Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYL5HK1)

• DOT Name: Microtubule cross-linking factor 2 (MTCL2)
• Synonyms: SOGA family member 1; Suppressor of glucose by autophagy; Suppressor of glucose, autophagy-associated protein 1
• Gene Name: MTCL2
• UniProt ID: MTCL2_HUMAN
• Pfam ID: PF14818 ; PF11365
• Sequence:
  MEAPAAEPPVRGCGPQPAPAPAPAPERKKSHRAPSPARPKDVAGWSLAKGRRGPGPGSAV
  ACSAAFSSRPDKKGRAVAPGARGAGVRVAGVRTGVRAKGRPRSGAGPRPPPPPPSLTDSS
  SEVSDCASEEARLLGLELALSSDAESAAGGPAGVRTGQPAQPAPSAQQPPRPPASPDEPS
  VAASSVGSSRLPLSASLAFSDLTEEMLDCGPSGLVRELEELRSENDYLKDEIEELRAEML
  EMRDVYMEEDVYQLQELRQQLDQASKTCRILQYRLRKAERRSLRAAQTGQVDGELIRGLE
  QDVKVSKDISMRLHKELEVVEKKRARLEEENEELRQRLIETELAKQVLQTELERPREHSL
  KKRGTRSLGKADKKTLVQEDSADLKCQLHFAKEESALMCKKLTKLAKENDSMKEELLKYR
  SLYGDLDSALSAEELADAPHSRETELKVHLKLVEEEANLLSRRIVELEVENRGLRAEMDD
  MKDHGGGCGGPEARLAFSALGGGECGESLAELRRHLQFVEEEAELLRRSSAELEDQNKLL
  LNELAKFRSEHELDVALSEDSCSVLSEPSQEELAAAKLQIGELSGKVKKLQYENRVLLSN
  LQRCDLASCQSTRPMLETDAEAGDSAQCVPAPLGETHESHAVRLCRAREAEVLPGLREQA
  ALVSKAIDVLVADANGFTAGLRLCLDNECADFRLHEAPDNSEGPRDTKLIHAILVRLSVL
  QQELNAFTRKADAVLGCSVKEQQESFSSLPPLGSQGLSKEILLAKDLGSDFQPPDFRDLP
  EWEPRIREAFRTGDLDSKPDPSRSFRPYRAEDNDSYASEIKELQLVLAEAHDSLRGLQEQ
  LSQERQLRKEEADNFNQKMVQLKEDQQRALLRREFELQSLSLQRRLEQKFWSQEKNMLVQ
  ESQQFKHNFLLLFMKLRWFLKRWRQGKVLPSEGDDFLEVNSMKELYLLMEEEEINAQHSD
  NKACTGDSWTQNTPNEYIKTLADMKVTLKELCWLLRDERRGLTELQQQFAKAKATWETER
  AELKGHTSQMELKTGKGAGERAGPDWKAALQREREEQQHLLAESYSAVMELTRQLQISER
  NWSQEKLQLVERLQGEKQQVEQQVKELQNRLSQLQKAADPWVLKHSELEKQDNSWKETRS
  EKIHDKEAVSEVELGGNGLKRTKSVSSMSEFESLLDCSPYLAGGDARGKKLPNNPAFGFV
  SSEPGDPEKDTKEKPGLSSRDCNHLGALACQDPPGRQMQRSYTAPDKTGIRVYYSPPVAR
  RLGVPVVHDKEGKIIIEPGFLFTTAKPKESAEADGLAESSYGRWLCNFSRQRLDGGSAGS
  PSAAGPGFPAALHDFEMSGNMSDDMKEITNCVRQAMRSGSLERKVKSTSSQTVGLASVGT
  QTIRTVSVGLQTDPPRSSLHGKAWSPRSSSLVSVRSKQISSSLDKVHSRIERPCCSPKYG
  SPKLQRRSVSKLDSSKDRSLWNLHQGKQNGSAWARSTTTRDSPVLRNINDGLSSLFSVVE
  HSGSTESVWKLGMSETRAKPEPPKYGIVQEFFRNVCGRAPSPTSSAGEEGTKKPEPLSPA
  SYHQPEGVARILNKKAAKLGSSEEVRLTMLPQVGKDGVLRDGDGAVVLPNEDAVCDCSTQ
  SLTSCFARSSRSAIRHSPSKCRLHPSESSWGGEERALPPSE
• Function: Microtubule-associated factor that enables integration of the centrosomal and Golgi-associated microtubules on the Golgi membrane, supporting directional migration. Preferentially acts on the perinuclear microtubules accumulated around the Golgi. Associates with the Golgi membrane through the N-terminal coiled-coil region and directly binds microtubules through the C-terminal domain. Required for faithful chromosome segregation during mitosis. Regulates autophagy by playing a role in the reduction of glucose production in an adiponectin- and insulin-dependent manner.

Molecular Interaction Atlas (MIA) of This DOT

4 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 Microtubule cross-linking factor 2 (MTCL2).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Microtubule cross-linking factor 2 (MTCL2).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Microtubule cross-linking factor 2 (MTCL2).	[8]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Microtubule cross-linking factor 2 (MTCL2).	[10]

8 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 Microtubule cross-linking factor 2 (MTCL2).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Microtubule cross-linking factor 2 (MTCL2).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Microtubule cross-linking factor 2 (MTCL2).	[4]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Microtubule cross-linking factor 2 (MTCL2).	[6]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Microtubule cross-linking factor 2 (MTCL2).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Microtubule cross-linking factor 2 (MTCL2).	[9]
UNC0379	DMD1E4J	Preclinical	UNC0379 decreases the expression of Microtubule cross-linking factor 2 (MTCL2).	[11]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of Microtubule cross-linking factor 2 (MTCL2).	[12]

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] 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.
• [3] 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.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [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] Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
• [7] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Epigenetic siRNA and chemical screens identify SETD8 inhibition as a therapeutic strategy for p53 activation in high-risk neuroblastoma. Cancer Cell. 2017 Jan 9;31(1):50-63.
• [12] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.