Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRJ3ZC5)

• DOT Name: Cytohesin-interacting protein (CYTIP)
• Synonyms: Cytohesin binder and regulator; CYBR; Cytohesin-associated scaffolding protein; CASP; Cytohesin-binding protein HE; Cbp HE; Pleckstrin homology Sec7 and coiled-coil domains-binding protein
• Gene Name: CYTIP
• Related Disease:
  Advanced cancer
  Gastric cancer
  Multiple sclerosis
  Non-small-cell lung cancer
  Stomach cancer
  Brain neoplasm
  Colorectal carcinoma
  Dementia
  Depression
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Herpes simplex infection
  Lung cancer
  Lung carcinoma
  Periodontal disease
  Plasma cell myeloma
  X-linked scapuloperoneal muscular dystrophy
  Gastrointestinal stromal tumour
  Non-hodgkin lymphoma
• UniProt ID: CYTIP_HUMAN
• PDB ID: 2Z17
• Pfam ID: PF00595
• Sequence:
  MSLQRLLQHSSNGNLADFCAGPAYSSYSTLTGSLTMDDNRRIQMLADTVATLPRGRKQLA
  LTRSSSLSDFSWSQRKLVTVEKQDNETFGFEIQSYRPQNQNACSSEMFTLICKIQEDSPA
  HCAGLQAGDVLANINGVSTEGFTYKQVVDLIRSSGNLLTIETLNGTMILKRTELEAKLQV
  LKQTLKQKWVEYRSLQLQEHRLLHGDAANCPSLENMDLDELSLFGPLPGPGPALVDRNRL
  SSESSCKSWLSSMTMDSEDGYQTCVSEDSSRGAFSRQTSTDDECFIPKEGDDFLRRSSSR
  RNRSISNTSSGSMSPLWEGNLSSMFGTLPRKSRKGSVRKQLLKFIPGLHRAVEEEESRF
• Function: By its binding to cytohesin-1 (CYTH1), it modifies activation of ARFs by CYTH1 and its precise function may be to sequester CYTH1 in the cytoplasm.
• Tissue Specificity: Expressed in lymph nodes, thymus, spleen, lung, peripheral blood leukocytes and bone marrow.

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Biomarker	[1]
Gastric cancer	DISXGOUK	Definitive	Biomarker	[2]
Multiple sclerosis	DISB2WZI	Definitive	Biomarker	[3]
Non-small-cell lung cancer	DIS5Y6R9	Definitive	Genetic Variation	[4]
Stomach cancer	DISKIJSX	Definitive	Biomarker	[2]
Brain neoplasm	DISY3EKS	Strong	Altered Expression	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[6]
Dementia	DISXL1WY	Strong	Biomarker	[7]
Depression	DIS3XJ69	Strong	Biomarker	[7]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Genetic Variation	[8]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[9]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[10]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[11]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[11]
Periodontal disease	DISJQHVN	Strong	Genetic Variation	[12]
Plasma cell myeloma	DIS0DFZ0	Strong	Genetic Variation	[13]
X-linked scapuloperoneal muscular dystrophy	DISBYRCR	Strong	Genetic Variation	[8]
Gastrointestinal stromal tumour	DIS6TJYS	moderate	Genetic Variation	[14]
Non-hodgkin lymphoma	DISS2Y8A	moderate	Genetic Variation	[15]

14 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 Cytohesin-interacting protein (CYTIP).	[16]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cytohesin-interacting protein (CYTIP).	[17]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Cytohesin-interacting protein (CYTIP).	[18]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Cytohesin-interacting protein (CYTIP).	[19]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Cytohesin-interacting protein (CYTIP).	[20]
Rigosertib	DMOSTXF	Phase 3	Rigosertib increases the expression of Cytohesin-interacting protein (CYTIP).	[21]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Cytohesin-interacting protein (CYTIP).	[22]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cytohesin-interacting protein (CYTIP).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Cytohesin-interacting protein (CYTIP).	[25]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Cytohesin-interacting protein (CYTIP).	[26]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Cytohesin-interacting protein (CYTIP).	[27]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Cytohesin-interacting protein (CYTIP).	[28]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Cytohesin-interacting protein (CYTIP).	[29]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Cytohesin-interacting protein (CYTIP).	[30]

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 decreases the methylation of Cytohesin-interacting protein (CYTIP).	[23]

References

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• [8] A functional variant at the miR-885-5p binding site of CASP3 confers risk of both index and second primary malignancies in patients with head and neck cancer.FASEB J. 2013 Apr;27(4):1404-12. doi: 10.1096/fj.12-223420. Epub 2012 Dec 27.
• [9] Caspase polymorphisms and prognosis of hepatocellular carcinoma.PLoS One. 2017 Apr 28;12(4):e0176802. doi: 10.1371/journal.pone.0176802. eCollection 2017.
• [10] Human Cytomegalovirus-Induced Degradation of CYTIP Modulates Dendritic Cell Adhesion and Migration.Front Immunol. 2017 Apr 21;8:461. doi: 10.3389/fimmu.2017.00461. eCollection 2017.
• [11] A literature-based systematic HuGE review and meta-analysis show that CASP gene family polymorphisms are associated with risk of lung cancer.Genet Mol Res. 2013 Jan 4;12(3):3057-69. doi: 10.4238/2013.January.4.22.
• [12] Assessment of CASP gene polymorphisms in periodontal disease.Genet Mol Res. 2015 Dec 22;14(4):18069-77. doi: 10.4238/2015.December.22.33.
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• [16] 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.
• [17] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [18] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [19] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [20] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [21] ON 01910.Na is selectively cytotoxic for chronic lymphocytic leukemia cells through a dual mechanism of action involving PI3K/AKT inhibition and induction of oxidative stress. Clin Cancer Res. 2012 Apr 1;18(7):1979-91. doi: 10.1158/1078-0432.CCR-11-2113. Epub 2012 Feb 20.
• [22] Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. Mol Immunol. 2007 May;44(12):3222-33.
• [23] 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.
• [24] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [25] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [26] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
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• [28] CD34+ derived macrophage and dendritic cells display differential responses to paraquat. Toxicol In Vitro. 2021 Sep;75:105198. doi: 10.1016/j.tiv.2021.105198. Epub 2021 Jun 9.
• [29] Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.
• [30] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.