Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ7NW96)

• DOT Name: Protein O-mannosyl-transferase TMTC1 (TMTC1)
• Synonyms: EC 2.4.1.109; Transmembrane O-mannosyltransferase targeting cadherins 1; Transmembrane and tetratricopeptide repeat-containing 1
• Gene Name: TMTC1
• Related Disease:
  Breast carcinoma
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Endometrium neoplasm
  Mental disorder
  Myelopathy
  Obesity
  Schizophrenia
• UniProt ID: TMTC1_HUMAN
• EC Number: 2.4.1.109
• Pfam ID: PF08409 ; PF13424 ; PF13432 ; PF14559 ; PF07719
• Sequence:
  MVVTTSARGGGGDRTPSRRRGCGLAPAGAAALLAGASCLCYGRSLQGEFVHDDVWAIVNN
  PDVRPGAPLRWGIFTNDFWGKGMAENTSHKSYRPLCVLTFKLNIFLTGMNPFYFHAVNII
  LHCLVTLVLMYTCDKTVFKNRGLAFVTALLFAVHPIHTEAVAGIVGRADVLACLLFLLAF
  LSYNRSLDQGCVGGSFPSTVSPFFLLLSLFLGTCAMLVKETGITVFGVCLVYDLFSLSNK
  QDKSSNGALCPRSPQQPGSPQPSSLPGHPHRENGKQQRFPHKGAWGGCHSPLPPEPKSSG
  FPVSPRAVWSMMRFLTYSYLLAFNVWLLLAPVTLCYDWQVGSIPLVETIWDMRNLATIFL
  AVVMALLSLHCLAAFKRLEHKEVLVGLLFLVFPFIPASNLFFRVGFVVAERVLYMPSMGY
  CILFVHGLSKLCTWLNRCGATTLIVSTVLLLLLFSWKTVKQNEIWLSRESLFRSGVQTLP
  HNAKVHYNYANFLKDQGRNKEAIYHYRTALKLYPRHASALNNLGTLTRDTAEAKMYYQRA
  LQLHPQHNRALFNLGNLLKSQEKKEEAITLLKDSIKYGPEFADAYSSLASLLAEQERFKE
  AEEIYQTGIKNCPDSSDLHNNYGVFLVDTGLPEKAVAHYQQAIKLSPSHHVAMVNLGRLY
  RSLGENSMAEEWYKRALQVAHKAEILSPLGALYYNTGRYEEALQIYQEAAALQPSQRELR
  LALAQVLAVMGQTKEAEKMTNHIVSEETGCLECYRLLSAIYSKQENHDKALDAIDKALQL
  KPKDPKVISELFFTKGNQLREQNLLDKAFESYRVAVQLNPDQAQAWMNMGGIQHIKGKYV
  SARAYYERALQLVPDSKLLKENLAKLDRLEKRLQEVREKDQT
• Function: Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. The 4 members of the TMTC family are O-mannosyl-transferases dedicated primarily to the cadherin superfamily, each member seems to have a distinct role in decorating the cadherin domains with O-linked mannose glycans at specific regions. Also acts as O-mannosyl-transferase on other proteins such as PDIA3.

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[1]
Colon cancer	DISVC52G	Strong	Genetic Variation	[2]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[2]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[2]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[2]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[2]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[2]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[2]
Endometrium neoplasm	DIS6OS2L	Strong	Genetic Variation	[2]
Mental disorder	DIS3J5R8	Strong	Genetic Variation	[3]
Myelopathy	DISXV8FG	Strong	Biomarker	[4]
Obesity	DIS47Y1K	Strong	Biomarker	[5]
Schizophrenia	DISSRV2N	Limited	Genetic Variation	[6]

18 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 Protein O-mannosyl-transferase TMTC1 (TMTC1).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein O-mannosyl-transferase TMTC1 (TMTC1).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein O-mannosyl-transferase TMTC1 (TMTC1).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein O-mannosyl-transferase TMTC1 (TMTC1).	[10]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein O-mannosyl-transferase TMTC1 (TMTC1).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Protein O-mannosyl-transferase TMTC1 (TMTC1).	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Protein O-mannosyl-transferase TMTC1 (TMTC1).	[13]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Protein O-mannosyl-transferase TMTC1 (TMTC1).	[15]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Protein O-mannosyl-transferase TMTC1 (TMTC1).	[16]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Protein O-mannosyl-transferase TMTC1 (TMTC1).	[17]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Protein O-mannosyl-transferase TMTC1 (TMTC1).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein O-mannosyl-transferase TMTC1 (TMTC1).	[19]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Protein O-mannosyl-transferase TMTC1 (TMTC1).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein O-mannosyl-transferase TMTC1 (TMTC1).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein O-mannosyl-transferase TMTC1 (TMTC1).	[22]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein O-mannosyl-transferase TMTC1 (TMTC1).	[23]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein O-mannosyl-transferase TMTC1 (TMTC1).	[24]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Protein O-mannosyl-transferase TMTC1 (TMTC1).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Protein O-mannosyl-transferase TMTC1 (TMTC1).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein O-mannosyl-transferase TMTC1 (TMTC1).	[18]

References

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• [11] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [12] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
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• [19] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [20] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
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• [25] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.