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8U8A

Cryo-EM structure of LRRK2 bound to type II inhibitor ponatinib

Functional Information from GO Data
ChainGOidnamespacecontents
B0000139cellular_componentGolgi membrane
B0000149molecular_functionSNARE binding
B0000165biological_processMAPK cascade
B0000287molecular_functionmagnesium ion binding
B0001934biological_processpositive regulation of protein phosphorylation
B0003779molecular_functionactin binding
B0003924molecular_functionGTPase activity
B0004672molecular_functionprotein kinase activity
B0004674molecular_functionprotein serine/threonine kinase activity
B0004706molecular_functionJUN kinase kinase kinase activity
B0004709molecular_functionMAP kinase kinase kinase activity
B0005096molecular_functionGTPase activator activity
B0005515molecular_functionprotein binding
B0005524molecular_functionATP binding
B0005525molecular_functionGTP binding
B0005615cellular_componentextracellular space
B0005737cellular_componentcytoplasm
B0005739cellular_componentmitochondrion
B0005741cellular_componentmitochondrial outer membrane
B0005743cellular_componentmitochondrial inner membrane
B0005759cellular_componentmitochondrial matrix
B0005764cellular_componentlysosome
B0005768cellular_componentendosome
B0005783cellular_componentendoplasmic reticulum
B0005789cellular_componentendoplasmic reticulum membrane
B0005794cellular_componentGolgi apparatus
B0005798cellular_componentGolgi-associated vesicle
B0005802cellular_componenttrans-Golgi network
B0005829cellular_componentcytosol
B0005856cellular_componentcytoskeleton
B0005886cellular_componentplasma membrane
B0005902cellular_componentmicrovillus
B0006338biological_processchromatin remodeling
B0006468biological_processprotein phosphorylation
B0006606biological_processprotein import into nucleus
B0006897biological_processendocytosis
B0006914biological_processautophagy
B0006979biological_processresponse to oxidative stress
B0007005biological_processmitochondrion organization
B0007029biological_processendoplasmic reticulum organization
B0007030biological_processGolgi organization
B0007040biological_processlysosome organization
B0007154biological_processcell communication
B0007165biological_processsignal transduction
B0007254biological_processJNK cascade
B0007266biological_processRho protein signal transduction
B0007283biological_processspermatogenesis
B0007528biological_processneuromuscular junction development
B0008017molecular_functionmicrotubule binding
B0008021cellular_componentsynaptic vesicle
B0008104biological_processprotein localization
B0008340biological_processdetermination of adult lifespan
B0009267biological_processcellular response to starvation
B0009966biological_processregulation of signal transduction
B0010468biological_processregulation of gene expression
B0010506biological_processregulation of autophagy
B0010508biological_processpositive regulation of autophagy
B0010955biological_processnegative regulation of protein processing
B0010977biological_processnegative regulation of neuron projection development
B0014041biological_processregulation of neuron maturation
B0015631molecular_functiontubulin binding
B0016242biological_processnegative regulation of macroautophagy
B0016301molecular_functionkinase activity
B0016310biological_processphosphorylation
B0016787molecular_functionhydrolase activity
B0017075molecular_functionsyntaxin-1 binding
B0018105biological_processpeptidyl-serine phosphorylation
B0018107biological_processpeptidyl-threonine phosphorylation
B0019722biological_processcalcium-mediated signaling
B0021756biological_processstriatum development
B0021772biological_processolfactory bulb development
B0022028biological_processtangential migration from the subventricular zone to the olfactory bulb
B0030154biological_processcell differentiation
B0030159molecular_functionsignaling receptor complex adaptor activity
B0030182biological_processneuron differentiation
B0030276molecular_functionclathrin binding
B0030424cellular_componentaxon
B0030425cellular_componentdendrite
B0030426cellular_componentgrowth cone
B0030672cellular_componentsynaptic vesicle membrane
B0031267molecular_functionsmall GTPase binding
B0031398biological_processpositive regulation of protein ubiquitination
B0031410cellular_componentcytoplasmic vesicle
B0031647biological_processregulation of protein stability
B0031966cellular_componentmitochondrial membrane
B0032091biological_processnegative regulation of protein binding
B0032092biological_processpositive regulation of protein binding
B0032436biological_processpositive regulation of proteasomal ubiquitin-dependent protein catabolic process
B0032473cellular_componentcytoplasmic side of mitochondrial outer membrane
B0032760biological_processpositive regulation of tumor necrosis factor production
B0032839cellular_componentdendrite cytoplasm
B0034211molecular_functionGTP-dependent protein kinase activity
B0034260biological_processnegative regulation of GTPase activity
B0034599biological_processcellular response to oxidative stress
B0034614biological_processcellular response to reactive oxygen species
B0035556biological_processintracellular signal transduction
