Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI87RS5)

DOT Name Exonuclease 1 (EXO1)
Synonyms hExo1; EC 3.1.-.-; Exonuclease I; hExoI
Gene Name EXO1
Related Disease
Autosomal dominant polycystic kidney disease ( )
Cervical cancer ( )
Cervical carcinoma ( )
Adenocarcinoma ( )
Ataxia-telangiectasia ( )
Bladder cancer ( )
Bloom syndrome ( )
Breast cancer ( )
Carcinoma of liver and intrahepatic biliary tract ( )
Colonic neoplasm ( )
Colorectal neoplasm ( )
Fanconi anemia complementation group A ( )
Fanconi's anemia ( )
Gastric cancer ( )
Head and neck cancer ( )
Head and neck carcinoma ( )
Hepatitis B virus infection ( )
Liver cancer ( )
Lung cancer ( )
Lung carcinoma ( )
Lung neoplasm ( )
Malignant neoplasm ( )
Non-small-cell lung cancer ( )
Oral cancer ( )
Pneumonia ( )
Pneumonitis ( )
Retinoblastoma ( )
Stomach cancer ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Xeroderma pigmentosum ( )
Pancreatic cancer ( )
Squamous cell carcinoma ( )
Werner syndrome ( )
Lynch syndrome 1 ( )
Lynch syndrome 2 ( )
Adult glioblastoma ( )
Astrocytoma ( )
Basal cell carcinoma ( )
Basal cell neoplasm ( )
Breast carcinoma ( )
Breast neoplasm ( )
Colorectal adenoma ( )
Glioblastoma multiforme ( )
Hepatocellular carcinoma ( )
Melanoma ( )
Prostate cancer ( )
Prostate carcinoma ( )
Lynch syndrome ( )
UniProt ID
EXO1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
3QE9; 3QEA; 3QEB; 5UZV; 5V04; 5V05; 5V06; 5V07; 5V08; 5V09; 5V0A; 5V0B; 5V0C; 5V0D; 5V0E; 7MXQ; 7MXR; 7MXS; 7MXT; 7MXU; 7MXV; 7MXW; 7MXX
EC Number
3.1.-.-
Pfam ID
PF00867 ; PF00752
Sequence
MGIQGLLQFIKEASEPIHVRKYKGQVVAVDTYCWLHKGAIACAEKLAKGEPTDRYVGFCM
KFVNMLLSHGIKPILVFDGCTLPSKKEVERSRRERRQANLLKGKQLLREGKVSEARECFT
RSINITHAMAHKVIKAARSQGVDCLVAPYEADAQLAYLNKAGIVQAIITEDSDLLAFGCK
KVILKMDQFGNGLEIDQARLGMCRQLGDVFTEEKFRYMCILSGCDYLSSLRGIGLAKACK
VLRLANNPDIVKVIKKIGHYLKMNITVPEDYINGFIRANNTFLYQLVFDPIKRKLIPLNA
YEDDVDPETLSYAGQYVDDSIALQIALGNKDINTFEQIDDYNPDTAMPAHSRSHSWDDKT
CQKSANVSSIWHRNYSPRPESGTVSDAPQLKENPSTVGVERVISTKGLNLPRKSSIVKRP
RSAELSEDDLLSQYSLSFTKKTKKNSSEGNKSLSFSEVFVPDLVNGPTNKKSVSTPPRTR
NKFATFLQRKNEESGAVVVPGTRSRFFCSSDSTDCVSNKVSIQPLDETAVTDKENNLHES
EYGDQEGKRLVDTDVARNSSDDIPNNHIPGDHIPDKATVFTDEESYSFESSKFTRTISPP
TLGTLRSCFSWSGGLGDFSRTPSPSPSTALQQFRRKSDSPTSLPENNMSDVSQLKSEESS
DDESHPLREEACSSQSQESGEFSLQSSNASKLSQCSSKDSDSEESDCNIKLLDSQSDQTS
KLRLSHFSKKDTPLRNKVPGLYKSSSADSLSTTKIKPLGPARASGLSKKPASIQKRKHHN
AENKPGLQIKLNELWKNFGFKKDSEKLPPCKKPLSPVRDNIQLTPEAEEDIFNKPECGRV
QRAIFQ
Function
5'->3' double-stranded DNA exonuclease which may also possess a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in DNA mismatch repair (MMR) to excise mismatch-containing DNA tracts directed by strand breaks located either 5' or 3' to the mismatch. Also exhibits endonuclease activity against 5'-overhanging flap structures similar to those generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. Required for somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin genes. Essential for male and female meiosis.
Tissue Specificity Highly expressed in bone marrow, testis and thymus. Expressed at lower levels in colon, lymph nodes, ovary, placenta, prostate, small intestine, spleen and stomach.
KEGG Pathway
Mismatch repair (hsa03430 )
Reactome Pathway
Mismatch repair (MMR) directed by MSH2 (R-HSA-5358606 )
HDR through Single Strand Annealing (SSA) (R-HSA-5685938 )
HDR through Homologous Recombination (HRR) (R-HSA-5685942 )
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) (R-HSA-5693554 )
Resolution of D-loop Structures through Holliday Junction Intermediates (R-HSA-5693568 )
Homologous DNA Pairing and Strand Exchange (R-HSA-5693579 )
Processing of DNA double-strand break ends (R-HSA-5693607 )
Presynaptic phase of homologous DNA pairing and strand exchange (R-HSA-5693616 )
Regulation of TP53 Activity through Phosphorylation (R-HSA-6804756 )
G2/M DNA damage checkpoint (R-HSA-69473 )
Defective homologous recombination repair (HRR) due to BRCA1 loss of function (R-HSA-9701192 )
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function (R-HSA-9704331 )
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function (R-HSA-9704646 )
Impaired BRCA2 binding to RAD51 (R-HSA-9709570 )
Impaired BRCA2 binding to PALB2 (R-HSA-9709603 )
Mismatch repair (MMR) directed by MSH2 (R-HSA-5358565 )

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Autosomal dominant polycystic kidney disease DISBHWUI Definitive Altered Expression [1]
Cervical cancer DISFSHPF Definitive Genetic Variation [2]
Cervical carcinoma DIST4S00 Definitive Genetic Variation [2]
Adenocarcinoma DIS3IHTY Strong Altered Expression [3]
Ataxia-telangiectasia DISP3EVR Strong Biomarker [4]
Bladder cancer DISUHNM0 Strong Biomarker [5]
Bloom syndrome DISKXQ7J Strong Biomarker [6]
Breast cancer DIS7DPX1 Strong Altered Expression [7]
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W Strong Altered Expression [3]
Colonic neoplasm DISSZ04P Strong Altered Expression [8]
Colorectal neoplasm DISR1UCN Strong Biomarker [9]
Fanconi anemia complementation group A DIS8PZLI Strong Biomarker [10]
Fanconi's anemia DISGW6Q8 Strong Biomarker [10]
Gastric cancer DISXGOUK Strong Genetic Variation [11]
Head and neck cancer DISBPSQZ Strong Genetic Variation [12]
Head and neck carcinoma DISOU1DS Strong Genetic Variation [12]
Hepatitis B virus infection DISLQ2XY Strong Biomarker [13]
Liver cancer DISDE4BI Strong Altered Expression [3]
Lung cancer DISCM4YA Strong Genetic Variation [14]
Lung carcinoma DISTR26C Strong Genetic Variation [14]
Lung neoplasm DISVARNB Strong Genetic Variation [15]
Malignant neoplasm DISS6SNG Strong Genetic Variation [16]
Non-small-cell lung cancer DIS5Y6R9 Strong Genetic Variation [17]
Oral cancer DISLD42D Strong Genetic Variation [18]
Pneumonia DIS8EF3M Strong Biomarker [19]
Pneumonitis DIS88E0K Strong Biomarker [19]
Retinoblastoma DISVPNPB Strong Genetic Variation [20]
Stomach cancer DISKIJSX Strong Genetic Variation [11]
Urinary bladder cancer DISDV4T7 Strong Biomarker [5]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [5]
Xeroderma pigmentosum DISQ9H19 Strong Biomarker [21]
Pancreatic cancer DISJC981 moderate Biomarker [22]
Squamous cell carcinoma DISQVIFL moderate Genetic Variation [23]
Werner syndrome DISZY45W moderate Biomarker [24]
Lynch syndrome 1 DISSABLZ Disputed Biomarker [8]
Lynch syndrome 2 DISRLYU1 Disputed Biomarker [8]
Adult glioblastoma DISVP4LU Limited Biomarker [25]
Astrocytoma DISL3V18 Limited Altered Expression [25]
Basal cell carcinoma DIS7PYN3 Limited Genetic Variation [26]
Basal cell neoplasm DIS37IXW Limited Genetic Variation [26]
Breast carcinoma DIS2UE88 Limited Altered Expression [7]
