Details of Drug Off-Target (DOT)

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

DOT Name SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1 (SMARCAL1)
Synonyms EC 3.6.4.-; HepA-related protein; hHARP; Sucrose nonfermenting protein 2-like 1
Gene Name SMARCAL1
Related Disease
Schimke immuno-osseous dysplasia ( )
T-cell immunodeficiency ( )
Adult glioblastoma ( )
Adult lymphoma ( )
Adult respiratory distress syndrome ( )
Advanced cancer ( )
Arteriosclerosis ( )
Atypical hemolytic uremic syndrome ( )
Benign prostatic hyperplasia ( )
Cerebrovascular disease ( )
Cervical Intraepithelial neoplasia ( )
Chromosomal disorder ( )
Coffin-Siris syndrome ( )
Focal segmental glomerulosclerosis ( )
Glioblastoma multiforme ( )
Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration ( )
Lymphoma ( )
Lymphoma, non-Hodgkin, familial ( )
Neoplasm ( )
Nephropathy ( )
Nephrotic syndrome ( )
Non-hodgkin lymphoma ( )
Pantothenate kinase-associated neurodegeneration ( )
Pediatric lymphoma ( )
Prostate cancer ( )
Prostate carcinoma ( )
Skeletal dysplasia ( )
Spondyloepiphyseal dysplasia ( )
Spondyloepiphyseal dysplasia congenita ( )
T-cell lymphoma ( )
Adenovirus infection ( )
Osteochondrodysplasia ( )
Pulmonary emphysema ( )
Steroid-resistant nephrotic syndrome ( )
Undifferentiated carcinoma ( )
Chronic renal failure ( )
End-stage renal disease ( )
Kidney failure ( )
UniProt ID
SMAL1_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
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PDB ID
4MQV
EC Number
3.6.4.-
Pfam ID
PF07443 ; PF00271 ; PF00176
Sequence
MSLPLTEEQRKKIEENRQKALARRAEKLLAEQHQRTSSGTSIAGNPFQAKQGPSQNFPRE
SCKPVSHGVIFKQQNLSSSSNADQRPHDSHSFQAKGIWKKPEEMPTACPGHSPRSQMALT
GISPPLAQSPPEVPKQQLLSYELGQGHAQASPEIRFTPFANPTHKPLAKPKSSQETPAHS
SGQPPRDAKLEAKTAKASPSGQNISYIHSSSESVTPRTEGRLQQKSGSSVQKGVNSQKGK
CVRNGDRFQVLIGYNAELIAVFKTLPSKNYDPDTKTWNFSMNDYSALMKAAQSLPTVNLQ
PLEWAYGSSESPSTSSEGQAGLPSAPSLSFVKGRCMLISRAYFEADISYSQDLIALFKQM
DSRRYDVKTRKWSFLLEEHSKLIAKVRCLPQVQLDPLPTTLTLAFASQLKKTSLSLTPDV
PEADLSEVDPKLVSNLMPFQRAGVNFAIAKGGRLLLADDMGLGKTIQAICIAAFYRKEWP
LLVVVPSSVRFTWEQAFLRWLPSLSPDCINVVVTGKDRLTAGLINIVSFDLLSKLEKQLK
TPFKVVIIDESHFLKNSRTARCRAAMPVLKVAKRVILLSGTPAMSRPAELYTQIIAVKPT
FFPQFHAFGLRYCDAKRMPWGWDYSGSSNLGELKLLLEEAVMLRRLKSDVLSQLPAKQRK
IVVIAPGRINARTRAALDAAAKEMTTKDKTKQQQKDALILFFNRTAEAKIPSVIEYILDL
LESGREKFLVFAHHKVVLDAITQELERKHVQHIRIDGSTSSAEREDLCQQFQLSERHAVA
VLSITAANMGLTFSSADLVVFAELFWNPGVLIQAEDRVHRIGQTSSVGIHYLVAKGTADD
YLWPLIQEKIKVLAEAGLSETNFSEMTESTDYLYKDPKQQKIYDLFQKSFEKEGSDMELL
EAAESFDPGSASGTSGSSSQNMGDTLDESSLTASPQKKRRFEFFDNWDSFTSPL
Function
ATP-dependent annealing helicase that binds selectively to fork DNA relative to ssDNA or dsDNA and catalyzes the rewinding of the stably unwound DNA. Rewinds single-stranded DNA bubbles that are stably bound by replication protein A (RPA). Acts throughout the genome to reanneal stably unwound DNA, performing the opposite reaction of many enzymes, such as helicases and polymerases, that unwind DNA. May play an important role in DNA damage response by acting at stalled replication forks.
Tissue Specificity Ubiquitously expressed, with high levels in testis.