B0035564biological_processregulation of kidney size
B0035640biological_processexploration behavior
B0035641biological_processlocomotory exploration behavior
B0035751biological_processregulation of lysosomal lumen pH
B0036479molecular_functionperoxidase inhibitor activity
B0039706molecular_functionco-receptor binding
B0040012biological_processregulation of locomotion
B0042391biological_processregulation of membrane potential
B0042802molecular_functionidentical protein binding
B0042803molecular_functionprotein homodimerization activity
B0042995cellular_componentcell projection
B0043005cellular_componentneuron projection
B0043025cellular_componentneuronal cell body
B0043068biological_processpositive regulation of programmed cell death
B0043195cellular_componentterminal bouton
B0043204cellular_componentperikaryon
B0043231cellular_componentintracellular membrane-bounded organelle
B0043406biological_processpositive regulation of MAP kinase activity
B0044024molecular_functionhistone H2AS1 kinase activity
B0044325molecular_functiontransmembrane transporter binding
B0044753cellular_componentamphisome
B0044754cellular_componentautolysosome
B0045121cellular_componentmembrane raft
B0045202cellular_componentsynapse
B0045335cellular_componentphagocytic vesicle
B0045746biological_processnegative regulation of Notch signaling pathway
B0045860biological_processpositive regulation of protein kinase activity
B0046039biological_processGTP metabolic process
B0046777biological_processprotein autophosphorylation
B0048312biological_processintracellular distribution of mitochondria
B0048812biological_processneuron projection morphogenesis
B0051018molecular_functionprotein kinase A binding
B0051646biological_processmitochondrion localization
B0051770biological_processpositive regulation of nitric-oxide synthase biosynthetic process
B0051900biological_processregulation of mitochondrial depolarization
B0051966biological_processregulation of synaptic transmission, glutamatergic
B0060070biological_processcanonical Wnt signaling pathway
B0060079biological_processexcitatory postsynaptic potential
B0060159biological_processregulation of dopamine receptor signaling pathway
B0060161biological_processpositive regulation of dopamine receptor signaling pathway
B0060628biological_processregulation of ER to Golgi vesicle-mediated transport
B0060828biological_processregulation of canonical Wnt signaling pathway
B0061001biological_processregulation of dendritic spine morphogenesis
B0070062cellular_componentextracellular exosome
B0070585biological_processprotein localization to mitochondrion
B0070971cellular_componentendoplasmic reticulum exit site
B0070973biological_processprotein localization to endoplasmic reticulum exit site
B0071287biological_processcellular response to manganese ion
B0071407biological_processcellular response to organic cyclic compound
B0090140biological_processregulation of mitochondrial fission
B0090263biological_processpositive regulation of canonical Wnt signaling pathway
B0090394biological_processnegative regulation of excitatory postsynaptic potential
B0097487cellular_componentmultivesicular body, internal vesicle
B0098794cellular_componentpostsynapse
B0098978cellular_componentglutamatergic synapse
B0099400cellular_componentcaveola neck
B0099523cellular_componentpresynaptic cytosol
B0106310molecular_functionprotein serine kinase activity
B0140058biological_processneuron projection arborization
B0141161biological_processregulation of cAMP/PKA signal transduction
B1900242biological_processregulation of synaptic vesicle endocytosis
B1900244biological_processpositive regulation of synaptic vesicle endocytosis
B1902236biological_processnegative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
B1902499biological_processpositive regulation of protein autoubiquitination
B1902692biological_processregulation of neuroblast proliferation
B1902803biological_processregulation of synaptic vesicle transport
B1902823biological_processnegative regulation of late endosome to lysosome transport
B1902902biological_processnegative regulation of autophagosome assembly
B1903125biological_processnegative regulation of thioredoxin peroxidase activity by peptidyl-threonine phosphorylation
B1903215biological_processnegative regulation of protein targeting to mitochondrion
B1903217biological_processnegative regulation of protein processing involved in protein targeting to mitochondrion
B1903351biological_processcellular response to dopamine
B1903980biological_processpositive regulation of microglial cell activation
B1904713molecular_functionbeta-catenin destruction complex binding
B1904887biological_processWnt signalosome assembly
B1905279biological_processregulation of retrograde transport, endosome to Golgi
B1905289biological_processregulation of CAMKK-AMPK signaling cascade
B1990904cellular_componentribonucleoprotein complex
B1990909cellular_componentWnt signalosome
B2000172biological_processregulation of branching morphogenesis of a nerve
B2000300biological_processregulation of synaptic vesicle exocytosis
B2000377biological_processregulation of reactive oxygen species metabolic process
