Details of Drug Off-Target (DOT)

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

• DOT Name: Solute carrier family 46 member 2 (SLC46A2)
• Synonyms: Thymic stromal cotransporter homolog
• Gene Name: SLC46A2
• UniProt ID: S46A2_HUMAN
• Pfam ID: PF07690
• Sequence:
  MSPEVTCPRRGHLPRFHPRTWVEPVVASSQVAASLYDAGLLLVVKASYGTGGSSNHSASP
  SPRGALEDQQQRAISNFYIIYNLVVGLSPLLSAYGLGWLSDRYHRKISICMSLLGFLLSR
  LGLLLKVLLDWPVEVLYGAAALNGLFGGFSAFWSGVMALGSLGSSEGRRSVRLILIDLML
  GLAGFCGSMASGHLFKQMAGHSGQGLILTACSVSCASFALLYSLLVLKVPESVAKPSQEL
  PAVDTVSGTVGTYRTLDPDQLDQQYAVGHPPSPGKAKPHKTTIALLFVGAIIYDLAVVGT
  VDVIPLFVLREPLGWNQVQVGYGMAAGYTIFITSFLGVLVFSRCFRDTTMIMIGMVSFGS
  GALLLAFVKETYMFYIARAVMLFALIPVTTIRSAMSKLIKGSSYGKVFVILQLSLALTGV
  VTSTLYNKIYQLTMDMFVGSCFALSSFLSFLAIIPISIVAYKQVPLSPYGDIIEK
• Function: Proton-coupled transporter that delivers pathogen-associated or danger-associated molecular patterns to cytosolic pattern recognition receptors as part of the innate immune response to microbes or tissue injury. Has selectivity toward muropeptides that contain the amino acid diaminopimelic acid (DAP-type peptidoglycan muropeptides) including Tri-DAP and tracheal toxin (TCT), common in Gram-negative bacteria and Gram-positive bacilli. In the context of immune recognition of skin microbiota, shuttles bacterial muropeptides across the endolysosomal membranes into the cytosol for recognition by NOD1, triggering MYD88-dependent secretion of IL1A and neutrophil recruitment in a pyroptosis-type inflammatory process. To a lesser extent and redundantly, transports muramyl dipeptides derived from most bacterial proteoglycans, eliciting NOD2 receptor activation and downstream inflammatory responses. Postulated to function as a dominant importer of cyclic GMP-AMP dinucleotides (cGAMPs) in monocyte and macrophage cell lineages. Selectively imports cGAMPs derived from pathogenic bacteria such as 3'3'-cGAMP thus providing for differential immune recognition of pathogenic versus commensal bacteria. During tumorigenesis may transport extracellular tumor-derived 2'3'-cGAMP across the plasma membrane of M1-polarized macrophages to activate the anti-tumoral stimulator of interferon genes (STING) pathway. The transport mechanism, its electrogenicity and stoichiometry remain to be elucidated (Probable).
• Tissue Specificity: Strongly expressed in the adult thymus. Expressed in spleen, lymph nodes, thymus, PBL, bone marrow and fetal liver. Expressed in monocytes and pre-dendridic cells.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Solute carrier family 46 member 2 (SLC46A2).	[1]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Solute carrier family 46 member 2 (SLC46A2).	[2]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Solute carrier family 46 member 2 (SLC46A2).	[4]

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 increases the methylation of Solute carrier family 46 member 2 (SLC46A2).	[3]

References

• [1] 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.
• [2] Vitamin D3 transactivates the zinc and manganese transporter SLC30A10 via the Vitamin D receptor. J Steroid Biochem Mol Biol. 2016 Oct;163:77-87.
• [3] 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.
• [4] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.