Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW4Z65J)

• DOT Name: Pericentrin (PCNT)
• Synonyms: Kendrin; Pericentrin-B
• Gene Name: PCNT
• Related Disease:
  Microcephalic osteodysplastic primordial dwarfism type II
  Seckel syndrome 1
  Seckel syndrome 2
  Autosomal recessive primary microcephaly
  Bipolar disorder
  Blast phase chronic myelogenous leukemia, BCR-ABL1 positive
  Breast cancer
  Breast carcinoma
  Cerebrovascular disease
  Chromosomal disorder
  Ciliopathy
  Depression
  Epithelial ovarian cancer
  facioscapulohumeral muscular dystrophy
  Frontometaphyseal dysplasia 1
  Hepatocellular carcinoma
  Isolated growth hormone deficiency type IA
  Lung neoplasm
  Major depressive disorder
  Mantle cell lymphoma
  Mental disorder
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Prostate carcinoma
  Psychotic disorder
  Seckel syndrome
  Type-1/2 diabetes
  Advanced cancer
  Lung adenocarcinoma
  Moyamoya disease
  Cardiomyopathy
  Colorectal carcinoma
  Isolated congenital microcephaly
  Parkinson disease
• UniProt ID: PCNT_HUMAN
• Pfam ID: PF10495
• Sequence:
  MEVEQEQRRRKVEAGRTKLAHFRQRKTKGDSSHSEKKTAKRKGSAVDASVQEESPVTKED
  SALCGGGDICKSTSCDDTPDGAGGAFAAQPEDCDGEKREDLEQLQQKQVNDHPPEQCGMF
  TVSDHPPEQHGMFTVGDHPPEQRGMFTVSDHPPEQHGMFTVSDHPPEQRGMFTISDHQPE
  QRGMFTVSDHTPEQRGIFTISDHPAEQRGMFTKECEQECELAITDLESGREDEAGLHQSQ
  AVHGLELEALRLSLSNMHTAQLELTQANLQKEKETALTELREMLNSRRAQELALLQSRQQ
  HELELLREQHAREKEEVVLRCGQEAAELKEKLQSEMEKNAQIVKTLKEDWESEKDLCLEN
  LRKELSAKHQSEMEDLQNQFQKELAEQRAELEKIFQDKNQAERALRNLESHHQAAIEKLR
  EDLQSEHGRCLEDLEFKFKESEKEKQLELENLQASYEDLKAQSQEEIRRLWSQLDSARTS
  RQELSELHEQLLARTSRVEDLEQLKQREKTQHESELEQLRIYFEKKLRDAEKTYQEDLTL
  LQQRLQGAREDALLDSVEVGLSCVGLEEKPEKGRKDHVDELEPERHKESLPRFQAELEES
  HRHQLEALESPLCIQHEGHVSDRCCVETSALGHEWRLEPSEGHSQELPWVHLQGVQDGDL
  EADTERAARVLGLETEHKVQLSLLQTELKEEIELLKIENRNLYGKLQHETRLKDDLEKVK
  HNLIEDHQKELNNAKQKTELMKQEFQRKETDWKVMKEELQREAEEKLTLMLLELREKAES
  EKQTIINKFELREAEMRQLQDQQAAQILDLERSLTEQQGRLQQLEQDLTSDDALHCSQCG
  REPPTAQDGELAALHVKEDCALQLMLARSRFLEERKEITEKFSAEQDAFLQEAQEQHARE
  LQLLQERHQQQLLSVTAELEARHQAALGELTASLESKQGALLAARVAELQTKHAADLGAL
  ETRHLSSLDSLESCYLSEFQTIREEHRQALELLRADFEEQLWKKDSLHQTILTQELEKLK
  RKHEGELQSVRDHLRTEVSTELAGTVAHELQGVHQGEFGSEKKTALHEKEETLRLQSAQA
  QPFHQEEKESLSLQLQKKNHQVQQLKDQVLSLSHEIEECRSELEVLQQRRERENREGANL
  LSMLKADVNLSHSERGALQDALRRLLGLFGETLRAAVTLRSRIGERVGLCLDDAGAGLAL
  STAPALEETWSDVALPELDRTLSECAEMSSVAEISSHMRESFLMSPESVRECEQPIRRVF
  QSLSLAVDGLMEMALDSSRQLEEARQIHSRFEKEFSFKNEETAQVVRKHQELLECLKEES
  AAKAELALELHKTQGTLEGFKVETADLKEVLAGKEDSEHRLVLELESLRRQLQQAAQEQA
  ALREECTRLWSRGEATATDAEAREAALRKEVEDLTKEQSETRKQAEKDRSALLSQMKILE
  SELEEQLSQHRGCAKQAEAVTALEQQVASLDKHLRNQRQFMDEQAAEREHEREEFQQEIQ
