Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY9ZKHE)

• DOT Name: Microtubule cross-linking factor 1 (MTCL1)
• Synonyms: Coiled-coil domain-containing protein 165; PAR-1-interacting protein; SOGA family member 2
• Gene Name: MTCL1
• Related Disease:
  Cerebellar ataxia
  Chronic obstructive pulmonary disease
• UniProt ID: MTCL1_HUMAN
• Pfam ID: PF14818 ; PF11365
• Sequence:
  METLNGPAGGGAPDAKLQPPGQHHRHHHLHPVAERRRLHRAPSPARPFLKDLHARPAAPG
  PAVPSSGRAPAPAAPRSPNLAGKAPPSPGSLAAPGRLSRRSGGVPGAKDKPPPGAGARAA
  GGAKAALGSRRAARVAPAEPLSRAGKPPGAEPPSAAAKGRKAKRGSRAPPARTVGPPTPA
  ARIPAVTLAVTSVAGSPARCSRISHTDSSSDLSDCPSEPLSDEQRLLPAASSDAESGTGS
  SDREPPRGAPTPSPAARGAPPGSPEPPALLAAPLAAGACPGGRSIPSGVSGGFAGPGVAE
  DVRGRSPPERPVPGTPKEPSLGEQSRLVPAAEEEELLREMEELRSENDYLKDELDELRAE
  MEEMRDSYLEEDVYQLQELRRELDRANKNCRILQYRLRKAEQKSLKVAETGQVDGELIRS
  LEQDLKVAKDVSVRLHHELKTVEEKRAKAEDENETLRQQMIEVEISKQALQNELERLKES
  SLKRRSTREMYKEKKTFNQDDSADLRCQLQFAKEEAFLMRKKMAKLGREKDELEQELQKY
  KSLYGDVDSPLPTGEAGGPPSTREAELKLRLKLVEEEANILGRKIVELEVENRGLKAEME
  DMRGQQEREGPGRDHAPSIPTSPFGDSLESSTELRRHLQFVEEEAELLRRSISEIEDHNR
  QLTHELSKFKFEPPREPGWLGEGASPGAGGGAPLQEELKSARLQISELSGKVLKLQHENH
  ALLSNIQRCDLAAHLGLRAPSPRDSDAESDAGKKESDGEESRLPQPKREGPVGGESDSEE
  MFEKTSGFGSGKPSEASEPCPTELLKAREDSEYLVTLKHEAQRLERTVERLITDTDSFLH
  DAGLRGGAPLPGPGLQGEEEQGEGDQQEPQLLGTINAKMKAFKKELQAFLEQVNRIGDGL
  SPLPHLTESSSFLSTVTSVSRDSPIGNLGKELGPDLQSRLKEQLEWQLGPARGDERESLR
  LRAARELHRRADGDTGSHGLGGQTCFSLEMEEEHLYALRWKELEMHSLALQNTLHERTWS
  DEKNLMQQELRSLKQNIFLFYVKLRWLLKHWRQGKQMEEEGEEFTEGEHPETLSRLGELG
  VQGGHQADGPDHDSDRGCGFPVGEHSPHSRVQIGDHSLRLQTADRGQPHKQVVENQQLFS
  AFKALLEDFRAELREDERARLRLQQQYASDKAAWDVEWAVLKCRLEQLEEKTENKLGELG
  SSAESKGALKKEREVHQKLLADSHSLVMDLRWQIHHSEKNWNREKVELLDRLDRDRQEWE
  RQKKEFLWRIEQLQKENSPRRGGSFLCDQKDGNVRPFPHQGSLRMPRPVAMWPCADADSI
  PFEDRPLSKLKESDRCSASENLYLDALSLDDEPEEPPAHRPEREFRNRLPEEEENHKGNL
  QRAVSVSSMSEFQRLMDISPFLPEKGLPSTSSKEDVTPPLSPDDLKYIEEFNKSWDYTPN
  RGHNGGGPDLWADRTEVGRAGHEDSTEPFPDSSWYLTTSVTMTTDTMTSPEHCQKQPLRS
  HVLTEQSGLRVLHSPPAVRRVDSITAAGGEGPFPTSRARGSPGDTKGGPPEPMLSRWPCT
  SPRHSRDYVEGARRPLDSPLCTSLGFASPLHSLEMSKNLSDDMKEVAFSVRNAICSGPGE
  LQVKDMACQTNGSRTMGTQTVQTISVGLQTEALRGSGVTSSPHKCLTPKAGGGATPVSSP
  SRSLRSRQVAPAIEKVQAKFERTCCSPKYGSPKLQRKPLPKADQPNNRTSPGMAQKGYSE
  SAWARSTTTRESPVHTTINDGLSSLFNIIDHSPVVQDPFQKGLRAGSRSRSAEPRPELGP
  GQETGTNSRGRSPSPIGVGSEMCREEGGEGTPVKQDLSAPPGYTLTENVARILNKKLLEH
  ALKEERRQAAHGPPGLHSDSHSLGDTAEPGPMENQTVLLTAPWGL
• Function: Microtubule-associated factor involved in the late phase of epithelial polarization and microtubule dynamics regulation. Plays a role in the development and maintenance of non-centrosomal microtubule bundles at the lateral membrane in polarized epithelial cells. Required for faithful chromosome segregation during mitosis.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cerebellar ataxia	DIS9IRAV	Strong	Biomarker	[1]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Genetic Variation	[2]

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 Microtubule cross-linking factor 1 (MTCL1).	[3]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Microtubule cross-linking factor 1 (MTCL1).	[14]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Microtubule cross-linking factor 1 (MTCL1).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Microtubule cross-linking factor 1 (MTCL1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Microtubule cross-linking factor 1 (MTCL1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Microtubule cross-linking factor 1 (MTCL1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Microtubule cross-linking factor 1 (MTCL1).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Microtubule cross-linking factor 1 (MTCL1).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Microtubule cross-linking factor 1 (MTCL1).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Microtubule cross-linking factor 1 (MTCL1).	[10]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Microtubule cross-linking factor 1 (MTCL1).	[11]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Microtubule cross-linking factor 1 (MTCL1).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Microtubule cross-linking factor 1 (MTCL1).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Microtubule cross-linking factor 1 (MTCL1).	[15]

References

• [1] A study in a Polish ataxia cohort indicates genetic heterogeneity and points to MTCL1 as a novel candidate gene.Clin Genet. 2019 Mar;95(3):415-419. doi: 10.1111/cge.13489. Epub 2019 Jan 8.
• [2] Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations.Nat Genet. 2019 Mar;51(3):494-505. doi: 10.1038/s41588-018-0342-2. Epub 2019 Feb 25.
• [3] 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.
• [4] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [5] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [6] 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.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] 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.
• [10] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [13] Inter- and intra-laboratory study to determine the reproducibility of toxicogenomics datasets. Toxicology. 2011 Nov 28;290(1):50-8.
• [14] 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.
• [15] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.