Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

Annotation inferences using phylogenetic trees

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

Automatic assignment of GO terms using logical inference, based on on inter-ontology links

Automatic Gene Ontology annotation based on Rhea mapping

Electronic Gene Ontology annotations created by ARBA machine learning models

Combined Automated Annotation using Multiple IEA Methods

Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity.

The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity.

Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, and mutant LRRK2 induces neuronal degeneration.

Kinase activity of mutant LRRK2 mediates neuronal toxicity.

The familial Parkinsonism gene LRRK2 regulates neurite process morphology.

Localization of LRRK2 to membranous and vesicular structures in mammalian brain.

Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity.

GTP binding is essential to the protein kinase activity of LRRK2, a causative gene product for familial Parkinson's disease.

Identification of potential protein interactors of Lrrk2.

The R1441C mutation of LRRK2 disrupts GTP hydrolysis.

Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase.

The chaperone activity of heat shock protein 90 is critical for maintaining the stability of leucine-rich repeat kinase 2.

The Parkinson disease-associated leucine-rich repeat kinase 2 (LRRK2) is a dimer that undergoes intramolecular autophosphorylation.

LRRK2 regulates synaptic vesicle endocytosis.

Large-scale proteomics and phosphoproteomics of urinary exosomes.

The Parkinson disease protein leucine-rich repeat kinase 2 transduces death signals via Fas-associated protein with death domain and caspase-8 in a cellular model of neurodegeneration.

CHIP regulates leucine-rich repeat kinase-2 ubiquitination, degradation, and toxicity.

The Parkinson disease-associated protein kinase LRRK2 exhibits MAPKKK activity and phosphorylates MKK3/6 and MKK4/7, in vitro.

Interaction of elongation factor 1-alpha with leucine-rich repeat kinase 2 impairs kinase activity and microtubule bundling in vitro.

Lrrk2 phosphorylates alpha synuclein at serine 129: Parkinson disease implications.

Mutations in the LRRK2 Roc-COR tandem domain link Parkinson's disease to Wnt signalling pathways.

LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model.

Leucine-Rich Repeat Kinase 2 interacts with Parkin, DJ-1 and PINK-1 in a Drosophila melanogaster model of Parkinson's disease.

Homo- and heterodimerization of ROCO kinases: LRRK2 kinase inhibition by the LRRK2 ROCO fragment.

The Parkinson's disease kinase LRRK2 autophosphorylates its GTPase domain at multiple sites.

MKK6 binds and regulates expression of Parkinson's disease-related protein LRRK2.

Heterodimerization of Lrrk1-Lrrk2: Implications for LRRK2-associated Parkinson disease.

LRRK2 and the stress response: interaction with MKKs and JNK-interacting proteins.

Membrane localization of LRRK2 is associated with increased formation of the highly active LRRK2 dimer and changes in its phosphorylation.

14-3-3 binding to LRRK2 is disrupted by multiple Parkinson's disease-associated mutations and regulates cytoplasmic localization.

Impaired dopaminergic neurotransmission and microtubule-associated protein tau alterations in human LRRK2 transgenic mice.

Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression.

ARHGEF7 (Beta-PIX) acts as guanine nucleotide exchange factor for leucine-rich repeat kinase 2.

Insight into the mode of action of the LRRK2 Y1699C pathogenic mutant.

LRRK2 kinase regulates synaptic morphology through distinct substrates at the presynaptic and postsynaptic compartments of the Drosophila neuromuscular junction.

Adult neurogenesis and neurite outgrowth are impaired in LRRK2 G2019S mice.

LRRK2 controls synaptic vesicle storage and mobilization within the recycling pool.

LRRK2 mutant iPSC-derived DA neurons demonstrate increased susceptibility to oxidative stress.

Expression of leucine-rich repeat kinase 2 (LRRK2) inhibits the processing of uMtCK to induce cell death in a cell culture model system.

Rac1 protein rescues neurite retraction caused by G2019S leucine-rich repeat kinase 2 (LRRK2).

Synaptic vesicle trafficking and Parkinson's disease.

