Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY8RFVW)

• DOT Name: Serine/threonine-protein kinase MRCK gamma (CDC42BPG)
• Synonyms: EC 2.7.11.1; CDC42-binding protein kinase gamma; DMPK-like gamma; Myotonic dystrophy kinase-related CDC42-binding kinase gamma; MRCK gamma; MRCKG; Myotonic dystrophy protein kinase-like gamma; Myotonic dystrophy protein kinase-like alpha
• Gene Name: CDC42BPG
• Related Disease: Membranous glomerulonephritis
• UniProt ID: MRCKG_HUMAN
• EC Number: 2.7.11.1
• Pfam ID: PF00130 ; PF00780 ; PF08826 ; PF00069 ; PF00433
• Sequence:
  MERRLRALEQLARGEAGGCPGLDGLLDLLLALHHELSSGPLRRERSVAQFLSWASPFVSK
  VKELRLQRDDFEILKVIGRGAFGEVTVVRQRDTGQIFAMKMLHKWEMLKRAETACFREER
  DVLVKGDSRWVTTLHYAFQDEEYLYLVMDYYAGGDLLTLLSRFEDRLPPELAQFYLAEMV
  LAIHSLHQLGYVHRDVKPDNVLLDVNGHIRLADFGSCLRLNTNGMVDSSVAVGTPDYISP
  EILQAMEEGKGHYGPQCDWWSLGVCAYELLFGETPFYAESLVETYGKIMNHEDHLQFPPD
  VPDVPASAQDLIRQLLCRQEERLGRGGLDDFRNHPFFEGVDWERLASSTAPYIPELRGPM
  DTSNFDVDDDTLNHPGTLPPPSHGAFSGHHLPFVGFTYTSGSHSPESSSEAWAALERKLQ
  CLEQEKVELSRKHQEALHAPTDHRELEQLRKEVQTLRDRLPEMLRDKASLSQTDGPPAGS
  PGQDSDLRQELDRLHRELAEGRAGLQAQEQELCRAQGQQEELLQRLQEAQEREAATASQT
  RALSSQLEEARAAQRELEAQVSSLSRQVTQLQGQWEQRLEESSQAKTIHTASETNGMGPP
  EGGPQEAQLRKEVAALREQLEQAHSHRPSGKEEALCQLQEENRRLSREQERLEAELAQEQ
  ESKQRLEGERRETESNWEAQLADILSWVNDEKVSRGYLQALATKMAEELESLRNVGTQTL
  PARPLDHQWKARRLQKMEASARLELQSALEAEIRAKQGLQERLTQVQEAQLQAERRLQEA
  EKQSQALQQELAMLREELRARGPVDTKPSNSLIPFLSFRSSEKDSAKDPGISGEATRHGG
  EPDLRPEGRRSLRMGAVFPRAPTANTASTEGLPAKPGSHTLRPRSFPSPTKCLRCTSLML
  GLGRQGLGCDACGYFCHTTCAPQAPPCPVPPDLLRTALGVHPETGTGTAYEGFLSVPRPS
  GVRRGWQRVFAALSDSRLLLFDAPDLRLSPPSGALLQVLDLRDPQFSATPVLASDVIHAQ
  SRDLPRIFRVTTSQLAVPPTTCTVLLLAESEGERERWLQVLGELQRLLLDARPRPRPVYT
  LKEAYDNGLPLLPHTLCAAILDQDRLALGTEEGLFVIHLRSNDIFQVGECRRVQQLTLSP
  SAGLLVVLCGRGPSVRLFALAELENIEVAGAKIPESRGCQVLAAGSILQARTPVLCVAVK
  RQVLCYQLGPGPGPWQRRIRELQAPATVQSLGLLGDRLCVGAAGGFALYPLLNEAAPLAL
  GAGLVPEELPPSRGGLGEALGAVELSLSEFLLLFTTAGIYVDGAGRKSRGHELLWPAAPM
  GWGYAAPYLTVFSENSIDVFDVRRAEWVQTVPLKKVRPLNPEGSLFLYGTEKVRLTYLRN
  QLAEKDEFDIPDLTDNSRRQLFRTKSKRRFFFRVSEEQQKQQRREMLKDPFVRSKLISPP
  TNFNHLVHVGPANGRPGARDKSPAPEEKGRVARGSGPQRPHSFSEALRRPASMGSEGLGG
  DADPMKRKPWTSLSSESVSCPQGSLSPATSLMQVSERPRSLPLSPELESSP
• Function: May act as a downstream effector of CDC42 in cytoskeletal reorganization. Contributes to the actomyosin contractility required for cell invasion, through the regulation of MYPT1 and thus MLC2 phosphorylation.
• Tissue Specificity: Expressed in heart and skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Membranous glomerulonephritis	DISFSUKQ	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Serine/threonine-protein kinase MRCK gamma (CDC42BPG).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Serine/threonine-protein kinase MRCK gamma (CDC42BPG).	[6]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Serine/threonine-protein kinase MRCK gamma (CDC42BPG).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Serine/threonine-protein kinase MRCK gamma (CDC42BPG).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Serine/threonine-protein kinase MRCK gamma (CDC42BPG).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Serine/threonine-protein kinase MRCK gamma (CDC42BPG).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Serine/threonine-protein kinase MRCK gamma (CDC42BPG).	[7]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Serine/threonine-protein kinase MRCK gamma (CDC42BPG).	[9]

References

• [1] The putative role of MALDI-MSI in the study of Membranous Nephropathy.Biochim Biophys Acta Proteins Proteom. 2017 Jul;1865(7):865-874. doi: 10.1016/j.bbapap.2016.11.013. Epub 2016 Nov 24.
• [2] 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.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] 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.
• [7] 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.
• [8] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [9] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.