Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH4VAP9)

DOT Name Activating signal cointegrator 1 complex subunit 1 (ASCC1)
Synonyms ASC-1 complex subunit p50; Trip4 complex subunit p50
Gene Name ASCC1
Related Disease
Breast carcinoma ( )
Spinal muscular atrophy with congenital bone fractures 2 ( )
Adult glioblastoma ( )
Advanced cancer ( )
Alzheimer disease ( )
Arthrogryposis ( )
Astrocytoma ( )
B-cell neoplasm ( )
Barrett esophagus ( )
Breast cancer ( )
Breast neoplasm ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Endometrial carcinoma ( )
Fetal akinesia deformation sequence 1 ( )
Glioblastoma multiforme ( )
Glioma ( )
Head-neck squamous cell carcinoma ( )
Melanoma ( )
Myocardial infarction ( )
Neoplasm ( )
Neuroblastoma ( )
OPTN-related open angle glaucoma ( )
Osteoarthritis ( )
Pancreatic cancer ( )
Polycythemia ( )
Prostate cancer ( )
Psychotic disorder ( )
Rheumatoid arthritis ( )
Small lymphocytic lymphoma ( )
Spinal muscular atrophy ( )
Type-1/2 diabetes ( )
Epithelial ovarian cancer ( )
Nasopharyngeal carcinoma ( )
Ovarian cancer ( )
Thyroid gland carcinoma ( )
Acute myelogenous leukaemia ( )
Bipolar disorder ( )
Cervical cancer ( )
Cervical carcinoma ( )
Cognitive impairment ( )
Coronary heart disease ( )
Mental disorder ( )
Non-small-cell lung cancer ( )
Prostate carcinoma ( )
Ulcerative colitis ( )
UniProt ID
ASCC1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF10469 ; PF00013
Sequence
MEVLRPQLIRIDGRNYRKNPVQEQTYQHEEDEEDFYQGSMECADEPCDAYEVEQTPQGFR
STLRAPSLLYNLIHLNTSNDCGFQKITLDCQNIYTWKSRHIVGKRGDTRKKIEMETKTSI
SIPKPGQDGEIVITGQHRNGVISARTRIDVLLDTFRRKQPFTHFLAFFLNEVEVQEGFLR
FQEEVLAKCSMDHGVDSSIFQNPKKLHLTIGMLVLLSEEEIQQTCEMLQQCKEEFINDIS
GGKPLEVEMAGIEYMNDDPGMVDVLYAKVHMKDGSNRLQELVDRVLERFQASGLIVKEWN
SVKLHATVMNTLFRKDPNAEGRYNLYTAEGKYIFKERESFDGRNILKSFALLPRLEYNDA
ISAHCNLCLPGSSDSPASASQVAGITGVSDAYSQSLPGKS
Function
Plays a role in DNA damage repair as component of the ASCC complex. Part of the ASC-1 complex that enhances NF-kappa-B, SRF and AP1 transactivation. In cells responding to gastrin-activated paracrine signals, it is involved in the induction of SERPINB2 expression by gastrin. May also play a role in the development of neuromuscular junction.
Tissue Specificity Ubiquitous.
