Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOFT19G)

DOT Name Integrator complex subunit 11 (INTS11)
Synonyms Int11; EC 3.1.27.-; Cleavage and polyadenylation-specific factor 3-like protein; CPSF3-like protein; Protein related to CPSF subunits of 68 kDa; RC-68
Gene Name INTS11
Related Disease
Dementia ( )
Neoplasm ( )
Crohn disease ( )
Pancreatic cancer ( )
Ulcerative colitis ( )
Inflammatory bowel disease ( )
UniProt ID
INT11_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
5V8W; 7BFP; 7BFQ; 7CUN; 7PKS; 7YCX
EC Number
3.1.27.-
Pfam ID
PF10996 ; PF21386 ; PF16661 ; PF07521
Sequence
MPEIRVTPLGAGQDVGRSCILVSIAGKNVMLDCGMHMGFNDDRRFPDFSYITQNGRLTDF
LDCVIISHFHLDHCGALPYFSEMVGYDGPIYMTHPTQAICPILLEDYRKIAVDKKGEANF
FTSQMIKDCMKKVVAVHLHQTVQVDDELEIKAYYAGHVLGAAMFQIKVGSESVVYTGDYN
MTPDRHLGAAWIDKCRPNLLITESTYATTIRDSKRCRERDFLKKVHETVERGGKVLIPVF
ALGRAQELCILLETFWERMNLKVPIYFSTGLTEKANHYYKLFIPWTNQKIRKTFVQRNMF
EFKHIKAFDRAFADNPGPMVVFATPGMLHAGQSLQIFRKWAGNEKNMVIMPGYCVQGTVG
HKILSGQRKLEMEGRQVLEVKMQVEYMSFSAHADAKGIMQLVGQAEPESVLLVHGEAKKM
EFLKQKIEQELRVNCYMPANGETVTLPTSPSIPVGISLGLLKREMAQGLLPEAKKPRLLH
GTLIMKDSNFRLVSSEQALKELGLAEHQLRFTCRVHLHDTRKEQETALRVYSHLKSVLKD
HCVQHLPDGSVTVESVLLQAAAPSEDPGTKVLLVSWTYQDEELGSFLTSLLKKGLPQAPS
Function
Catalytic component of the Integrator (INT) complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. The Integrator complex is associated with the C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A) and is recruited to the U1 and U2 snRNAs genes. Mediates the snRNAs 3' cleavage. Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the INT complex.
Reactome Pathway
RNA polymerase II transcribes snRNA genes (R-HSA-6807505 )

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Dementia DISXL1WY Strong Biomarker [1]
Neoplasm DISZKGEW Strong Biomarker [2]
Crohn disease DIS2C5Q8 moderate Genetic Variation [3]
Pancreatic cancer DISJC981 moderate Biomarker [4]
Ulcerative colitis DIS8K27O moderate Genetic Variation [3]
Inflammatory bowel disease DISGN23E Limited Genetic Variation [5]
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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
4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Integrator complex subunit 11 (INTS11). [6]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Integrator complex subunit 11 (INTS11). [8]
Demecolcine DMCZQGK Approved Demecolcine decreases the expression of Integrator complex subunit 11 (INTS11). [10]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Integrator complex subunit 11 (INTS11). [10]
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3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the methylation of Integrator complex subunit 11 (INTS11). [7]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Integrator complex subunit 11 (INTS11). [9]
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of Integrator complex subunit 11 (INTS11). [11]
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References

1 Predictors of progression from mild cognitive impairment to dementia in the placebo-arm of a clinical trial population.J Alzheimers Dis. 2013;36(1):79-85. doi: 10.3233/JAD-122233.
2 Monomethyl auristatin E-conjugated anti-EGFR antibody inhibits the growth of human EGFR-positive non-small cell lung cancer.Cancer Chemother Pharmacol. 2019 Jul;84(1):61-72. doi: 10.1007/s00280-019-03848-9. Epub 2019 Apr 29.
3 Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.Nat Genet. 2015 Sep;47(9):979-986. doi: 10.1038/ng.3359. Epub 2015 Jul 20.
4 Development of a Novel EGFR-Targeting Antibody-Drug Conjugate for Pancreatic Cancer Therapy.Target Oncol. 2019 Feb;14(1):93-105. doi: 10.1007/s11523-018-0616-8.
5 Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease.Nat Genet. 2017 Feb;49(2):256-261. doi: 10.1038/ng.3760. Epub 2017 Jan 9.
6 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
7 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.
8 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.
9 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.
10 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
11 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.