Nomenclature: leucine-rich repeat kinase 2

Abbreviated Name: LRRK2

Family: Leucine-rich repeat kinase (LRRK) family

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

Contents

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 2527 12q12 LRRK2 leucine-rich repeat kinase 2
Mouse - 2527 15 F1 Lrrk2 leucine-rich repeat kinase 2
Rat - 2526 7q35 Lrrk2 leucine-rich repeat kinase 2
Previous and Unofficial Names
Parkinson disease (autosomal dominant) 8
Park8
ROCO2
DKFZp434H2111
FLJ45829
RIPK7
leucine-rich repeat serine/threonine-protein kinase 2
cI-46
LOC381026
Database Links
BRENDA
Ensembl Gene
Entrez Gene
ExplorEnz
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG BRITE Hierarchy
KEGG Gene
OMIM
Orphanet Gene
PhosphoSitePlus
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase
PDB Id:  3D6T
Resolution:  2.43Å
Species:  Human
References:  3
Enzyme Reaction
EC Number: 2.7.11.1
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: 2,4

Key to terms and symbols Click column headers to sort
Target used in screen: LRRK2
Ligand Sp. Type Action Affinity Units
TAE 684 Hs Inhibitor Inhibition 8.85 pKd
staurosporine Hs Inhibitor Inhibition 8.51 pKd
lestaurtinib Hs Inhibitor Inhibition 8.44 pKd
R406 Hs Inhibitor Inhibition 7.44 pKd
SU-14813 Hs Inhibitor Inhibition 7.14 pKd
sunitinib Hs Inhibitor Inhibition 6.96 pKd
JNJ-28312141 Hs Inhibitor Inhibition 6.72 pKd
ruxolitinib Hs Inhibitor Inhibition 6.54 pKd
PP-242 Hs Inhibitor Inhibition 6.54 pKd
KW-2449 Hs Inhibitor Inhibition 6.46 pKd
Target used in screen: LRRK2(G2019S)
Ligand Sp. Type Action Affinity Units
staurosporine Hs Inhibitor Inhibition 9.41 pKd
TAE 684 Hs Inhibitor Inhibition 9.07 pKd
lestaurtinib Hs Inhibitor Inhibition 8.6 pKd
R406 Hs Inhibitor Inhibition 7.57 pKd
KW-2449 Hs Inhibitor Inhibition 7.35 pKd
SU-14813 Hs Inhibitor Inhibition 7.15 pKd
sunitinib Hs Inhibitor Inhibition 7.12 pKd
ruxolitinib Hs Inhibitor Inhibition 7.05 pKd
GSK-1838705A Hs Inhibitor Inhibition 6.77 pKd
midostaurin Hs Inhibitor Inhibition 6.74 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/LRRK2
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
K-252a Hs Inhibitor Inhibition 0.3
staurosporine Hs Inhibitor Inhibition 1.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 1.3
SU11652 Hs Inhibitor Inhibition 1.4
SU6656 Hs Inhibitor Inhibition 1.8
SB 218078 Hs Inhibitor Inhibition 1.9
Cdk2 inhibitor IV Hs Inhibitor Inhibition 2.2
sunitinib Hs Inhibitor Inhibition 3.3
JAK3 inhibitor VI Hs Inhibitor Inhibition 6.2
SU11274 Hs Inhibitor Inhibition 6.6
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Parkinson disease 8, autosomal dominant
OMIM:  607060
Orphanet:  2828
References: 
Mutations not determined

REFERENCES

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. Deng J, Lewis PA, Greggio E, Sluch E, Beilina A, Cookson MR. (2008) Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase. Proc. Natl. Acad. Sci. U.S.A.105 (5): 1499-504. [PMID:18230735]

4. 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]

To cite this database page, please use the following:

Leucine-rich repeat kinase (LRRK) family: leucine-rich repeat kinase 2. Last modified on 12/03/2014. Accessed on 29/07/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=2059.

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