  RLEGQLRQAAKPQPWGPRDSQQAPLDGEVELLQQKLREKLDEFNELAIQKESADRQVLMQ
  EEEIKRLEEMNINIRKKVAQLQEEVEKQKNIVKGLEQDKEVLKKQQMSSLLLASTLQSTL
  DAGRCPEPPSGSPPEGPEIQLEVTQRALLRRESEVLDLKEQLEKMKGDLESKNEEILHLN
  LKLDMQNSQTAVSLRELEEENTSLKVIYTRSSEIEELKATIENLQENQKRLQKEKAEEIE
  QLHEVIEKLQHELSLMGPVVHEVSDSQAGSLQSELLCSQAGGPRGQALQGELEAALEAKE
  ALSRLLADQERRHSQALEALQQRLQGAEEAAELQLAELERNVALREAEVEDMASRIQEFE
  AALKAKEATIAERNLEIDALNQRKAAHSAELEAVLLALARIRRALEQQPLAAGAAPPELQ
  WLRAQCARLSRQLQVLHQRFLRCQVELDRRQARRATAHTRVPGAHPQPRMDGGAKAQVTG
  DVEASHDAALEPVVPDPQGDLQPVLVTLKDAPLCKQEGVMSVLTVCQRQLQSELLLVKNE
  MRLSLEDGGKGKEKVLEDCQLPKVDLVAQVKQLQEKLNRLLYSMTFQNVDAADTKSLWPM
  ASAHLLESSWSDDSCDGEEPDISPHIDTCDANTATGGVTDVIKNQAIDACDANTTPGGVT
  DVIKNWDSLIPDEMPDSPIQEKSECQDMSLSSPTSVLGGSRHQSHTAEAGPRKSPVGMLD
  LSSWSSPEVLRKDWTLEPWPSLPVTPHSGALSLCSADTSLGDRADTSLPQTQGPGLLCSP
  GVSAAALALQWAESPPADDHHVQRTAVEKDVEDFITTSFDSQETLSSPPPGLEGKADRSE
  KSDGSGFGARLSPGSGGPEAQTAGPVTPASISGRFQPLPEAMKEKEVRPKHVKALLQMVR
  DESHQILALSEGLAPPSGEPHPPRKEDEIQDISLHGGKTQEVPTACPDWRGDLLQVVQEA
  FEKEQEMQGVELQPRLSGSDLGGHSSLLERLEKIIREQGDLQEKSLEHLRLPDRSSLLSE
  IQALRAQLRMTHLQNQEKLQHLRTALTSAEARGSQQEHQLRRQVELLAYKVEQEKCIAGD
  LQKTLSEEQEKANSVQKLLAAEQTVVRDLKSDLCESRQKSEQLSRSLCEVQQEVLQLRSM
  LSSKENELKAALQELESEQGKGRALQSQLEEEQLRHLQRESQSAKALEELRASLETQRAQ
  SSRLCVALKHEQTAKDNLQKELRIEHSRCEALLAQERSQLSELQKDLAAEKSRTLELSEA
  LRHERLLTEQLSQRTQEACVHQDTQAHHALLQKLKEEKSRVVDLQAMLEKVQQQALHSQQ
  QLEAEAQKHCEALRREKEVSATLKSTVEALHTQKRELRCSLEREREKPAWLQAELEQSHP
  RLKEQEGRKAARRSAEARQSPAAAEQWRKWQRDKEKLRELELQRQRDLHKIKQLQQTVRD
  LESKDEVPGSRLHLGSARRAAGSDADHLREQQRELEAMRQRLLSAARLLTSFTSQAVDRT
  VNDWTSSNEKAVMSLLHTLEELKSDLSRPTSSQKKMAAELQFQFVDVLLKDNVSLTKALS
  TVTQEKLELSRAVSKLEKLLKHHLQKGCSPSRSERSAWKPDETAPQSSLRRPDPGRLPPA
  ASEEAHTSNVKMEKLYLHYLRAESFRKALIYQKKYLLLLIGGFQDSEQETLSMIAHLGVF
  PSKAERKITSRPFTRFRTAVRVVIAILRLRFLVKKWQEVDRKGALAQGKAPRPGPRARQP
  QSPPRTRESPPTRDVPSGHTRDPARGRRLAAAASPHSGGRATPSPNSRLERSLTASQDPE
  HSLTEYIHHLEVIQQRLGGVLPDSTSKKSCHPMIKQ
• Function: Integral component of the filamentous matrix of the centrosome involved in the initial establishment of organized microtubule arrays in both mitosis and meiosis. Plays a role, together with DISC1, in the microtubule network formation. Is an integral component of the pericentriolar material (PCM). May play an important role in preventing premature centrosome splitting during interphase by inhibiting NEK2 kinase activity at the centrosome.
• Tissue Specificity: Expressed in all tissues tested, including placenta, liver, kidney and thymus.
• 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)
  Chaperone Mediated Autophagy (R-HSA-9613829)
  Late endosomal microautophagy (R-HSA-9615710)
  Aggrephagy (R-HSA-9646399)
  Regulation of PLK1 Activity at G2/M Transition (R-HSA-2565942)

