Lrrk Leucine-rich repeat kinase [Drosophila melanogaster (fruit fly)] - Gene

Summary

Official Symbol: Lrrkprovided by FlyBase
Official Full Name: Leucine-rich repeat kinaseprovided by FlyBase
Primary source: FLYBASE:FBgn0038816
Locus tag: Dmel_CG5483
See related: AllianceGenome:FB:FBgn0038816
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Drosophila melanogaster
Lineage: Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea; Drosophilidae; Drosophila; Sophophora
Also known as: CG5483; CT17358; dLrrk; dLRRK; dLrrk2; dLRRK2; Dmel\CG5483; lrrk; LRRK; Lrrk2; LRRK2
Summary: Enables protein serine/threonine kinase activity and small GTPase binding activity. Involved in several processes, including establishment of Golgi localization; regulation of organelle organization; and regulation of synapse organization. Located in several cellular components, including bounding membrane of organelle; dendritic tree; and subsynaptic reticulum. Is expressed in spermatozoon. Used to study Parkinson's disease; Parkinson's disease 8; and late onset Parkinson's disease. Human ortholog(s) of this gene implicated in osteosclerotic metaphyseal dysplasia. Orthologous to human LRRK1 (leucine rich repeat kinase 1). [provided by Alliance of Genome Resources, Dec 2024]
Orthologs: all
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Genomic context

Location:: 92F3-92F4; 3-69 cM

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
Release 6.54	current	Release 6 plus ISO1 MT (GCF_000001215.4)	3R	NT_033777.3 (20635480..20644279)
Release 5.57	previous assembly	Release 5 (GCF_000001215.2)	3R	NT_033777.2 (16461202..16470001)

Chromosome 3R - NT_033777.3 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Tyrosine Metabolism Pathway Is Downregulated in Dopaminergic Neurons with LRRK2 Overexpression in Drosophila.
Title: Tyrosine Metabolism Pathway Is Downregulated in Dopaminergic Neurons with LRRK2 Overexpression in Drosophila.
Dopamine neuron-specific LRRK2 G2019S effects on gene expression revealed by translatome profiling.
Title: Dopamine neuron-specific LRRK2 G2019S effects on gene expression revealed by translatome profiling.
aberrant function of LRRK2 may lead to destabilization of neural circuits.
Title: LRRK2 regulates retrograde synaptic compensation at the Drosophila neuromuscular junction.
Data support the view that LRRK2/Lrrk is a gene/protein involved in oxidative stress-signaling leading to neurodegenerative process and loss of DAergic neurons and that reduced/suppressed LRRK2 expression might delay or prevent motor symptoms and/or frank Parkinsonism in individuals at risk to suffer autosomal dominant Parkinsonism.
Title: Knockdown transgenic Lrrk Drosophila resists paraquat-induced locomotor impairment and neurodegeneration: A therapeutic strategy for Parkinson's disease.
EndophilinA-induced macroautophagy is activated when the kinase LRRK2 phosphorylates the EndophilinA-BAR domain and is blocked in animals where EndophilinA cannot be phosphorylated. Functionally, deregulation of the EndophilinA phosphorylation state accelerates activity-induced neurodegeneration.
Title: A LRRK2-Dependent EndophilinA Phosphoswitch Is Critical for Macroautophagy at Presynaptic Terminals.
Our findings demonstrated that lovastatin restored LRRK2-G2019S neurite degeneration by augmenting Akt/NRF2 pathway and inhibiting downstream GSK3beta activity, which decreased phospho-tau levels. We suggested that lovastatin is a potential disease-modifying agent for LRRK2-G2019S parkinsonism.
Title: Lovastatin protects neurite degeneration in LRRK2-G2019S parkinsonism through activating the Akt/Nrf pathway and inhibiting GSK3β activity.
Our results suggest LRRK2 may be involved in a wide variety of cellular processes and the results from this screen provide an important genetic resource for further evaluation of LRRK2 function
Title: LRRK2(I2020T) functional genetic interactors that modify eye degeneration and dopaminergic cell loss in Drosophila.
The study reveals a pathogenic pathway for LRRK2 mutations causing dendrite degeneration.
Title: Lrrk regulates the dynamic profile of dendritic Golgi outposts through the golgin Lava lamp.
LRRK2 containing pathogenic Roc-COR domain mutations associates with deacetylated microtubules, and inhibits axonal transport in primary neurons and in Drosophila.
Title: Increasing microtubule acetylation rescues axonal transport and locomotor deficits caused by LRRK2 Roc-COR domain mutations.
phosphorylation of the ribosomal protein s15 key to the increased bulk protein synthesis, age-related dopamine neuron loss and climbing defects in G2019S LRRK2 transgenic Drosophila
Title: Abberant protein synthesis in G2019S LRRK2 Drosophila Parkinson disease-related phenotypes.