LRRK2 directly phosphorylates Akt1 as a possible physiological substrate: impairment of the kinase activity by Parkinson's disease-associated mutations.

LRRK2 expression in idiopathic and G2019S positive Parkinson's disease subjects: a morphological and quantitative study.

Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3 exacerbating oxidative stress-induced neuronal death.

Dysregulated LRRK2 signaling in response to endoplasmic reticulum stress leads to dopaminergic neuron degeneration in C. elegans.

The kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel disease.

Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP.

LRRK2 regulates mitochondrial dynamics and function through direct interaction with DLP1.

LRRK2 phosphorylates tubulin-associated tau but not the free molecule: LRRK2-mediated regulation of the tau-tubulin association and neurite outgrowth.

GTPase activity and neuronal toxicity of Parkinson's disease-associated LRRK2 is regulated by ArfGAP1.

ArfGAP1 is a GTPase activating protein for LRRK2: reciprocal regulation of ArfGAP1 by LRRK2.

The G2385R variant of leucine-rich repeat kinase 2 associated with Parkinson's disease is a partial loss-of-function mutation.

Leucine-rich repeat kinase 2 disturbs mitochondrial dynamics via Dynamin-like protein.

Comparison of tear protein levels in breast cancer patients and healthy controls using a de novo proteomic approach.

G2019S leucine-rich repeat kinase 2 causes uncoupling protein-mediated mitochondrial depolarization.

Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson's disease.

LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6.

Biochemical characterization of highly purified leucine-rich repeat kinases 1 and 2 demonstrates formation of homodimers.

The importance of Wnt signalling for neurodegeneration in Parkinson's disease.

LRRK2 controls an EndoA phosphorylation cycle in synaptic endocytosis.

Progressive degeneration of human neural stem cells caused by pathogenic LRRK2.

LRRK2 interactions with α-synuclein in Parkinson's disease brains and in cell models.

Dominant-negative effects of LRRK2 heterodimers: a possible mechanism of neurodegeneration in Parkinson's disease caused by LRRK2 I2020T mutation.

GTPase activity regulates kinase activity and cellular phenotypes of Parkinson's disease-associated LRRK2.

RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson's disease risk.

Interplay of LRRK2 with chaperone-mediated autophagy.

Down-regulation of LRRK2 in control and DAT transfected HEK cells increases manganese-induced oxidative stress and cell toxicity.

Inhibition of excessive mitochondrial fission reduced aberrant autophagy and neuronal damage caused by LRRK2 G2019S mutation.

Inhibition of LRRK2 kinase activity stimulates macroautophagy.

Identification of protein phosphatase 1 as a regulator of the LRRK2 phosphorylation cycle.

LRRK2 phosphorylates Snapin and inhibits interaction of Snapin with SNAP-25.

LRRK2 phosphorylates novel tau epitopes and promotes tauopathy.

The regulation and deregulation of Wnt signaling by PARK genes in health and disease.

Leucine-rich repeat kinase 2 regulates tau phosphorylation through direct activation of glycogen synthase kinase-3β.

Pathogenic Parkinson's disease mutations across the functional domains of LRRK2 alter the autophagic/lysosomal response to starvation.

The role of oxidative stress in Parkinson's disease.

A direct interaction between leucine-rich repeat kinase 2 and specific β-tubulin isoforms regulates tubulin acetylation.

Functional interaction of Parkinson's disease-associated LRRK2 with members of the dynamin GTPase superfamily.

Parkinson-related LRRK2 mutation R1441C/G/H impairs PKA phosphorylation of LRRK2 and disrupts its interaction with 14-3-3.

Mutant LRRK2 toxicity in neurons depends on LRRK2 levels and synuclein but not kinase activity or inclusion bodies.

Thiol peroxidases ameliorate LRRK2 mutant-induced mitochondrial and dopaminergic neuronal degeneration in Drosophila.

LRRK2 regulates synaptogenesis and dopamine receptor activation through modulation of PKA activity.

Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease.

LRRK2, but not pathogenic mutants, protects against H2O2 stress depending on mitochondrial function and endocytosis in a yeast model.

Parkinson disease-associated mutation R1441H in LRRK2 prolongs the "active state" of its GTPase domain.

