Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1ZMRHL)

DOT Name Centrosomal protein of 120 kDa (CEP120)
Synonyms Cep120; Coiled-coil domain-containing protein 100
Gene Name CEP120
Related Disease
Ciliopathy ( )
Joubert syndrome 1 ( )
Joubert syndrome 31 ( )
Meckel syndrome, type 1 ( )
Plasma cell myeloma ( )
Short-rib thoracic dysplasia 13 with or without polydactyly ( )
Jeune syndrome ( )
Joubert syndrome ( )
Joubert syndrome with ocular defect ( )
UniProt ID
CE120_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
4ICW; 4ICX; 6FLJ; 6FLK
Pfam ID
PF00168 ; PF12416
Sequence
MVSKSDQLLIVVSILEGRHFPKRPKHMLVVEAKFDGEQLATDPVDHTDQPEFATELAWEI
DRKALHQHRLQRTPIKLQCFALDPVTSAKETIGYIVLDLRTAQETKQAPKWYQLLSNKYT
KFKSEIQISIALETDTKPPVDSFKAKGAPPRDGKVPAILAGLDPRDIVAVLNEEGGYHQI
GPAEYCTDSFIMSVTIAFATQLEQLIPCTMKLPERQPEFFFYYSLLGNDVTNEPFNDLIN
PNFEPERASVRIRSSVEILRVYLALQSKLQIHLCCGDQSLGSTEIPLTGLLKKGSTEINQ
HPVTVEGAFTLDPPNRAKQKLAPIPVELAPTVGVSVALQREGIDSQSLIELKTQNEHEPE
HSKKKVLTPIKEKTLTGPKSPTVSPVPSHNQSPPTKDDATESEVESLQYDKDTKPNPKAS
SSVPASLAQLVTTSNASEVASGQKIAVPATSHHFCFSIDLRSIHALEIGFPINCILRYSY
PFFGSAAPIMTNPPVEVRKNMEVFLPQSYCAFDFATMPHQLQDTFLRIPLLVELWHKDKM
SKDLLLGIARIQLSNILSSEKTRFLGSNGEQCWRQTYSESVPVIAAQGSNNRIADLSYTV
TLEDYGLVKMREIFISDSSQGVSAVQQKPSSLPPAPCPSEIQTEPRETLEYKAALELEMW
KEMQEDIFENQLKQKELAHMQALAEEWKKRDRERESLVKKKVAEYTILEGKLQKTLIDLE
KREQQLASVESELQREKKELQSERQRNLQELQDSIRRAKEDCIHQVELERLKIKQLEEDK
HRLQQQLNDAENKYKILEKEFQQFKDQQNNKPEIRLQSEINLLTLEKVELERKLESATKS
KLHYKQQWGRALKELARLKQREQESQMARLKKQQEELEQMRLRYLAAEEKDTVKTERQEL
LDIRNELNRLRQQEQKQYQDSTEIASGKKDGPHGSVLEEGLDDYLTRLIEERDTLMRTGV
YNHEDRIISELDRQIREILAKSNASN
Function
Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome. Involved in the processes that regulate centrosome-mediated interkinetic nuclear migration (INM) of neural progenitors and for proper positioning of neurons during brain development. Also implicated in the migration and selfrenewal of neural progenitors. Required for centriole duplication and maturation during mitosis and subsequent ciliogenesis. Required for the recruitment of CEP295 to the proximal end of new-born centrioles at the centriolar microtubule wall during early S phase in a PLK4-dependent manner.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Ciliopathy DIS10G4I Definitive Genetic Variation [1]
Joubert syndrome 1 DISC9Q82 Strong Biomarker [2]
Joubert syndrome 31 DIS1TGGQ Strong Autosomal recessive [3]
Meckel syndrome, type 1 DIS4YWZU Strong Biomarker [2]
Plasma cell myeloma DIS0DFZ0 Strong Genetic Variation [4]
Short-rib thoracic dysplasia 13 with or without polydactyly DISAAU3T Strong Autosomal recessive [3]
Jeune syndrome DISLC357 Supportive Autosomal recessive [5]
Joubert syndrome DIS7P5CO Supportive Autosomal recessive [2]
Joubert syndrome with ocular defect DISDJVUI Supportive Autosomal recessive [2]
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⏷ Show the Full List of 9 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
11 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 Centrosomal protein of 120 kDa (CEP120). [6]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Centrosomal protein of 120 kDa (CEP120). [7]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Centrosomal protein of 120 kDa (CEP120). [8]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Centrosomal protein of 120 kDa (CEP120). [9]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Centrosomal protein of 120 kDa (CEP120). [10]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Centrosomal protein of 120 kDa (CEP120). [11]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Centrosomal protein of 120 kDa (CEP120). [12]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Centrosomal protein of 120 kDa (CEP120). [13]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Centrosomal protein of 120 kDa (CEP120). [14]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Centrosomal protein of 120 kDa (CEP120). [15]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Centrosomal protein of 120 kDa (CEP120). [16]
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⏷ Show the Full List of 11 Drug(s)

References

1 CEP120 interacts with C2CD3 and Talpid3 and is required for centriole appendage assembly and ciliogenesis.Sci Rep. 2019 Apr 15;9(1):6037. doi: 10.1038/s41598-019-42577-0.
2 Mutations in CEP120 cause Joubert syndrome as well as complex ciliopathy phenotypes. J Med Genet. 2016 Sep;53(9):608-15. doi: 10.1136/jmedgenet-2016-103832. Epub 2016 May 6.
3 Talpid3-binding centrosomal protein Cep120 is required for centriole duplication and proliferation of cerebellar granule neuron progenitors. PLoS One. 2014 Sep 24;9(9):e107943. doi: 10.1371/journal.pone.0107943. eCollection 2014.
4 Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma.Nat Commun. 2018 Sep 13;9(1):3707. doi: 10.1038/s41467-018-04989-w.
5 A founder CEP120 mutation in Jeune asphyxiating thoracic dystrophy expands the role of centriolar proteins in skeletal ciliopathies. Hum Mol Genet. 2015 Mar 1;24(5):1410-9. doi: 10.1093/hmg/ddu555. Epub 2014 Oct 30.
6 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
7 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.
8 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.
9 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.
10 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.
11 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
12 The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
13 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
14 Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
15 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.
16 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.