Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW3KB1I)

DOT Name Protein artemis (DCLRE1C)
Synonyms EC 3.1.-.-; DNA cross-link repair 1C protein; Protein A-SCID; SNM1 homolog C; hSNM1C; SNM1-like protein
Gene Name DCLRE1C
Related Disease
Coronary atherosclerosis ( )
Non-insulin dependent diabetes ( )
Severe combined immunodeficiency due to DCLRE1C deficiency ( )
Adult lymphoma ( )
Advanced cancer ( )
Alcohol dependence ( )
Anxiety ( )
B-cell neoplasm ( )
Bone osteosarcoma ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Burkitt lymphoma ( )
Colitis ( )
Depression ( )
Endometriosis ( )
Epithelial ovarian cancer ( )
Gastric cancer ( )
Herpes simplex infection ( )
Inflammatory bowel disease ( )
Leukemia ( )
Lymphoma ( )
Lymphoproliferative syndrome ( )
Malignant soft tissue neoplasm ( )
Metastatic malignant neoplasm ( )
Migraine disorder ( )
Neoplasm ( )
Osteosarcoma ( )
Ovarian cancer ( )
Pediatric lymphoma ( )
Plasma cell myeloma ( )
Prostate cancer ( )
Prostate carcinoma ( )
Sarcoma ( )
Severe combined immunodeficiency ( )
Squamous cell carcinoma ( )
Stomach cancer ( )
Colorectal carcinoma ( )
Isolated congenital microcephaly ( )
leukaemia ( )
Omenn syndrome ( )
Cognitive impairment ( )
Acute myelogenous leukaemia ( )
Anxiety disorder ( )
Coronary heart disease ( )
Melanoma ( )
Pancreatic ductal carcinoma ( )
Rheumatoid arthritis ( )
UniProt ID
DCR1C_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
3W1B; 3W1G; 4HTP; 6TT5; 6WNL; 6WO0; 7ABS; 7AF1; 7AFS; 7AFU; 7AGI; 7APV; 7SGL; 7TYR
EC Number
3.1.-.-
Pfam ID
PF07522
Sequence
MSSFEGQMAEYPTISIDRFDRENLRARAYFLSHCHKDHMKGLRAPTLKRRLECSLKVYLY
CSPVTKELLLTSPKYRFWKKRIISIEIETPTQISLVDEASGEKEEIVVTLLPAGHCPGSV
MFLFQGNNGTVLYTGDFRLAQGEAARMELLHSGGRVKDIQSVYLDTTFCDPRFYQIPSRE
ECLSGVLELVRSWITRSPYHVVWLNCKAAYGYEYLFTNLSEELGVQVHVNKLDMFRNMPE
ILHHLTTDRNTQIHACRHPKAEEYFQWSKLPCGITSRNRIPLHIISIKPSTMWFGERSRK
TNVIVRTGESSYRACFSFHSSYSEIKDFLSYLCPVNAYPNVIPVGTTMDKVVEILKPLCR
SSQSTEPKYKPLGKLKRARTVHRDSEEEDDYLFDDPLPIPLRHKVPYPETFHPEVFSMTA
VSEKQPEKLRQTPGCCRAECMQSSRFTNFVDCEESNSESEEEVGIPASLQGDLGSVLHLQ
KADGDVPQWEVFFKRNDEITDESLENFPSSTVAGGSQSPKLFSDSDGESTHISSQNSSQS
THITEQGSQGWDSQSDTVLLSSQERNSGDITSLDKADYRPTIKENIPASLMEQNVICPKD
TYSDLKSRDKDVTIVPSTGEPTTLSSETHIPEEKSLLNLSTNADSQSSSDFEVPSTPEAE
LPKREHLQYLYEKLATGESIAVKKRKCSLLDT
Function
Nuclease involved in DNA non-homologous end joining (NHEJ); required for double-strand break repair and V(D)J recombination. Required for V(D)J recombination, the process by which exons encoding the antigen-binding domains of immunoglobulins and T-cell receptor proteins are assembled from individual V, (D), and J gene segments. V(D)J recombination is initiated by the lymphoid specific RAG endonuclease complex, which generates site specific DNA double strand breaks (DSBs). These DSBs present two types of DNA end structures: hairpin sealed coding ends and phosphorylated blunt signal ends. These ends are independently repaired by the non homologous end joining (NHEJ) pathway to form coding and signal joints respectively. This protein exhibits single-strand specific 5'-3' exonuclease activity in isolation and acquires endonucleolytic activity on 5' and 3' hairpins and overhangs when in a complex with PRKDC. The latter activity is required specifically for the resolution of closed hairpins prior to the formation of the coding joint. Also required for the repair of complex DSBs induced by ionizing radiation, which require substantial end-processing prior to religation by NHEJ.
