Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQI3VBA)

• DOT Name: Centriolin (CNTRL)
• Synonyms: Centrosomal protein 1; Centrosomal protein of 110 kDa; Cep110
• Gene Name: CNTRL
• Related Disease:
  Chromosomal disorder
  Lymphatic malformation 1
  Peeling skin syndrome 1
  Potocki-Shaffer syndrome
  Systemic sclerosis
  Autoimmune disease
  Myeloproliferative neoplasm
  Osteoarthritis
  Advanced cancer
  Melanoma
  Neoplasm
  AIDS-related lymphoma
  Arthritis
  Leukemia
• UniProt ID: CNTRL_HUMAN
• Pfam ID: PF14580
• Sequence:
  MKKGSQQKIFSKAKIPSSSHSPIPSSMSNMRSRSLSPLIGSETLPFHSGGQWCEQVEIAD
  ENNMLLDYQDHKGADSHAGVRYITEALIKKLTKQDNLALIKSLNLSLSKDGGKKFKYIEN
  LEKCVKLEVLNLSYNLIGKIEKLDKLLKLRELNLSYNKISKIEGIENMCNLQKLNLAGNE
  IEHIPVWLGKKLKSLRVLNLKGNKISSLQDISKLKPLQDLISLILVENPVVTLPHYLQFT
  IFHLRSLESLEGQPVTTQDRQEAFERFSLEEVERLERDLEKKMIETEELKSKQTRFLEEI
  KNQDKLNKSLKEEAMLQKQSCEELKSDLNTKNELLKQKTIELTRACQKQYELEQELAFYK
  IDAKFEPLNYYPSEYAEIDKAPDESPYIGKSRYKRNMFATESYIIDSAQAVQIKKMEPDE
  QLRNDHMNLRGHTPLDTQLEDKEKKISAAQTRLSELHDEIEKAEQQILRATEEFKQLEEA
  IQLKKISEAGKDLLYKQLSGRLQLVNKLRQEALDLELQMEKQKQEIAGKQKEIKDLQIAI
  DSLDSKDPKHSHMKAQKSGKEQQLDIMNKQYQQLESRLDEILSRIAKETEEIKDLEEQLT
  EGQIAANEALKKDLEGVISGLQEYLGTIKGQATQAQNECRKLRDEKETLLQRLTEVEQER
  DQLEIVAMDAENMRKELAELESALQEQHEVNASLQQTQGDLSAYEAELEARLNLRDAEAN
  QLKEELEKVTRLTQLEQSALQAELEKERQALKNALGKAQFSEEKEQENSELHAKLKHLQD
  DNNLLKQQLKDFQNHLNHVVDGLVRPEEVAARVDELRRKLKLGTGEMNIHSPSDVLGKSL
  ADLQKQFSEILARSKWERDEAQVRERKLQEEMALQQEKLATGQEEFRQACERALEARMNF
  DKRQHEARIQQMENEIHYLQENLKSMEEIQGLTDLQLQEADEEKERILAQLRELEKKKKL
  EDAKSQEQVFGLDKELKKLKKAVATSDKLATAELTIAKDQLKSLHGTVMKINQERAEELQ
  EAERFSRKAAQAARDLTRAEAEIELLQNLLRQKGEQFRLEMEKTGVGTGANSQVLEIEKL
  NETMERQRTEIARLQNVLDLTGSDNKGGFENVLEEIAELRREVSYQNDYISSMADPFKRR
  GYWYFMPPPPSSKVSSHSSQATKDSGVGLKYSASTPVRKPRPGQQDGKEGSQPPPASGYW
  VYSPIRSGLHKLFPSRDADSGGDSQEESELDDQEEPPFVPPPGYMMYTVLPDGSPVPQGM
  ALYAPPPPLPNNSRPLTPGTVVYGPPPAGAPMVYGPPPPNFSIPFIPMGVLHCNVPEHHN
  LENEVSRLEDIMQHLKSKKREERWMRASKRQSEKEMEELHHNIDDLLQEKKSLECEVEEL
  HRTVQKRQQQKDFIDGNVESLMTELEIEKSLKHHEDIVDEIECIEKTLLKRRSELREADR
  LLAEAESELSCTKEKTKNAVEKFTDAKRSLLQTESDAEELERRAQETAVNLVKADQQLRS
  LQADAKDLEQHKIKQEEILKEINKIVAAKDSDFQCLSKKKEKLTEELQKLQKDIEMAERN
  EDHHLQVLKESEVLLQAKRAELEKLKSQVTSQQQEMAVLDRQLGHKKEELHLLQGSMVQA
  KADLQEALRLGETEVTEKCNHIREVKSLLEELSFQKGELNVQISERKTQLTLIKQEIEKE
  EENLQVVLRQMSKHKTELKNILDMLQLENHELQGLKLQHDQRVSELEKTQVAVLEEKLEL
  ENLQQISQQQKGEIEWQKQLLERDKREIERMTAESRALQSCVECLSKEKEDLQEKCDIWE
  KKLAQTKRVLAAAEENSKMEQSNLEKLELNVRKLQQELDQLNRDKLSLHNDISAMQQQLQ
  EKREAVNSLQEELANVQDHLNLAKQDLLHTTKHQDVLLSEQTRLQKDISEWANRFEDCQK
  EEETKQQQLQVLQNEIEENKLKLVQQEMMFQRLQKERESEESKLETSKVTLKEQQHQLEK
  ELTDQKSKLDQVLSKVLAAEERVRTLQEEERWCESLEKTLSQTKRQLSEREQQLVEKSGE
  LLALQKEADSMRADFSLLRNQFLTERKKAEKQVASLKEALKIQRSQLEKNLLEQKQENSC
  IQKEMATIELVAQDNHERARRLMKELNQMQYEYTELKKQMANQKDLERRQMEISDAMRTL
  KSEVKDEIRTSLKNLNQFLPELPADLEAILERNENLEGELESLKENLPFTMNEGPFEEKL
  NFSQVHIMDEHWRGEALREKLRHREDRLKAQLRHCMSKQAEVLIKGKRQTEGTLHSLRRQ
  VDALGELVTSTSADSASSPSLSQLESSLTEDSQLGQNQEKNASAR
• Function: Involved in cell cycle progression and cytokinesis. During the late steps of cytokinesis, anchors exocyst and SNARE complexes at the midbody, thereby allowing secretory vesicle-mediated abscission.
• Tissue Specificity: Widely expressed with highest levels in testis and trachea.
• Reactome Pathway:
  Loss of Nlp from mitotic centrosomes (R-HSA-380259)
  Recruitment of mitotic centrosome proteins and complexes (R-HSA-380270)
  Loss of proteins required for interphase microtubule organization from the centrosome (R-HSA-380284)
  Recruitment of NuMA to mitotic centrosomes (R-HSA-380320)
  Anchoring of the basal body to the plasma membrane (R-HSA-5620912)
  AURKA Activation by TPX2 (R-HSA-8854518)
  Regulation of PLK1 Activity at G2/M Transition (R-HSA-2565942)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chromosomal disorder	DISM5BB5	Definitive	Genetic Variation	[1]
Lymphatic malformation 1	DIS857QZ	Definitive	Genetic Variation	[1]
Peeling skin syndrome 1	DIS35574	Definitive	Biomarker	[2]
Potocki-Shaffer syndrome	DISKGU59	Definitive	Biomarker	[2]
Systemic sclerosis	DISF44L6	Definitive	Biomarker	[2]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[3]
Myeloproliferative neoplasm	DIS5KAPA	Strong	Genetic Variation	[4]
Osteoarthritis	DIS05URM	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[6]
Melanoma	DIS1RRCY	moderate	Biomarker	[6]
Neoplasm	DISZKGEW	moderate	Biomarker	[6]
AIDS-related lymphoma	DISSLRAU	Limited	Biomarker	[7]
Arthritis	DIST1YEL	Limited	Biomarker	[8]
Leukemia	DISNAKFL	Limited	Biomarker	[9]

