Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF54V3W)

• DOT Name: Chromatin remodeling regulator CECR2 (CECR2)
• Synonyms: Cat eye syndrome critical region protein 2
• Gene Name: CECR2
• Related Disease:
  Anencephaly
  DiGeorge syndrome
  Shprintzen-Goldberg syndrome
  Acute myelogenous leukaemia
  Neural tube defect
• UniProt ID: CECR2_HUMAN
• PDB ID: 3NXB; 5V84
• Pfam ID: PF00439
• Sequence:
  MCPEEGGAAGLGELRSWWEVPAIAHFCSLFRTAFRLPDFEIEELEAALHRDDVEFISDLI
  ACLLQGCYQRRDITPQTFHSYLEDIINYRWELEEGKPNPLREASFQDLPLRTRVEILHRL
  CDYRLDADDVFDLLKGLDADSLRVEPLGEDNSGALYWYFYGTRMYKEDPVQGKSNGELSL
  SRESEGQKNVSSIPGKTGKRRGRPPKRKKLQEEILLSEKQEENSLASEPQTRHGSQGPGQ
  GTWWLLCQTEEEWRQVTESFRERTSLRERQLYKLLSEDFLPEICNMIAQKGKRPQRTKAE
  LHPRWMSDHLSIKPVKQEETPVLTRIEKQKRKEEEEERQILLAVQKKEQEQMLKEERKRE
  LEEKVKAVEGMCSVRVVWRGACLSTSRPVDRAKRRKLREERAWLLAQGKELPPELSHLDP
  NSPMREEKKTKDLFELDDDFTAMYKVLDVVKAHKDSWPFLEPVDESYAPNYYQIIKAPMD
  ISSMEKKLNGGLYCTKEEFVNDMKTMFRNCRKYNGESSEYTKMSDNLERCFHRAMMKHFP
  GEDGDTDEEFWIREDEKREKRRSRAGRSGGSHVWTRSRDPEGSSRKQQPMENGGKSLPPT
  RRAPSSGDDQSSSSTQPPREVGTSNGRGFSHPLHCGGTPSQAPFLNQMRPAVPGTFGPLR
  GSDPATLYGSSGVPEPHPGEPVQQRQPFTMQPPVGINSLRGPRLGTPEEKQMCGGLTHLS
  NMGPHPGSLQLGQISGPSQDGSMYAPAQFQPGFIPPRHGGAPARPPDFPESSEIPPSHMY
  RSYKYLNRVHSAVWNGNHGATNQGPLGPDEKPHLGPGPSHQPRTLGHVMDSRVMRPPVPP
  NQWTEQSGFLPHGVPSSGYMRPPCKSAGHRLQPPPVPAPSSLFGAPAQALRGVQGGDSMM
  DSPEMIAMQQLSSRVCPPGVPYHPHQPAHPRLPGPFPQVAHPMSVTVSAPKPALGNPGRA
  PENSEAQEPENDQAEPLPGLEEKPPGVGTSEGVYLTQLPHPTPPLQTDCTRQSSPQERET
  VGPELKSSSSESADNCKAMKGKNPWPSDSSYPGPAAQGCVRDLSTVADRGALSENGVIGE
  ASPCGSEGKGLGSSGSEKLLCPRGRTLQETMPCTGQNAATPPSTDPGLTGGTVSQFPPLY
  MPGLEYPNSAAHYHISPGLQGVGPVMGGKSPASHPQHFPPRGFQSNHPHSGGFPRYRPPQ
  GMRYSYHPPPQPSYHHYQRTPYYACPQSFSDWQRPLHPQGSPSGPPASQPPPPRSLFSDK
  NAMASLQGCETLNAALTSPTRMDAVAAKVPNDGQNPGPEEEKLDESMERPESPKEFLDLD
  NHNAATKRQSSLSASEYLYGTPPPLSSGMGFGSSAFPPHSVMLQTGPPYTPQRPASHFQP
  RAYSSPVAALPPHHPGATQPNGLSQEGPIYRCQEEGLGHFQAVMMEQIGTRSGIRGPFQE
  MYRPSGMQMHPVQSQASFPKTPTAATSQEEVPPHKPPTLPLDQS
• Function: Regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair. The complexes do not have the ability to slide mononucleosomes to the center of a DNA template. The CERF-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the CERF-5 ISWI chromatin remodeling complex. Plays a role in various processes during development: required during embryogenesis for neural tube closure and inner ear development. In adults, required for spermatogenesis, via the formation of ISWI-type chromatin complexes. In histone-modifying complexes, CECR2 recognizes and binds acylated histones: binds histones that are acetylated and/or butyrylated. May also be involved through its interaction with LRPPRC in the integration of cytoskeletal network with vesicular trafficking, nucleocytosolic shuttling, transcription, chromosome remodeling and cytokinesis.
• Tissue Specificity: Highly expressed in skeletal muscle, thymus, placenta and lung. Expressed at lower level in brain, heart, colon, spleen, kidney.
• KEGG Pathway: ATP-dependent chromatin remodeling (hsa03082)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anencephaly	DISIYW6T	Strong	Biomarker	[1]
DiGeorge syndrome	DIST1RKO	Strong	Genetic Variation	[2]
Shprintzen-Goldberg syndrome	DISQH6P3	Strong	Genetic Variation	[2]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[3]
Neural tube defect	DIS5J95E	Limited	Genetic Variation	[4]

5 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Chromatin remodeling regulator CECR2 (CECR2).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Chromatin remodeling regulator CECR2 (CECR2).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Chromatin remodeling regulator CECR2 (CECR2).	[7]
Marinol	DM70IK5	Approved	Marinol increases the expression of Chromatin remodeling regulator CECR2 (CECR2).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Chromatin remodeling regulator CECR2 (CECR2).	[11]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Chromatin remodeling regulator CECR2 (CECR2).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Chromatin remodeling regulator CECR2 (CECR2).	[10]

References

• [1] Strain-specific modifier genes of Cecr2-associated exencephaly in mice: genetic analysis and identification of differentially expressed candidate genes.Physiol Genomics. 2012 Jan 18;44(1):35-46. doi: 10.1152/physiolgenomics.00124.2011. Epub 2011 Nov 1.
• [2] Prenatal detection and characterization of a small supernumerary marker chromosome (sSMC) derived from chromosome 22 with apparently normal phenotype.Prenat Diagn. 2006 Oct;26(10):898-902. doi: 10.1002/pd.1520.
• [3] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [4] Genetic backgrounds and modifier genes of NTD mouse models: An opportunity for greater understanding of the multifactorial etiology of neural tube defects.Birth Defects Res. 2017 Jan 30;109(2):140-152. doi: 10.1002/bdra.23554.
• [5] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [6] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [7] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [8] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [9] 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.
• [10] 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.
• [11] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.