Breast neoplasm DISNGJLM Limited Altered Expression [27]
Colorectal adenoma DISTSVHM Limited Genetic Variation [28]
Glioblastoma multiforme DISK8246 Limited Biomarker [25]
Hepatocellular carcinoma DIS0J828 Limited Genetic Variation [29]
Melanoma DIS1RRCY Limited Altered Expression [30]
Prostate cancer DISF190Y Limited Biomarker [31]
Prostate carcinoma DISMJPLE Limited Biomarker [31]
Lynch syndrome DIS3IW5F Refuted Autosomal dominant [32]
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⏷ Show the Full List of 49 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
26 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate affects the expression of Exonuclease 1 (EXO1). [33]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Exonuclease 1 (EXO1). [34]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Exonuclease 1 (EXO1). [35]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Exonuclease 1 (EXO1). [36]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Exonuclease 1 (EXO1). [37]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Exonuclease 1 (EXO1). [38]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Exonuclease 1 (EXO1). [39]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Exonuclease 1 (EXO1). [40]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Exonuclease 1 (EXO1). [41]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Exonuclease 1 (EXO1). [41]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Exonuclease 1 (EXO1). [42]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Exonuclease 1 (EXO1). [43]
Demecolcine DMCZQGK Approved Demecolcine decreases the expression of Exonuclease 1 (EXO1). [44]
Cannabidiol DM0659E Approved Cannabidiol decreases the expression of Exonuclease 1 (EXO1). [45]
Troglitazone DM3VFPD Approved Troglitazone decreases the expression of Exonuclease 1 (EXO1). [46]
Azathioprine DMMZSXQ Approved Azathioprine decreases the expression of Exonuclease 1 (EXO1). [47]
Dasatinib DMJV2EK Approved Dasatinib decreases the expression of Exonuclease 1 (EXO1). [48]
Lucanthone DMZLBUO Approved Lucanthone decreases the expression of Exonuclease 1 (EXO1). [49]
Palbociclib DMD7L94 Approved Palbociclib decreases the expression of Exonuclease 1 (EXO1). [50]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of Exonuclease 1 (EXO1). [51]
GSK2110183 DMZHB37 Phase 2 GSK2110183 decreases the expression of Exonuclease 1 (EXO1). [52]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Exonuclease 1 (EXO1). [53]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Exonuclease 1 (EXO1). [54]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN decreases the expression of Exonuclease 1 (EXO1). [56]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of Exonuclease 1 (EXO1). [40]
Glyphosate DM0AFY7 Investigative Glyphosate decreases the expression of Exonuclease 1 (EXO1). [58]
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⏷ Show the Full List of 26 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of Exonuclease 1 (EXO1). [55]
Coumarin DM0N8ZM Investigative Coumarin affects the phosphorylation of Exonuclease 1 (EXO1). [57]
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References

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2 A single nucleotide polymorphism in EXO1 gene is associated with cervical cancer susceptibility in Chinese patients.Int J Gynecol Cancer. 2012 Feb;22(2):220-5. doi: 10.1097/IGC.0b013e318234fd8a.
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26 Combined analysis of keratinocyte cancers identifies novel genome-wide loci.Hum Mol Genet. 2019 Sep 15;28(18):3148-3160. doi: 10.1093/hmg/ddz121.
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