Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0Q9OUQ)

• DOT Name: RING finger protein 112 (RNF112)
• Synonyms: EC 2.3.2.27; Brain finger protein; Zinc finger protein 179
• Gene Name: RNF112
• Related Disease:
  Tuberculosis
  Alzheimer disease
  Autoimmune disease
  Autoimmune haemolytic anaemia
  Autoimmune thrombocytopenia
  Glioma
  Idiopathic thrombocytopenic purpura
  Neoplasm
  Promyelocytic leukaemia
  Smith-Magenis syndrome
  Syphilis
  Thyroiditis
  Amyotrophic lateral sclerosis
  Intellectual disability
• UniProt ID: RN112_HUMAN
• EC Number: 2.3.2.27
• Pfam ID: PF02263 ; PF00097
• Sequence:
  MPRPALSVTSFCHRLGKRERKQSFMGNSGNSWSHTPFPKLELGLGPQPMAPRELPTCSIC
  LERLRDPISLDCGHDFCIRCFSTHRLPGCEPPCCPECRKICKQKRGLRSLGEKMKLLPQR
  PLPPALQETCPVRAEPLLLVRINASGGLILRMGAINRCLKHPLARDTPVCLLAVLGEQHS
  GKSFLLNHLLQGLPGLESGEGGRPRGGEASLQGCRWGANGLARGIWMWSHPFLLGKEGKK
  VAVFLVDTGDAMSPELSRETRIKLCALTTMLSSYQILSTSQELKDTDLDYLEMFVHVAEV
  MGKHYGMVPIQHLDLLVRDSSHPNKAGQGHVGNIFQRLSGRYPKVQELLQGKRARCCLLP
  APGRRRMNQGHASPGDTDDDFRHLLGAYVSDVLSAAPQHAKSRCQGYWNEGRAVARGDRR
  LLTGQQLAQEIKNLSGWMGRTGPGFTSPDEMAAQLHDLRKVEAAKREFEEYVRQQDVATK
  RIFSALRVLPDTMRNLLSTQKDAILARHGVALLCKGRDQTLEALEAELQATAKAFMDSYT
  MRFCGHLAAVGGAVGAGLMGLAGGVVGAGMAAAALAAEAGMVAAGAAVGATGAAVVGGGV
  GAGLAATVGCMEKEEDERLLEGDREPLLQEE
• Function: E3 ubiquitin-protein ligase that plays an important role in neuronal differentiation, including neurogenesis and gliogenesis, during brain development. During embryonic development initiates neuronal differentiation by inducing cell cycle arrest at the G0/G1 phase through up-regulation of cell-cycle regulatory proteins. Plays a role not only in the fetal period during the development of the nervous system, but also in the adult brain, where it is involved in the maintenance of neural functions and protection of the nervous tissue cells from oxidative stress-induced damage. Exhibits GTPase and E3 ubiquitin-protein ligase activities. Regulates dendritic spine density and synaptic neurotransmission; its ability to hydrolyze GTP is involved in the maintenance of dendritic spine density.
• Tissue Specificity: Predominantly expressed in brain . Decreased expression in glioma brain tumors as compared to normal brains (at protein level) .

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Tuberculosis	DIS2YIMD	Definitive	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[3]
Autoimmune haemolytic anaemia	DIS7MS3M	Strong	Biomarker	[3]
Autoimmune thrombocytopenia	DISNF0OI	Strong	Biomarker	[3]
Glioma	DIS5RPEH	Strong	Biomarker	[4]
Idiopathic thrombocytopenic purpura	DISFKGJU	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[3]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[2]
Smith-Magenis syndrome	DISG4G6X	Strong	Biomarker	[5]
Syphilis	DISJ73BS	Strong	Biomarker	[3]
Thyroiditis	DISTCV24	Strong	Biomarker	[3]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[6]
Intellectual disability	DISMBNXP	Limited	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of RING finger protein 112 (RNF112).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of RING finger protein 112 (RNF112).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of RING finger protein 112 (RNF112).	[9]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of RING finger protein 112 (RNF112).	[10]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of RING finger protein 112 (RNF112).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of RING finger protein 112 (RNF112).	[13]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of RING finger protein 112 (RNF112).	[14]

References

• [1] Effect of Brazil's conditional cash transfer programme on tuberculosis incidence.Int J Tuberc Lung Dis. 2017 Jul 1;21(7):790-796. doi: 10.5588/ijtld.16.0599.
• [2] Increase of zinc finger protein 179 in response to CCAAT/enhancer binding protein delta conferring an antiapoptotic effect in astrocytes of Alzheimer's disease.Mol Neurobiol. 2015 Feb;51(1):370-82. doi: 10.1007/s12035-014-8714-9. Epub 2014 May 1.
• [3] Biologic false-positive serologic tests for syphilis and other serologic abnormalities in autoimmune hemolytic anemia and thrombocytopenic purpura.Medicine (Baltimore). 1989 Mar;68(2):67-84. doi: 10.1097/00005792-198903000-00001.
• [4] Znf179 induces differentiation and growth arrest of human primary glioblastoma multiforme in a p53-dependent cell cycle pathway.Sci Rep. 2017 Jul 6;7(1):4787. doi: 10.1038/s41598-017-05305-0.
• [5] Molecular cloning, localization, and developmental expression of mouse brain finger protein (Bfp)/ZNF179: distribution of bfp mRNA partially coincides with the affected areas of Smith-Magenis syndrome.Genomics. 1998 Nov 15;54(1):59-69. doi: 10.1006/geno.1998.5541.
• [6] Znf179 E3 ligase-mediated TDP-43 polyubiquitination is involved in TDP-43- ubiquitinated inclusions (UBI) (+)-related neurodegenerative pathology.J Biomed Sci. 2018 Nov 8;25(1):76. doi: 10.1186/s12929-018-0479-4.
• [7] Cloning, genomic structure, and expression of mouse ring finger protein gene Znf179.Genomics. 1998 May 1;49(3):394-400. doi: 10.1006/geno.1998.5285.
• [8] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [9] 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.
• [10] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [11] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [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.
• [13] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [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.