LRRK2 (Leucine-rich repeat serine/threonine-protein kinase 2) is a large multi-domain ROCO family protein with dual enzymatic activities - a serine/threonine protein kinase (EC 2.7.11.1) and a GTPase (EC 3.6.5.-). The protein contains ARM/ANK/LRR repeats, ROC (Ras of complex proteins) GTPase domain, COR (C-terminal of ROC) domain, kinase domain, and WD40 repeats. LRRK2 phosphorylates a subset of Rab GTPases (primarily Rab8A, Rab10, Rab12, Rab29) at their switch II regions, regulating endolysosomal trafficking and ciliogenesis. It is predominantly cytosolic but dynamically recruited to Golgi, endosomes, and lysosomes where its Rab substrates reside. Mutations in LRRK2 are the most common genetic cause of familial Parkinson's disease (PARK8).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0035556 intracellular signal transduction | IBA GO_REF:0000033 | ACCEPT | Summary: LRRK2 is a multi-domain ROCO protein kinase that phosphorylates Rab GTPases (Rab8, Rab10, Rab12, Rab29) to regulate endolysosomal trafficking and ciliogenesis. This broad BP term accurately captures its signaling role. Reason: LRRK2 functions as a serine/threonine kinase that transduces signals by phosphorylating Rab GTPases, thereby regulating downstream cellular processes. The IBA annotation is appropriate as LRRK2 is clearly involved in intracellular signal transduction via its kinase and GTPase activities. Supporting Evidence: PMID:30398148 Parkinson's disease-associated LRRK2 kinase phosphorylates multiple Rab GTPases, including Rab8A and Rab10. file:human/LRRK2/LRRK2-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Plasma membrane - LRRK2 can localize to membranes but cytosol is predominant. Reason: Plasma membrane - LRRK2 can localize to membranes but cytosol is predominant. |
| GO:0030425 dendrite | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Dendrite localization is tissue-specific in neurons, not a core localization. Reason: Dendrite localization is tissue-specific in neurons, not a core localization. |
| GO:0007029 endoplasmic reticulum organization | IBA GO_REF:0000033 | ACCEPT | Summary: ER organization is related to LRRK2 role in Sec16A regulation at ER exit sites. Reason: ER organization is related to LRRK2 role in Sec16A regulation at ER exit sites. |
| GO:0007030 Golgi organization | IBA GO_REF:0000033 | ACCEPT | Summary: Golgi organization - LRRK2 regulates Golgi-related trafficking through Rab phosphorylation. Reason: Golgi organization - LRRK2 regulates Golgi-related trafficking through Rab phosphorylation. |
| GO:0010508 positive regulation of autophagy | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Positive regulation of autophagy is a downstream effect of trafficking disruption, not core function. Reason: Positive regulation of autophagy is a downstream effect of trafficking disruption, not core function. |
| GO:0031344 regulation of cell projection organization | IBA GO_REF:0000033 | ACCEPT | Summary: Regulation of cell projection organization - includes ciliogenesis. Reason: Regulation of cell projection organization - includes ciliogenesis. |
| GO:0060159 regulation of dopamine receptor signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Regulation of dopamine receptor signaling pathway - tissue-specific. Reason: Regulation of dopamine receptor signaling pathway - tissue-specific. |
| GO:0060828 regulation of canonical Wnt signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Regulation of canonical Wnt signaling pathway - LRRK2 acts as scaffold but not core function. Reason: Regulation of canonical Wnt signaling pathway - LRRK2 acts as scaffold but not core function. |
| GO:1900242 regulation of synaptic vesicle endocytosis | IBA GO_REF:0000033 | ACCEPT | Summary: Regulation of synaptic vesicle endocytosis - well-documented LRRK2 function. Reason: Regulation of synaptic vesicle endocytosis - well-documented LRRK2 function. |
| GO:0004706 JUN kinase kinase kinase activity | IBA GO_REF:0000033 | UNDECIDED | Summary: JUN kinase kinase kinase activity - reported but may not be physiological core function. Reason: JUN kinase kinase kinase activity - reported but may not be physiological core function. |
| GO:0098794 postsynapse | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Postsynapse is a tissue-specific neuronal localization. Reason: Postsynapse is a tissue-specific neuronal localization. |
