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protein kinase N1

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Target id: 1520

Nomenclature: protein kinase N1

Abbreviated Name: PKN1

Family: Protein kinase N (PKN) family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 942 19p13.12 PKN1 protein kinase N1
Mouse - 946 8 40.22 cM Pkn1 protein kinase N1
Rat - 946 19q11 Pkn1 protein kinase N1
Previous and Unofficial Names Click here for help
PAK1 | PRK1 | PRKCL1 | protein kinase C-like 1 | protease-activated kinase 1 | protein kinase PKN | Stk3 | DBK | protein kinase C-related kinase 1
Database Links Click here for help
Alphafold Q16512 (Hs), P70268 (Mm), Q63433 (Rn)
BRENDA 2.7.11.13
CATH/Gene3D 2.60.40.150
ChEMBL Target CHEMBL3384 (Hs)
Ensembl Gene ENSG00000123143 (Hs), ENSMUSG00000057672 (Mm), ENSRNOG00000004131 (Rn)
Entrez Gene 5585 (Hs), 320795 (Mm), 29355 (Rn)
Human Protein Atlas ENSG00000123143 (Hs)
KEGG Enzyme 2.7.11.13
KEGG Gene hsa:5585 (Hs), mmu:320795 (Mm), rno:29355 (Rn)
OMIM 601032 (Hs)
Pharos Q16512 (Hs)
RefSeq Nucleotide NM_002741 (Hs), NM_177262 (Mm), NM_017175 (Rn)
RefSeq Protein NP_002732 (Hs), NP_796236 (Mm), NP_001186522 (Mm), NP_058871 (Rn)
UniProtKB Q16512 (Hs), P70268 (Mm), Q63433 (Rn)
Wikipedia PKN1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  CRYSTAL STRUCTURE OF HUMAN RHOA COMPLEXED WITH THE EFFECTOR DOMAIN OF THE PROTEIN KINASE PKN/PRK1
PDB Id:  1CXZ
Resolution:  2.2Å
Species:  Human
References:  6
Enzyme Reaction Click here for help
EC Number: 2.7.11.13

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
staurosporine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.0 pIC50 3
⤷ pIC50 9.0 (IC50 1x10-9 M) [3]
RKI-1447 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition >9.0 pIC50 8
⤷ pIC50 >9.0 (IC50 <1x10-9 M) [8]
tofacitinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.9 pIC50 7
⤷ pIC50 6.9 (IC50 1.22x10-7 M) [7]
compound 20 [PMID: 22136433] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.5 pIC50 5
⤷ pIC50 6.5 (IC50 3.1x10-7 M) [5]
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: 2,10
Key to terms and symbols Click column headers to sort
Target used in screen: PKN1
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.9 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.3 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.0 pKd
GSK690693 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.5 pKd
tofacitinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.8 pKd
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 6.7 pKd
A-674563 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.7 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.5 pKd
ruboxistaurin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.5 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 6.2 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/PKN1(PRK1)
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 0.1
K-252a Small molecule or natural product Hs Inhibitor Inhibition 1.3
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 1.4
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 2.7
Ro-32-0432 Small molecule or natural product Hs Inhibitor Inhibition 7.1
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.7
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 10.3
H-89 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 14.3
JAK3 inhibitor VI Small molecule or natural product Hs Inhibitor Inhibition 14.4
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 15.5
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
Evidence suggests that PKN1 plays a role in modulation of the NF-κB signalling pathway. Specifically, in Salmonella infection, PKN1 is hijacked by a bacterial effector protein which results in inhibition of NF-κB-dependent gene expression (i.e. inhibition of production of the proinflammatory cytokines that would normally effect bacterial destruction and removal) [4]. PKN1 also plays a role in germinal center formation, by negatively regulating Akt kinase downstream of the B cell receptor [11], and SNPs in PKN1 (and several other genes) are suggestively associated with the presence of ectopic germinal center-like structures in the minor salivary glands of some patients (25%) with the autoimmune disease, primary Sjögren's syndrome [9].
Immuno Process Associations
Immuno Process:  T cell (activation)
Immuno Process:  B cell (activation)
Immuno Process:  Immune regulation
Immuno Process:  Immune system development
Immuno Process:  Cellular signalling

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. Hall MD, Salam NK, Hellawell JL, Fales HM, Kensler CB, Ludwig JA, Szakács G, Hibbs DE, Gottesman MM. (2009) Synthesis, activity, and pharmacophore development for isatin-beta-thiosemicarbazones with selective activity toward multidrug-resistant cells. J Med Chem, 52 (10): 3191-204. [PMID:19397322]

4. Haraga A, Miller SI. (2006) A Salmonella type III secretion effector interacts with the mammalian serine/threonine protein kinase PKN1. Cell Microbiol, 8 (5): 837-46. [PMID:16611232]

5. Huber K, Brault L, Fedorov O, Gasser C, Filippakopoulos P, Bullock AN, Fabbro D, Trappe J, Schwaller J, Knapp S et al.. (2012) 7,8-dichloro-1-oxo-β-carbolines as a versatile scaffold for the development of potent and selective kinase inhibitors with unusual binding modes. J Med Chem, 55 (1): 403-13. [PMID:22136433]

6. Maesaki R, Ihara K, Shimizu T, Kuroda S, Kaibuchi K, Hakoshima T. (1999) The structural basis of Rho effector recognition revealed by the crystal structure of human RhoA complexed with the effector domain of PKN/PRK1. Mol Cell, 4 (5): 793-803. [PMID:10619026]

7. Ostrovskyi D, Rumpf T, Eib J, Lumbroso A, Slynko I, Klaeger S, Heinzlmeir S, Forster M, Gehringer M, Pfaffenrot E et al.. (2016) Tofacitinib and analogs as inhibitors of the histone kinase PRK1 (PKN1). Future Med Chem, 8 (13): 1537-51. [PMID:27572962]

8. Pireddu R, Forinash KD, Sun NN, Martin MP, Sung SS, Alexander B, Zhu JY, Guida WC, Schönbrunn E, Sebti SM et al.. (2012) Pyridylthiazole-based ureas as inhibitors of Rho associated protein kinases (ROCK1 and 2). Medchemcomm, 3 (6): 699-709. [PMID:23275831]

9. Reksten TR, Johnsen SJ, Jonsson MV, Omdal R, Brun JG, Theander E, Eriksson P, Wahren-Herlenius M, Jonsson R, Nordmark G. (2014) Genetic associations to germinal centre formation in primary Sjogren's syndrome. Ann Rheum Dis, 73 (6): 1253-8. [PMID:23606706]

10. 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]

11. Yasui T, Sakakibara-Yada K, Nishimura T, Morita K, Tada S, Mosialos G, Kieff E, Kikutani H. (2012) Protein kinase N1, a cell inhibitor of Akt kinase, has a central role in quality control of germinal center formation. Proc Natl Acad Sci USA, 109 (51): 21022-7. [PMID:23223530]

How to cite this page

Protein kinase N (PKN) family: protein kinase N1. Last modified on 08/03/2017. Accessed on 19/09/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1520.