Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU7C3GQ)

• DOT Name: CXADR-like membrane protein (CLMP)
• Synonyms: Adipocyte adhesion molecule; Coxsackie- and adenovirus receptor-like membrane protein; CAR-like membrane protein
• Gene Name: CLMP
• Related Disease:
  Congenital short bowel syndrome, autosomal recessive
  Congenital short bowel syndrome
  Chronic intestinal pseudoobstruction
  Granular corneal dystrophy type II
• UniProt ID: CLMP_HUMAN
• Pfam ID: PF13895 ; PF07686
• Sequence:
  MSLLLLLLLVSYYVGTLGTHTEIKRVAEEKVTLPCHHQLGLPEKDTLDIEWLLTDNEGNQ
  KVVITYSSRHVYNNLTEEQKGRVAFASNFLAGDASLQIEPLKPSDEGRYTCKVKNSGRYV
  WSHVILKVLVRPSKPKCELEGELTEGSDLTLQCESSSGTEPIVYYWQRIREKEGEDERLP
  PKSRIDYNHPGRVLLQNLTMSYSGLYQCTAGNEAGKESCVVRVTVQYVQSIGMVAGAVTG
  IVAGALLIFLLVWLLIRRKDKERYEEEERPNEIREDAEAPKARLVKPSSSSSGSRSSRSG
  SSSTRSTANSASRSQRTLSTDAAPQPGLATQAYSLVGPEVRGSEPKKVHHANLTKAETTP
  SMIPSQSRAFQTV
• Function: May be involved in the cell-cell adhesion. May play a role in adipocyte differentiation and development of obesity. Is required for normal small intestine development.
• Tissue Specificity: Predominantly expressed in epithelial cells within different tissues and in the white adipose tissue. Expressed at high levels in small intestine and placenta, at intermediate levels in the heart, skeletal muscle, colon, spleen, kidney and lung and at low levels in the liver and peripheral blood leukocytes. Highly abundant in the intestine during embryo and fetal development (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital short bowel syndrome, autosomal recessive	DISLUA6O	Strong	Autosomal recessive	[1]
Congenital short bowel syndrome	DIS2A1HB	Supportive	Autosomal recessive	[1]
Chronic intestinal pseudoobstruction	DISR68AN	Limited	Genetic Variation	[2]
Granular corneal dystrophy type II	DISAEE20	Limited	Altered Expression	[3]

10 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 CXADR-like membrane protein (CLMP).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of CXADR-like membrane protein (CLMP).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of CXADR-like membrane protein (CLMP).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of CXADR-like membrane protein (CLMP).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of CXADR-like membrane protein (CLMP).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of CXADR-like membrane protein (CLMP).	[9]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of CXADR-like membrane protein (CLMP).	[10]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of CXADR-like membrane protein (CLMP).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of CXADR-like membrane protein (CLMP).	[13]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of CXADR-like membrane protein (CLMP).	[15]

2 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 CXADR-like membrane protein (CLMP).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of CXADR-like membrane protein (CLMP).	[14]

References

• [1] CLMP is required for intestinal development, and loss-of-function mutations cause congenital short-bowel syndrome. Gastroenterology. 2012 Mar;142(3):453-462.e3. doi: 10.1053/j.gastro.2011.11.038. Epub 2011 Dec 7.
• [2] Two new mutations of the CLMP gene identified in a newborn presenting congenital short-bowel syndrome.Clin Res Hepatol Gastroenterol. 2016 Dec;40(6):e65-e67. doi: 10.1016/j.clinre.2015.12.018. Epub 2016 Oct 4.
• [3] Skin barrier damage after exposure to paraphenylenediamine.J Allergy Clin Immunol. 2020 Feb;145(2):619-631.e2. doi: 10.1016/j.jaci.2019.11.023. Epub 2019 Nov 26.
• [4] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [5] 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.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] 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.
• [8] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [9] 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.
• [10] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [11] Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.