Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO1OII0)

DOT Name DNA repair-scaffolding protein (SPIDR)
Synonyms Scaffolding protein involved in DNA repair
Gene Name SPIDR
Related Disease
Acute lymphocytic leukaemia ( )
Colorectal carcinoma ( )
Ovarian dysgenesis 1 ( )
Turner syndrome ( )
Bloom syndrome ( )
Gonadal dysgenesis ( )
46 XX gonadal dysgenesis ( )
Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation ( )
Ovarian dysgenesis 9 ( )
UniProt ID
SPIDR_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF14950 ; PF14951
Sequence
MPRGSRARGSKRKRSWNTECPSFPGERPLQVRRAGLRTAGAAASLSEAWLRCGEGFQNTS
GNPSLTAEEKTITEKHLELCPRPKQETTTSKSTSGLTDITWSSSGSDLSDEDKTLSQLQR
DELQFIDWEIDSDRAEASDCDEFEDDEGAVEISDCASCASNQSLTSDEKLSELPKPSSIE
ILEYSSDSEKEDDLENVLLIDSESPHKYHVQFASDARQIMERLIDPRTKSTETILHTPQK
PTAKFPRTPENSAKKKLLRGGLAERLNGLQNRERSAISLWRHQCISYQKTLSGRKSGVLT
VKILELHEECAMQVAMCEQLLGSPATSSSQSVAPRPGAGLKVLFTKETAGYLRGRPQDTV
RIFPPWQKLIIPSGSCPVILNTYFCEKVVAKEDSEKTCEVYCPDIPLPRRSISLAQMFVI
KGLTNNSPEIQVVCSGVATTGTAWTHGHKEAKQRIPTSTPLRDSLLDVVESQGAASWPGA
GVRVVVQRVYSLPSRDSTRGQQGASSGHTDPAGTRACLLVQDACGMFGEVHLEFTMSKAR
QLEGKSCSLVGMKVLQKVTRGRTAGIFSLIDTLWPPAIPLKTPGRDQPCEEIKTHLPPPA
LCYILTAHPNLGQIDIIDEDPIYKLYQPPVTRCLRDILQMNDLGTRCSFYATVIYQKPQL
KSLLLLEQREIWLLVTDVTLQTKEERDPRLPKTLLVYVAPLCVLGSEVLEALAGAAPHSL
FFKDALRDQGRIVCAERTVLLLQKPLLSVVSGASSCELPGPVMLDSLDSATPVNSICSVQ
GTVVGVDESTAFSWPVCDMCGNGRLEQRPEDRGAFSCGDCSRVVTSPVLKRHLQVFLDCR
SRPQCRVKVKLLQRSISSLLRFAAGEDGSYEVKSVLGKEVGLLNCFVQSVTAHPTSCIGL
EEIELLSAGGASAEH
Function
Plays a role in DNA double-strand break (DBS) repair via homologous recombination (HR). Serves as a scaffolding protein that helps to promote the recruitment of DNA-processing enzymes like the helicase BLM and recombinase RAD51 to site of DNA damage, and hence contributes to maintain genomic integrity.
Reactome Pathway
Resolution of D-loop Structures through Holliday Junction Intermediates (R-HSA-5693568 )

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute lymphocytic leukaemia DISPX75S Strong Genetic Variation [1]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [1]
Ovarian dysgenesis 1 DISXIXHW Strong GermlineCausalMutation [2]
Turner syndrome DIS2035C Strong Biomarker [2]
Bloom syndrome DISKXQ7J moderate Biomarker [3]
Gonadal dysgenesis DISIL2ZI moderate Biomarker [2]
46 XX gonadal dysgenesis DISBB9HA Supportive Autosomal dominant [2]
Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation DIS56JR8 Disputed Autosomal recessive [4]
Ovarian dysgenesis 9 DIS7T52Q Limited Autosomal recessive [5]
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⏷ Show the Full List of 9 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
8 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of DNA repair-scaffolding protein (SPIDR). [6]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of DNA repair-scaffolding protein (SPIDR). [7]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of DNA repair-scaffolding protein (SPIDR). [8]
Decitabine DMQL8XJ Approved Decitabine affects the expression of DNA repair-scaffolding protein (SPIDR). [10]
Marinol DM70IK5 Approved Marinol decreases the expression of DNA repair-scaffolding protein (SPIDR). [11]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of DNA repair-scaffolding protein (SPIDR). [12]
Tocopherol DMBIJZ6 Phase 2 Tocopherol decreases the expression of DNA repair-scaffolding protein (SPIDR). [13]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of DNA repair-scaffolding protein (SPIDR). [14]
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⏷ Show the Full List of 8 Drug(s)
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of DNA repair-scaffolding protein (SPIDR). [9]
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of DNA repair-scaffolding protein (SPIDR). [15]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of DNA repair-scaffolding protein (SPIDR). [16]
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References

1 Instability at the FRA8I common fragile site disrupts the genomic integrity of the KIAA0146, CEBPD and PRKDC genes in colorectal cancer.Cancer Lett. 2013 Aug 9;336(1):85-95. doi: 10.1016/j.canlet.2013.04.007. Epub 2013 Apr 16.
2 A Biallelic Mutation in the Homologous Recombination Repair Gene SPIDR Is Associated With Human Gonadal Dysgenesis. J Clin Endocrinol Metab. 2017 Feb 1;102(2):681-688. doi: 10.1210/jc.2016-2714.
3 Scaffolding protein SPIDR/KIAA0146 connects the Bloom syndrome helicase with homologous recombination repair.Proc Natl Acad Sci U S A. 2013 Jun 25;110(26):10646-51. doi: 10.1073/pnas.1220921110. Epub 2013 Mar 18.
4 A genomics approach to male infertility. Genet Med. 2020 Dec;22(12):1967-1975. doi: 10.1038/s41436-020-0916-0. Epub 2020 Jul 28.
5 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
6 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.
7 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
8 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
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 Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
11 JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
12 LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
13 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.
14 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
15 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.
16 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.