| GO:0000139 Golgi membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Golgi membrane localization - LRRK2 is recruited to Golgi membranes where Rab29 resides. Reason: Golgi membrane localization - LRRK2 is recruited to Golgi membranes where Rab29 resides. |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | ACCEPT | Summary: Nucleotide binding - required for kinase and GTPase activities. Reason: Nucleotide binding - required for kinase and GTPase activities. |
| GO:0003924 GTPase activity | IEA GO_REF:0000116 | ACCEPT | Summary: GTPase activity is a core function of LRRK2 ROC domain. The ROC domain binds and hydrolyzes GTP. Reason: GTPase activity is a core function of LRRK2 ROC domain. The ROC domain binds and hydrolyzes GTP. |
| GO:0004672 protein kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Protein kinase activity is a core function of LRRK2, phosphorylating Rab GTPases and other substrates. Reason: Protein kinase activity is a core function of LRRK2, phosphorylating Rab GTPases and other substrates. |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Protein serine/threonine kinase activity is a core enzymatic function of LRRK2. The kinase domain phosphorylates Rab GTPases at their switch II regions. Reason: Protein serine/threonine kinase activity is a core enzymatic function of LRRK2. The kinase domain phosphorylates Rab GTPases at their switch II regions. |
| GO:0005096 GTPase activator activity | IEA GO_REF:0000043 | UNDECIDED | Summary: GTPase activator activity - LRRK2 has intrinsic GTPase activity but GAP activity on other GTPases is unclear. Reason: GTPase activator activity - LRRK2 has intrinsic GTPase activity but GAP activity on other GTPases is unclear. |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: ATP binding is required for LRRK2 kinase activity. Reason: ATP binding is required for LRRK2 kinase activity. |
| GO:0005525 GTP binding | IEA GO_REF:0000120 | ACCEPT | Summary: GTP binding is essential for LRRK2 ROC domain function and regulates kinase activity. Reason: GTP binding is essential for LRRK2 ROC domain function and regulates kinase activity. |
| GO:0005741 mitochondrial outer membrane | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Mitochondrial outer membrane - reported but may be minor. Reason: Mitochondrial outer membrane - reported but may be minor. |
| GO:0005764 lysosome | IEA GO_REF:0000120 | ACCEPT | Summary: Lysosome localization is consistent with LRRK2 role in endolysosomal trafficking. Reason: Lysosome localization is consistent with LRRK2 role in endolysosomal trafficking. |
| GO:0005768 endosome | IEA GO_REF:0000120 | ACCEPT | Summary: Endosome localization is consistent with LRRK2 role in regulating Rab-dependent trafficking. Reason: Endosome localization is consistent with LRRK2 role in regulating Rab-dependent trafficking. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: ER membrane - related to ER exit site function. Reason: ER membrane - related to ER exit site function. |
| GO:0005829 cytosol | IEA GO_REF:0000117 | ACCEPT | Summary: Cytosol is the predominant localization of LRRK2, from which it is recruited to membranes. Reason: Cytosol is the predominant localization of LRRK2, from which it is recruited to membranes. |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Cytoskeleton - microtubule association documented. Reason: Cytoskeleton - microtubule association documented. |
| GO:0006914 autophagy | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: Autophagy effects are downstream of LRRK2 trafficking disruption, not a direct evolved function. Reason: Autophagy effects are downstream of LRRK2 trafficking disruption, not a direct evolved function. |
| GO:0007030 Golgi organization | IEA GO_REF:0000117 | ACCEPT | Summary: Golgi organization - LRRK2 regulates Golgi-related trafficking through Rab phosphorylation. Reason: Golgi organization - LRRK2 regulates Golgi-related trafficking through Rab phosphorylation. |
| GO:0007166 cell surface receptor signaling pathway | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Cell surface receptor signaling pathway - very broad. Reason: Cell surface receptor signaling pathway - very broad. |
| GO:0009653 anatomical structure morphogenesis | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Anatomical structure morphogenesis is very broad. Reason: Anatomical structure morphogenesis is very broad. |
| GO:0009968 negative regulation of signal transduction | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Negative regulation of signal transduction - broad. Reason: Negative regulation of signal transduction - broad. |
