Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDOE6U8)

• DOT Name: GRIP and coiled-coil domain-containing protein 1 (GCC1)
• Synonyms: Golgi coiled-coil protein 1
• Gene Name: GCC1
• Related Disease:
  Cocaine addiction
  Non-insulin dependent diabetes
  Head-neck squamous cell carcinoma
• UniProt ID: GCC1_HUMAN
• Pfam ID: PF01465
• Sequence:
  MEKFGMNFGGGPSKKDLLETIETQKKQLLQYQARLKDVVRAYKSLLKEKEALEASIKVLS
  VSHEADVGLAGVQLPGLTFPDSVDDRCSTHSEDSTGTATSLDTAASLTSTKGEFGVEDDR
  PARGPPPPKSEEASWSESGVSSSSGDGPFAGGEVDKRLHQLKTQLATLTSSLATVTQEKS
  RMEASYLADKKKMKQDLEDASNKAEEERARLEGELKGLQEQIAETKARLITQQHDRAQEQ
  SDHALMLRELQKLLQEERTQRQDLELRLEETREALAGRAYAAEQMEGFELQTKQLTREVE
  ELKSELQAIRDEKNQPDPRLQELQEEAARLKSHFQAQLQQEMRKTALAEDQLRQQSQVEE
  QRVAALENQISEVSELLGTYEKAKQKDQLAIQKLKERILQLDLENKTLALAASSRSPLDS
  HGEESSLDVNVLKDKMEKLKRLLQVAARKSQVTLDVEKLCDLEIMPSSEAADGEKATALY
  YQQELKQLKEEFERYKMRAQVVLKSKNTKDGNLGKELEAAQEQLAELKEKYISLRLSCEE
  LEHQHQQEADDWKQELARLQQLHRQELERCQLDFRDRTLKLEEELHKQRDRALAVLTEKD
  LELEQLRSVALASGLPGRRSPVGGGGPGDPADTSSSDSLTQALQLAAANEPTFFLYAEQL
  ARKEVEITSLRKQKHRLEVEVHQLQDRLLEEGERHREEVAALQSHIEKNIRDQSREGANL
  EYLKNIIYRFLTLPDSLGRQQTLTAILTILHFSPEEKQVIMRLPTSASWWPSGKR
• Function: Probably involved in maintaining Golgi structure.
• Reactome Pathway: Retrograde transport at the Trans-Golgi-Network (R-HSA-6811440)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cocaine addiction	DISHTRXG	Strong	Biomarker	[1]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[2]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of GRIP and coiled-coil domain-containing protein 1 (GCC1).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of GRIP and coiled-coil domain-containing protein 1 (GCC1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of GRIP and coiled-coil domain-containing protein 1 (GCC1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of GRIP and coiled-coil domain-containing protein 1 (GCC1).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of GRIP and coiled-coil domain-containing protein 1 (GCC1).	[8]
Cocaine	DMSOX7I	Approved	Cocaine increases the expression of GRIP and coiled-coil domain-containing protein 1 (GCC1).	[1]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of GRIP and coiled-coil domain-containing protein 1 (GCC1).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of GRIP and coiled-coil domain-containing protein 1 (GCC1).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of GRIP and coiled-coil domain-containing protein 1 (GCC1).	[13]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of GRIP and coiled-coil domain-containing protein 1 (GCC1).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of GRIP and coiled-coil domain-containing protein 1 (GCC1).	[12]

References

• [1] Transcriptional changes common to human cocaine, cannabis and phencyclidine abuse. PLoS One. 2006 Dec 27;1(1):e114. doi: 10.1371/journal.pone.0000114.
• [2] Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.Nat Genet. 2011 Dec 11;44(1):67-72. doi: 10.1038/ng.1019.
• [3] Integration of high-risk human papillomavirus into cellular cancer-related genes in head and neck cancer cell lines.Head Neck. 2017 May;39(5):840-852. doi: 10.1002/hed.24729. Epub 2017 Feb 25.
• [4] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] 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.
• [8] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [9] Transcriptional changes common to human cocaine, cannabis and phencyclidine abuse. PLoS One. 2006 Dec 27;1(1):e114. doi: 10.1371/journal.pone.0000114.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [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] 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.