Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTZ63A6)

• DOT Name: RAB6A-GEF complex partner protein 2 (RGP1)
• Synonyms: Retrograde Golgi transport protein RGP1 homolog
• Gene Name: RGP1
• UniProt ID: RGP1_HUMAN
• Pfam ID: PF08737
• Sequence:
  MIEVVAELSRGPVFLAGEALECVVTVTNPLPPTATSASSEALAWASAQIHCQFHASESRV
  ALPPPDSSQPDVQPDSQTVFLPHRGERGQCILSTPPKILFCDLRLDPGESKSYSYSEVLP
  IEGPPSFRGQSVKYVYKLTIGCQRVNSPITLLRVPLRVLVLTGLQDVRFPQDEAVAPSSP
  FLEEDEGGKKDSWLAELAGERLMAATSCRSLHLYNISDGRGKVGTFGIFKSVYRLGEDVV
  GTLNLGEGTVACLQFSVSLQTEERVQPEYQRRRGAGGVPSVSHVTHARHQESCLHTTRTS
  FSLPIPLSSTPGFCTAIVSLKWRLHFEFVTSREPGLVLLPPVEQPEPTTWTGPEQVPVDT
  FSWDLPIKVLPTSPTLASYAAPGPSTSTITI
• Function: The RIC1-RGP1 complex acts as a guanine nucleotide exchange factor (GEF), which activates RAB6A by exchanging bound GDP for free GTP and may thereby required for efficient fusion of endosome-derived vesicles with the Golgi compartment. The RIC1-RGP1 complex participates in the recycling of mannose-6-phosphate receptors.
• Reactome Pathway:
  Retrograde transport at the Trans-Golgi-Network (R-HSA-6811440)
  RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198)
  Intra-Golgi traffic (R-HSA-6811438)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	RAB6A-GEF complex partner protein 2 (RGP1) affects the response to substance of Temozolomide.	[6]
DTI-015	DMXZRW0	Approved	RAB6A-GEF complex partner protein 2 (RGP1) affects the response to substance of DTI-015.	[6]

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 RAB6A-GEF complex partner protein 2 (RGP1).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of RAB6A-GEF complex partner protein 2 (RGP1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of RAB6A-GEF complex partner protein 2 (RGP1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of RAB6A-GEF complex partner protein 2 (RGP1).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of RAB6A-GEF complex partner protein 2 (RGP1).	[5]

References

• [1] 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.
• [2] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [3] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] 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.
• [6] Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to O6-alkylating agents in human glioblastomas. J Clin Oncol. 2006 Jan 10;24(2):274-87. doi: 10.1200/JCO.2005.02.9405. Epub 2005 Dec 19.