| GO:0010468 regulation of gene expression | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Regulation of gene expression - very broad downstream effect. Reason: Regulation of gene expression - very broad downstream effect. |
| GO:0016192 vesicle-mediated transport | IEA GO_REF:0000117 | ACCEPT | Summary: Vesicle-mediated transport - core function via Rab GTPase phosphorylation regulating trafficking. Reason: Vesicle-mediated transport - core function via Rab GTPase phosphorylation regulating trafficking. |
| GO:0016301 kinase activity | IEA GO_REF:0000043 | ACCEPT | Summary: Kinase activity is a core function - LRRK2 is a dual-function kinase/GTPase. Reason: Kinase activity is a core function - LRRK2 is a dual-function kinase/GTPase. |
| GO:0016740 transferase activity | IEA GO_REF:0000043 | ACCEPT | Summary: Transferase activity - parent term of kinase activity. Reason: Transferase activity - parent term of kinase activity. |
| GO:0016787 hydrolase activity | IEA GO_REF:0000043 | ACCEPT | Summary: Hydrolase activity - parent term of GTPase activity. Reason: Hydrolase activity - parent term of GTPase activity. |
| GO:0030154 cell differentiation | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: Cell differentiation is very broad. Reason: Cell differentiation is very broad. |
| GO:0030159 signaling receptor complex adaptor activity | IEA GO_REF:0000117 | UNDECIDED | Summary: Signaling receptor complex adaptor activity - Wnt scaffold role. Reason: Signaling receptor complex adaptor activity - Wnt scaffold role. |
| GO:0030162 regulation of proteolysis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Regulation of proteolysis - broad. Reason: Regulation of proteolysis - broad. |
| GO:0030182 neuron differentiation | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Neuron differentiation is developmental. Reason: Neuron differentiation is developmental. |
| GO:0030424 axon | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Axon localization is tissue-specific in neurons. Reason: Axon localization is tissue-specific in neurons. |
| GO:0030425 dendrite | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Dendrite localization is tissue-specific in neurons, not a core localization. Reason: Dendrite localization is tissue-specific in neurons, not a core localization. |
| GO:0030672 synaptic vesicle membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Synaptic vesicle membrane is tissue-specific. Reason: Synaptic vesicle membrane is tissue-specific. |
| GO:0031410 cytoplasmic vesicle | IEA GO_REF:0000120 | ACCEPT | Summary: Cytoplasmic vesicle - consistent with trafficking role. Reason: Cytoplasmic vesicle - consistent with trafficking role. |
| GO:0035640 exploration behavior | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Exploration behavior is a high-level organismal phenotype. Reason: Exploration behavior is a high-level organismal phenotype. |
| GO:0042391 regulation of membrane potential | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Regulation of membrane potential - neuronal effect. Reason: Regulation of membrane potential - neuronal effect. |
| GO:0043195 terminal bouton | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Terminal bouton is tissue-specific neuronal localization. Reason: Terminal bouton is tissue-specific neuronal localization. |
| GO:0043204 perikaryon | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Perikaryon (neuronal cell body) is tissue-specific localization. Reason: Perikaryon (neuronal cell body) is tissue-specific localization. |
| GO:0045335 phagocytic vesicle | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Phagocytic vesicle - macrophage-specific. Reason: Phagocytic vesicle - macrophage-specific. |
| GO:0048513 animal organ development | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Animal organ development is very broad. Reason: Animal organ development is very broad. |
| GO:0050804 modulation of chemical synaptic transmission | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Modulation of chemical synaptic transmission - tissue-specific. Reason: Modulation of chemical synaptic transmission - tissue-specific. |
| GO:0051239 regulation of multicellular organismal process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Regulation of multicellular organismal process - very broad. Reason: Regulation of multicellular organismal process - very broad. |
