Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB218WL)

• DOT Name: DENN domain-containing protein 2C (DENND2C)
• Gene Name: DENND2C
• UniProt ID: DEN2C_HUMAN
• Pfam ID: PF03455 ; PF02141 ; PF03456
• Sequence:
  MDVGFSRTTVQTLSRSHCKNIKQKISQWEGRANGISNPEKWCPKDFGVRYNCHQEIRLKK
  NPIAERKSKNLDVTSRENVGLDINENTKSHDQSENENKKHEYDDTHFFKNESESNWVCSR
  VKEIESCKEDVLDPETSLPPGNFYTSQILWKKIEALPPDKLLNLALEHCDSSEKELNFRV
  LDSSYGITKSLENIYSEPEGQECGPSINPLPKPRRTFRYLSESGVTPYKERNCDKKYCEN
  NSCAQSSLASSQEPEPKKYGGKIRGRSKRKSFEFEDIQHFRNRNSQTIREELGRNSGSAL
  YYTQSEDNIYEDIIYPTKENPYEDIPVQPLPMWRSPSAWKLPPAKSAFKAPKLPPKPQFL
  HRKTMEVKNSQAYLRSKLTKDTTLPVTLTEWKLFRAGEVANTKRKNLPRLVLKIDDIFES
  KRGKKKVKLHSYTGKELPPTKGETSGNESDAEYLPKNRHKRLAQLQPSSKRNPHYQTLER
  DLIELQEQQLFELFVVVSLQKKPSGISYIPQVIQQFPGKDDHGYKQSKDMEERLKVIPKF
  CFPDSKDWMPTSELKSETFSFVLTGEDGSRWFGYCKKLLPVGKGKRLPEVYCMVSRLGCF
  NLFSKILDEVEKRREMSPALVYPFMRSVMEAPFPAPGRTITVKSYLPGAGDESIELCRPL
  DSRLEHVDFKCLFKCLSVCHLIRVCASLLLERRVIFVANSLSTLSKCGHAVVATLYPFTW
  QHTYIPVLPASMIDIVCSPTPFLIGILSCSLPQLQDLPIEEVLIVDLCADKFLQEVSDED
  EILPPKLQAALMQILEERNEILTQEQNFSQDVTLNSLVSEAFVRFFVELVGHYSLNMTVT
  ERGERVFQREPFRKSHTSRSVRHFLDLFMETQMFAGFIQDRELRKSGVKGLFEIRAIQYL
  ETIPESEPSGMNRILRSLGSKMKFLQKK
• Function: Guanine nucleotide exchange factor (GEF) which may activate RAB9A and RAB9B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form.
• Reactome Pathway: RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of DENN domain-containing protein 2C (DENND2C).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DENN domain-containing protein 2C (DENND2C).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of DENN domain-containing protein 2C (DENND2C).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of DENN domain-containing protein 2C (DENND2C).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of DENN domain-containing protein 2C (DENND2C).	[6]
Marinol	DM70IK5	Approved	Marinol decreases the expression of DENN domain-containing protein 2C (DENND2C).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of DENN domain-containing protein 2C (DENND2C).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of DENN domain-containing protein 2C (DENND2C).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of DENN domain-containing protein 2C (DENND2C).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of DENN domain-containing protein 2C (DENND2C).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of DENN domain-containing protein 2C (DENND2C).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of DENN domain-containing protein 2C (DENND2C).	[13]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of DENN domain-containing protein 2C (DENND2C).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of DENN domain-containing protein 2C (DENND2C).	[5]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] 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.
• [7] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [11] 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.
• [12] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [13] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [14] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.