C0000139cellular_componentGolgi membrane
C0000149molecular_functionSNARE binding
C0000165biological_processMAPK cascade
C0000287molecular_functionmagnesium ion binding
C0001934biological_processpositive regulation of protein phosphorylation
C0003779molecular_functionactin binding
C0003924molecular_functionGTPase activity
C0004672molecular_functionprotein kinase activity
C0004674molecular_functionprotein serine/threonine kinase activity
C0004706molecular_functionJUN kinase kinase kinase activity
C0004709molecular_functionMAP kinase kinase kinase activity
C0005096molecular_functionGTPase activator activity
C0005515molecular_functionprotein binding
C0005524molecular_functionATP binding
C0005525molecular_functionGTP binding
C0005615cellular_componentextracellular space
C0005737cellular_componentcytoplasm
C0005739cellular_componentmitochondrion
C0005741cellular_componentmitochondrial outer membrane
C0005743cellular_componentmitochondrial inner membrane
C0005759cellular_componentmitochondrial matrix
C0005764cellular_componentlysosome
C0005768cellular_componentendosome
C0005783cellular_componentendoplasmic reticulum
C0005789cellular_componentendoplasmic reticulum membrane
C0005794cellular_componentGolgi apparatus
C0005798cellular_componentGolgi-associated vesicle
C0005802cellular_componenttrans-Golgi network
C0005829cellular_componentcytosol
C0005856cellular_componentcytoskeleton
C0005886cellular_componentplasma membrane
C0005902cellular_componentmicrovillus
C0006338biological_processchromatin remodeling
C0006468biological_processprotein phosphorylation
C0006606biological_processprotein import into nucleus
C0006897biological_processendocytosis
C0006914biological_processautophagy
C0006979biological_processresponse to oxidative stress
C0007005biological_processmitochondrion organization
C0007029biological_processendoplasmic reticulum organization
C0007030biological_processGolgi organization
C0007040biological_processlysosome organization
C0007154biological_processcell communication
C0007165biological_processsignal transduction
C0007254biological_processJNK cascade
C0007266biological_processRho protein signal transduction
C0007283biological_processspermatogenesis
C0007528biological_processneuromuscular junction development
C0008017molecular_functionmicrotubule binding
C0008021cellular_componentsynaptic vesicle
C0008104biological_processprotein localization
C0008340biological_processdetermination of adult lifespan
C0009267biological_processcellular response to starvation
C0009966biological_processregulation of signal transduction
C0010468biological_processregulation of gene expression
C0010506biological_processregulation of autophagy
C0010508biological_processpositive regulation of autophagy
C0010955biological_processnegative regulation of protein processing
C0010977biological_processnegative regulation of neuron projection development
C0014041biological_processregulation of neuron maturation
C0015631molecular_functiontubulin binding
C0016242biological_processnegative regulation of macroautophagy
C0016301molecular_functionkinase activity
C0016310biological_processphosphorylation
C0016787molecular_functionhydrolase activity
C0017075molecular_functionsyntaxin-1 binding
C0018105biological_processpeptidyl-serine phosphorylation
C0018107biological_processpeptidyl-threonine phosphorylation
C0019722biological_processcalcium-mediated signaling
C0021756biological_processstriatum development
C0021772biological_processolfactory bulb development
C0022028biological_processtangential migration from the subventricular zone to the olfactory bulb
C0030154biological_processcell differentiation
C0030159molecular_functionsignaling receptor complex adaptor activity
C0030182biological_processneuron differentiation
C0030276molecular_functionclathrin binding
C0030424cellular_componentaxon
C0030425cellular_componentdendrite
C0030426cellular_componentgrowth cone
C0030672cellular_componentsynaptic vesicle membrane
C0031267molecular_functionsmall GTPase binding
C0031398biological_processpositive regulation of protein ubiquitination
C0031410cellular_componentcytoplasmic vesicle
C0031647biological_processregulation of protein stability
C0031966cellular_componentmitochondrial membrane
C0032091biological_processnegative regulation of protein binding
C0032092biological_processpositive regulation of protein binding
C0032436biological_processpositive regulation of proteasomal ubiquitin-dependent protein catabolic process
C0032473cellular_componentcytoplasmic side of mitochondrial outer membrane
C0032760biological_processpositive regulation of tumor necrosis factor production
C0032839cellular_componentdendrite cytoplasm
C0034211molecular_functionGTP-dependent protein kinase activity
C0034260biological_processnegative regulation of GTPase activity
C0034599biological_processcellular response to oxidative stress
C0034614biological_processcellular response to reactive oxygen species
C0035556biological_processintracellular signal transduction
C0035564biological_processregulation of kidney size
C0035640biological_processexploration behavior
C0035641biological_processlocomotory exploration behavior
C0035751biological_processregulation of lysosomal lumen pH
