Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXPTR8R)

• DOT Name: Disco-interacting protein 2 homolog A (DIP2A)
• Synonyms: DIP2 homolog A; EC 6.2.1.1
• Gene Name: DIP2A
• Related Disease:
  Adult glioblastoma
  Glioblastoma multiforme
  Advanced cancer
  Autism
  Breast cancer
  Breast carcinoma
  Lung adenocarcinoma
  Neoplasm
  Non-small-cell lung cancer
  Autism spectrum disorder
• UniProt ID: DIP2A_HUMAN
• EC Number: 6.2.1.1
• Pfam ID: PF00501 ; PF06464
• Sequence:
  MADRGCPLEAAPLPAEVRESLAELELELSEGDITQKGYEKKRAKLLARYIPLIQGIDPSL
  QAENRIPGPSQTTAAAPKQQKSRPTASRDERFRSDVHTEAVQAALAKYKERKMPMPSKRR
  SVLVHSSVETYTPPDTSSASEDEGSLRRPGRLTSTPLQSHSSVEPWLDRVIQGSSTSSSA
  SSTSSHPGGRPTTAPSAAATPGAAATTALAGLEAHTHIDLHSAPPDVTTGLVEHSYFERP
  QVASVRSVPRGCSGSMLETADGVPVNSRVSSKIQQLLNTLKRPKRPPLKEFFVDDFEELL
  EVQQPDPNQPKPEGSETSVLRGEPLTAGVPRPPSLLATLQRWGTTQPKSPCLTALDTTGK
  AVYTLTYGKLWSRSLKLAYTLLNKLTSKNEPLLKPGDRVALVFPNSDPVMFMVAFYGCLL
  AELVPVPIEVPLTRKDAGSQQVGFLLGSCGVFLALTTDACQKGLPKAQTGEVAAFKGWPP
  LSWLVIDGKHLAKPPKDWHPLAQDTGTGTAYIEYKTSKEGSTVGVTVSHASLLAQCRALT
  QACGYSEAETLTNVLDFKRDAGLWHGVLTSVMNRMHVVSVPYALMKANPLSWIQKVCFYK
  ARAALVKSRDMHWSLLAQRGQRDVSLSSLRMLIVADGANPWSISSCDAFLNVFQSRGLRP
  EVICPCASSPEALTVAIRRPPDLGGPPPRKAVLSMNGLSYGVIRVDTEEKLSVLTVQDVG
  QVMPGANVCVVKLEGTPYLCKTDEVGEICVSSSATGTAYYGLLGITKNVFEAVPVTTGGA
  PIFDRPFTRTGLLGFIGPDNLVFIVGKLDGLMVTGVRRHNADDVVATALAVEPMKFVYRG
  RIAVFSVTVLHDDRIVLVAEQRPDASEEDSFQWMSRVLQAIDSIHQVGVYCLALVPANTL
  PKAPLGGIHISETKQRFLEGTLHPCNVLMCPHTCVTNLPKPRQKQPEVGPASMIVGNLVA
  GKRIAQASGRELAHLEDSDQARKFLFLADVLQWRAHTTPDHPLFLLLNAKGTVTSTATCV
  QLHKRAERVAAALMEKGRLSVGDHVALVYPPGVDLIAAFYGCLYCGCVPVTVRPPHPQNL
  GTTLPTVKMIVEVSKSACVLTTQAVTRLLRSKEAAAAVDIRTWPTILDTDDIPKKKIASV
  FRPPSPDVLAYLDFSVSTTGILAGVKMSHAATSALCRSIKLQCELYPSRQIAICLDPYCG
  LGFALWCLCSVYSGHQSVLVPPLELESNVSLWLSAVSQYKARVTFCSYSVMEMCTKGLGA
  QTGVLRMKGVNLSCVRTCMVVAEERPRIALTQSFSKLFKDLGLPARAVSTTFGCRVNVAI
  CLQGTAGPDPTTVYVDMRALRHDRVRLVERGSPHSLPLMESGKILPGVKVIIAHTETKGP
  LGDSHLGEIWVSSPHNATGYYTVYGEEALHADHFSARLSFGDTQTIWARTGYLGFLRRTE
  LTDASGGRHDALYVVGSLDETLELRGMRYHPIDIETSVIRAHRSIAECAVFTWTNLLVVV
  VELDGLEQDALDLVALVTNVVLEEHYLVVGVVVIVDPGVIPINSRGEKQRMHLRDGFLAD
  QLDPIYVAYNM
• Function: Catalyzes the de novo synthesis of acetyl-CoA in vitro. Promotes acetylation of CTTN, possibly by providing the acetyl donor, ensuring correct dendritic spine morphology and synaptic transmission. Binds to follistatin-related protein FSTL1 and may act as a cell surface receptor for FSTL1, contributing to AKT activation and subsequent FSTL1-induced survival and function of endothelial cells and cardiac myocytes.
• Tissue Specificity: Low expression in all tissues tested.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Definitive	Biomarker	[1]
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Autism	DISV4V1Z	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[5]
Autism spectrum disorder	DISXK8NV	Limited	Autosomal dominant	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Disco-interacting protein 2 homolog A (DIP2A).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Disco-interacting protein 2 homolog A (DIP2A).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Disco-interacting protein 2 homolog A (DIP2A).	[9]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Disco-interacting protein 2 homolog A (DIP2A).	[11]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Disco-interacting protein 2 homolog A (DIP2A).	[12]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Disco-interacting protein 2 homolog A (DIP2A).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Disco-interacting protein 2 homolog A (DIP2A).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Disco-interacting protein 2 homolog A (DIP2A).	[13]

References

• [1] Fstl1/DIP2A/MGMT signaling pathway plays important roles in temozolomide resistance in glioblastoma.Oncogene. 2019 Apr;38(15):2706-2721. doi: 10.1038/s41388-018-0596-2. Epub 2018 Dec 12.
• [2] Note of Caution for the Aqueous Behaviour of Metal-Based Drug Candidates.ChemMedChem. 2020 Feb 17;15(4):345-348. doi: 10.1002/cmdc.201900677. Epub 2020 Jan 21.
• [3] Autism candidate gene DIP2A regulates spine morphogenesis via acetylation of cortactin.PLoS Biol. 2019 Oct 10;17(10):e3000461. doi: 10.1371/journal.pbio.3000461. eCollection 2019 Oct.
• [4] The biological effect of the nitroimidazole derivative of a polypyridyl ruthenium complex on cancer and endothelial cells.Metallomics. 2015 Mar;7(3):553-66. doi: 10.1039/c5mt00037h.
• [5] Blocking the FSTL1-DIP2A Axis Improves Anti-tumor Immunity.Cell Rep. 2018 Aug 14;24(7):1790-1801. doi: 10.1016/j.celrep.2018.07.043.
• [6] 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.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [9] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [10] 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.
• [11] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [12] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [13] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [14] 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.