| GO:0051247 positive regulation of protein metabolic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Positive regulation of protein metabolic process - broad. Reason: Positive regulation of protein metabolic process - broad. |
| GO:0060627 regulation of vesicle-mediated transport | IEA GO_REF:0000117 | ACCEPT | Summary: Regulation of vesicle-mediated transport - core trafficking function. Reason: Regulation of vesicle-mediated transport - core trafficking function. |
| GO:0070013 intracellular organelle lumen | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Intracellular organelle lumen - very broad. Reason: Intracellular organelle lumen - very broad. |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Protein serine kinase activity - LRRK2 phosphorylates serine/threonine residues on Rab substrates. Reason: Protein serine kinase activity - LRRK2 phosphorylates serine/threonine residues on Rab substrates. |
| GO:1902531 regulation of intracellular signal transduction | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Regulation of intracellular signal transduction - broad. Reason: Regulation of intracellular signal transduction - broad. |
| GO:1904887 Wnt signalosome assembly | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Wnt signalosome assembly - via LRP6 bridging. Reason: Wnt signalosome assembly - via LRP6 bridging. |
| GO:0005515 protein binding | IPI PMID:16321986 The Parkinson disease causing LRRK2 mutation I2020T is assoc... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:16321986 Dec 1. The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity. |
| GO:0005515 protein binding | IPI PMID:16352719 Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, ... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:16352719 Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, and mutant LRRK2 induces neuronal degeneration. |
| GO:0005515 protein binding | IPI PMID:17400507 Identification of potential protein interactors of Lrrk2. | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:17400507 Identification of potential protein interactors of Lrrk2. |
| GO:0005515 protein binding | IPI PMID:18367605 The chaperone activity of heat shock protein 90 is critical ... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:18367605 The chaperone activity of heat shock protein 90 is critical for maintaining the stability of leucine-rich repeat kinase 2. |
| GO:0005515 protein binding | IPI PMID:18445495 LRRK2 regulates synaptic vesicle endocytosis. | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:18445495 Epub 2008 Mar 5. LRRK2 regulates synaptic vesicle endocytosis. |
| GO:0005515 protein binding | IPI PMID:19176810 The Parkinson disease protein leucine-rich repeat kinase 2 t... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:19176810 The Parkinson disease protein leucine-rich repeat kinase 2 transduces death signals via Fas-associated protein with death domain and caspase-8 in a cellular model of neurodegeneration. |
| GO:0005515 protein binding | IPI PMID:19196961 CHIP regulates leucine-rich repeat kinase-2 ubiquitination, ... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:19196961 CHIP regulates leucine-rich repeat kinase-2 ubiquitination, degradation, and toxicity. |
| GO:0005515 protein binding | IPI PMID:19559761 Interaction of elongation factor 1-alpha with leucine-rich r... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:19559761 Interaction of elongation factor 1-alpha with leucine-rich repeat kinase 2 impairs kinase activity and microtubule bundling in vitro. |
| GO:0005515 protein binding | IPI PMID:19625296 Mutations in the LRRK2 Roc-COR tandem domain link Parkinson'... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:19625296 Jul 22. Mutations in the LRRK2 Roc-COR tandem domain link Parkinson's disease to Wnt signalling pathways. |
| GO:0005515 protein binding | IPI PMID:19712061 Homo- and heterodimerization of ROCO kinases: LRRK2 kinase i... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:19712061 Epub 2009 Aug 27. Homo- and heterodimerization of ROCO kinases: LRRK2 kinase inhibition by the LRRK2 ROCO fragment. |
| GO:0005515 protein binding | IPI PMID:20067578 MKK6 binds and regulates expression of Parkinson's disease-r... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:20067578 Epub 2010 Jan 7. MKK6 binds and regulates expression of Parkinson's disease-related protein LRRK2. |
