Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTICII2L)

DOT Name Protein O-mannosyl-transferase TMEM260 (TMEM260)
Synonyms EC 2.4.1.109; Transmembrane protein 260
Gene Name TMEM260
Related Disease
Alcohol dependence ( )
Structural heart defects and renal anomalies syndrome ( )
Advanced cancer ( )
Lymphoma, non-Hodgkin, familial ( )
Non-hodgkin lymphoma ( )
Acute myelogenous leukaemia ( )
UniProt ID
TM260_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
2.4.1.109
Pfam ID
PF11028
Sequence
MSPHGDGRGQAQGRAVRVGLRRSGGIRGGVAVFAAVAAVFTFTLPPSVPGGDSGELITAA
HELGVAHPPGYPLFTLVAKLAITLFPFGSIAYRVNLLCGLFGAVAASLLFFTVFRLSGSS
AGGILAAGVFSFSRLTWQWSIAAEVFSLNNLFVGLLMALTVHFEEAATAKERSKVAKIGA
FCCGLSLCNQHTIILYVLCIIPWILFQLLKKKELSLGSLLKLSLYFSAGLLPYVHLPISS
YLNHARWTWGDQTTLQGFLTHFLREEYGTFSLAKSEIGSSMSEILLSQVTNMRTELSFNI
QALAVCANICLATKDRQNPSLVWLFTGMFCIYSLFFAWRANLDISKPLFMGVVERFWMQS
NAVVAVLAGIGLAAVVSETNRVLNSNGLQCLEWLSATLFVVYQIYSNYSVCDQRTNYVID
KFAKNLLTSMPHDAIILLRGDLPGNSLRYMHYCEGLRPDISLVDQEMMTYEWYLPKMAKH
LPGVNFPGNRWNPVEGILPSGMVTFNLYHFLEVNKQKETFVCIGIHEGDPTWKKNYSLWP
WGSCDKLVPLEIVFNPEEWIKLTKSIYNWTEEYGRFDPSSWESVANEEMWQARMKTPFFI
FNLAETAHMPSKVKAQLYAQAYDLYKEIVYLQKEHPVNWHKNYAIACERMLRLQARDADP
EVLLSETIRHFRLYSQKAPNDPQQADILGALKHLRKELQSLRNRKNV
Function
O-mannosyl-transferase that transfers mannosyl residues to the hydroxyl group of serine or threonine residues of proteins. Specifically glycosylates the IPT/TIG domain of target proteins, such as MET and MST1R/RON. TMEM260-mediated O-mannosylated residues are composed of single mannose glycans that are not elongated or modified.
Tissue Specificity
.Expressed in brain, heart, kidney, liver, lung, pancreas and placenta but are not detected in skeletal muscle.; [Isoform 3]: Expressed in brain, heart, kidney, liver, lung, pancreas and placenta but are not detected in skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Alcohol dependence DIS4ZSCO Strong Genetic Variation [1]
Structural heart defects and renal anomalies syndrome DISFU9CC Strong Autosomal recessive [2]
Advanced cancer DISAT1Z9 moderate Genetic Variation [3]
Lymphoma, non-Hodgkin, familial DISCXYIZ moderate Genetic Variation [3]
Non-hodgkin lymphoma DISS2Y8A moderate Genetic Variation [3]
Acute myelogenous leukaemia DISCSPTN Limited Genetic Variation [4]
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⏷ Show the Full List of 6 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Protein O-mannosyl-transferase TMEM260 (TMEM260). [5]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Protein O-mannosyl-transferase TMEM260 (TMEM260). [9]
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3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Protein O-mannosyl-transferase TMEM260 (TMEM260). [6]
Tocopherol DMBIJZ6 Phase 2 Tocopherol decreases the expression of Protein O-mannosyl-transferase TMEM260 (TMEM260). [7]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Protein O-mannosyl-transferase TMEM260 (TMEM260). [8]
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References

1 Genome-wide association study of alcohol dependence implicates KIAA0040 on chromosome 1q.Neuropsychopharmacology. 2012 Jan;37(2):557-66. doi: 10.1038/npp.2011.229. Epub 2011 Sep 28.
2 Mutations in TMEM260 Cause a Pediatric Neurodevelopmental, Cardiac, and Renal Syndrome. Am J Hum Genet. 2017 Apr 6;100(4):666-675. doi: 10.1016/j.ajhg.2017.02.007. Epub 2017 Mar 16.
3 A polymorphism at the microRNA binding site in the 3' untranslated region of C14orf101 is associated with non-Hodgkin lymphoma overall survival.Cancer Genet. 2014 Apr;207(4):141-6. doi: 10.1016/j.cancergen.2014.03.007. Epub 2014 Mar 22.
4 Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
5 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.
6 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
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 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.
9 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.