Leucine-rich repeat kinase 2 binds to neuronal vesicles through protein interactions mediated by its C-terminal WD40 domain.

The Parkinson disease-linked LRRK2 protein mutation I2020T stabilizes an active state conformation leading to increased kinase activity.

Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in Parkinson's disease.

MAP1B rescues LRRK2 mutant-mediated cytotoxicity.

A Parkinson's disease gene regulatory network identifies the signaling protein RGS2 as a modulator of LRRK2 activity and neuronal toxicity.

LRRK2 kinase activity regulates synaptic vesicle trafficking and neurotransmitter release through modulation of LRRK2 macro-molecular complex.

Differential protein-protein interactions of LRRK1 and LRRK2 indicate roles in distinct cellular signaling pathways.

LRRK2 kinase activity and biology are not uniformly predicted by its autophosphorylation and cellular phosphorylation site status.

Leucine-rich repeat kinase 2 regulates Sec16A at ER exit sites to allow ER-Golgi export.

LRRK2 transport is regulated by its novel interacting partner Rab32.

Dysregulation of lysosomal morphology by pathogenic LRRK2 is corrected by TPC2 inhibition.

Threonine 56 phosphorylation of Bcl-2 is required for LRRK2 G2019S-induced mitochondrial depolarization and autophagy.

Phosphorylation of LRRK2 by casein kinase 1α regulates trans-Golgi clustering via differential interaction with ARHGEF7.

LRRK2 functions in synaptic vesicle endocytosis through a kinase-dependent mechanism.

An early endosome regulator, Rab5b, is an LRRK2 kinase substrate.

LRRK2 Promotes Tau Accumulation, Aggregation and Release.

The LINK-A lncRNA activates normoxic HIF1α signalling in triple-negative breast cancer.

Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases.

Identification of protein phosphatase 2A as an interacting protein of leucine-rich repeat kinase 2.

Protective LRRK2 R1398H Variant Enhances GTPase and Wnt Signaling Activity.

Ubiqutination via K27 and K29 chains signals aggregation and neuronal protection of LRRK2 by WSB1.

G2385R and I2020T Mutations Increase LRRK2 GTPase Activity.

Structural model of the dimeric Parkinson's protein LRRK2 reveals a compact architecture involving distant interdomain contacts.

LRRK2 and RAB7L1 coordinately regulate axonal morphology and lysosome integrity in diverse cellular contexts.

LRRK2 enhances Nod1/2-mediated inflammatory cytokine production by promoting Rip2 phosphorylation.

Structural interface between LRRK2 and 14-3-3 protein.

Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD activity and neurotoxicity in Parkinson's disease.

Comparative Protein Interaction Network Analysis Identifies Shared and Distinct Functions for the Human ROCO Proteins.

P62/SQSTM1 is a novel leucine-rich repeat kinase 2 (LRRK2) substrate that enhances neuronal toxicity.

The LRRK2 Variant E193K Prevents Mitochondrial Fission Upon MPP+ Treatment by Altering LRRK2 Binding to DRP1.

A pathway for Parkinson's Disease LRRK2 kinase to block primary cilia and Sonic hedgehog signaling in the brain.

Parkinson's disease-associated LRRK2-G2019S mutant acts through regulation of SERCA activity to control ER stress in astrocytes.

LRRK2 binds to the Rab32 subfamily in a GTP-dependent manner via its armadillo domain.

Structural Basis for Rab8a Recruitment of RILPL2 via LRRK2 Phosphorylation of Switch 2.

Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.

Genomewide Association Studies of LRRK2 Modifiers of Parkinson's Disease.

Rab29-dependent asymmetrical activation of leucine-rich repeat kinase 2.

Systematic rare variant analyses identify RAB32 as a susceptibility gene for familial Parkinson's disease.

Phosphorylated GPNMB recruits PTK6 and LRRK2 in the presence of LINC01139

LINC01139 facilitates PTK6 autophosphorylation

LINC01139 promotes phosphorylation of HIF1A by PTK6

LINC01139 promotes phosphorylation of HIF1A by LRRK2

Deep research report on LRRK2