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NIMA related kinase 1

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Target id: 2114

Nomenclature: NIMA related kinase 1

Abbreviated Name: NEK1

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 - 1258 4q33 NEK1 NIMA related kinase 1
Mouse - 1203 8 30.91 cM Nek1 NIMA (never in mitosis gene a)-related expressed kinase 1
Rat - 1200 16p12 Nek1 NIMA-related kinase 1
Previous and Unofficial Names Click here for help
kat | kidney, anemia and testis
Database Links Click here for help
Alphafold Q96PY6 (Hs), P51954 (Mm)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL5855 (Hs)
Ensembl Gene ENSG00000137601 (Hs), ENSMUSG00000031644 (Mm), ENSRNOG00000010418 (Rn)
Entrez Gene 4750 (Hs), 18004 (Mm), 290705 (Rn)
Human Protein Atlas ENSG00000137601 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:4750 (Hs), mmu:18004 (Mm), rno:290705 (Rn)
OMIM 604588 (Hs)
Orphanet ORPHA258621 (Hs)
Pharos Q96PY6 (Hs)
RefSeq Nucleotide NM_001199397 (Hs), NM_175089 (Mm), NM_001106082 (Rn)
RefSeq Protein NP_036356 (Hs), NP_780298 (Mm), NP_001099552 (Rn)
UniProtKB Q96PY6 (Hs), P51954 (Mm)
Wikipedia NEK1 (Hs)
Selected 3D Structures Click here for help
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 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 31 [PMID: 20936789] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 6.8 pIC50 4
⤷ pIC50 6.8 (IC50 1.7x10-7 M) [4]
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: 2,5
Key to terms and symbols Click column headers to sort
Target used in screen: NEK1
Ligand Sp. Type Action Value Parameter
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.8 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.1 pKd
GSK-461364A Small molecule or natural product Hs Inhibitor Inhibition 5.7 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.6 pKd
ruboxistaurin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition <5.5 pKd
SB203580 Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition <5.5 pKd
erlotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition <5.5 pKd
linifanib Small molecule or natural product Hs Inhibitor Inhibition <5.5 pKd
GSK690693 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition <5.5 pKd
masitinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand 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 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
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 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 4.0
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.1
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 15.2
Tpl2 kinase inhibitor Small molecule or natural product Hs Inhibitor Inhibition 20.5
SU11274 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 23.5
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 34.3
K-252a Small molecule or natural product Hs Inhibitor Inhibition 36.2
PDK1/Akt/Flt dual pathway inhibitor Small molecule or natural product Hs Inhibitor Inhibition 46.3
JAK inhibitor I Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 49.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 50.9
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Amyotrophic lateral sclerosis
Disease Ontology: DOID:332
Orphanet: ORPHA803
Role:  Loss of function NEK1 mutations and the Arg261His NEK1 variant have been identified as genetic factors which confer susceptibility to familial and sporadic amyotrophic lateral sclerosis. These risk variants were detected in 3% of ALS cases tested.
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 Click here for help
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 PT, 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. Nat Genet, 48 (9): 1037-42. [PMID:27455347]

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 16/09/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2114.