Reactome Pathway
ALKBH3 mediated reversal of alkylation damage (R-HSA-112126 )

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Breast carcinoma DIS2UE88 Definitive Altered Expression [1]
Spinal muscular atrophy with congenital bone fractures 2 DIS8J9SD Definitive Autosomal recessive [2]
Adult glioblastoma DISVP4LU Strong Biomarker [3]
Advanced cancer DISAT1Z9 Strong Altered Expression [4]
Alzheimer disease DISF8S70 Strong Biomarker [5]
Arthrogryposis DISC81CM Strong Biomarker [6]
Astrocytoma DISL3V18 Strong Altered Expression [7]
B-cell neoplasm DISVY326 Strong Biomarker [8]
Barrett esophagus DIS416Y7 Strong Biomarker [9]
Breast cancer DIS7DPX1 Strong Altered Expression [1]
Breast neoplasm DISNGJLM Strong Altered Expression [10]
Colon cancer DISVC52G Strong Altered Expression [11]
Colon carcinoma DISJYKUO Strong Altered Expression [11]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [4]
Endometrial carcinoma DISXR5CY Strong Altered Expression [12]
Fetal akinesia deformation sequence 1 DISKDI9L Strong Biomarker [6]
Glioblastoma multiforme DISK8246 Strong Biomarker [13]
Glioma DIS5RPEH Strong Biomarker [3]
Head-neck squamous cell carcinoma DISF7P24 Strong Biomarker [14]
Melanoma DIS1RRCY Strong Altered Expression [15]
Myocardial infarction DIS655KI Strong Altered Expression [16]
Neoplasm DISZKGEW Strong Biomarker [17]
Neuroblastoma DISVZBI4 Strong Altered Expression [18]
OPTN-related open angle glaucoma DISDR98A Strong Biomarker [19]
Osteoarthritis DIS05URM Strong Biomarker [20]
Pancreatic cancer DISJC981 Strong Biomarker [21]
Polycythemia DIS8B6VW Strong Genetic Variation [22]
Prostate cancer DISF190Y Strong Altered Expression [23]
Psychotic disorder DIS4UQOT Strong Biomarker [24]
Rheumatoid arthritis DISTSB4J Strong Biomarker [25]
Small lymphocytic lymphoma DIS30POX Strong Altered Expression [26]
Spinal muscular atrophy DISTLKOB Strong Posttranslational Modification [27]
Type-1/2 diabetes DISIUHAP Strong Biomarker [28]
Epithelial ovarian cancer DIS56MH2 moderate Biomarker [29]
Nasopharyngeal carcinoma DISAOTQ0 moderate Biomarker [30]
Ovarian cancer DISZJHAP moderate Biomarker [29]
Thyroid gland carcinoma DISMNGZ0 moderate Altered Expression [31]
Acute myelogenous leukaemia DISCSPTN Limited Biomarker [32]
Bipolar disorder DISAM7J2 Limited Genetic Variation [33]
Cervical cancer DISFSHPF Limited Altered Expression [34]
Cervical carcinoma DIST4S00 Limited Altered Expression [34]
Cognitive impairment DISH2ERD Limited Biomarker [35]
Coronary heart disease DIS5OIP1 Limited Genetic Variation [36]
Mental disorder DIS3J5R8 Limited Biomarker [37]
Non-small-cell lung cancer DIS5Y6R9 Limited Altered Expression [38]
Prostate carcinoma DISMJPLE Limited Altered Expression [39]
Ulcerative colitis DIS8K27O Limited Altered Expression [40]
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⏷ Show the Full List of 47 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
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Activating signal cointegrator 1 complex subunit 1 (ASCC1). [41]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Activating signal cointegrator 1 complex subunit 1 (ASCC1). [42]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Activating signal cointegrator 1 complex subunit 1 (ASCC1). [43]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Activating signal cointegrator 1 complex subunit 1 (ASCC1). [44]
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References

1 MUC1 induces M2 type macrophage influx during postpartum mammary gland involution and triggers breast cancer.Oncotarget. 2017 Dec 15;9(3):3446-3458. doi: 10.18632/oncotarget.23316. eCollection 2018 Jan 9.
2 Mutations in Subunits of the Activating Signal Cointegrator 1 Complex Are Associated with Prenatal Spinal Muscular Atrophy and Congenital Bone Fractures. Am J Hum Genet. 2016 Mar 3;98(3):473-489. doi: 10.1016/j.ajhg.2016.01.006. Epub 2016 Feb 25.
3 Absence of host NF-B p50 induces murine glioblastoma tumor regression, increases survival, and decreases T-cell induction of tumor-associated macrophage M2 polarization.Cancer Immunol Immunother. 2018 Oct;67(10):1491-1503. doi: 10.1007/s00262-018-2184-2. Epub 2018 Jul 21.
4 Protumor Steering of Cancer Inflammation by p50 NF-B Enhances Colorectal Cancer Progression.Cancer Immunol Res. 2018 May;6(5):578-593. doi: 10.1158/2326-6066.CIR-17-0036. Epub 2018 Mar 27.
5 Complex regulation of acute and chronic neuroinflammatory responses in mouse models deficient for nuclear factor kappa B p50 subunit.Neurobiol Dis. 2014 Apr;64:16-29. doi: 10.1016/j.nbd.2013.12.003. Epub 2013 Dec 15.
6 Molecular autopsy in maternal-fetal medicine.Genet Med. 2018 Apr;20(4):420-427. doi: 10.1038/gim.2017.111. Epub 2017 Jul 20.