Molecular Interaction Atlas (MIA) of This DOT

35 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Microcephalic osteodysplastic primordial dwarfism type II	DISHUS57	Definitive	Autosomal recessive	[1]
Seckel syndrome 1	DISLNT6G	Definitive	Biomarker	[2]
Seckel syndrome 2	DISOV2MU	Definitive	Biomarker	[3]
Autosomal recessive primary microcephaly	DIS29IE3	Strong	Biomarker	[4]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[5]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	DIS3KLUX	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[8]
Cerebrovascular disease	DISAB237	Strong	Biomarker	[9]
Chromosomal disorder	DISM5BB5	Strong	Biomarker	[10]
Ciliopathy	DIS10G4I	Strong	Genetic Variation	[11]
Depression	DIS3XJ69	Strong	Altered Expression	[12]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[13]
facioscapulohumeral muscular dystrophy	DISSE0H0	Strong	Genetic Variation	[14]
Frontometaphyseal dysplasia 1	DIS2MB3L	Strong	Genetic Variation	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[15]
Isolated growth hormone deficiency type IA	DISLPIAM	Strong	Genetic Variation	[16]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[17]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[18]
Mantle cell lymphoma	DISFREOV	Strong	Altered Expression	[19]
Mental disorder	DIS3J5R8	Strong	Biomarker	[20]
Neoplasm	DISZKGEW	Strong	Biomarker	[21]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[13]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[13]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[22]
Psychotic disorder	DIS4UQOT	Strong	Biomarker	[5]
Seckel syndrome	DISEVUBA	Strong	Biomarker	[23]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[24]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[25]
Lung adenocarcinoma	DISD51WR	moderate	Biomarker	[26]
Moyamoya disease	DISO62CA	Moderate	Autosomal recessive	[27]
Cardiomyopathy	DISUPZRG	Limited	Genetic Variation	[28]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[29]
Isolated congenital microcephaly	DISUXHZ6	Limited	Biomarker	[30]
Parkinson disease	DISQVHKL	Limited	Biomarker	[31]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Gefitinib	DM15F0X	Approved	Pericentrin (PCNT) decreases the response to substance of Gefitinib.	[26]

6 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 Pericentrin (PCNT).	[32]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Pericentrin (PCNT).	[34]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Pericentrin (PCNT).	[35]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Pericentrin (PCNT).	[36]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Pericentrin (PCNT).	[32]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Pericentrin (PCNT).	[38]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Pericentrin (PCNT).	[33]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Pericentrin (PCNT).	[37]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Pericentrin (PCNT).	[39]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Pericentrin (PCNT).	[40]

References

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• [4] STIL microcephaly mutations interfere with APC/C-mediated degradation and cause centriole amplification.Curr Biol. 2014 Feb 17;24(4):351-60. doi: 10.1016/j.cub.2013.12.016. Epub 2014 Jan 30.
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• [23] Angelman syndrome protein UBE3A interacts with primary microcephaly protein ASPM, localizes to centrosomes and regulates chromosome segregation.PLoS One. 2011;6(5):e20397. doi: 10.1371/journal.pone.0020397. Epub 2011 May 25.
• [24] Pericentrin expression in pancreatic cells is associated impaired glucose tolerance.Am J Transl Res. 2019 Apr 15;11(4):2257-2268. eCollection 2019.
• [25] Zirconium-Porphyrin PCN-222: pH-responsive Controlled Anticancer Drug Oridonin.Evid Based Complement Alternat Med. 2018 Dec 4;2018:3249023. doi: 10.1155/2018/3249023. eCollection 2018.
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• [27] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
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• [29] Array CGH identifies distinct DNA copy number profiles of oncogenes and tumor suppressor genes in chromosomal- and microsatellite-unstable sporadic colorectal carcinomas.J Mol Med (Berl). 2007 Mar;85(3):293-304. doi: 10.1007/s00109-006-0126-5. Epub 2006 Dec 2.
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• [37] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [38] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
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• [40] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.
• [41] Identification of protein expression alterations in gefitinib-resistant human lung adenocarcinoma: PCNT and mPR play key roles in the development of gefitinib-associated resistance. Toxicol Appl Pharmacol. 2015 Nov 1;288(3):359-73. doi: 10.1016/j.taap.2015.08.008. Epub 2015 Aug 20.