leukaemia
• UniProt ID: C144A_HUMAN
• Pfam ID: PF14915 ; PF12001
• Sequence:
  MASWGGEKRGGAEGSPKPAVYATRKTPSVGSQGDQWYLGYPGDQWSSGFPYSWWKNSVGS
  ESKHGEGALDQPQHDVRLEDLGELHRAARSGDVPGVEHILAPGDTGVDKRDRKKSIQQLV
  PEYKEKQTPESLPQNNNPDWHPTNLTLSDETCQRSKNLKVDDKCPSVSPSMPENQSATKE
  LGQMNLTEREKMDTGVVLLSGNDTLHDLCQSQLPENKESKEAEQDSELTSEEEQERLKGC
  ENKQPQKTSQEPEMAKDCDREDIPIYPVLPHVQKSEEMWIEQGKLEWKNQLKLVINELKQ
  RFGEIYEKYKIPACPEEEPLLDNSTRGTDVKDIPFNLTNNIPGCEEEDASEISVSVVFET
  FPEQKEPSLKNIIHPYYHPYSGSQEHVCQSSSKFHLHENKLDCDNDNKPGIGHIFSTDKN
  FHNDASTKKARNPEVVMVEMKEDQEFDLQMTKNMNQNSDSGSTNNYKSLKPKLENLSSLP
  PDSDRTSEVYLHEELQQDMQKFKNEVNTLEEEFLALKKEDVQLHKDVEEEMEKHRSNSTE
  LSGTLTDGTTVGNDDDGLNQQIPRKENGEHDRPADKTSNEKNEVKNQIYPEADFADSMEP
  SEIASEDCELSHSVYENFMLLIEQLRMEYKDSASLPRIQDTFCLCEHLLKLKNNHCDQLT
  VKLKQMENMVSVLQNELSETKKTKLQLELQKIEWEKELYDLRLALKQENEEKRNADMLYN
  KDSEQLRIKEEECGKVVETKQQLKWNLRRLVKELRTVRNNLDLVVQERNDAQKQLSEEQD
  ARILQDQILTSKQKELEMARKKMNSEISHRHQKEKDLFHEDCMLQEEIALLRLEIDTIKN
  QNKQKEKKYFEDIEAVKEKNDNLQKIIKLNEETLTETILQYSGQLNNLTAENKILNSELE
  NGKQNQERLEIEMESYRCRLAAAVRDCDQSQTARDLKLDFQRTRQEWVRLHDKMKVDMSG
  LQAKNEILSEKLSNAESKINSLQIQLHNTRDALGRESLILERVQRDLSQTQCQKKETEQM
  YQIEQSKLKKYIAKQESVEERLSQLQSENMLLRQQLDDAHKKANSQEKTSSTIQDQFHSA
  AKNLQAESEKQILSLQEKNKELMDEYNHLKERMDQCEKEKAGRKIDLTEAQETVPSRCLH
  LDAENEVLQLQQTLFSMKAIQKQCETLQKNKKQLKQEVVNLKSYMERNMLERGKAEWHKL
  LIEERARKEIEEKLNEAILTLQKQAAVSHEQLVQLREDNTTSIKTQMELTIKDLESEISR
  IKTSQADFNKTELERYKELYLEEVKVRESLSNELSRTNEMIAEVSTQLTVEKEQTRSRSL
  FTAYATRPVLESPCVGNLNDSEGLNRKHIPRKKRSALKDMESYLLKMQQKLQNDLTAEVA
  GSSQTGLHRIPQCSSFSSSSLHLLLCSICQPFFLILQLLLNMNLDPI
• Function: May play a role in preventing the formation of kidney stones through inhibition of calcium oxalate monohydrate (COM) crystallization, attenuating COM-induced apoptotic injury to renal epithelial cells. May exhibit antilithiatic (preventing the formation of kidney stones) activity through crystal binding, hindering the crystal attachment to renal epithelial cells, a pre-requisite to initiate inflammatory response.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[1]

4 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 Coiled-coil domain-containing protein 144A (CCDC144A).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Coiled-coil domain-containing protein 144A (CCDC144A).	[3]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Coiled-coil domain-containing protein 144A (CCDC144A).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Coiled-coil domain-containing protein 144A (CCDC144A).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Coiled-coil domain-containing protein 144A (CCDC144A).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Coiled-coil domain-containing protein 144A (CCDC144A).	[7]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Coiled-coil domain-containing protein 144A (CCDC144A).	[8]

References

• [1] 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.
• [2] 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.
• [3] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.