C0036479molecular_functionperoxidase inhibitor activity
C0039706molecular_functionco-receptor binding
C0040012biological_processregulation of locomotion
C0042391biological_processregulation of membrane potential
C0042802molecular_functionidentical protein binding
C0042803molecular_functionprotein homodimerization activity
C0042995cellular_componentcell projection
C0043005cellular_componentneuron projection
C0043025cellular_componentneuronal cell body
C0043068biological_processpositive regulation of programmed cell death
C0043195cellular_componentterminal bouton
C0043204cellular_componentperikaryon
C0043231cellular_componentintracellular membrane-bounded organelle
C0043406biological_processpositive regulation of MAP kinase activity
C0044024molecular_functionhistone H2AS1 kinase activity
C0044325molecular_functiontransmembrane transporter binding
C0044753cellular_componentamphisome
C0044754cellular_componentautolysosome
C0045121cellular_componentmembrane raft
C0045202cellular_componentsynapse
C0045335cellular_componentphagocytic vesicle
C0045746biological_processnegative regulation of Notch signaling pathway
C0045860biological_processpositive regulation of protein kinase activity
C0046039biological_processGTP metabolic process
C0046777biological_processprotein autophosphorylation
C0048312biological_processintracellular distribution of mitochondria
C0048812biological_processneuron projection morphogenesis
C0051018molecular_functionprotein kinase A binding
C0051646biological_processmitochondrion localization
C0051770biological_processpositive regulation of nitric-oxide synthase biosynthetic process
C0051900biological_processregulation of mitochondrial depolarization
C0051966biological_processregulation of synaptic transmission, glutamatergic
C0060070biological_processcanonical Wnt signaling pathway
C0060079biological_processexcitatory postsynaptic potential
C0060159biological_processregulation of dopamine receptor signaling pathway
C0060161biological_processpositive regulation of dopamine receptor signaling pathway
C0060628biological_processregulation of ER to Golgi vesicle-mediated transport
C0060828biological_processregulation of canonical Wnt signaling pathway
C0061001biological_processregulation of dendritic spine morphogenesis
C0070062cellular_componentextracellular exosome
C0070585biological_processprotein localization to mitochondrion
C0070971cellular_componentendoplasmic reticulum exit site
C0070973biological_processprotein localization to endoplasmic reticulum exit site
C0071287biological_processcellular response to manganese ion
C0071407biological_processcellular response to organic cyclic compound
C0090140biological_processregulation of mitochondrial fission
C0090263biological_processpositive regulation of canonical Wnt signaling pathway
C0090394biological_processnegative regulation of excitatory postsynaptic potential
C0097487cellular_componentmultivesicular body, internal vesicle
C0098794cellular_componentpostsynapse
C0098978cellular_componentglutamatergic synapse
C0099400cellular_componentcaveola neck
C0099523cellular_componentpresynaptic cytosol
C0106310molecular_functionprotein serine kinase activity
C0140058biological_processneuron projection arborization
C0141161biological_processregulation of cAMP/PKA signal transduction
C1900242biological_processregulation of synaptic vesicle endocytosis
C1900244biological_processpositive regulation of synaptic vesicle endocytosis
C1902236biological_processnegative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
C1902499biological_processpositive regulation of protein autoubiquitination
C1902692biological_processregulation of neuroblast proliferation
C1902803biological_processregulation of synaptic vesicle transport
C1902823biological_processnegative regulation of late endosome to lysosome transport
C1902902biological_processnegative regulation of autophagosome assembly
C1903125biological_processnegative regulation of thioredoxin peroxidase activity by peptidyl-threonine phosphorylation
C1903215biological_processnegative regulation of protein targeting to mitochondrion
C1903217biological_processnegative regulation of protein processing involved in protein targeting to mitochondrion
C1903351biological_processcellular response to dopamine
C1903980biological_processpositive regulation of microglial cell activation
C1904713molecular_functionbeta-catenin destruction complex binding
C1904887biological_processWnt signalosome assembly
C1905279biological_processregulation of retrograde transport, endosome to Golgi
C1905289biological_processregulation of CAMKK-AMPK signaling cascade
C1990904cellular_componentribonucleoprotein complex
C1990909cellular_componentWnt signalosome
C2000172biological_processregulation of branching morphogenesis of a nerve
C2000300biological_processregulation of synaptic vesicle exocytosis
C2000377biological_processregulation of reactive oxygen species metabolic process
Functional Information from PROSITE/UniProt
site_idPS00107
Number of Residues22
DetailsPROTEIN_KINASE_ATP Protein kinases ATP-binding region signature. LGDGSFGSVYrAayegee............VAVK
ChainResidueDetails
BLEU1885-LYS1906

