Details of Drug Off-Target (DOT)

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

• DOT Name: Dermokine (DMKN)
• Synonyms: Epidermis-specific secreted protein SK30/SK89
• Gene Name: DMKN
• Related Disease:
  Atopic dermatitis
  Colorectal carcinoma
  Congenital ichthyosiform erythroderma
  Matthew-Wood syndrome
  Non-syndromic ichthyosis
  Pancreatic cancer
  Psoriasis
  Skin carcinoma
  Skin disease
  Squamous cell carcinoma
  Colonic neoplasm
  Neoplasm
• UniProt ID: DMKN_HUMAN
• PDB ID: 4F20
• Sequence:
  MKFQGPLACLLLALCLGSGEAGPLQSGEESTGTNIGEALGHGLGDALSEGVGKAIGKEAG
  GAAGSKVSEALGQGTREAVGTGVRQVPGFGVADALGNRVGEAAHALGNTGHEIGRQAEDV
  IRHGADAVRGSWQGVPGHNGAWETSGGHGIFGSQGGLGGQGQGNPGGLGTPWVHGYPGNS
  AGSFGMNPQGAPWGQGGNGGPPNFGTNTQGAVAQPGYGSVRASNQNEGCTNPPPSGSGGG
  SSNSGGGSGSQSGSSGSGSNGDNNNGSSSGGSSSGSSSGGSSGGSSGGSSGNSGGSRGDS
  GSESSWGSSTGSSSGNHGGSGGGNGHKPGCEKPGNEARGSGESGIQNSETSPGMFNFDTF
  WKNFKSKLGFINWDAINKNQVPPPSTRALLYFSRLWEDFKQNTPFLNWKAIIEGADASSL
  QKRAGRDDQNYNYNQHAYPTAYGGKYSVKTPAKGGVSPSSSASRVQPGLLQWVKFW
• Function: May act as a soluble regulator of keratinocyte differentiation.
• Tissue Specificity: Expressed in epidermis; in the spinous and granular layers and in placenta. Also found in the epithelia of the small intestine, macrophages of the lung and endothelial cells of the lung. Isoform 15 is expressed in epidermis and placenta. Isoform 1 is expressed in epidermis.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atopic dermatitis	DISTCP41	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Congenital ichthyosiform erythroderma	DISV8HQX	Strong	Biomarker	[1]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[3]
Non-syndromic ichthyosis	DISZ9QBQ	Strong	Biomarker	[1]
Pancreatic cancer	DISJC981	Strong	Biomarker	[3]
Psoriasis	DIS59VMN	Strong	Biomarker	[1]
Skin carcinoma	DISUZREN	Strong	Biomarker	[3]
Skin disease	DISDW8R6	Strong	Altered Expression	[4]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[4]
Colonic neoplasm	DISSZ04P	Limited	Biomarker	[2]
Neoplasm	DISZKGEW	Limited	Altered Expression	[2]

3 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 Dermokine (DMKN).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Dermokine (DMKN).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Dermokine (DMKN).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Dermokine (DMKN).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Dermokine (DMKN).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Dermokine (DMKN).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Dermokine (DMKN).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Dermokine (DMKN).	[10]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Dermokine (DMKN).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Dermokine (DMKN).	[12]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Dermokine (DMKN).	[13]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Dermokine (DMKN).	[16]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the expression of Dermokine (DMKN).	[17]

References

• [1] Homeostatic Function of Dermokine in the Skin Barrier and Inflammation.J Invest Dermatol. 2020 Apr;140(4):838-849.e9. doi: 10.1016/j.jid.2019.09.011. Epub 2019 Oct 25.
• [2] Dermokine as a novel biomarker for early-stage colorectal cancer.J Gastroenterol. 2010 Dec;45(12):1201-11. doi: 10.1007/s00535-010-0279-4. Epub 2010 Jul 21.
• [3] Dermokine contributes to epithelial-mesenchymal transition through increased activation of signal transducer and activator of transcription 3 in pancreatic cancer.Cancer Sci. 2017 Nov;108(11):2130-2141. doi: 10.1111/cas.13347. Epub 2017 Sep 15.
• [4] Altered expression of dermokine in skin disorders.J Eur Acad Dermatol Venereol. 2013 Jul;27(7):867-75. doi: 10.1111/j.1468-3083.2012.04598.x. Epub 2012 May 31.
• [5] 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.
• [6] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [7] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [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] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer. Toxicol Appl Pharmacol. 2015 Jun 1;285(2):79-88.
• [14] 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.
• [15] 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.
• [16] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [17] Global changes in gene regulation demonstrate that unconjugated bilirubin is able to upregulate and activate select components of the endoplasmic reticulum stress response pathway. J Biochem Mol Toxicol. 2010 Mar-Apr;24(2):73-88.