Tissue Specificity Ubiquitously expressed, with highest levels in the kidney, lung, pancreas and placenta (at the mRNA level). Expression is not increased in thymus or bone marrow, sites of V(D)J recombination.
KEGG Pathway
Non-homologous end-joining (hsa03450 )
Primary immunodeficiency (hsa05340 )
Reactome Pathway
Nonhomologous End-Joining (NHEJ) (R-HSA-5693571 )

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Coronary atherosclerosis DISKNDYU Definitive Biomarker [1]
Non-insulin dependent diabetes DISK1O5Z Definitive Genetic Variation [1]
Severe combined immunodeficiency due to DCLRE1C deficiency DISR36ZW Definitive Autosomal recessive [2]
Adult lymphoma DISK8IZR Strong Biomarker [3]
Advanced cancer DISAT1Z9 Strong Biomarker [4]
Alcohol dependence DIS4ZSCO Strong Biomarker [5]
Anxiety DISIJDBA Strong Biomarker [6]
B-cell neoplasm DISVY326 Strong Biomarker [7]
Bone osteosarcoma DIST1004 Strong Biomarker [8]
Breast cancer DIS7DPX1 Strong Biomarker [9]
Breast carcinoma DIS2UE88 Strong Biomarker [9]
Breast neoplasm DISNGJLM Strong Genetic Variation [10]
Burkitt lymphoma DIS9D5XU Strong Biomarker [11]
Colitis DISAF7DD Strong Biomarker [12]
Depression DIS3XJ69 Strong Biomarker [5]
Endometriosis DISX1AG8 Strong Biomarker [13]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [14]
Gastric cancer DISXGOUK Strong Biomarker [15]
Herpes simplex infection DISL1SAV Strong Biomarker [16]
Inflammatory bowel disease DISGN23E Strong Genetic Variation [17]
Leukemia DISNAKFL Strong Biomarker [3]
Lymphoma DISN6V4S Strong Biomarker [3]
Lymphoproliferative syndrome DISMVL8O Strong Biomarker [18]
Malignant soft tissue neoplasm DISTC6NO Strong Biomarker [19]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [20]
Migraine disorder DISFCQTG Strong Genetic Variation [21]
Neoplasm DISZKGEW Strong Biomarker [22]
Osteosarcoma DISLQ7E2 Strong Biomarker [8]
Ovarian cancer DISZJHAP Strong Biomarker [14]
Pediatric lymphoma DIS51BK2 Strong Biomarker [3]
Plasma cell myeloma DIS0DFZ0 Strong Biomarker [22]
Prostate cancer DISF190Y Strong Biomarker [23]
Prostate carcinoma DISMJPLE Strong Biomarker [23]
Sarcoma DISZDG3U Strong Biomarker [19]
Severe combined immunodeficiency DIS6MF4Q Strong Genetic Variation [24]
Squamous cell carcinoma DISQVIFL Strong Biomarker [25]
Stomach cancer DISKIJSX Strong Biomarker [15]
Colorectal carcinoma DIS5PYL0 moderate Biomarker [26]
Isolated congenital microcephaly DISUXHZ6 moderate Biomarker [27]
leukaemia DISS7D1V moderate Biomarker [3]
Omenn syndrome DIS2C887 Supportive Autosomal recessive [28]
Cognitive impairment DISH2ERD Disputed Biomarker [29]
Acute myelogenous leukaemia DISCSPTN Limited Biomarker [30]
Anxiety disorder DISBI2BT Limited Genetic Variation [31]
Coronary heart disease DIS5OIP1 Limited Biomarker [32]
Melanoma DIS1RRCY Limited Biomarker [33]
Pancreatic ductal carcinoma DIS26F9Q Limited Biomarker [34]
Rheumatoid arthritis DISTSB4J Limited Biomarker [35]
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⏷ Show the Full List of 48 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 3 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Cisplatin DMRHGI9 Approved Protein artemis (DCLRE1C) decreases the response to substance of Cisplatin. [45]
Mitomycin DMH0ZJE Approved Protein artemis (DCLRE1C) decreases the response to substance of Mitomycin. [45]
Hydroxyurea DMOQVU9 Approved Protein artemis (DCLRE1C) increases the response to substance of Hydroxyurea. [45]
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9 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 Protein artemis (DCLRE1C). [36]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Protein artemis (DCLRE1C). [37]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Protein artemis (DCLRE1C). [38]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Protein artemis (DCLRE1C). [39]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Protein artemis (DCLRE1C). [40]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Protein artemis (DCLRE1C). [41]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Protein artemis (DCLRE1C). [42]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Protein artemis (DCLRE1C). [43]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Protein artemis (DCLRE1C). [44]
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⏷ Show the Full List of 9 Drug(s)

References

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4 Cellular Therapies for the Treatment of Hematological Malignancies; Swine Are an Ideal Preclinical Model.Front Oncol. 2019 Jun 21;9:418. doi: 10.3389/fonc.2019.00418. eCollection 2019.