Molecular Interaction Atlas (MIA) of This DOT

38 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Schimke immuno-osseous dysplasia DISGEL3Z Definitive Autosomal recessive [1]
T-cell immunodeficiency DISHMPS5 Definitive Genetic Variation [2]
Adult glioblastoma DISVP4LU Strong Genetic Variation [3]
Adult lymphoma DISK8IZR Strong Altered Expression [4]
Adult respiratory distress syndrome DISIJV47 Strong Biomarker [5]
Advanced cancer DISAT1Z9 Strong Biomarker [6]
Arteriosclerosis DISK5QGC Strong Genetic Variation [7]
Atypical hemolytic uremic syndrome DIS6FUDJ Strong Genetic Variation [8]
Benign prostatic hyperplasia DISI3CW2 Strong Biomarker [9]
Cerebrovascular disease DISAB237 Strong Genetic Variation [10]
Cervical Intraepithelial neoplasia DISXP757 Strong Genetic Variation [11]
Chromosomal disorder DISM5BB5 Strong Biomarker [12]
Coffin-Siris syndrome DIS8L03H Strong Genetic Variation [13]
Focal segmental glomerulosclerosis DISJNHH0 Strong Genetic Variation [14]
Glioblastoma multiforme DISK8246 Strong Genetic Variation [3]
Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration DISBN8XM Strong Biomarker [15]
Lymphoma DISN6V4S Strong Altered Expression [4]
Lymphoma, non-Hodgkin, familial DISCXYIZ Strong Biomarker [16]
Neoplasm DISZKGEW Strong Biomarker [6]
Nephropathy DISXWP4P Strong Genetic Variation [8]
Nephrotic syndrome DISSPSC2 Strong CausalMutation [17]
Non-hodgkin lymphoma DISS2Y8A Strong Biomarker [16]
Pantothenate kinase-associated neurodegeneration DIS50V55 Strong Biomarker [15]
Pediatric lymphoma DIS51BK2 Strong Altered Expression [4]
Prostate cancer DISF190Y Strong Biomarker [9]
Prostate carcinoma DISMJPLE Strong Biomarker [9]
Skeletal dysplasia DIS5Z8U6 Strong Genetic Variation [7]
Spondyloepiphyseal dysplasia DIS1JG9A Strong Genetic Variation [18]
Spondyloepiphyseal dysplasia congenita DISLC6W8 Strong Genetic Variation [18]
T-cell lymphoma DISSXRTQ Strong Genetic Variation [6]
Adenovirus infection DISUYSBZ moderate Biomarker [19]
Osteochondrodysplasia DIS9SPWW moderate Genetic Variation [7]
Pulmonary emphysema DIS5M7HZ moderate Genetic Variation [20]
Steroid-resistant nephrotic syndrome DISVEBC9 moderate Biomarker [21]
Undifferentiated carcinoma DISIAZST moderate Genetic Variation [22]
Chronic renal failure DISGG7K6 Limited Biomarker [23]
End-stage renal disease DISXA7GG Limited Biomarker [23]
Kidney failure DISOVQ9P Limited Genetic Variation [2]
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⏷ Show the Full List of 38 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 SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1 (SMARCAL1). [24]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1 (SMARCAL1). [25]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1 (SMARCAL1). [26]
Cisplatin DMRHGI9 Approved Cisplatin affects the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1 (SMARCAL1). [27]
Ivermectin DMDBX5F Approved Ivermectin increases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1 (SMARCAL1). [28]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1 (SMARCAL1). [29]
Decitabine DMQL8XJ Approved Decitabine affects the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1 (SMARCAL1). [27]
geraniol DMS3CBD Investigative geraniol increases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1 (SMARCAL1). [33]
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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
Fulvestrant DM0YZC6 Approved Fulvestrant decreases the methylation of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1 (SMARCAL1). [30]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1 (SMARCAL1). [31]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1 (SMARCAL1). [32]
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References

