InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: LRRK2

Summary

InnateDB Protein

IDBP-27263.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

LRRK2

Protein Name

leucine-rich repeat kinase 2

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000298910

InnateDB Gene

IDBG-27257 (LRRK2)

Protein Structure

UniProt Annotation

Function

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). Phosphorylates PRDX3. May also have GTPase activity. May play a role in the phosphorylation of proteins central to Parkinson disease. {ECO:0000269PubMed:17114044, ECO:0000269PubMed:20949042, ECO:0000269PubMed:21850687, ECO:0000269PubMed:22012985, ECO:0000269PubMed:23395371}.

Subcellular Localization

Membrane; Peripheral membrane protein. Cytoplasm. Perikaryon. Mitochondrion. Golgi apparatus. Cell projection, axon. Cell projection, dendrite. Endoplasmic reticulum {ECO:0000250}. Cytoplasmic vesicle {ECO:0000250}. Endosome {ECO:0000250}. Lysosome {ECO:0000250}. Mitochondrion outer membrane {ECO:0000250}. Mitochondrion inner membrane {ECO:0000250}. Mitochondrion matrix {ECO:0000250}. Note=Predominantly associated with intracytoplasmic vesicular and membranous structures (By similarity). Localized in the cytoplasm and associated with cellular membrane structures. Predominantly associated with the mitochondrial outer membrane of the mitochondria. Colocalized with RAB29 along tubular structures emerging from Golgi apparatus. Localizes in intracytoplasmic punctate structures of neuronal perikarya and dendritic and axonal processes. {ECO:0000250}.

Disease Associations

Parkinson disease 8 (PARK8) [MIM:607060]: A slowly progressive neurodegenerative disorder characterized by bradykinesia, rigidity, resting tremor, postural instability, neuronal loss in the substantia nigra, and the presence of neurofibrillary MAPT (tau)-positive and Lewy bodies in some patients. {ECO:0000269PubMed:15541308, ECO:0000269PubMed:15541309, ECO:0000269PubMed:15680455, ECO:0000269PubMed:15680456, ECO:0000269PubMed:15680457, ECO:0000269PubMed:15726496, ECO:0000269PubMed:15732108, ECO:0000269PubMed:15811454, ECO:0000269PubMed:15852371, ECO:0000269PubMed:15880653, ECO:0000269PubMed:15925109, ECO:0000269PubMed:15929036, ECO:0000269PubMed:16102999, ECO:0000269PubMed:16157901, ECO:0000269PubMed:16157908, ECO:0000269PubMed:16157909, ECO:0000269PubMed:16172858, ECO:0000269PubMed:16240353, ECO:0000269PubMed:16247070, ECO:0000269PubMed:16250030, ECO:0000269PubMed:16251215, ECO:0000269PubMed:16272164, ECO:0000269PubMed:16272257, ECO:0000269PubMed:16298482, ECO:0000269PubMed:16333314, ECO:0000269PubMed:16533964, ECO:0000269PubMed:18213618, ECO:0000269PubMed:22956510}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Expressed in the brain. Expressed in pyramidal neurons in all cortical laminae of the visual cortex, in neurons of the substantia nigra pars compacta and caudate putamen (at protein level). Expressed throughout the adult brain, but at a lower level than in heart and liver. Also expressed in placenta, lung, skeletal muscle, kidney and pancreas. In the brain, expressed in the cerebellum, cerebral cortex, medulla, spinal cord occipital pole, frontal lobe, temporal lobe and putamen. Expression is particularly high in brain dopaminoceptive areas. {ECO:0000269PubMed:15541308, ECO:0000269PubMed:15541309, ECO:0000269PubMed:16532471, ECO:0000269PubMed:17120249}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 361 experimentally validated interaction(s) in this database.
They are also associated with 35 interaction(s) predicted by orthology.