7 Aberrant nuclear factor-kappaB activity and its participation in the growth of human malignant astrocytoma.J Neurosurg. 2002 May;96(5):909-17. doi: 10.3171/jns.2002.96.5.0909.
8 MicroRNA Mediate Visfatin and Resistin Induction of Oxidative Stress in Human Osteoarthritic Synovial Fibroblasts Via NF-B Pathway.Int J Mol Sci. 2019 Oct 20;20(20):5200. doi: 10.3390/ijms20205200.
9 Germline mutations in MSR1, ASCC1, and CTHRC1 in patients with Barrett esophagus and esophageal adenocarcinoma.JAMA. 2011 Jul 27;306(4):410-9. doi: 10.1001/jama.2011.1029.
10 Selective activation of NF-kappa B subunits in human breast cancer: potential roles for NF-kappa B2/p52 and for Bcl-3.Oncogene. 2000 Feb 24;19(9):1123-31. doi: 10.1038/sj.onc.1203412.
11 Inflexinol inhibits colon cancer cell growth through inhibition of nuclear factor-kappaB activity via direct interaction with p50.Mol Cancer Ther. 2009 Jun;8(6):1613-24. doi: 10.1158/1535-7163.MCT-08-0694. Epub 2009 Jun 9.
12 SNP55, a new functional polymorphism of MDM2-P2 promoter, contributes to allele-specific expression of MDM2 in endometrial cancers.BMC Med Genet. 2015 Aug 21;16:67. doi: 10.1186/s12881-015-0216-8.
13 Temozolomide Treatment Induces lncRNA MALAT1 in an NF-B and p53 Codependent Manner in Glioblastoma.Cancer Res. 2019 May 15;79(10):2536-2548. doi: 10.1158/0008-5472.CAN-18-2170. Epub 2019 Apr 2.
14 NFB-p50 as a blood based protein marker for early diagnosis and prognosis of head and neck squamous cell carcinoma.Biochem Biophys Res Commun. 2015 Nov 13;467(2):248-53. doi: 10.1016/j.bbrc.2015.09.181. Epub 2015 Oct 3.
15 Coexpression of major histocompatibility complex class II with chemokines and nuclear NFkappaB p50 in melanoma: a rational for their association with poor prognosis.Melanoma Res. 2009 Aug;19(4):226-37. doi: 10.1097/CMR.0b013e32832e0bc3.
16 Targeted deletion of nuclear factor kappaB p50 enhances cardiac remodeling and dysfunction following myocardial infarction.Circ Res. 2009 Mar 13;104(5):699-706. doi: 10.1161/CIRCRESAHA.108.189746. Epub 2009 Jan 24.
17 The tumor suppressor Sef is a scaffold for the classical NF-B/RELA:P50 signaling module.Cell Signal. 2019 Jul;59:110-121. doi: 10.1016/j.cellsig.2019.01.009. Epub 2019 Mar 9.
18 N-myc suppresses major histocompatibility complex class I gene expression through down-regulation of the p50 subunit of NF-kappa B.EMBO J. 1993 Jan;12(1):195-200. doi: 10.1002/j.1460-2075.1993.tb05645.x.
19 Role of Pattern Electroretinogram in Ocular Hypertension and Early Glaucoma.J Glaucoma. 2019 Oct;28(10):871-877. doi: 10.1097/IJG.0000000000001325.
20 Methylsulfonylmethane and mobilee prevent negative effect of IL-1 in human chondrocyte cultures via NF-B signaling pathway.Int Immunopharmacol. 2018 Dec;65:129-139. doi: 10.1016/j.intimp.2018.10.004. Epub 2018 Oct 10.
21 Intracellular annexin A2 regulates NF-B signaling by binding to the p50 subunit: implications for gemcitabine resistance in pancreatic cancer.Cell Death Dis. 2015 Jan 22;6(1):e1606. doi: 10.1038/cddis.2014.558.
22 The complete evaluation of erythrocytosis: congenital and acquired.Leukemia. 2009 May;23(5):834-44. doi: 10.1038/leu.2009.54. Epub 2009 Mar 19.
23 Constitutive activation of nuclear factor kappaB p50/p65 and Fra-1 and JunD is essential for deregulated interleukin 6 expression in prostate cancer.Cancer Res. 2003 May 1;63(9):2206-15.