site_idPS00108
Number of Residues13
DetailsPROTEIN_KINASE_ST Serine/Threonine protein kinases active-site signature. IiYrDLKphNVLL
ChainResidueDetails
BILE1990-LEU2002

site_idPS00626
Number of Residues11
DetailsRCC1_2 Regulator of chromosome condensation (RCC1) signature 2. IGTGgGHILLL
ChainResidueDetails
BILE2427-LEU2437

Functional Information from SwissProt/UniProt
site_idSWS_FT_FI1
Number of Residues2
DetailsACT_SITE: Proton acceptor => ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-ProRule:PRU10027
ChainResidueDetails
BASP1994
CASP1994

site_idSWS_FT_FI2
Number of Residues2
DetailsBINDING: BINDING => ECO:0000255|PROSITE-ProRule:PRU00758, ECO:0000269|PubMed:18230735
ChainResidueDetails
BGLY1341
CGLY1341

site_idSWS_FT_FI3
Number of Residues4
DetailsBINDING: BINDING => ECO:0000255|PROSITE-ProRule:PRU00159
ChainResidueDetails
BLEU1885
BLYS1906
CLEU1885
CLYS1906

site_idSWS_FT_FI4
Number of Residues4
DetailsBINDING: BINDING => ECO:0000255|PROSITE-ProRule:PRU00758
ChainResidueDetails
BGLU2098
BASN2295
CGLU2098
CASN2295

site_idSWS_FT_FI5
Number of Residues2
DetailsMOD_RES: Phosphoserine => ECO:0000269|PubMed:28202711, ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29212815
ChainResidueDetails
BSER910
CSER910

site_idSWS_FT_FI6
Number of Residues2
DetailsMOD_RES: Phosphoserine => ECO:0000269|PubMed:28202711, ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29127255, ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30635421
ChainResidueDetails
BSER935
CSER935

site_idSWS_FT_FI7
Number of Residues4
DetailsMOD_RES: Phosphoserine => ECO:0000269|PubMed:28202711, ECO:0000269|PubMed:29212815
ChainResidueDetails
BSER955
BSER973
CSER955
CSER973

site_idSWS_FT_FI8
Number of Residues2
DetailsMOD_RES: Phosphoserine => ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30635421
ChainResidueDetails
BSER1292
CSER1292

site_idSWS_FT_FI9
Number of Residues2
DetailsMOD_RES: Phosphoserine => ECO:0000269|PubMed:28202711
ChainResidueDetails
BSER1444
CSER1444

225946

PDB entries from 2024-10-09

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