Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZCQZN5)

• DOT Name: Centromere protein J (CENPJ)
• Synonyms: CENP-J; Centrosomal P4.1-associated protein; LAG-3-associated protein; LYST-interacting protein 1
• Gene Name: CENPJ
• Related Disease:
  Microcephaly 6 with or without short stature
  Paralysis
  Seckel syndrome 4
  3MC syndrome 2
  Acute respiratory failure
  Adult respiratory distress syndrome
  Anxiety
  Anxiety disorder
  Bronchiolitis
  Bronchopulmonary dysplasia
  Cardiac failure
  Congenital alveolar dysplasia
  Congestive heart failure
  Depression
  Ehlers-Danlos syndrome
  Glioma
  Insomnia
  Isolated congenital microcephaly
  Isolated growth hormone deficiency type IA
  Microcephaly 6, primary, autosomal recessive
  Microcephaly 7, primary, autosomal recessive
  Non-insulin dependent diabetes
  Obesity
  Occipital horn syndrome
  Overhydrated hereditary stomatocytosis
  Pneumonia
  Pneumothorax
  Thyroid gland carcinoma
  Thyroid gland papillary carcinoma
  Chronic obstructive pulmonary disease
  Hypertension, pregnancy-induced
  Neoplasm
  Osteoarthritis
  Autosomal recessive primary microcephaly
  Seckel syndrome
  Acute bronchitis
  Multinodular goiter
  Peutz-Jeghers syndrome
  Post-traumatic stress disorder
  Rheumatoid arthritis
• UniProt ID: CENPJ_HUMAN
• PDB ID: 5EIB; 5ITZ; 7Q1E; 7Q1F; 7Z0F; 7Z0G
• Pfam ID: PF07202
• Sequence:
  MFLMPTSSELNSGQNFLTQWMTNPSRAGVILNRGFPILEADKEKRAAVDISTSFPIKGTH
  FSDSFSFINEEDSLLEEQKLESNNPYKPQSDKSETHTAFPCIKKGPQVAACHSAPGHQEE
  NKNDFIPDLASEFKEGAYKDPLFKKLEQLKEVQQKKQEQLKRQQLEQLQRLMEEQEKLLT
  MVSGQCTLPGLSLLPDDQSQKHRSPGNTTTGERATCCFPSYVYPDPTQEETYPSNILSHE
  QSNFCRTAHGDFVLTSKRASPNLFSEAQYQEAPVEKNNLKEENRNHPTGESILCWEKVTE
  QIQEANDKNLQKHDDSSEVANIEERPIKAAIGERKQTFEDYLEEQIQLEEQELKQKQLKE
  AEGPLPIKAKPKQPFLKRGEGLARFTNAKSKFQKGKESKLVTNQSTSEDQPLFKMDRQQL
  QRKTALKNKELCADNPILKKDSKARTKSGSVTLSQKPKMLKCSNRKSLSPSGLKIQTGKK
  CDGQFRDQIKFENKVTSNNKENVTECPKPCDTGCTGWNKTQGKDRLPLSTGPASRLAAKS
  PIRETMKESESSLDVSLQKKLETWEREKEKENLELDEFLFLEQAADEISFSSNSSFVLKI
  LERDQQICKGHRMSSTPVKAVPQKTNPADPISHCNRSEDLDHTAREKESECEVAPKQLHS
  LSSADELREQPCKIRKAVQKSTSENQTEWNARDDEGVPNSDSSTDSEEQLDVTIKPSTED
  RERGISSREDSPQVCDDKGPFKDTRTQEDKRRDVDLDLSDKDYSSDESIMESIKHKVSEP
  SRSSSLSLSKMDFDDERTWTDLEENLCNHDVVLGNESTYGTPQTCYPNNEIGILDKTIKR
  KIAPVKRGEDLSKSRRSRSPPTSELMMKFFPSLKPKPKSDSHLGNELKLNISQDQPPGDN
  ARSQVLREKIIELETEIEKFKAENASLAKLRIERESALEKLRKEIADFEQQKAKELARIE
  EFKKEEMRKLQKERKVFEKYTTAARTFPDKKEREEIQTLKQQIADLREDLKRKETKWSST
  HSRLRSQIQMLVRENTDLREEIKVMERFRLDAWKRAEAIESSLEVEKKDKLANTSVRFQN
  SQISSGTQVEKYKKNYLPMQGNPPRRSKSAPPRDLGNLDKGQAASPREPLEPLNFPDPEY
  KEEEEDQDIQGEISHPDGKVEKVYKNGCRVILFPNGTRKEVSADGKTITVTFFNGDVKQV
  MPDQRVIYYYAAAQTTHTTYPEGLEVLHFSSGQIEKHYPDGRKEITFPDQTVKNLFPDGQ
  EESIFPDGTIVRVQRDGNKLIEFNNGQRELHTAQFKRREYPDGTVKTVYANGHQETKYRS
  GRIRVKDKEGNVLMDTEL
• Function: Plays an important role in cell division and centrosome function by participating in centriole duplication. Inhibits microtubule nucleation from the centrosome. Involved in the regulation of slow processive growth of centriolar microtubules. Acts as a microtubule plus-end tracking protein that stabilizes centriolar microtubules and inhibits microtubule polymerization and extension from the distal ends of centrioles. Required for centriole elongation and for STIL-mediated centriole amplification. 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. May be involved in the control of centriolar-microtubule growth by acting as a regulator of tubulin release.
• 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)
  TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain (R-HSA-6804115)
  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

