Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1N2S2K)

• DOT Name: Melanoma antigen recognized by T-cells 1 (MLANA)
• Synonyms: MART-1; Antigen LB39-AA; Antigen SK29-AA; Protein Melan-A
• Gene Name: MLANA
• UniProt ID: MAR1_HUMAN
• PDB ID: 2GT9; 2GTW; 2GTZ; 2GUO; 3HG1; 3L6F; 3MRO; 3MRP; 3MRQ; 3QDM; 3QEQ; 3QFD; 4EUP; 4JFF; 4L3E; 4QOK; 4WJ5; 5E9D; 5NHT; 5NQK; 6D78; 6DKP; 6TMO; 7TR4
• Pfam ID: PF14991
• Sequence:
  MPREDAHFIYGYPKKGHGHSYTTAEEAAGIGILTVILGVLLLIGCWYCRRRNGYRALMDK
  SLHVGTQCALTRRCPQEGFDHRDSKVSLQEKNCEPVVPNAPPAYEKLSAEQSPPPYSP
• Function: Involved in melanosome biogenesis by ensuring the stability of GPR143. Plays a vital role in the expression, stability, trafficking, and processing of melanocyte protein PMEL, which is critical to the formation of stage II melanosomes.
• Tissue Specificity: Expression is restricted to melanoma and melanocyte cell lines and retina.

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Melanoma antigen recognized by T-cells 1 (MLANA) affects the response to substance of Etoposide.	[7]

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 Melanoma antigen recognized by T-cells 1 (MLANA).	[1]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Melanoma antigen recognized by T-cells 1 (MLANA).	[2]
Vemurafenib	DM62UG5	Approved	Vemurafenib increases the expression of Melanoma antigen recognized by T-cells 1 (MLANA).	[3]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Melanoma antigen recognized by T-cells 1 (MLANA).	[4]

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 increases the methylation of Melanoma antigen recognized by T-cells 1 (MLANA).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Melanoma antigen recognized by T-cells 1 (MLANA).	[6]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [3] PLX4032 Mediated Melanoma Associated Antigen Potentiation in Patient Derived Primary Melanoma Cells. J Cancer. 2015 Oct 29;6(12):1320-30. doi: 10.7150/jca.11126. eCollection 2015.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.