Details of Drug Off-Target (DOT)

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

• DOT Name: Cell growth regulator with RING finger domain protein 1 (CGRRF1)
• Synonyms: Cell growth regulatory gene 19 protein; RING finger protein 197
• Gene Name: CGRRF1
• Related Disease:
  Breast cancer
  Breast carcinoma
  Endometrial cancer
  Endometrial carcinoma
  Neoplasm
  Obesity
  Age-related macular degeneration
• UniProt ID: CGRF1_HUMAN
• PDB ID: 2EA5
• Pfam ID: PF13920
• Sequence:
  MAAVFLVTLYEYSPLFYIAVVFTCFIVTTGLVLGWFGWDVPVILRNSEETQFSTRVFKKQ
  MRQVKNPFGLEITNPSSASITTGITLTTDCLEDSLLTCYWGCSVQKLYEALQKHVYCFRI
  STPQALEDALYSEYLYQEQYFIKKDSKEEIYCQLPRDTKIEDFGTVPRSRYPLVALLTLA
  DEDDREIYDIISMVSVIHIPDRTYKLSCRILYQYLLLAQGQFHDLKQLFMSANNNFTPSN
  NSSSEEKNTDRSLLEKVGLSESEVEPSEENSKDCVVCQNGTVNWVLLPCRHTCLCDGCVK
  YFQQCPMCRQFVQESFALCSQKEQDKDKPKTL
• Function: Able to inhibit growth in several cell lines.
• Tissue Specificity: Ubiquitously expressed with high expression in testis and the cerebellum.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Endometrial cancer	DISW0LMR	Strong	Altered Expression	[2]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Obesity	DIS47Y1K	Strong	Biomarker	[2]
Age-related macular degeneration	DIS0XS2C	moderate	Genetic Variation	[3]

1 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 Cell growth regulator with RING finger domain protein 1 (CGRRF1).	[4]

8 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 Cell growth regulator with RING finger domain protein 1 (CGRRF1).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cell growth regulator with RING finger domain protein 1 (CGRRF1).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Cell growth regulator with RING finger domain protein 1 (CGRRF1).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Cell growth regulator with RING finger domain protein 1 (CGRRF1).	[8]
Gefitinib	DM15F0X	Approved	Gefitinib increases the expression of Cell growth regulator with RING finger domain protein 1 (CGRRF1).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Cell growth regulator with RING finger domain protein 1 (CGRRF1).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Cell growth regulator with RING finger domain protein 1 (CGRRF1).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Cell growth regulator with RING finger domain protein 1 (CGRRF1).	[12]

References

• [1] CGRRF1, a growth suppressor, regulates EGFR ubiquitination in breast cancer.Breast Cancer Res. 2019 Dec 4;21(1):134. doi: 10.1186/s13058-019-1212-2.
• [2] CGRRF1 as a novel biomarker of tissue response to metformin in the context of obesity.Gynecol Oncol. 2014 Apr;133(1):83-9. doi: 10.1016/j.ygyno.2013.12.006.
• [3] Rare variants and loci for age-related macular degeneration in the Ohio and Indiana Amish.Hum Genet. 2019 Oct;138(10):1171-1182. doi: 10.1007/s00439-019-02050-4. Epub 2019 Jul 31.
• [4] 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.
• [5] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [6] 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.
• [7] 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.
• [8] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [9] Identification of genes linked to gefitinib treatment in prostate cancer cell lines with or without resistance to androgen: a clue to application of gefitinib to hormone-resistant prostate cancer. Oncol Rep. 2006 Jun;15(6):1453-60.
• [10] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [11] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.