Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4GICNY)

• DOT Name: MAM domain-containing protein 2 (MAMDC2)
• Synonyms: MAM domain-containing proteoglycan; Mamcan
• Gene Name: MAMDC2
• UniProt ID: MAMC2_HUMAN
• Pfam ID: PF00629
• Sequence:
  MLLRGVLLALQALQLAGALDLPAGSCAFEESTCGFDSVLASLPWILNEEGHYIYVDTSFG
  KQGEKAVLLSPDLQAEEWSCLRLVYQITTSSESLSDPSQLNLYMRFEDESFDRLLWSAKE
  PSDSWLIASLDLQNSSKKFKILIEGVLGQGNTASIALFEIKMTTGYCIECDFEENHLCGF
  VNRWNPNVNWFVGGGSIRNVHSILPQDHTFKSELGHYMYVDSVYVKHFQEVAQLISPLTT
  APMAGCLSFYYQIQQGNDNVFSLYTRDVAGLYEEIWKADRPGNAAWNLAEVEFSAPYPME
  VIFEVAFNGPKGGYVALDDISFSPVHCQNQTELLFSAVEASCNFEQDLCNFYQDKEGPGW
  TRVKVKPNMYRAGDHTTGLGYYLLANTKFTSQPGYIGRLYGPSLPGNLQYCLRFHYAIYG
  FLKMSDTLAVYIFEENHVVQEKIWSVLESPRGVWMQAEITFKKPMPTKVVFMSLCKSFWD
  CGLVALDDITIQLGSCSSSEKLPPPPGECTFEQDECTFTQEKRNRSSWHRRRGETPTSYT
  GPKGDHTTGVGYYMYIEASHMVYGQKARLLSRPLRGVSGKHCLTFFYHMYGGGTGLLSVY
  LKKEEDSEESLLWRRRGEQSISWLRALIEYSCERQHQIIFEAIRGVSIRSDIAIDDVKFQ
  AGPCGEMEDTTQQSSGYSEDLNEIEY

Molecular Interaction Atlas (MIA) of This DOT

13 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 MAM domain-containing protein 2 (MAMDC2).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of MAM domain-containing protein 2 (MAMDC2).	[2]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of MAM domain-containing protein 2 (MAMDC2).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of MAM domain-containing protein 2 (MAMDC2).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of MAM domain-containing protein 2 (MAMDC2).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of MAM domain-containing protein 2 (MAMDC2).	[6]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of MAM domain-containing protein 2 (MAMDC2).	[7]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of MAM domain-containing protein 2 (MAMDC2).	[8]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of MAM domain-containing protein 2 (MAMDC2).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of MAM domain-containing protein 2 (MAMDC2).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of MAM domain-containing protein 2 (MAMDC2).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of MAM domain-containing protein 2 (MAMDC2).	[13]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of MAM domain-containing protein 2 (MAMDC2).	[14]

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 MAM domain-containing protein 2 (MAMDC2).	[11]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] 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.
• [4] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [5] 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.
• [6] 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.
• [7] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [8] Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 2006 Mar 1;66(5):2765-77.
• [9] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [10] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [11] 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.
• [12] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [13] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [14] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.