Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1H27HO)

• DOT Name: Serine/threonine-protein kinase Nek2 (NEK2)
• Synonyms: EC 2.7.11.1; HSPK 21; Never in mitosis A-related kinase 2; NimA-related protein kinase 2; NimA-like protein kinase 1
• Gene Name: NEK2
• Related Disease:
  Retinitis pigmentosa
  Retinitis pigmentosa 67
• UniProt ID: NEK2_HUMAN
• PDB ID: 2JAV; 2W5A; 2W5B; 2W5H; 2WQO; 2XK3; 2XK4; 2XK6; 2XK7; 2XK8; 2XKC; 2XKD; 2XKE; 2XKF; 2XNM; 2XNN; 2XNO; 2XNP; 4A4X; 4AFE; 5M51; 5M53; 5M55; 5M57; 6SGD; 6SGH; 6SGI; 6SGK; 6SK9; 6TM5
• EC Number: 2.7.11.1
• Pfam ID: PF00069
• Sequence:
  MPSRAEDYEVLYTIGTGSYGRCQKIRRKSDGKILVWKELDYGSMTEAEKQMLVSEVNLLR
  ELKHPNIVRYYDRIIDRTNTTLYIVMEYCEGGDLASVITKGTKERQYLDEEFVLRVMTQL
  TLALKECHRRSDGGHTVLHRDLKPANVFLDGKQNVKLGDFGLARILNHDTSFAKTFVGTP
  YYMSPEQMNRMSYNEKSDIWSLGCLLYELCALMPPFTAFSQKELAGKIREGKFRRIPYRY
  SDELNEIITRMLNLKDYHRPSVEEILENPLIADLVADEQRRNLERRGRQLGEPEKSQDSS
  PVLSELKLKEIQLQERERALKAREERLEQKEQELCVRERLAEDKLARAENLLKNYSLLKE
  RKFLSLASNPELLNLPSSVIKKKVHFSGESKENIMRSENSESQLTSKSKCKDLKKRLHAA
  QLRAQALSDIEKNYQLKSRQILGMR
• Function: Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. Regulates centrosome separation (essential for the formation of bipolar spindles and high-fidelity chromosome separation) by phosphorylating centrosomal proteins such as CROCC, CEP250 and NINL, resulting in their displacement from the centrosomes. Regulates kinetochore microtubule attachment stability in mitosis via phosphorylation of NDC80. Involved in regulation of mitotic checkpoint protein complex via phosphorylation of CDC20 and MAD2L1. Plays an active role in chromatin condensation during the first meiotic division through phosphorylation of HMGA2. Phosphorylates: PPP1CC; SGO1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Phosphorylates CEP68 and CNTLN directly or indirectly. NEK2-mediated phosphorylation of CEP68 promotes CEP68 dissociation from the centrosome and its degradation at the onset of mitosis. Involved in the regulation of centrosome disjunction. Phosphorylates CCDC102B either directly or indirectly which causes CCDC102B to dissociate from the centrosome and allows for centrosome separation ; [Isoform 1]: Phosphorylates and activates NEK11 in G1/S-arrested cells; [Isoform 2]: Not present in the nucleolus and, in contrast to isoform 1, does not phosphorylate and activate NEK11 in G1/S-arrested cells.
• Tissue Specificity: Isoform 1 and isoform 2 are expressed in peripheral blood T-cells and a wide variety of transformed cell types. Isoform 1 and isoform 4 are expressed in the testis. Up-regulated in various cancer cell lines, as well as primary breast tumors.
• Reactome Pathway:
  Regulation of PLK1 Activity at G2/M Transition (R-HSA-2565942)
  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)
  APC-Cdc20 mediated degradation of Nek2A (R-HSA-179409)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Retinitis pigmentosa	DISCGPY8	Supportive	Autosomal dominant	[1]
Retinitis pigmentosa 67	DISEQFM4	Limited	Autosomal recessive	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[11]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[11]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[12]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[13]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[14]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[15]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[16]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[17]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[18]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[19]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[20]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[21]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[22]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[23]
Bicalutamide	DMZMSPF	Approved	Bicalutamide decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[24]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[25]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[14]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[19]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[27]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[28]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[30]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[31]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[8]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[32]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[33]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[34]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[35]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE increases the expression of Serine/threonine-protein kinase Nek2 (NEK2).	[19]

References

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