Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7K9YZV)

• DOT Name: Gametogenetin-binding protein 2 (GGNBP2)
• Synonyms: Laryngeal carcinoma-related protein 1; Protein ZNF403
• Gene Name: GGNBP2
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Castration-resistant prostate carcinoma
  Chagas disease
  Epithelial ovarian cancer
  Estrogen-receptor positive breast cancer
  Glioma
  Intestinal cancer
  Laryngeal carcinoma
  Male infertility
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Triple negative breast cancer
  Neuroblastoma
  Amyotrophic lateral sclerosis
• UniProt ID: GGNB2_HUMAN
• PDB ID: 8BFJ
• Sequence:
  MARLVAVCRDGEEEFPFERRQIPLYIDDTLTMVMEFPDNVLNLDGHQNNGAQLKQFIQRH
  GMLKQQDLSIAMVVTSREVLSALSQLVPCVGCRRSVERLFSQLVESGNPALEPLTVGPKG
  VLSVTRSCMTDAKKLYTLFYVHGSKLNDMIDAIPKSKKNKRCQLHSLDTHKPKPLGGCWM
  DVWELMSQECRDEVVLIDSSCLLETLETYLRKHRFCTDCKNKVLRAYNILIGELDCSKEK
  GYCAALYEGLRCCPHERHIHVCCETDFIAHLLGRAEPEFAGGRRERHAKTIDIAQEEVLT
  CLGIHLYERLHRIWQKLRAEEQTWQMLFYLGVDALRKSFEMTVEKVQGISRLEQLCEEFS
  EEERVRELKQEKKRQKRKNRRKNKCVCDIPTPLQTADEKEVSQEKETDFIENSSCKACGS
  TEDGNTCVEVIVTNENTSCTCPSSGNLLGSPKIKKGLSPHCNGSDCGYSSSMEGSETGSR
  EGSDVACTEGICNHDEHGDDSCVHHCEDKEDDGDSCVECWANSEENDTKGKNKKKKKKSK
  ILKCDEHIQKLGSCITDPGNRETSGNTMHTVFHRDKTKDTHPESCCSSEKGGQPLPWFEH
  RKNVPQFAEPTETLFGPDSGKGAKSLVELLDESECTSDEEIFISQDEIQSFMANNQSFYS
  NREQYRQHLKEKFNKYCRLNDHKRPICSGWLTTAGAN
• Function: May be involved in spermatogenesis.
• Tissue Specificity: Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Expressed more abundantly in heart, pancreas and skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Castration-resistant prostate carcinoma	DISVGAE6	Strong	Altered Expression	[2]
Chagas disease	DIS8KNVF	Strong	Biomarker	[3]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[4]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Biomarker	[1]
Glioma	DIS5RPEH	Strong	Altered Expression	[5]
Intestinal cancer	DISYCNF1	Strong	Biomarker	[6]
Laryngeal carcinoma	DISNHCIV	Strong	Altered Expression	[7]
Male infertility	DISY3YZZ	Strong	Genetic Variation	[8]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[4]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[4]
Prostate cancer	DISF190Y	Strong	Biomarker	[2]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[2]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[1]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[9]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Genetic Variation	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Gametogenetin-binding protein 2 (GGNBP2).	[11]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Gametogenetin-binding protein 2 (GGNBP2).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Gametogenetin-binding protein 2 (GGNBP2).	[13]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Gametogenetin-binding protein 2 (GGNBP2).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Gametogenetin-binding protein 2 (GGNBP2).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Gametogenetin-binding protein 2 (GGNBP2).	[15]

References

• [1] GGNBP2 suppresses triple-negative breast cancer aggressiveness through inhibition of IL-6/STAT3 signaling activation.Breast Cancer Res Treat. 2019 Feb;174(1):65-78. doi: 10.1007/s10549-018-5052-z. Epub 2018 Nov 19.
• [2] Effects of gametogenetin-binding protein 2 on proliferation, invasion and migration of prostate cancer PC-3 cells.Andrologia. 2020 Mar;52(2):e13488. doi: 10.1111/and.13488. Epub 2019 Dec 3.
• [3] Biological Activities of Novel Derivatives of Differentiation-Inducing Factor 3 from Dictyostelium discoideum.Biol Pharm Bull. 2017;40(11):1941-1947. doi: 10.1248/bpb.b17-00484.
• [4] ZFP403, a novel tumor suppressor, inhibits the proliferation and metastasis in ovarian cancer.Gynecol Oncol. 2017 Nov;147(2):418-425. doi: 10.1016/j.ygyno.2017.08.025. Epub 2017 Aug 31.
• [5] GGNBP2 Suppresses the Proliferation, Invasion, and Migration of Human Glioma Cells.Oncol Res. 2017 May 24;25(5):831-842. doi: 10.3727/096504016X14816726393937. Epub 2016 Dec 15.
• [6] Differentiation-inducing factor-3 inhibits intestinal tumor growth invitro and invivo.J Pharmacol Sci. 2015 Apr;127(4):446-55. doi: 10.1016/j.jphs.2015.03.005. Epub 2015 Mar 24.
• [7] Molecular cloning and characterization of LCRG1 a novel gene localized to the tumor suppressor locus D17S800-D17S930.Cancer Lett. 2004 Jun 8;209(1):75-85. doi: 10.1016/j.canlet.2003.11.034.
• [8] Ggnbp2-Null Mutation in Mice Leads to Male Infertility due to a Defect at the Spermiogenesis Stage.Am J Pathol. 2017 Nov;187(11):2508-2519. doi: 10.1016/j.ajpath.2017.07.016. Epub 2017 Aug 18.
• [9] Isolation, tissue expression, and chromosomal assignment of a novel human gene which encodes a protein with RING finger motif.J Hum Genet. 1998;43(4):272-4. doi: 10.1007/s100380050088.
• [10] A Genome-wide Expression Association Analysis Identifies Genes and Pathways Associated with Amyotrophic Lateral Sclerosis.Cell Mol Neurobiol. 2018 Apr;38(3):635-639. doi: 10.1007/s10571-017-0512-2. Epub 2017 Jun 21.
• [11] 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.
• [12] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [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] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.