MultifacetedProtDB - Bologna Biocomputing Group

EC number	EC number description
2.7.11.1	Transferases; Transferring phosphorus-containing groups; Protein-serine/threonine kinases; non-specific serine/threonine protein kinase
3.6.5.-	Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement;

Structure

PDB	Resolution (Å)	PDB name
2ZEJ	2.0	Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase
3D6T	2.43	Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase
5MY9	1.327	Crystal structure of human 14-3-3 sigma in complex with LRRK2 peptide pS935
5MYC	1.459	Crystal structure of human 14-3-3 sigma in complex with LRRK2 peptide pS910
6DLO	2.7	Crystal structure of LRRK2 WD40 domain dimer
6DLP	4.0	Crystal structure of LRRK2 WD40 domain dimer
6OJE	1.95	Dimeric structure of LRRK2 GTPase domain
6OJF	1.6	Dimeric structure of LRRK2 GTPase domain
6VNO	3.5	Cryo-EM structure of the C-terminal half of the Parkinson's Disease-linked protein Leucine Rich Repeat Kinase 2 (LRRK2)
6VP6	3.47	Cryo-EM structure of the C-terminal half of the Parkinson's Disease-linked protein Leucine Rich Repeat Kinase 2 (LRRK2)
6VP7	3.5	Cryo-EM structure of the C-terminal half of the Parkinson's Disease-linked protein Leucine Rich Repeat Kinase 2 (LRRK2)
6XAF	1.968	1.9A crystal structure of the GTPase domain of Parkinson's disease-associated protein LRRK2 carrying R1398H
6XR4	14.0	Integrative in situ structure of Parkinsons disease-linked human LRRK2
7LHT	3.5	Structure of the LRRK2 dimer
7LHW	3.7	Structure of the LRRK2 monomer
7LI3	3.8	Structure of the LRRK2 G2019S mutant
7LI4	3.1	Structure of LRRK2 after symmetry expansion
7THY	5.2	Structure of Leucine Rich Repeat Kinase 2's ROC domain interacting with the microtubule facing the minus end
7THZ	5.0	Structure of Leucine Rich Repeat Kinase 2's ROC domain interacting with the microtubule facing the plus end

GO term

GO ontology	GO term	GO description
Biological Process	GO:0046039	GTP metabolic process
Biological Process	GO:0007030	Golgi organization
Biological Process	GO:0007254	JNK cascade
Biological Process	GO:0000165	MAPK cascade
Biological Process	GO:1904887	Wnt signalosome assembly
Biological Process	GO:0006914	autophagy
Biological Process	GO:0019722	calcium-mediated signaling
Biological Process	GO:0060070	canonical Wnt signaling pathway
Biological Process	GO:1903351	cellular response to dopamine
Biological Process	GO:0071287	cellular response to manganese ion
Biological Process	GO:0034599	cellular response to oxidative stress
Biological Process	GO:0009267	cellular response to starvation
Biological Process	GO:0071356	cellular response to tumor necrosis factor
Biological Process	GO:0008340	determination of adult lifespan
Biological Process	GO:0006897	endocytosis
Biological Process	GO:0007029	endoplasmic reticulum organization
Biological Process	GO:0060079	excitatory postsynaptic potential
Biological Process	GO:0035640	exploration behavior
Biological Process	GO:0048312	intracellular distribution of mitochondria
Biological Process	GO:0035556	intracellular signal transduction
Biological Process	GO:0035641	locomotory exploration behavior
Biological Process	GO:0007040	lysosome organization
Biological Process	GO:0051646	mitochondrion localization
Biological Process	GO:0007005	mitochondrion organization
Biological Process	GO:0034260	negative regulation of GTPase activity
Biological Process	GO:0032088	negative regulation of NF-kappaB transcription factor activity
Biological Process	GO:1902902	negative regulation of autophagosome assembly
Biological Process	GO:1902236	negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
Biological Process	GO:0090394	negative regulation of excitatory postsynaptic potential
Biological Process	GO:1903206	negative regulation of hydrogen peroxide-induced cell death
Biological Process	GO:1902823	negative regulation of late endosome to lysosome transport
Biological Process	GO:0016242	negative regulation of macroautophagy
Biological Process	GO:0010977	negative regulation of neuron projection development
Biological Process	GO:0032091	negative regulation of protein binding
Biological Process	GO:0001933	negative regulation of protein phosphorylation
Biological Process	GO:0010955	negative regulation of protein processing
Biological Process	GO:1903217	negative regulation of protein processing involved in protein targeting to mitochondrion
Biological Process	GO:1903215	negative regulation of protein targeting to mitochondrion
Biological Process	GO:1903125	negative regulation of thioredoxin peroxidase activity by peptidyl-threonine phosphorylation
Biological Process	GO:0007528	neuromuscular junction development
Biological Process	GO:0140058	neuron projection arborization
Biological Process	GO:0048812	neuron projection morphogenesis
Biological Process	GO:0021772	olfactory bulb development
Biological Process	GO:0018105	peptidyl-serine phosphorylation
Biological Process	GO:0018107	peptidyl-threonine phosphorylation
Biological Process	GO:0016310	phosphorylation
Biological Process	GO:0043406	positive regulation of MAP kinase activity
Biological Process	GO:0010508	positive regulation of autophagy
Biological Process	GO:0090263	positive regulation of canonical Wnt signaling pathway
Biological Process	GO:0060161	positive regulation of dopamine receptor signaling pathway
Biological Process	GO:1903980	positive regulation of microglial cell activation
Biological Process	GO:0051770	positive regulation of nitric-oxide synthase biosynthetic process
Biological Process	GO:0043068	positive regulation of programmed cell death
Biological Process	GO:0032436	positive regulation of proteasomal ubiquitin-dependent protein catabolic process
Biological Process	GO:1902499	positive regulation of protein autoubiquitination
Biological Process	GO:0032092	positive regulation of protein binding
Biological Process	GO:0045860	positive regulation of protein kinase activity
Biological Process	GO:0001934	positive regulation of protein phosphorylation
Biological Process	GO:0031398	positive regulation of protein ubiquitination
Biological Process	GO:1900244	positive regulation of synaptic vesicle endocytosis
Biological Process	GO:0032760	positive regulation of tumor necrosis factor production
Biological Process	GO:0046777	protein autophosphorylation
Biological Process	GO:0006606	protein import into nucleus
Biological Process	GO:0008104	protein localization
Biological Process	GO:0070973	protein localization to endoplasmic reticulum exit site
Biological Process	GO:0070585	protein localization to mitochondrion
Biological Process	GO:0006468	protein phosphorylation
Biological Process	GO:0072593	reactive oxygen species metabolic process
Biological Process	GO:1905289	regulation of CAMKK-AMPK signaling cascade
Biological Process	GO:0060628	regulation of ER to Golgi vesicle-mediated transport
Biological Process	GO:0010506	regulation of autophagy
Biological Process	GO:2000172	regulation of branching morphogenesis of a nerve
Biological Process	GO:0060828	regulation of canonical Wnt signaling pathway
Biological Process	GO:0061001	regulation of dendritic spine morphogenesis
Biological Process	GO:0060159	regulation of dopamine receptor signaling pathway
Biological Process	GO:0035564	regulation of kidney size
Biological Process	GO:0040012	regulation of locomotion
Biological Process	GO:0035751	regulation of lysosomal lumen pH
Biological Process	GO:0042391	regulation of membrane potential
Biological Process	GO:0051900	regulation of mitochondrial depolarization
Biological Process	GO:0090140	regulation of mitochondrial fission
Biological Process	GO:1902692	regulation of neuroblast proliferation
Biological Process	GO:1901214	regulation of neuron death
Biological Process	GO:0014041	regulation of neuron maturation
Biological Process	GO:0010738	regulation of protein kinase A signaling
Biological Process	GO:0031647	regulation of protein stability
Biological Process	GO:1905279	regulation of retrograde transport, endosome to Golgi
Biological Process	GO:0051966	regulation of synaptic transmission, glutamatergic
Biological Process	GO:2000300	regulation of synaptic vesicle exocytosis
Biological Process	GO:1902803	regulation of synaptic vesicle transport
Biological Process	GO:0006979	response to oxidative stress
Biological Process	GO:0007283	spermatogenesis
Biological Process	GO:0021756	striatum development
Biological Process	GO:0022028	tangential migration from the subventricular zone to the olfactory bulb
Molecular Function	GO:0005524	ATP binding
Molecular Function	GO:0005525	GTP binding
Molecular Function	GO:0034211	GTP-dependent protein kinase activity
Molecular Function	GO:0005096	GTPase activator activity
Molecular Function	GO:0003924	GTPase activity
Molecular Function	GO:0004706	JUN kinase kinase kinase activity
Molecular Function	GO:0004709	MAP kinase kinase kinase activity
Molecular Function	GO:0000149	SNARE binding
Molecular Function	GO:0003779	actin binding
Molecular Function	GO:1904713	beta-catenin destruction complex binding
Molecular Function	GO:0030276	clathrin binding
Molecular Function	GO:0039706	co-receptor binding
Molecular Function	GO:0042802	identical protein binding
Molecular Function	GO:0016301	kinase activity
Molecular Function	GO:0000287	magnesium ion binding
Molecular Function	GO:0008017	microtubule binding
Molecular Function	GO:0036479	peroxidase inhibitor activity
Molecular Function	GO:0042803	protein homodimerization activity
Molecular Function	GO:0051018	protein kinase A binding
Molecular Function	GO:0004672	protein kinase activity
Molecular Function	GO:0106310	protein serine kinase activity
Molecular Function	GO:0004674	protein serine/threonine kinase activity
Molecular Function	GO:0005102	signaling receptor binding
Molecular Function	GO:0030159	signaling receptor complex adaptor activity
Molecular Function	GO:0031267	small GTPase binding
Molecular Function	GO:0017075	syntaxin-1 binding
Molecular Function	GO:0044325	transmembrane transporter binding
Molecular Function	GO:0015631	tubulin binding
Cellular Component	GO:0005794	Golgi apparatus
Cellular Component	GO:0000139	Golgi membrane
Cellular Component	GO:0005798	Golgi-associated vesicle
Cellular Component	GO:1990909	Wnt signalosome
Cellular Component	GO:0044753	amphisome
Cellular Component	GO:0044754	autolysosome
Cellular Component	GO:0030424	axon
Cellular Component	GO:0016323	basolateral plasma membrane
Cellular Component	GO:0099400	caveola neck
Cellular Component	GO:0005737	cytoplasm
Cellular Component	GO:0032473	cytoplasmic side of mitochondrial outer membrane
Cellular Component	GO:0031410	cytoplasmic vesicle
Cellular Component	GO:0005856	cytoskeleton
Cellular Component	GO:0005829	cytosol
Cellular Component	GO:0030425	dendrite
Cellular Component	GO:0032839	dendrite cytoplasm
Cellular Component	GO:0005783	endoplasmic reticulum
Cellular Component	GO:0070971	endoplasmic reticulum exit site
Cellular Component	GO:0005789	endoplasmic reticulum membrane
Cellular Component	GO:0005768	endosome
Cellular Component	GO:0070062	extracellular exosome
Cellular Component	GO:0005615	extracellular space
Cellular Component	GO:0098978	glutamatergic synapse
Cellular Component	GO:0030426	growth cone
Cellular Component	GO:0016234	inclusion body
Cellular Component	GO:0043231	intracellular membrane-bounded organelle
Cellular Component	GO:0005764	lysosome
Cellular Component	GO:0005902	microvillus
Cellular Component	GO:0005743	mitochondrial inner membrane
Cellular Component	GO:0005759	mitochondrial matrix
Cellular Component	GO:0031966	mitochondrial membrane
Cellular Component	GO:0005741	mitochondrial outer membrane
Cellular Component	GO:0005739	mitochondrion
Cellular Component	GO:0097487	multivesicular body, internal vesicle
Cellular Component	GO:0043005	neuron projection
Cellular Component	GO:0043025	neuronal cell body
Cellular Component	GO:0043204	perikaryon
Cellular Component	GO:0005886	plasma membrane
Cellular Component	GO:0098794	postsynapse
Cellular Component	GO:0099523	presynaptic cytosol
Cellular Component	GO:1990904	ribonucleoprotein complex
Cellular Component	GO:0030672	synaptic vesicle membrane
Cellular Component	GO:0043195	terminal bouton
Cellular Component	GO:0005802	trans-Golgi network

InterPro / Pfam

InterPro	InterPro name
IPR000719	Protein kinase domain
IPR001611	Leucine-rich repeat
IPR003591	Leucine-rich repeat, typical subtype
IPR005225	Small GTP-binding protein domain
IPR008271	Serine/threonine-protein kinase, active site
IPR011009	Protein kinase-like domain superfamily
IPR011989	Armadillo-like helical
IPR015943	WD40/YVTN repeat-like-containing domain superfamily
IPR016024	Armadillo-type fold
IPR017441	Protein kinase, ATP binding site
IPR020859	Roc domain
IPR025875	Leucine rich repeat 4
IPR027417	P-loop containing nucleoside triphosphate hydrolase
IPR032171	C-terminal of Roc (COR) domain
IPR032675	Leucine-rich repeat domain superfamily
IPR036322	WD40-repeat-containing domain superfamily
IPR036770	Ankyrin repeat-containing domain superfamily

Pfam	Pfam name
PF00069	Protein kinase domain
PF08477	Ras of Complex, Roc, domain of DAPkinase
PF12799	Leucine Rich repeats (2 copies)
PF13855	Leucine rich repeat
PF16095	C-terminal of Roc, COR, domain

Reactome

Reactome	Reactome Name	Node type	Reactome Root	Reactome Root Name
R-HSA-8857538	PTK6 promotes HIF1A stabilization	Leaf	R-HSA-162582	Signal Transduction

Subcellular location

Location	ECO term	Pubmed
Cell projection, axon	ECO:0000269	PubMed:17120249
Cell projection, dendrite	ECO:0000269	PubMed:17120249
Cell projection, dendrite	ECO:0000269	PubMed:21850687
Cytoplasm, cytoskeleton	ECO:0000269	PubMed:35266954
Cytoplasmic vesicle	ECO:0000269	PubMed:16321986
Cytoplasmic vesicle	ECO:0000269	PubMed:16352719
Cytoplasmic vesicle	ECO:0000269	PubMed:26014385
Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane	ECO:0000269	PubMed:24687852
Endoplasmic reticulum membrane	ECO:0000269	PubMed:16321986
Endoplasmic reticulum membrane	ECO:0000269	PubMed:25201882
Endosome	ECO:0000250
Golgi apparatus membrane	ECO:0000269	PubMed:16321986
Golgi apparatus membrane	ECO:0000269	PubMed:23395371
Lysosome	ECO:0000269	PubMed:17120249
Mitochondrion outer membrane	ECO:0000269	PubMed:16269541
Mitochondrion outer membrane	ECO:0000269	PubMed:16321986
Mitochondrion outer membrane	ECO:0000269	PubMed:17120249
Mitochondrion outer membrane	ECO:0000269	PubMed:29212815
Perikaryon	ECO:0000269	PubMed:17120249

Interactor | Variant | Drug

Phenotype

HPO ID	HPO name
HP:0000006	Autosomal dominant inheritance
HP:0000338	Hypomimic face
HP:0000551	Color vision defect
HP:0000651	Diplopia
HP:0000713	Agitation
HP:0000716	Depression
HP:0000726	Dementia
HP:0000727	Frontal lobe dementia
HP:0000735	Impaired social interactions
HP:0000736	Short attention span
HP:0000738	Hallucinations
HP:0000739	Anxiety
HP:0000741	Apathy
HP:0000744	Low frustration tolerance
HP:0001257	Spasticity
HP:0001268	Mental deterioration
HP:0001300	Parkinsonism
HP:0001332	Dystonia
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0001824	Weight loss
HP:0002014	Diarrhea
HP:0002015	Dysphagia
HP:0002018	Nausea
HP:0002019	Constipation
HP:0002063	Rigidity
HP:0002067	Bradykinesia
HP:0002120	Cerebral cortical atrophy
HP:0002141	Gait imbalance
HP:0002171	Gliosis
HP:0002172	Postural instability
HP:0002304	Akinesia
HP:0002322	Resting tremor
HP:0002359	Frequent falls
HP:0002360	Sleep disturbance
HP:0002362	Shuffling gait
HP:0002367	Visual hallucinations
HP:0002548	Parkinsonism with favorable response to dopaminergic medication
HP:0002578	Gastroparesis
HP:0003394	Muscle spasm
HP:0003584	Late onset
HP:0003677	Slowly progressive
HP:0003829	Typified by incomplete penetrance
HP:0004409	Hyposmia
HP:0004926	Orthostatic hypotension due to autonomic dysfunction
HP:0005340	Spastic/hyperactive bladder
HP:0011960	Substantia nigra gliosis
HP:0012332	Abnormal autonomic nervous system physiology
HP:0012450	Chronic constipation
HP:0012452	Restless legs
HP:0025269	Panic attack
HP:0030014	Female sexual dysfunction
HP:0031435	Monotonic speech
HP:0040307	Male sexual dysfunction
HP:0100315	Lewy bodies
HP:0100543	Cognitive impairment
HP:0100660	Dyskinesia
HP:0100710	Impulsivity
HP:0100753	Schizophrenia
HP:0100785	Insomnia

Tissue and cell type

Tissue	Cell type	Expression level	Reliability
appendix	glandular cells	Low	Approved
bronchus	respiratory epithelial cells	Low	Approved
caudate	neuronal cells	Low	Approved
cerebellum	Purkinje cells	Low	Approved
cerebellum	cells in granular layer	Low	Approved
cerebellum	cells in molecular layer	Low	Approved
cerebral cortex	endothelial cells	Low	Approved
epididymis	glandular cells	Low	Approved
heart muscle	cardiomyocytes	Low	Approved
kidney	cells in tubules	High	Approved
liver	cholangiocytes	Low	Approved
liver	hepatocytes	Low	Approved
lung	alveolar cells	Medium	Approved
lung	macrophages	Low	Approved
pancreas	exocrine glandular cells	Low	Approved
skeletal muscle	myocytes	Low	Approved
stomach 2	glandular cells	Low	Approved
testis	cells in seminiferous ducts	Low	Approved
tonsil	germinal center cells	Low	Approved
tonsil	squamous epithelial cells	Low	Approved

Disease name	MONDO ID	ICD10	ICD10 chapter	OMIM	Orphanet
autosomal dominant parkinson disease 8	MONDO:0011764	G20	chapter6, Diseases of the nervous system	OMIM:607060
obsolete hereditary late onset parkinson disease	MONDO:0018466	G20	chapter6, Diseases of the nervous system

Summary of Q5S007

Gene: LRRK2, PARK8
Protein: Leucine-rich repeat serine/threonine-protein kinase 2

Structure

GO term

InterPro / Pfam

Reactome

Subcellular location

Interactor | Variant | Drug

Phenotype

Tissue and cell type

Disease

Summary of Q5S007

Gene: LRRK2, PARK8 Protein: Leucine-rich repeat serine/threonine-protein kinase 2

Structure

GO term

InterPro / Pfam

Reactome

Subcellular location

Interactor | Variant | Drug

Phenotype

Tissue and cell type

Disease

Gene: LRRK2, PARK8
Protein: Leucine-rich repeat serine/threonine-protein kinase 2