24 Auditory sensory gating in young adolescents with early-onset psychosis: a comparison with attention deficit/hyperactivity disorder.Neuropsychopharmacology. 2020 Mar;45(4):649-655. doi: 10.1038/s41386-019-0555-9. Epub 2019 Oct 24.
25 A Truncated Variant of ASCC1, a Novel Inhibitor of NF-B, Is Associated with Disease Severity in Patients with Rheumatoid Arthritis.J Immunol. 2015 Dec 1;195(11):5415-20. doi: 10.4049/jimmunol.1501532. Epub 2015 Oct 26.
26 Genetic variants associated with autoimmunity drive NFB signaling and responses to inflammatory stimuli.Sci Transl Med. 2015 Jun 10;7(291):291ra93. doi: 10.1126/scitranslmed.aaa9223.
27 SMN deficiency causes pain hypersensitivity in a mild SMA mouse model through enhancing excitability of nociceptive dorsal root ganglion neurons.Sci Rep. 2019 Apr 24;9(1):6493. doi: 10.1038/s41598-019-43053-5.
28 Divergent responses to kisspeptin in children with delayed puberty.JCI Insight. 2018 Apr 19;3(8):e99109. doi: 10.1172/jci.insight.99109. eCollection 2018 Apr 19.
29 p50 nuclear factor-kappaB overexpression in tumor-associated macrophages inhibits M1 inflammatory responses and antitumor resistance.Cancer Res. 2006 Dec 1;66(23):11432-40. doi: 10.1158/0008-5472.CAN-06-1867.
30 Activation of nuclear factor-kappaB p50 homodimer/Bcl-3 complexes in nasopharyngeal carcinoma.Cancer Res. 2003 Dec 1;63(23):8293-301.
31 The levels of NF-B p50 and NF-B p65 play a role in thyroid carcinoma malignancy in vivo.J Int Med Res. 2018 Oct;46(10):4092-4099. doi: 10.1177/0300060518785846. Epub 2018 Jul 17.
32 CCAAT/enhancer binding protein alpha (C/EBPalpha) and C/EBPalpha myeloid oncoproteins induce bcl-2 via interaction of their basic regions with nuclear factor-kappaB p50.Mol Cancer Res. 2005 Oct;3(10):585-96. doi: 10.1158/1541-7786.MCR-05-0111.
33 Systematic review of cognitive event related potentials in euthymic bipolar disorder.Clin Neurophysiol. 2018 Sep;129(9):1854-1865. doi: 10.1016/j.clinph.2018.05.025. Epub 2018 Jun 27.
34 Coexpression of Notch1 and NF-kappaB signaling pathway components in human cervical cancer progression.Gynecol Oncol. 2007 Feb;104(2):352-61. doi: 10.1016/j.ygyno.2006.08.054. Epub 2006 Nov 13.
35 P50 inhibition deficit in patients with chronic schizophrenia: Relationship with cognitive impairment of MATRICS consensus cognitive battery.Schizophr Res. 2020 Jan;215:105-112. doi: 10.1016/j.schres.2019.11.012. Epub 2019 Nov 25.
36 -94 ATTG insertion/deletion polymorphism of the NFKB1 gene is associated with coronary artery disease in Han and Uygur women in China.Genet Test Mol Biomarkers. 2014 Jun;18(6):430-8. doi: 10.1089/gtmb.2013.0431. Epub 2014 May 12.
37 Clinical and Cognitive Significance of Auditory Sensory Processing Deficits in Schizophrenia.Am J Psychiatry. 2018 Mar 1;175(3):275-283. doi: 10.1176/appi.ajp.2017.16111203. Epub 2017 Dec 5.
38 Altered expression of the p50 subunit of the NF-kappa B transcription factor complex in non-small cell lung carcinoma.Oncogene. 1995 Sep 7;11(5):999-1003.
39 Tumor necrosis factor-related apoptosis-inducing ligand-mediated activation of mitochondria-associated nuclear factor-kappaB in prostatic carcinoma cell lines.Mol Cancer Res. 2004 Oct;2(10):574-84.
40 Cytokine gene transcription by NF-kappa B family members in patients with inflammatory bowel disease.Ann N Y Acad Sci. 1998 Nov 17;859:149-59. doi: 10.1111/j.1749-6632.1998.tb11119.x.
41 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.
42 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.
43 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
44 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.