Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAFO4YR)

• DOT Name: Probable E3 ubiquitin-protein ligase makorin-3 (MKRN3)
• Synonyms: EC 2.3.2.27; RING finger protein 63; RING-type E3 ubiquitin transferase makorin-3; Zinc finger protein 127
• Gene Name: MKRN3
• Related Disease:
  Angelman syndrome
  Autism
  Central precocious puberty
  Maple syrup urine disease
  Prader-Willi syndrome
  Precocious puberty
  Precocious puberty, central, 2
  Smallpox
  Trichohepatoenteric syndrome
  Polycystic ovarian syndrome
• UniProt ID: MKRN3_HUMAN
• EC Number: 2.3.2.27
• Pfam ID: PF15815 ; PF00097 ; PF14608 ; PF18044
• Sequence:
  MEEPAAPSEAHEAAGAQAGAEAAREGVSGPDLPVCEPSGESAAPDSALPHAARGWAPFPV
  APVPAHLRRGGLRPAPASGGGAWPSPLPSRSSGIWTKQIICRYYIHGQCKEGENCRYSHD
  LSGRKMATEGGVSPPGASAGGGPSTAAHIEPPTQEVAEAPPAASSLSLPVIGSAAERGFF
  EAERDNADRGAAGGAGVESWADAIEFVPGQPYRGRWVASAPEAPLQSSETERKQMAVGSG
  LRFCYYASRGVCFRGESCMYLHGDICDMCGLQTLHPMDAAQREEHMRACIEAHEKDMELS
  FAVQRGMDKVCGICMEVVYEKANPNDRRFGILSNCNHSFCIRCIRRWRSARQFENRIVKS
  CPQCRVTSELVIPSEFWVEEEEEKQKLIQQYKEAMSNKACRYFAEGRGNCPFGDTCFYKH
  EYPEGWGDEPPGPGGGSFSAYWHQLVEPVRMGEGNMLYKSIKKELVVLRLASLLFKRFLS
  LRDELPFSEDQWDLLHYELEEYFNLIL
• Function: E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Angelman syndrome	DIS4QVXO	Strong	Genetic Variation	[1]
Autism	DISV4V1Z	Strong	Altered Expression	[2]
Central precocious puberty	DISW1TFK	Strong	Genetic Variation	[3]
Maple syrup urine disease	DIS61XRH	Strong	Genetic Variation	[4]
Prader-Willi syndrome	DISYWMLU	Strong	Genetic Variation	[5]
Precocious puberty	DISYI2XZ	Strong	Genetic Variation	[6]
Precocious puberty, central, 2	DISFW0QI	Strong	Autosomal dominant	[7]
Smallpox	DIS9EABZ	Strong	Biomarker	[8]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Genetic Variation	[9]
Polycystic ovarian syndrome	DISZ2BNG	moderate	Genetic Variation	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Urethane	DM7NSI0	Phase 4	Urethane affects the expression of Probable E3 ubiquitin-protein ligase makorin-3 (MKRN3).	[11]

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 decreases the methylation of Probable E3 ubiquitin-protein ligase makorin-3 (MKRN3).	[12]

References

• [1] DNA methylation patterns in human tissues of uniparental origin using a zinc-finger gene (ZNF127) from the Angelman/Prader-Willi region.Am J Med Genet. 1996 Jan 11;61(2):140-6. doi: 10.1002/(SICI)1096-8628(19960111)61:2<140::AID-AJMG7>3.0.CO;2-0.
• [2] Duplication of the 15q11-q13 region: clinical and genetic study of 30 new cases.Eur J Med Genet. 2014 Jan;57(1):5-14. doi: 10.1016/j.ejmg.2013.10.008. Epub 2013 Nov 12.
• [3] MKRN3 Interacts With Several Proteins Implicated in Puberty Timing but Does Not Influence GNRH1 Expression.Front Endocrinol (Lausanne). 2019 Feb 8;10:48. doi: 10.3389/fendo.2019.00048. eCollection 2019.
• [4] Application of droplet digital PCR in the analysis of genome integration and organization of the transgene in BAC transgenic mice.Sci Rep. 2018 Apr 27;8(1):6638. doi: 10.1038/s41598-018-25001-x.
• [5] A case of familial central precocious puberty caused by a novel mutation in the makorin RING finger protein 3 gene.BMC Endocr Disord. 2015 Oct 23;15:60. doi: 10.1186/s12902-015-0056-8.
• [6] Investigation of MKRN3 Mutation in Patients with Familial Central Precocious Puberty.J Clin Res Pediatr Endocrinol. 2018 Jul 31;10(3):223-229. doi: 10.4274/jcrpe.5506. Epub 2018 Feb 28.
• [7] 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.
• [8] A novel imprinted gene, encoding a RING zinc-finger protein, and overlapping antisense transcript in the Prader-Willi syndrome critical region.Hum Mol Genet. 1999 May;8(5):783-93. doi: 10.1093/hmg/8.5.783.
• [9] Exclusion mapping of the Cohen syndrome gene from the Prader-Willi syndrome locus.Clin Genet. 1990 Dec;38(6):422-6. doi: 10.1111/j.1399-0004.1990.tb03607.x.
• [10] Outcomes of Patients with Central Precocious Puberty Due to Loss-of-Function Mutations in the MKRN3 Gene after Treatment with Gonadotropin-Releasing Hormone Analog.Neuroendocrinology. 2020;110(7-8):705-713. doi: 10.1159/000504446. Epub 2019 Oct 31.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] 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.