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NIMA related kinase 2

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Target not currently curated in GtoImmuPdb

Target id: 2117

Nomenclature: NIMA related kinase 2

Abbreviated Name: NEK2

Family: NIMA (never in mitosis gene a)- related kinase (NEK) family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 445 1q32.3 NEK2 NIMA related kinase 2
Mouse - 443 1 96.94 cM Nek2 NIMA (never in mitosis gene a)-related expressed kinase 2
Rat - 443 13 q27 Nek2 NIMA-related kinase 2
Previous and Unofficial Names Click here for help
HSPK 21 | NLK1 | NIMA (never in mitosis gene a)-related expressed kinase 2 | NIMA-related kinase 2
Database Links Click here for help
Alphafold P51955 (Hs), O35942 (Mm)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL3835 (Hs)
Ensembl Gene ENSG00000117650 (Hs), ENSMUSG00000026622 (Mm), ENSRNOG00000004487 (Rn)
Entrez Gene 4751 (Hs), 18005 (Mm), 114482 (Rn)
Human Protein Atlas ENSG00000117650 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:4751 (Hs), mmu:18005 (Mm), rno:114482 (Rn)
OMIM 604043 (Hs)
Orphanet ORPHA368150 (Hs)
Pharos P51955 (Hs)
RefSeq Nucleotide NM_001204182 (Hs), NM_010892 (Mm), NM_053691 (Rn)
RefSeq Protein NP_002488 (Hs), NP_035022 (Mm), NP_446143 (Rn)
UniProtKB P51955 (Hs), O35942 (Mm)
Wikipedia NEK2 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  HUMAN NEK2 KINASE ADP-BOUND
PDB Id:  2W5A
Resolution:  1.55Å
Species:  Human
References:  6
Image of receptor 3D structure from RCSB PDB
Description:  STRUCTURE OF NEK2 BOUND TO AMINOPYRAZINE COMPOUND 12
PDB Id:  2XKD
Resolution:  1.96Å
Species:  Human
References:  7
Enzyme Reaction Click here for help
EC Number: 2.7.11.1

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 2 [PMID: 21627121] Small molecule or natural product Primary target of this compound Hs Inhibition >8.2 pIC50 5
⤷ pIC50 >8.2 (IC50 <6x10-9 M) [5]
GSK579289A Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.7 pIC50 3
⤷ pIC50 7.7 (IC50 2.1x10-8 M) [3]
compound 31 [PMID: 20936789] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.6 pIC50 7
⤷ pIC50 6.6 (IC50 2.3x10-7 M) [7]
DiscoveRx KINOMEscan® screen Click here for help
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 2,8
Key to terms and symbols Click column headers to sort
Target used in screen: NEK2
Ligand Sp. Type Action Value Parameter
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
neratinib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 6.6 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.6 pKd
GSK-461364A Small molecule or natural product Hs Inhibitor Inhibition 6.6 pKd
PHA-665752 Small molecule or natural product Hs Inhibitor Inhibition 6.2 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.1 pKd
pazopanib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 6.0 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 6.0 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 5.8 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.8 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen Click here for help
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx

Reference: 1,4
Key to terms and symbols Click column headers to sort
Target used in screen: NEK2/NEK2
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.6
SU11274 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 50.8 39.0 22.0
GSK-3 inhibitor X Small molecule or natural product Hs Inhibitor Inhibition 73.9 101.0 87.0
Tpl2 kinase inhibitor Small molecule or natural product Hs Inhibitor Inhibition 75.2 104.0 96.0
AG 1295 Small molecule or natural product Hs Inhibitor Inhibition 75.7 92.0 105.0
fascaplysin Small molecule or natural product Hs Inhibitor Inhibition 77.1 90.0 87.0
SU11652 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 77.2 67.0 18.0
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 77.2 64.0 39.0
PDK1/Akt/Flt dual pathway inhibitor Small molecule or natural product Hs Inhibitor Inhibition 77.7 84.0 85.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 79.9 63.5 29.5
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Retinitis pigmentosa 67; RP67
Synonyms: Retinitis pigmentosa [Orphanet: ORPHA791] [Disease Ontology: DOID:10584]
Disease Ontology: DOID:10584
OMIM: 615565
Orphanet: ORPHA791

References

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1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]

2. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]

3. Emmitte KA, Adjabeng GM, Adjebang GM, Andrews CW, Alberti JG, Bambal R, Chamberlain SD, Davis-Ward RG, Dickson HD, Hassler DF et al.. (2009) Design of potent thiophene inhibitors of polo-like kinase 1 with improved solubility and reduced protein binding. Bioorg Med Chem Lett, 19 (6): 1694-7. [PMID:19237286]

4. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem J, 451 (2): 313-28. [PMID:23398362]

5. Henise JC, Taunton J. (2011) Irreversible Nek2 kinase inhibitors with cellular activity. J Med Chem, 54 (12): 4133-46. [PMID:21627121]

6. Westwood I, Cheary DM, Baxter JE, Richards MW, van Montfort RL, Fry AM, Bayliss R. (2009) Insights into the conformational variability and regulation of human Nek2 kinase. J Mol Biol, 386 (2): 476-85. [PMID:19124027]

7. Whelligan DK, Solanki S, Taylor D, Thomson DW, Cheung KM, Boxall K, Mas-Droux C, Barillari C, Burns S, Grummitt CG et al.. (2010) Aminopyrazine inhibitors binding to an unusual inactive conformation of the mitotic kinase Nek2: SAR and structural characterization. J Med Chem, 53 (21): 7682-98. [PMID:20936789]

8. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem Biol, 17 (11): 1241-9. [PMID:21095574]

How to cite this page

NIMA (never in mitosis gene a)- related kinase (NEK) family: NIMA related kinase 2. Last modified on 29/01/2016. Accessed on 13/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2117.