40 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Microcephaly 6 with or without short stature	DISBDL4S	Definitive	Autosomal recessive	[1]
Paralysis	DISF9I3O	Definitive	Biomarker	[2]
Seckel syndrome 4	DIS9EOT2	Definitive	Autosomal recessive	[3]
3MC syndrome 2	DISAXCJJ	Strong	Biomarker	[4]
Acute respiratory failure	DIS5KQ5Y	Strong	Biomarker	[5]
Adult respiratory distress syndrome	DISIJV47	Strong	Biomarker	[6]
Anxiety	DISIJDBA	Strong	Biomarker	[7]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[7]
Bronchiolitis	DISEE9BG	Strong	Biomarker	[8]
Bronchopulmonary dysplasia	DISO0BY5	Strong	Biomarker	[9]
Cardiac failure	DISDC067	Strong	Biomarker	[10]
Congenital alveolar dysplasia	DIS1IYUN	Strong	Biomarker	[11]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[10]
Depression	DIS3XJ69	Strong	Biomarker	[7]
Ehlers-Danlos syndrome	DISSVBRR	Strong	Genetic Variation	[12]
Glioma	DIS5RPEH	Strong	Biomarker	[13]
Insomnia	DIS0AFR7	Strong	Biomarker	[14]
Isolated congenital microcephaly	DISUXHZ6	Strong	Genetic Variation	[15]
Isolated growth hormone deficiency type IA	DISLPIAM	Strong	Genetic Variation	[15]
Microcephaly 6, primary, autosomal recessive	DISWFNUJ	Strong	Autosomal recessive	[16]
Microcephaly 7, primary, autosomal recessive	DISY36JJ	Strong	Genetic Variation	[17]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[18]
Obesity	DIS47Y1K	Strong	Altered Expression	[19]
Occipital horn syndrome	DISBA58S	Strong	Biomarker	[20]
Overhydrated hereditary stomatocytosis	DIS6TF7I	Strong	Biomarker	[20]
Pneumonia	DIS8EF3M	Strong	Biomarker	[21]
Pneumothorax	DISP86H1	Strong	Genetic Variation	[22]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[23]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Biomarker	[24]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[25]
Hypertension, pregnancy-induced	DISHNU25	moderate	Biomarker	[26]
Neoplasm	DISZKGEW	moderate	Altered Expression	[27]
Osteoarthritis	DIS05URM	moderate	Biomarker	[28]
Autosomal recessive primary microcephaly	DIS29IE3	Supportive	Autosomal recessive	[29]
Seckel syndrome	DISEVUBA	Supportive	Autosomal recessive	[15]
Acute bronchitis	DIS0X75X	Limited	Biomarker	[8]
Multinodular goiter	DISZQJH7	Limited	Biomarker	[30]
Peutz-Jeghers syndrome	DISF27ZJ	Limited	Biomarker	[31]
Post-traumatic stress disorder	DISHL1EY	Limited	Biomarker	[32]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[33]

18 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 Centromere protein J (CENPJ).	[34]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Centromere protein J (CENPJ).	[35]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Centromere protein J (CENPJ).	[36]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Centromere protein J (CENPJ).	[37]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Centromere protein J (CENPJ).	[38]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Centromere protein J (CENPJ).	[39]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Centromere protein J (CENPJ).	[40]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Centromere protein J (CENPJ).	[41]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Centromere protein J (CENPJ).	[42]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Centromere protein J (CENPJ).	[42]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Centromere protein J (CENPJ).	[38]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Centromere protein J (CENPJ).	[43]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Centromere protein J (CENPJ).	[44]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Centromere protein J (CENPJ).	[45]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Centromere protein J (CENPJ).	[46]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Centromere protein J (CENPJ).	[47]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Centromere protein J (CENPJ).	[48]
Flavone	DMEQH6J	Investigative	Flavone decreases the expression of Centromere protein J (CENPJ).	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the methylation of Centromere protein J (CENPJ).	[49]

References

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