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8 Caprin-1, a novel Cyr61-interacting protein, promotes osteosarcoma tumor growth and lung metastasis in mice.Biochim Biophys Acta. 2013 Aug;1832(8):1173-82. doi: 10.1016/j.bbadis.2013.03.014. Epub 2013 Mar 23.
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10 Synthesis of dihydronaphthalene analogues inspired by combretastatin A-4 and their biological evaluation as anticancer agents.Medchemcomm. 2018 Aug 24;9(10):1649-1662. doi: 10.1039/c8md00322j. eCollection 2018 Oct 1.
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17 DCLRE1C (ARTEMIS) mutations causing phenotypes ranging from atypical severe combined immunodeficiency to mere antibody deficiency.Hum Mol Genet. 2015 Dec 20;24(25):7361-72. doi: 10.1093/hmg/ddv437. Epub 2015 Oct 16.
18 Epstein-Barr virus lytic infection contributes to lymphoproliferative disease in a SCID mouse model.J Virol. 2005 Nov;79(22):13993-4003. doi: 10.1128/JVI.79.22.13993-14003.2005.
19 ARTEMIS stabilizes the genome and modulates proliferative responses in multipotent mesenchymal cells.BMC Biol. 2010 Oct 27;8:132. doi: 10.1186/1741-7007-8-132.
20 Mesenchymal stem cells as a vehicle for targeted delivery of CRAds to lung metastases of breast carcinoma.Breast Cancer Res Treat. 2007 Oct;105(2):157-67. doi: 10.1007/s10549-006-9449-8. Epub 2007 Jan 13.
21 Genome-wide meta-analysis identifies new susceptibility loci for migraine.Nat Genet. 2013 Aug;45(8):912-917. doi: 10.1038/ng.2676. Epub 2013 Jun 23.
22 Effects of miR?81a on the biological function of multiple myeloma.Oncol Rep. 2019 Jul;42(1):291-300. doi: 10.3892/or.2019.7160. Epub 2019 May 15.
23 Immuno-gene therapy of established prostate tumors using chimeric receptor-redirected human lymphocytes.Cancer Res. 2003 May 15;63(10):2470-6.
24 Severe combined immunodeficiency (SCID) presenting in childhood, with agammaglobulinemia, associated with novel compound heterozygous mutations in DCLRE1C.Clin Immunol. 2019 Mar;200:16-18. doi: 10.1016/j.clim.2018.12.019. Epub 2019 Jan 7.
25 Serial transplantation in SCID mice of an epidermodysplasia verruciformis-associated squamous cell carcinoma without alteration of its histological and virological features.Virology. 1996 Mar 1;217(1):380-3. doi: 10.1006/viro.1996.0127.
26 Silencing Artemis Enhances Colorectal Cancer Cell Sensitivity to DNA-Damaging Agents.Oncol Res. 2018 Dec 27;27(1):29-38. doi: 10.3727/096504018X15179694020751. Epub 2018 Feb 9.
27 Severe combined immunodeficiency and microcephaly in siblings with hypomorphic mutations in DNA ligase IV.Eur J Immunol. 2006 Jan;36(1):224-35. doi: 10.1002/eji.200535401.
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29 Clade C HIV-1 isolates circulating in Southern Africa exhibit a greater frequency of dicysteine motif-containing Tat variants than those in Southeast Asia and cause increased neurovirulence.Retrovirology. 2013 Jun 8;10:61. doi: 10.1186/1742-4690-10-61.
30 Evaluation of monoclonal antibody-mediated anti-acute myeloid leukemia immunotherapy in a SCID/hu model.Leuk Res. 1996 Jul;20(7):581-9. doi: 10.1016/0145-2126(96)00004-5.
31 Outcome of depressive and anxiety disorders among young adults: Results from the Longitudinal Finnish Health 2011 Study.Nord J Psychiatry. 2018 Apr;72(3):205-213. doi: 10.1080/08039488.2017.1418429. Epub 2017 Dec 25.
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35 Reduction of in vitro invasion and in vivo cartilage degradation in a SCID mouse model by loss of function of the fibrinolytic system of rheumatoid arthritis synovial fibroblasts.Arthritis Rheum. 2011 Sep;63(9):2584-94. doi: 10.1002/art.30439.
36 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
37 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
38 Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
39 Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
40 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
41 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
42 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
43 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
44 Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010 Oct 15;248(2):111-21.
45 Differences in sensitivity to DNA-damaging Agents between XRCC4- and Artemis-deficient human cells. J Radiat Res. 2011;52(4):415-24. doi: 10.1269/jrr.10168.