Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT5I9FM)

• DOT Name: GRIP and coiled-coil domain-containing protein 2 (GCC2)
• Synonyms: 185 kDa Golgi coiled-coil protein; GCC185; CLL-associated antigen KW-11; CTCL tumor antigen se1-1; Ran-binding protein 2-like 4; RanBP2L4; Renal carcinoma antigen NY-REN-53
• Gene Name: GCC2
• Related Disease:
  Chronic eosinophilic leukemia
  Lung adenocarcinoma
• UniProt ID: GCC2_HUMAN
• PDB ID: 3BBP
• Pfam ID: PF01465 ; PF16704
• Sequence:
  MEDLVQDGVASPATPGTGKSKLETLPKEDLIKFAKKQMMLIQKAKSRCTELEKEIEELRS
  KPVTEGTGDIIKALTERLDALLLEKAETEQQCLSLKKENIKMKQEVEDSVTKMGDAHKEL
  EQSHINYVKEIENLKNELMAVRSKYSEDKANLQKQLEEAMNTQLELSEQLKFQNNSEDNV
  KKLQEEIEKIRPGFEEQILYLQKQLDATTDEKKETVTQLQNIIEANSQHYQKNINSLQEE
  LLQLKAIHQEEVKELMCQIEASAKEHEAEINKLNELKENLVKQCEASEKNIQKKYECELE
  NLRKATSNANQDNQICSILLQENTFVEQVVNEKVKHLEDTLKELESQHSILKDEVTYMNN
  LKLKLEMDAQHIKDEFFHEREDLEFKINELLLAKEEQGCVIEKLKSELAGLNKQFCYTVE
  QHNREVQSLKEQHQKEISELNETFLSDSEKEKLTLMFEIQGLKEQCENLQQEKQEAILNY
  ESLREIMEILQTELGESAGKISQEFESMKQQQASDVHELQQKLRTAFTEKDALLETVNRL
  QGENEKLLSQQELVPELENTIKNLQEKNGVYLLSLSQRDTMLKELEGKINSLTEEKDDFI
  NKLKNSHEEMDNFHKKCEREERLILELGKKVEQTIQYNSELEQKVNELTGGLEETLKEKD
  QNDQKLEKLMVQMKVLSEDKEVLSAEVKSLYEENNKLSSEKKQLSRDLEVFLSQKEDVIL
  KEHITQLEKKLQLMVEEQDNLNKLLENEQVQKLFVKTQLYGFLKEMGSEVSEDSEEKDVV
  NVLQAVGESLAKINEEKCNLAFQRDEKVLELEKEIKCLQEESVVQCEELKSLLRDYEQEK
  VLLRKELEEIQSEKEALQSDLLEMKNANEKTRLENQNLLIQVEEVSQTCSKSEIHNEKEK
  CFIKEHENLKPLLEQKELRDRRAELILLKDSLAKSPSVKNDPLSSVKELEEKIENLEKEC
  KEKEEKINKIKLVAVKAKKELDSSRKETQTVKEELESLRSEKDQLSASMRDLIQGAESYK
  NLLLEYEKQSEQLDVEKERANNFEHRIEDLTRQLRNSTLQCETINSDNEDLLARIETLQS
  NAKLLEVQILEVQRAKAMVDKELEAEKLQKEQKIKEHATTVNELEELQVQLQKQKKQLQK
  TMQELELVKKDAQQTTLMNMEIADYERLMKELNQKLTNKNNKIEDLEQEIKIQKQKQETL
  QEEITSLQSSVQQYEEKNTKIKQLLVKTKKELADSKQAETDHLILQASLKGELEASQQQV
  EVYKIQLAEITSEKHKIHEHLKTSAEQHQRTLSAYQQRVTALQEECRAAKAEQATVTSEF
  ESYKVRVHNVLKQQKNKSMSQAETEGAKQEREHLEMLIDQLKIKLQDSQNNLQINVSELQ
  TLQSEHDTLLERHNKMLQETVSKEAELREKLCSIQSENMMMKSEHTQTVSQLTSQNEVLR
  NSFRDQVRHLQEEHRKTVETLQQQLSKMEAQLFQLKNEPTTRSPVSSQQSLKNLRERRNT
  DLPLLDMHTVTREEGEGMETTDTESVSSASTYTQSLEQLLNSPETKLEPPLWHAEFTKEE
  LVQKLSSTTKSADHLNGLLRETEATNAILMEQIKLLKSEIRRLERNQEREKSAANLEYLK
  NVLLQFIFLKPGSERERLLPVINTMLQLSPEEKGKLAAVAQGEEENASRSSGWASYLHSW
  SGLR
• Function: Golgin which probably tethers transport vesicles to the trans-Golgi network (TGN) and regulates vesicular transport between the endosomes and the Golgi. As a RAB9A effector it is involved in recycling of the mannose 6-phosphate receptor from the late endosomes to the TGN. May also play a role in transport between the recycling endosomes and the Golgi. Required for maintenance of the Golgi structure, it is involved in the biogenesis of noncentrosomal, Golgi-associated microtubules through recruitment of CLASP1 and CLASP2.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway: Salmonella infection (hsa05132)
• Reactome Pathway:
  Signaling by ALK fusions and activated point mutants (R-HSA-9725370)
  Retrograde transport at the Trans-Golgi-Network (R-HSA-6811440)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic eosinophilic leukemia	DISAJOUO	Strong	Biomarker	[1]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of GRIP and coiled-coil domain-containing protein 2 (GCC2).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of GRIP and coiled-coil domain-containing protein 2 (GCC2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of GRIP and coiled-coil domain-containing protein 2 (GCC2).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of GRIP and coiled-coil domain-containing protein 2 (GCC2).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of GRIP and coiled-coil domain-containing protein 2 (GCC2).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of GRIP and coiled-coil domain-containing protein 2 (GCC2).	[8]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of GRIP and coiled-coil domain-containing protein 2 (GCC2).	[9]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of GRIP and coiled-coil domain-containing protein 2 (GCC2).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of GRIP and coiled-coil domain-containing protein 2 (GCC2).	[12]

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 increases the methylation of GRIP and coiled-coil domain-containing protein 2 (GCC2).	[11]

References

• [1] A novel fusion gene involving PDGFRB and GCC2 in a chronic eosinophilic leukemia patient harboring t(2;5)(q37;q31).Mol Genet Genomic Med. 2019 Apr;7(4):e00591. doi: 10.1002/mgg3.591. Epub 2019 Jan 29.
• [2] GCC2-ALK as a targetable fusion in lung adenocarcinoma and its enduring clinical responses to ALK inhibitors.Lung Cancer. 2018 Jan;115:5-11. doi: 10.1016/j.lungcan.2017.10.011. Epub 2017 Oct 27.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [9] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [10] Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
• [11] 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.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.