10 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 Centriolin (CNTRL).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Centriolin (CNTRL).	[11]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Centriolin (CNTRL).	[12]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Centriolin (CNTRL).	[13]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Centriolin (CNTRL).	[14]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Centriolin (CNTRL).	[15]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Centriolin (CNTRL).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Centriolin (CNTRL).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Centriolin (CNTRL).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Centriolin (CNTRL).	[19]

References

• [1] Molecular cytogenetic aberrations in 21 Chinese patients with plasma cell leukemia.Int J Lab Hematol. 2009 Jun;31(3):338-43. doi: 10.1111/j.1751-553X.2008.01037.x. Epub 2008 Feb 18.
• [2] Antibodies against citrullinated alpha enolase peptides in primary Sjogren's syndrome.Clin Immunol. 2017 Oct;183:300-303. doi: 10.1016/j.clim.2017.09.012. Epub 2017 Sep 14.
• [3] Autoimmunity to specific citrullinated proteins gives the first clues to the etiology of rheumatoid arthritis.Immunol Rev. 2010 Jan;233(1):34-54. doi: 10.1111/j.0105-2896.2009.00850.x.
• [4] NIN, a gene encoding a CEP110-like centrosomal protein, is fused to PDGFRB in a patient with a t(5;14)(q33;q24) and an imatinib-responsive myeloproliferative disorder.Cancer Res. 2004 Apr 15;64(8):2673-6. doi: 10.1158/0008-5472.can-04-0144.
• [5] Association of Distinct Fine Specificities of Anti-Citrullinated Peptide Antibodies With Elevated Immune Responses to Prevotella intermedia in a Subgroup of Patients With Rheumatoid Arthritis and Periodontitis.Arthritis Rheumatol. 2017 Dec;69(12):2303-2313. doi: 10.1002/art.40227. Epub 2017 Oct 30.
• [6] TNF-receptor-1 adaptor protein FAN mediates TNF-induced B16 melanoma motility and invasion.Br J Cancer. 2013 Jul 23;109(2):422-32. doi: 10.1038/bjc.2013.242. Epub 2013 May 14.
• [7] Biscoclaurine alkaloid cepharanthine inhibits the growth of primary effusion lymphoma in vitro and in vivo and induces apoptosis via suppression of the NF-kappaB pathway.Int J Cancer. 2009 Sep 15;125(6):1464-72. doi: 10.1002/ijc.24521.
• [8] Immunization with Porphyromonas gingivalis enolase induces autoimmunity to mammalian -enolase and arthritis in DR4-IE-transgenic mice.Arthritis Rheum. 2011 Dec;63(12):3818-23. doi: 10.1002/art.30639.
• [9] Targeted therapy and disease monitoring in CNTRL-FGFR1-driven leukaemia.Pediatr Blood Cancer. 2019 Oct;66(10):e27897. doi: 10.1002/pbc.27897. Epub 2019 Jun 28.
• [10] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [11] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [12] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [13] DNA methylation inhibits p53-mediated survivin repression. Oncogene. 2009 May 14;28(19):2046-50. doi: 10.1038/onc.2009.62. Epub 2009 Apr 13.
• [14] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [15] 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.
• [16] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [17] 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.
• [18] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [19] 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.