NIMA related kinase 1 | NIMA (never in mitosis gene a)- related kinase (NEK) family | IUPHAR/BPS Guide to PHARMACOLOGY

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NIMA related kinase 1

Target not currently curated in GtoImmuPdb

Target id: 2114

Nomenclature: NIMA related kinase 1

Abbreviated Name: NEK1

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

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1258 4q32.3 NEK1 NIMA related kinase 1
Mouse - 1203 8 B3.1 Nek1 NIMA (never in mitosis gene a)-related expressed kinase 1
Rat - 1200 16p12 Nek1 NIMA-related kinase 1
Previous and Unofficial Names
kat | kidney, anemia and testis
Database Links
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of Human NIMA-related Kinase 1 (NEK1)
PDB Id:  4APC
Resolution:  2.1Å
Species:  Human
References: 
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of Human NIMA-related Kinase 1 (NEK1) with inhibitor.
PDB Id:  4B9D
Resolution:  1.9Å
Species:  Human
References: 
Enzyme Reaction
EC Number: 2.7.11.1

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 31 [PMID: 20936789] Hs Inhibition 6.8 pIC50 4
pIC50 6.8 (IC50 1.7x10-7 M) [4]
DiscoveRx KINOMEscan® screen
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: 2,5

Key to terms and symbols Click column headers to sort
Target used in screen: NEK1
Ligand Sp. Type Action Value Parameter
tamatinib Hs Inhibitor Inhibition 6.8 pKd
staurosporine Hs Inhibitor Inhibition 6.1 pKd
GSK-461364A Hs Inhibitor Inhibition 5.7 pKd
lestaurtinib Hs Inhibitor Inhibition 5.6 pKd
ruboxistaurin Hs Inhibitor Inhibition <5.5 pKd
SB203580 Hs Inhibitor Inhibition <5.5 pKd
erlotinib Hs Inhibitor Inhibition <5.5 pKd
GSK690693 Hs Inhibitor Inhibition <5.5 pKd
masitinib Hs Inhibitor Inhibition <5.5 pKd
A-674563 Hs Inhibitor Inhibition <5.5 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen
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

Key to terms and symbols Click column headers to sort
Target used in screen: nd/NEK1
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 4.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 6.1
bosutinib Hs Inhibitor Inhibition 15.2
Tpl2 kinase inhibitor Hs Inhibitor Inhibition 20.5
SU11274 Hs Inhibitor Inhibition 23.5
PKR inhibitor Hs Inhibitor Inhibition 34.3
K-252a Hs Inhibitor Inhibition 36.2
PDK1/Akt/Flt dual pathway inhibitor Hs Inhibitor Inhibition 46.3
JAK inhibitor I Hs Inhibitor Inhibition 49.0
SB 218078 Hs Inhibitor Inhibition 50.9
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Amyotrophic lateral sclerosis
Disease Ontology: DOID:332
Orphanet: ORPHA803
Role: 
References:  3
Disease:  Short-rib thoracic dysplasia 6 with or without polydactyly
Synonyms: Majewski syndrome [Disease Ontology: DOID:0050550]
Short rib-polydactyly syndrome, Majewski type [Orphanet: ORPHA93269]
Disease Ontology: DOID:0050550
OMIM: 263520
Orphanet: ORPHA93269
Biologically Significant Variants
Type:  Missense mutation
Species:  Human
Description:  Genetic risk variant for ALS.
Amino acid change:  Arg261His
References:  3

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. Kenna KP, van Doormaal PTC, Dekker AM, Ticozzi N, Kenna BJ, Diekstra FP, van Rheenen W, van Eijk KR, Jones AR, Keagle P et al.. (2016) NEK1 variants confer susceptibility to amyotrophic lateral sclerosis. Nature Genetics, advance online publication.

4. 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]

5. 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 1. Last modified on 27/07/2016. Accessed on 20/08/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2114.