Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDAORW4)

• DOT Name: Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit C (ANKRD52)
• Synonyms: PP6-ARS-C; Serine/threonine-protein phosphatase 6 regulatory subunit ARS-C; Ankyrin repeat domain-containing protein 52
• Gene Name: ANKRD52
• Related Disease:
  Bladder cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: ANR52_HUMAN
• Pfam ID: PF00023 ; PF12796 ; PF13637
• Sequence:
  MGILSITDQPPLVQAIFSRDVEEVRSLLSQKENINVLDQERRTPLHAAAYVGDVPILQLL
  LMSGANVNAKDTLWLTPLHRAAASRNEKVLGLLLAHSADVNARDKLWQTPLHVAAANRAT
  KCAEALAPLLSSLNVADRSGRSALHHAVHSGHLETVNLLLNKGASLNVCDKKERQPLHWA
  AFLGHLEVLKLLVARGADLGCKDRKGYGLLHTAAASGQIEVVKYLLRMGAEIDEPNAFGN
  TALHIACYLGQDAVAIELVNAGANVNQPNDKGFTPLHVAAVSTNGALCLELLVNNGADVN
  YQSKEGKSPLHMAAIHGRFTRSQILIQNGSEIDCADKFGNTPLHVAARYGHELLISTLMT
  NGADTARRGIHDMFPLHLAVLFGFSDCCRKLLSSGQLYSIVSSLSNEHVLSAGFDINTPD
  NLGRTCLHAAASGGNVECLNLLLSSGADLRRRDKFGRTPLHYAAANGSYQCAVTLVTAGA
  GVNEADCKGCSPLHYAAASDTYRRAEPHTPSSHDAEEDEPLKESRRKEAFFCLEFLLDNG
  ADPSLRDRQGYTAVHYAAAYGNRQNLELLLEMSFNCLEDVESTIPVSPLHLAAYNGHCEA
  LKTLAETLVNLDVRDHKGRTALFLATERGSTECVEVLTAHGASALIKERKRKWTPLHAAA
  ASGHTDSLHLLIDSGERADITDVMDAYGQTPLMLAIMNGHVDCVHLLLEKGSTADAADLR
  GRTALHRGAVTGCEDCLAALLDHDAFVLCRDFKGRTPIHLASACGHTAVLRTLLQAALST
  DPLDAGVDYSGYSPMHWASYTGHEDCLELLLEHSPFSYLEGNPFTPLHCAVINNQDSTTE
  MLLGALGAKIVNSRDAKGRTPLHAAAFADNVSGLRMLLQHQAEVNATDHTGRTALMTAAE
  NGQTAAVEFLLYRGKADLTVLDENKNTALHLACSKGHEKCALMILAETQDLGLINATNSA
  LQMPLHIAARNGLASVVQALLSHGATVLAVDEEGHTPALACAPNKDVADCLALILSTMKP
  FPPKDAVSPFSFSLLKNCSIAAAKTVGGCGALPHGASCPYSQERPGAIGLDGCYSE
• Function: Putative regulatory subunit of protein phosphatase 6 (PP6) that may be involved in the recognition of phosphoprotein substrates.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder cancer	DISUHNM0	Strong	Biomarker	[1]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[1]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit C (ANKRD52).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit C (ANKRD52).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit C (ANKRD52).	[4]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit C (ANKRD52).	[6]

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 Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit C (ANKRD52).	[5]

References

• [1] Cross-species analysis of the canine and human bladder cancer transcriptome and exome.Genes Chromosomes Cancer. 2017 Apr;56(4):328-343. doi: 10.1002/gcc.22441. Epub 2017 Jan 25.
• [2] 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.
• [3] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [4] 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.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.