Submit: New GeneRIF Correction See all GeneRIFs (20)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

NCBI Orthologs

Orthologs from OrthoDB

Gene Ontology Provided by FlyBase

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein serine/threonine kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables small GTPase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in autophagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in axo-dendritic transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to starvation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in establishment of Golgi localization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular distribution of mitochondria	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in locomotion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in lysosome localization	IGI Inferred from Genetic Interaction more info	PubMed
involved_in lysosome localization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of dendrite morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of negative regulation of neuron apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neuromuscular junction development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in regulation of autophagosome assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of microtubule cytoskeleton organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of synapse maturation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of synaptic vesicle endocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of terminal button organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in retrograde transport, endosome to Golgi	IGI Inferred from Genetic Interaction more info	PubMed
involved_in synapse organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in synaptic vesicle endocytosis	IGI Inferred from Genetic Interaction more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi stack	IDA Inferred from Direct Assay more info	PubMed
located_in cell body	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in dendritic branch point	IDA Inferred from Direct Assay more info	PubMed
located_in dendritic shaft	IDA Inferred from Direct Assay more info	PubMed
located_in late endosome membrane	IDA Inferred from Direct Assay more info	PubMed
located_in lysosomal membrane	IDA Inferred from Direct Assay more info	PubMed
located_in neuromuscular junction	IDA Inferred from Direct Assay more info	PubMed
located_in subsynaptic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in terminal bouton	IDA Inferred from Direct Assay more info	PubMed
located_in type I terminal bouton	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: Leucine-rich repeat kinase

Names: CG5483-PB; CG5483-PC; CG5483-PD; LRRK; LRRK2; Lrrk-PB; Lrrk-PC; Lrrk-PD; ortholog of LRRK2

NP_001097847.1

EC 2.7.11.1

NP_001262771.1

EC 2.7.11.1

NP_001262772.1

EC 2.7.11.1

NCBI Reference Sequences (RefSeq)

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Genome Annotation

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference assembly

Genomic

NT_033777.3 Reference assembly

Range

20635480..20644279

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001275843.1 → NP_001262772.1 Leucine-rich repeat kinase, isoform D [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_001262772.1

Status: REVIEWED

UniProtKB/TrEMBL

A0A0B4KHT3

Conserved Domains (10) summary

smart00221
Location:1796 → 2092

STYKc; Protein kinase; unclassified specificity

cd00204
Location:146 → 286

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

cd14000
Location:1801 → 2095

STKc_LRRK; Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase

sd00033
Location:547 → 569

LRR_RI; leucine-rich repeat [structural motif]

pfam12796
Location:364 → 464

Ank_2; Ankyrin repeats (3 copies)

pfam13637
Location:179 → 232

Ank_4; Ankyrin repeats (many copies)

pfam13855
Location:569 → 629

LRR_8; Leucine rich repeat

pfam16095
Location:1230 → 1471

COR; C-terminal of Roc, COR, domain

sd00045
Location:146 → 177

ANK; ANK repeat [structural motif]

cl21455
Location:993 → 1211

P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases
NM_001275842.1 → NP_001262771.1 Leucine-rich repeat kinase, isoform C [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_001262771.1

Status: REVIEWED

UniProtKB/TrEMBL

A0A0B4KH16

Conserved Domains (10) summary

smart00221
Location:1705 → 2001

STYKc; Protein kinase; unclassified specificity

cd00204
Location:55 → 195

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

cd14000
Location:1710 → 2004

STKc_LRRK; Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase

sd00033
Location:456 → 478

LRR_RI; leucine-rich repeat [structural motif]

pfam12796
Location:273 → 373

Ank_2; Ankyrin repeats (3 copies)

pfam13637
Location:88 → 141

Ank_4; Ankyrin repeats (many copies)

pfam13855
Location:478 → 538

LRR_8; Leucine rich repeat

pfam16095
Location:1139 → 1297

COR; C-terminal of Roc, COR, domain

sd00045
Location:55 → 86

ANK; ANK repeat [structural motif]

cl21455
Location:902 → 1120

P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases
NM_001104377.2 → NP_001097847.1 Leucine-rich repeat kinase, isoform B [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_001097847.1

Status: REVIEWED

UniProtKB/TrEMBL

Q0Q7G2, Q9VDJ9

Conserved Domains (10) summary

smart00221
Location:1728 → 2024

STYKc; Protein kinase; unclassified specificity

cd00204
Location:78 → 218

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

cd14000
Location:1733 → 2027

STKc_LRRK; Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase

sd00033
Location:479 → 501

LRR_RI; leucine-rich repeat [structural motif]

pfam12796
Location:296 → 396

Ank_2; Ankyrin repeats (3 copies)

pfam13637
Location:111 → 164

Ank_4; Ankyrin repeats (many copies)

pfam13855
Location:501 → 561

LRR_8; Leucine rich repeat

pfam16095
Location:1162 → 1320

COR; C-terminal of Roc, COR, domain

sd00045
Location:78 → 109

ANK; ANK repeat [structural motif]

cl21455
Location:925 → 1143

P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases