LRRK2 and MAP2K4

Data Source:
BioGRID (enzymatic study)

		LRRK2	MAP2K4
Description		leucine rich repeat kinase 2	mitogen-activated protein kinase kinase 4
Image
GO Annotations	Cellular Component	Golgi Membrane Extracellular Space Cytoplasm Mitochondrion Mitochondrial Outer Membrane Mitochondrial Inner Membrane Mitochondrial Matrix Lysosome Endosome Endoplasmic Reticulum Endoplasmic Reticulum Membrane Golgi Apparatus Golgi-associated Vesicle Trans-Golgi Network Cytosol Plasma Membrane Microvillus Inclusion Body Axon Dendrite Growth Cone Synaptic Vesicle Membrane Cytoplasmic Vesicle Mitochondrial Membrane Cytoplasmic Side Of Mitochondrial Outer Membrane Dendrite Cytoplasm Neuron Projection Neuronal Cell Body Terminal Bouton Perikaryon Intracellular Membrane-bounded Organelle Amphisome Autolysosome Membrane Raft Extracellular Exosome Endoplasmic Reticulum Exit Site Multivesicular Body, Internal Vesicle Postsynapse Glutamatergic Synapse Caveola Neck Presynaptic Cytosol Ribonucleoprotein Complex Wnt Signalosome	Nucleus Cytosol Axon Dendrite Cytoplasm Perikaryon
	Molecular Function	SNARE Binding Magnesium Ion Binding Actin Binding GTPase Activity Protein Kinase Activity Protein Serine/threonine Kinase Activity MAP Kinase Kinase Activity Protein Serine/threonine Phosphatase Activity GTPase Activator Activity Protein Binding ATP Binding GTP Binding Microtubule Binding Tubulin Binding Kinase Activity Syntaxin-1 Binding Signaling Receptor Complex Adaptor Activity Clathrin Binding Small GTPase Binding GTP-dependent Protein Kinase Activity Peroxidase Inhibitor Activity Co-receptor Binding Identical Protein Binding Protein Homodimerization Activity Ion Channel Binding Protein Kinase A Binding Protein Serine Kinase Activity Protein Threonine Kinase Activity Beta-catenin Destruction Complex Binding	Protein Kinase Activity Protein Serine/threonine Kinase Activity MAP Kinase Kinase Activity Protein Tyrosine Kinase Activity Protein Binding ATP Binding JUN Kinase Kinase Activity Mitogen-activated Protein Kinase Kinase Kinase Binding
	Biological Process	MAPK Cascade Activation Of MAPKK Activity Activation Of MAPK Activity Negative Regulation Of Protein Phosphorylation Positive Regulation Of Protein Phosphorylation Protein Phosphorylation Protein Dephosphorylation Protein Import Into Nucleus Endocytosis Autophagy Response To Oxidative Stress Mitochondrion Organization Endoplasmic Reticulum Organization Golgi Organization Lysosome Organization Signal Transduction Spermatogenesis Neuromuscular Junction Development Determination Of Adult Lifespan Cellular Response To Starvation Regulation Of Autophagy Positive Regulation Of Autophagy Regulation Of Protein Kinase A Signaling Negative Regulation Of Protein Processing Negative Regulation Of Neuron Projection Development Regulation Of Neuron Maturation Negative Regulation Of Macroautophagy Phosphorylation Peptidyl-serine Phosphorylation Peptidyl-threonine Phosphorylation Calcium-mediated Signaling Striatum Development Olfactory Bulb Development Tangential Migration From The Subventricular Zone To The Olfactory Bulb Positive Regulation Of Protein Ubiquitination Regulation Of Protein Stability Negative Regulation Of Protein Binding Positive Regulation Of Protein Binding Positive Regulation Of Proteasomal Ubiquitin-dependent Protein Catabolic Process Negative Regulation Of GTPase Activity Cellular Response To Oxidative Stress Cellular Protein Localization Intracellular Signal Transduction Regulation Of Kidney Size Exploration Behavior Locomotory Exploration Behavior Regulation Of Lysosomal Lumen PH Regulation Of Locomotion Regulation Of Membrane Potential Positive Regulation Of Programmed Cell Death Positive Regulation Of MAP Kinase Activity Positive Regulation Of GTPase Activity GTP Metabolic Process Protein Autophosphorylation Intracellular Distribution Of Mitochondria Neuron Projection Morphogenesis Mitochondrion Localization Positive Regulation Of Nitric-oxide Synthase Biosynthetic Process Regulation Of Mitochondrial Depolarization Regulation Of Synaptic Transmission, Glutamatergic Canonical Wnt Signaling Pathway Excitatory Postsynaptic Potential Regulation Of Dopamine Receptor Signaling Pathway Positive Regulation Of Dopamine Receptor Signaling Pathway Regulation Of ER To Golgi Vesicle-mediated Transport Regulation Of Canonical Wnt Signaling Pathway Regulation Of Dendritic Spine Morphogenesis Protein Localization To Mitochondrion Protein Localization To Endoplasmic Reticulum Exit Site Neuron Death Cellular Response To Manganese Ion Cellular Response To Organic Cyclic Compound Reactive Oxygen Species Metabolic Process Regulation Of Mitochondrial Fission Positive Regulation Of Canonical Wnt Signaling Pathway Negative Regulation Of Excitatory Postsynaptic Potential Neuron Projection Arborization Positive Regulation Of Synaptic Vesicle Endocytosis Regulation Of Neuron Death Negative Regulation Of Neuron Death Positive Regulation Of Histone Deacetylase Activity Negative Regulation Of Endoplasmic Reticulum Stress-induced Intrinsic Apoptotic Signaling Pathway Positive Regulation Of Protein Autoubiquitination Regulation Of Neuroblast Proliferation Regulation Of Synaptic Vesicle Transport Negative Regulation Of Late Endosome To Lysosome Transport Negative Regulation Of Autophagosome Assembly Negative Regulation Of Thioredoxin Peroxidase Activity By Peptidyl-threonine Phosphorylation Negative Regulation Of Hydrogen Peroxide-induced Cell Death Negative Regulation Of Protein Targeting To Mitochondrion Negative Regulation Of Protein Processing Involved In Protein Targeting To Mitochondrion Cellular Response To Dopamine Positive Regulation Of Microglial Cell Activation Wnt Signalosome Assembly Regulation Of Retrograde Transport, Endosome To Golgi Regulation Of CAMKK-AMPK Signaling Cascade Regulation Of Branching Morphogenesis Of A Nerve Regulation Of Synaptic Vesicle Exocytosis	Activation Of MAPK Activity Apoptotic Process Signal Transduction JNK Cascade Activation Of JUN Kinase Activity Response To Wounding Peptidyl-tyrosine Phosphorylation Positive Regulation Of Smooth Muscle Cell Apoptotic Process Fc-epsilon Receptor Signaling Pathway Positive Regulation Of Neuron Apoptotic Process Positive Regulation Of DNA Replication Positive Regulation Of Nitric-oxide Synthase Biosynthetic Process Cell Growth Involved In Cardiac Muscle Cell Development Cellular Response To Mechanical Stimulus Cellular Response To Sorbitol Negative Regulation Of Motor Neuron Apoptotic Process
Pathways		PTK6 promotes HIF1A stabilization	Oxidative Stress Induced Senescence Oxidative Stress Induced Senescence FCERI mediated MAPK activation JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 Uptake and function of anthrax toxins MAP3K8 (TPL2)-dependent MAPK1/3 activation
Drugs		Fostamatinib
Diseases		Lewy body dementia (LBD); Dementia with Lewy bodies (DLB) Parkinson's disease (PD)
GWAS		Cerebral amyloid deposition in APOEe4 non-carriers (PET imaging) ( 26252872) Chronic inflammatory diseases (ankylosing spondylitis, Crohn's disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy) ( 26974007) Crohn's disease ( 18587394 28067908 21102463) Daytime sleep phenotypes ( 27126917) Inflammatory bowel disease ( 28067908 23128233) Leprosy ( 25642632) Low density lipoprotein cholesterol levels ( 32154731) Mean platelet volume ( 32888494) Obesity-related traits ( 23251661) Parkinson's disease ( 21292315 19915576 25064009 31660654 27182965 24842889 28892059 22438815 28011712 21738487) Parkinson's disease or first degree relation to individual with Parkinson's disease ( 31701892) Pediatric autoimmune diseases ( 26301688) Platelet count ( 32888494) Platelet distribution width ( 32888494) Plateletcrit ( 32888494)	Asthma ( 32296059) Electrocardiogram morphology (amplitude at temporal datapoints) ( 32916098) Estimated glomerular filtration rate ( 31152163) Response to amphetamines ( 22952603)
Interacting Genes		144 interacting genes: ABLIM1 ACTB AFF4 AHCYL1 AHDC1 AKT1 ANKS4B APEX2 APP ARFGAP1 ARHGEF7 AURKB BAG1 BAG2 BAG3 C18orf25 C1orf87 CAMK1D CBLB CCDC43 CDC42EP3 CDKL3 CETN3 CHGB CRMP1 CUEDC1 CXCL11 CYREN DBF4B DDIT4 DIDO1 DUX3 DVL1 DVL2 DVL3 DYRK2 E2F4 ECHS1 EIF4EBP1 ENKUR ESRRG FAM184A FAM47B FAM90A1 FANCM FCHSD1 GTSF1 HIF1A HSPD1 ITGB3BP JHY KCTD18 KDM4D KLC2 L3MBTL3 LARP4 LARP7 LATS1 LGALS8 LINC01139 LRP6 MAP1B MAP2K3 MAP2K4 MAP2K6 MAP2K7 MAPT MATK MBP MLLT3 MRGBP MRPL19 MRPL28 MTA1 MYL9 NCBP3 NDUFAF7 NEK1 NSL1 PADI4 PDCL PHF20L1 PIK3CB PIK3R1 PLK1 POLR2M POU5F1 PPP1R8 PRKCZ PSME3IP1 PTPN23 RAB11FIP2 RAD51AP1 RALYL RAPGEF4 RASL11B RBIS RHBDD1 RIPK2 RIT1 RPAP3 RPS6KB2 SCEL SERF1A SH3GL2 SH3GL3 SKA3 SMTNL2 SPATS2 SQSTM1 STAC STK24 STK25 STK3 STK40 STN1 STRBP STUB1 SUPT4H1 SYNJ1 TAOK3 TAS2R60 TBC1D22B TCEA2 TCP10L TGIF2LX TRAF2 TTC27 TTLL1 TUBA1A UBXN10 UFD1 UQCRB USP39 VASH2 VGLL4 VN1R1 WSB1 WT1-AS XIRP2 ZAP70 ZFAND5 ZMYM5 ZRANB2	43 interacting genes: AKT1 ALDOB APP ARRB1 ARRB2 CFLAR CYLC2 DUSP22 EFNA4 FBP2 FLNA FLNC GEMIN5 ITCH JUN LRRK2 MAP2K6 MAP3K1 MAP3K10 MAP3K11 MAP3K12 MAP3K14 MAP3K2 MAP3K20 MAP3K3 MAP3K4 MAP3K5 MAP3K7 MAP3K8 MAP4K2 MAPK1 MAPK10 MAPK12 MAPK14 MAPK8 MAPK8IP3 MAPK9 NBR1 RBBP8 SPAG9 STX17 TRIB1 UBC
Entrez ID		120892	6416
HPRD ID		10613	03213
Ensembl ID		ENSG00000188906	ENSG00000065559
Uniprot IDs		Q17RV3 Q5S007	P45985
PDB IDs		2ZEJ 3D6T 5MY9 5MYC 6DLO 6DLP 6OJE 6OJF 6VNO 6VP6 6VP7 6XR4	3ALN 3ALO 3VUT
Enriched GO Terms of Interacting Partners?
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