1 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2 Eltrombopag (thrombopoietin-receptor agonist) and plasmapheresis as rescue therapy of acute post-renal transplant immune thrombocytopenia in a child with Schimke immuno-osseous dysplasia-case report.Pediatr Transplant. 2016 Dec;20(8):1148-1151. doi: 10.1111/petr.12828. Epub 2016 Sep 26.
3 The genomic landscape of TERT promoter wildtype-IDH wildtype glioblastoma.Nat Commun. 2018 May 25;9(1):2087. doi: 10.1038/s41467-018-04448-6.
4 Smarcal1 and Zranb3 Protect Replication Forks from Myc-Induced DNA Replication Stress.Cancer Res. 2019 Apr 1;79(7):1612-1623. doi: 10.1158/0008-5472.CAN-18-2705. Epub 2019 Jan 4.
5 Acute respiratory distress syndrome subphenotypes and differential response to simvastatin: secondary analysis of a randomised controlled trial.Lancet Respir Med. 2018 Sep;6(9):691-698. doi: 10.1016/S2213-2600(18)30177-2. Epub 2018 Aug 2.
6 Defective replication stress response inhibits lymphomagenesis and impairs lymphocyte reconstitution.Oncogene. 2017 May 4;36(18):2553-2564. doi: 10.1038/onc.2016.408. Epub 2016 Oct 31.
7 Chromatin changes in SMARCAL1 deficiency: A hypothesis for the gene expression alterations of Schimke immuno-osseous dysplasia.Nucleus. 2016 Nov;7(6):560-571. doi: 10.1080/19491034.2016.1255835.
8 Recurrent atypical haemolytic uraemic syndrome post kidney transplant due to a CD46 mutation in the setting of SMARCAL1-mediated inherited kidney disease.Nephrology (Carlton). 2017 Feb;22 Suppl 1:11-14. doi: 10.1111/nep.12933.
9 Involvement of heparin affin regulatory peptide in human prostate cancer.Prostate. 1999 Feb 1;38(2):126-36. doi: 10.1002/(sici)1097-0045(19990201)38:2<126::aid-pros6>3.0.co;2-c.
10 The pleiotropy associated with de novo variants in CHD4, CNOT3, and SETD5 extends to moyamoya angiopathy.Genet Med. 2020 Feb;22(2):427-431. doi: 10.1038/s41436-019-0639-2. Epub 2019 Sep 2.
11 Cervical intraepithelial neoplasia (CIN) in African women living with HIV: role and effect of rigorous histopathological review by a panel of pathologists in the HARP study endpoint determination.J Clin Pathol. 2018 Jan;71(1):40-45. doi: 10.1136/jclinpath-2017-204512. Epub 2017 Jun 9.
12 Restoration of Replication Fork Stability in BRCA1- and BRCA2-Deficient Cells by Inactivation of SNF2-Family Fork Remodelers.Mol Cell. 2017 Oct 19;68(2):414-430.e8. doi: 10.1016/j.molcel.2017.09.036.
13 Regulation of ATM and ATR by SMARCAL1 and BRG1.Biochim Biophys Acta Gene Regul Mech. 2018 Dec;1861(12):1076-1092. doi: 10.1016/j.bbagrm.2018.10.004. Epub 2018 Oct 11.
14 Genetic mutational testing of Chinese children with familial hematuria with biopsyproven FSGS.Mol Med Rep. 2018 Jan;17(1):1513-1526. doi: 10.3892/mmr.2017.8023. Epub 2017 Nov 10.
15 HARP syndrome is allelic with pantothenate kinase-associated neurodegeneration. Neurology. 2002 Jun 11;58(11):1673-4. doi: 10.1212/wnl.58.11.1673.
16 SMARCAL1 deficiency predisposes to non-Hodgkin lymphoma and hypersensitivity to genotoxic agents in vivo.Am J Med Genet A. 2012 Sep;158A(9):2204-13. doi: 10.1002/ajmg.a.35532. Epub 2012 Aug 7.
17 A novel SMARCAL1 mutation associated with a mild phenotype of Schimke immuno-osseous dysplasia (SIOD).BMC Nephrol. 2014 Mar 3;15:41. doi: 10.1186/1471-2369-15-41.
18 Schimke immunoosseous dysplasia: defining skeletal features.Eur J Pediatr. 2010 Jul;169(7):801-11. doi: 10.1007/s00431-009-1115-9. Epub 2009 Dec 15.
19 Adenovirus E1B 55-Kilodalton Protein Targets SMARCAL1 for Degradation during Infection and Modulates Cellular DNA Replication.J Virol. 2019 Jun 14;93(13):e00402-19. doi: 10.1128/JVI.00402-19. Print 2019 Jul 1.
20 Reduced elastogenesis: a clue to the arteriosclerosis and emphysematous changes in Schimke immuno-osseous dysplasia?.Orphanet J Rare Dis. 2012 Sep 22;7:70. doi: 10.1186/1750-1172-7-70.
21 Low renal but high extrarenal phenotype variability in Schimke immuno-osseous dysplasia.PLoS One. 2017 Aug 10;12(8):e0180926. doi: 10.1371/journal.pone.0180926. eCollection 2017.
22 Schimke Immunoosseous Dysplasia associated with undifferentiated carcinoma and a novel SMARCAL1 mutation in a child.Pediatr Blood Cancer. 2013 Sep;60(9):E88-90. doi: 10.1002/pbc.24542. Epub 2013 Apr 29.
23 Insights into the renal pathogenesis in Schimke immuno-osseous dysplasia: A renal histological characterization and expression analysis.J Histochem Cytochem. 2015 Jan;63(1):32-44. doi: 10.1369/0022155414558335. Epub 2014 Oct 15.
24 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.
25 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.
26 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
27 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.
28 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.
29 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
30 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.
31 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
32 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
33 Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.