Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ31XOT)

• DOT Name: Cyclin-dependent kinase 2-interacting protein (CINP)
• Synonyms: CDK2-interacting protein
• Gene Name: CINP
• Related Disease:
  Cognitive impairment
  Alzheimer disease
  Bipolar disorder
  Hepatitis C virus infection
  Neoplasm
  Retinoblastoma
• UniProt ID: CINP_HUMAN
• Sequence:
  MEAKTLGTVTPRKPVLSVSARKIKDNAADWHNLILKWETLNDAGFTTANNIANLKISLLN
  KDKIELDSSSPASKENEEKVCLEYNEELEKLCEELQATLDGLTKIQVKMEKLSSTTKGIC
  ELENYHYGEESKRPPLFHTWPTTHFYEVSHKLLEMYRKELLLKRTVAKELAHTGDPDLTL
  SYLSMWLHQPYVESDSRLHLESMLLETGHRAL
• Function: Component of the DNA replication complex, which interacts with two kinases, CDK2 and CDC7, thereby providing a functional and physical link between CDK2 and CDC7 during firing of the origins of replication. Regulates ATR-mediated checkpoint signaling in response to DNA damage. Also involved in the cytoplasmic maturation steps of pre-60S ribosomal particles by promoting the release of shuttling protein RSL24D1/RLP24 from the pre-ribosomal particles. Promotes maturation of pre-60S ribosome together with AFG2A, AFG2B and AIRIM.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cognitive impairment	DISH2ERD	Definitive	Genetic Variation	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[3]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Retinoblastoma	DISVPNPB	Strong	Altered Expression	[4]

4 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 Cyclin-dependent kinase 2-interacting protein (CINP).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cyclin-dependent kinase 2-interacting protein (CINP).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cyclin-dependent kinase 2-interacting protein (CINP).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cyclin-dependent kinase 2-interacting protein (CINP).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Cyclin-dependent kinase 2-interacting protein (CINP).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Cyclin-dependent kinase 2-interacting protein (CINP).	[11]

References

• [1] Differences Between Women With Traumatic and Idiopathic Chronic Neck Pain and Women Without Neck Pain: Interrelationships Among Disability, Cognitive Deficits, and Central Sensitization.Phys Ther. 2017 Mar 1;97(3):338-353. doi: 10.2522/ptj.20160259.
• [2] Neuropathology-driven Whole-genome Sequencing Study Points to Novel Candidate Genes for Healthy Brain Aging.Alzheimer Dis Assoc Disord. 2019 Jan-Mar;33(1):7-14. doi: 10.1097/WAD.0000000000000294.
• [3] The CINP Guidelines on the Definition and Evidence-Based Interventions for Treatment-Resistant Bipolar Disorder.Int J Neuropsychopharmacol. 2020 Apr 23;23(4):230-256. doi: 10.1093/ijnp/pyz064.
• [4] Hepatitis C virus NS5B protein delays s phase progression in human hepatocyte-derived cells by relocalizing cyclin-dependent kinase 2-interacting protein (CINP).J Biol Chem. 2011 Jul 29;286(30):26603-15. doi: 10.1074/jbc.M111.225672. Epub 2011 May 31.
• [5] CINP is a novel cofactor of KLF5 required for its role in the promotion of cell proliferation, survival and tumor growth.Int J Cancer. 2019 Feb 1;144(3):582-594. doi: 10.1002/ijc.31908. Epub 2018 Oct 26.
• [6] 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.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] 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.
• [10] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [11] 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.