Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

LRRK2 (Q5S007) - Overview - Molecular Target Synopsis

Protein


LRRK2, Leucine-rich repeat serine/threonine-protein kinase 2
Enzyme Classification 2.7.11.1
UniProt Q5S007

Also Known as LRRK2_HUMAN, LRRK2, PARK8

Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway. The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes. Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose 6 phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner. Regulates neuronal process morphology in the intact central nervous system (CNS). Plays a role in synaptic vesicle trafficking. Phosphorylates PRDX3. Has GTPase activity. May play a role in the phosphorylation of proteins central to Parkinson disease. Plays an important role in recuiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed:25201882). Homodimer. Interacts with PRKN, PRDX3, RAB29, TPCN2 and VPS35. Interacts (via ROC domain) with SEC16A (PubMed:25201882).

6DLO
CRYSTAL STRUCTURE OF LRRK2 WD40 DOMAIN DIMER
RCSB/PDB
Inspect Structure
See all 3D Structures for LRRK2

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


Gene Copy Number Variation


In COSMIC - Cell Lines Project LRRK2 has gain in 9 cell-lines, loss in 5 cell-lines and no signal in 991 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MALME_3M, M14, MDA_N

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: ZR-75-1, OCI-LY-10, TMD8

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: GM12878, CD14-positive monocyte, SK-N-SH

(see details)

RNA Interference


LRRK2 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: PCI30, 143B. (see details)

3D Structures


For LRRK2 there are:
6 structures (9 chains) solved
2 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


LRRK2 has been screened with 1450 compounds (3172 bioactivities), 847 compounds have bioactivities that show binding affinity of <= 500nM (1125 bioactivities). (see details)