Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNZ268J)

• DOT Name: Membrane-associated transporter protein (SLC45A2)
• Synonyms: Melanoma antigen AIM1; Protein AIM-1; Solute carrier family 45 member 2
• Gene Name: SLC45A2
• Related Disease: Oculocutaneous albinism type 4
• UniProt ID: S45A2_HUMAN
• Pfam ID: PF13347
• Sequence:
  MGSNSGQAGRHIYKSLADDGPFDSVEPPKRPTSRLIMHSMAMFGREFCYAVEAAYVTPVL
  LSVGLPSSLYSIVWFLSPILGFLLQPVVGSASDHCRSRWGRRRPYILTLGVMMLVGMALY
  LNGATVVAALIANPRRKLVWAISVTMIGVVLFDFAADFIDGPIKAYLFDVCSHQDKEKGL
  HYHALFTGFGGALGYLLGAIDWAHLELGRLLGTEFQVMFFFSALVLTLCFTVHLCSISEA
  PLTEVAKGIPPQQTPQDPPLSSDGMYEYGSIEKVKNGYVNPELAMQGAKNKNHAEQTRRA
  MTLKSLLRALVNMPPHYRYLCISHLIGWTAFLSNMLFFTDFMGQIVYRGDPYSAHNSTEF
  LIYERGVEVGCWGLCINSVFSSLYSYFQKVLVSYIGLKGLYFTGYLLFGLGTGFIGLFPN
  VYSTLVLCSLFGVMSSTLYTVPFNLITEYHREEEKERQQAPGGDPDNSVRGKGMDCATLT
  CMVQLAQILVGGGLGFLVNTAGTVVVVVITASAVALIGCCFVALFVRYVD
• Function: Proton-associated glucose and sucrose transporter. May be able to transport also fructose. Expressed at a late melanosome maturation stage where functions as proton/glucose exporter which increase lumenal pH by decreasing glycolysis. Regulates melanogenesis by maintaining melanosome neutralization that is initially initiated by transient OCA2 and required for a proper function of the tyrosinase TYR.
• Tissue Specificity: Expressed in mature melanocytes.
• Reactome Pathway: Melanin biosynthesis (R-HSA-5662702)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Oculocutaneous albinism type 4	DISI2JHV	Definitive	Autosomal recessive	[1]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
3-iodothyronamine	DM3L0F8	Investigative	Membrane-associated transporter protein (SLC45A2) affects the uptake of 3-iodothyronamine.	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Membrane-associated transporter protein (SLC45A2).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Membrane-associated transporter protein (SLC45A2).	[3]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Membrane-associated transporter protein (SLC45A2).	[3]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Membrane-associated transporter protein (SLC45A2).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Membrane-associated transporter protein (SLC45A2).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Membrane-associated transporter protein (SLC45A2).	[6]
Forskolin	DM6ITNG	Investigative	Forskolin increases the expression of Membrane-associated transporter protein (SLC45A2).	[4]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] 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.
• [3] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [4] Post-transcriptional regulation of melanin biosynthetic enzymes by cAMP and resveratrol in human melanocytes. J Invest Dermatol. 2007 Sep;127(9):2216-27. doi: 10.1038/sj.jid.5700840. Epub 2007 Apr 26.
• [5] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [6] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [7] Identification and characterization of 3-iodothyronamine intracellular transport. Endocrinology. 2009 Apr;150(4):1991-9.