Experimentally validated
Total	361 [view]
Protein-Protein	361 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	35 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000149	SNARE binding
GO:0001948	glycoprotein binding
GO:0003779	actin binding
GO:0003924	GTPase activity
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004708	MAP kinase kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004857	enzyme inhibitor activity
GO:0005096	GTPase activator activity
GO:0005488	binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0005525	GTP binding
GO:0015631	tubulin binding
GO:0016301	kinase activity
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0017048	Rho GTPase binding
GO:0017075	syntaxin-1 binding
GO:0030276	clathrin binding
GO:0034211	GTP-dependent protein kinase activity
GO:0042802	identical protein binding
GO:0042803	protein homodimerization activity
GO:0044325	ion channel binding
GO:0051018	protein kinase A binding

Biological Process

GO:0000165	MAPK cascade
GO:0000186	activation of MAPKK activity
GO:0000187	activation of MAPK activity
GO:0001933	negative regulation of protein phosphorylation
GO:0001934	positive regulation of protein phosphorylation
GO:0006184	GTP catabolic process
GO:0006468	protein phosphorylation
GO:0006914	autophagy
GO:0006979	response to oxidative stress
GO:0007264	small GTPase mediated signal transduction
GO:0007528	neuromuscular junction development
GO:0008340	determination of adult lifespan
GO:0010508	positive regulation of autophagy
GO:0010738	regulation of protein kinase A signaling
GO:0014041	regulation of neuron maturation
GO:0015031	protein transport
GO:0018105	peptidyl-serine phosphorylation
GO:0018107	peptidyl-threonine phosphorylation
GO:0021772	olfactory bulb development
GO:0022028	tangential migration from the subventricular zone to the olfactory bulb
GO:0031398	positive regulation of protein ubiquitination
GO:0032091	negative regulation of protein binding
GO:0032436	positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0034260	negative regulation of GTPase activity
GO:0034613	cellular protein localization
GO:0035556	intracellular signal transduction
GO:0035564	regulation of kidney size
GO:0035640	exploration behavior
GO:0035641	locomotory exploration behavior
GO:0040012	regulation of locomotion
GO:0042391	regulation of membrane potential
GO:0043068	positive regulation of programmed cell death
GO:0043547	positive regulation of GTPase activity
GO:0045087	innate immune response (InnateDB)
GO:0046777	protein autophosphorylation
GO:0048312	intracellular distribution of mitochondria
GO:0048812	neuron projection morphogenesis
GO:0051900	regulation of mitochondrial depolarization
GO:0051966	regulation of synaptic transmission, glutamatergic
GO:0060079	regulation of excitatory postsynaptic membrane potential
GO:0060159	regulation of dopamine receptor signaling pathway
GO:0060161	positive regulation of dopamine receptor signaling pathway
GO:0061001	regulation of dendritic spine morphogenesis
GO:0070997	neuron death
GO:0071407	cellular response to organic cyclic compound
GO:1901214	regulation of neuron death
GO:1902692	regulation of neuroblast proliferation
GO:1902803	regulation of synaptic vesicle transport
GO:1902823	negative regulation of late endosome to lysosome transport
GO:1903125	negative regulation of thioredoxin peroxidase activity by peptidyl-threonine phosphorylation
GO:2000172	regulation of branching morphogenesis of a nerve
GO:2000300	regulation of synaptic vesicle exocytosis

Cellular Component

GO:0005615	extracellular space
GO:0005622	intracellular
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005741	mitochondrial outer membrane
GO:0005743	mitochondrial inner membrane
GO:0005759	mitochondrial matrix
GO:0005764	lysosome
GO:0005768	endosome
GO:0005783	endoplasmic reticulum
GO:0005794	Golgi apparatus
GO:0005802	trans-Golgi network
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0008021	synaptic vesicle
GO:0016020	membrane
GO:0016234	inclusion body
GO:0030424	axon
GO:0030425	dendrite
GO:0031410	cytoplasmic vesicle
GO:0031966	mitochondrial membrane
GO:0032473	external side of mitochondrial outer membrane
GO:0032839	dendrite cytoplasm
GO:0043005	neuron projection
GO:0043025	neuronal cell body
GO:0043204	perikaryon
GO:0043231	intracellular membrane-bounded organelle
GO:0045121	membrane raft
GO:0045202	synapse
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR001611 Leucine-rich repeat
IPR001806 Small GTPase superfamily
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR003579 Small GTPase superfamily, Rab type
IPR003591 Leucine-rich repeat, typical subtype
IPR005225 Small GTP-binding protein domain
IPR006689 Small GTPase superfamily, ARF/SAR type
IPR011009 Protein kinase-like domain
IPR013684 Mitochondrial Rho-like
IPR016024 Armadillo-type fold
IPR017986 WD40-repeat-containing domain
IPR020635 Tyrosine-protein kinase, catalytic domain
IPR027417 P-loop containing nucleoside triphosphate hydrolase

PFAM