| GO:0005515 protein binding | IPI PMID:20144646 Heterodimerization of Lrrk1-Lrrk2: Implications for LRRK2-as... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:20144646 2010 Feb 6. Heterodimerization of Lrrk1-Lrrk2: Implications for LRRK2-associated Parkinson disease. |
| GO:0005515 protein binding | IPI PMID:20173330 LRRK2 and the stress response: interaction with MKKs and JNK... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:20173330 LRRK2 and the stress response: interaction with MKKs and JNK-interacting proteins. |
| GO:0005515 protein binding | IPI PMID:20642453 14-3-3 binding to LRRK2 is disrupted by multiple Parkinson's... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:20642453 14-3-3 binding to LRRK2 is disrupted by multiple Parkinson's disease-associated mutations and regulates cytoplasmic localization. |
| GO:0005515 protein binding | IPI PMID:20671708 Pathogenic LRRK2 negatively regulates microRNA-mediated tran... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:20671708 Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression. |
| GO:0005515 protein binding | IPI PMID:21048939 ARHGEF7 (Beta-PIX) acts as guanine nucleotide exchange facto... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:21048939 ARHGEF7 (Beta-PIX) acts as guanine nucleotide exchange factor for leucine-rich repeat kinase 2. |
| GO:0005515 protein binding | IPI PMID:21307259 LRRK2 controls synaptic vesicle storage and mobilization wit... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:21307259 LRRK2 controls synaptic vesicle storage and mobilization within the recycling pool. |
| GO:0005515 protein binding | IPI PMID:21370995 Expression of leucine-rich repeat kinase 2 (LRRK2) inhibits ... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:21370995 Expression of leucine-rich repeat kinase 2 (LRRK2) inhibits the processing of uMtCK to induce cell death in a cell culture model system. |
| GO:0005515 protein binding | IPI PMID:21454543 Rac1 protein rescues neurite retraction caused by G2019S leu... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:21454543 2011 Mar 16. Rac1 protein rescues neurite retraction caused by G2019S leucine-rich repeat kinase 2 (LRRK2). |
| GO:0005515 protein binding | IPI PMID:21658387 LRRK2 directly phosphorylates Akt1 as a possible physiologic... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:21658387 Epub 2011 Jun 2. LRRK2 directly phosphorylates Akt1 as a possible physiological substrate: impairment of the kinase activity by Parkinson's disease-associated mutations. |
| GO:0005515 protein binding | IPI PMID:21850687 Mutations in LRRK2 increase phosphorylation of peroxiredoxin... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:21850687 Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3 exacerbating oxidative stress-induced neuronal death. |
| GO:0005515 protein binding | IPI PMID:21983832 The kinase LRRK2 is a regulator of the transcription factor ... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:21983832 The kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel disease. |
| GO:0005515 protein binding | IPI PMID:22228096 LRRK2 regulates mitochondrial dynamics and function through ... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:22228096 Jan 6. LRRK2 regulates mitochondrial dynamics and function through direct interaction with DLP1. |
| GO:0005515 protein binding | IPI PMID:22303461 LRRK2 phosphorylates tubulin-associated tau but not the free... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:22303461 LRRK2 phosphorylates tubulin-associated tau but not the free molecule: LRRK2-mediated regulation of the tau-tubulin association and neurite outgrowth. |
| GO:0005515 protein binding | IPI PMID:22363216 GTPase activity and neuronal toxicity of Parkinson's disease... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:22363216 Feb 9. GTPase activity and neuronal toxicity of Parkinson's disease-associated LRRK2 is regulated by ArfGAP1. |
| GO:0005515 protein binding | IPI PMID:22612223 The G2385R variant of leucine-rich repeat kinase 2 associate... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:22612223 The G2385R variant of leucine-rich repeat kinase 2 associated with Parkinson's disease is a partial loss-of-function mutation. |
| GO:0005515 protein binding | IPI PMID:22639965 Leucine-rich repeat kinase 2 disturbs mitochondrial dynamics... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:22639965 Epub 2012 Jun 22. Leucine-rich repeat kinase 2 disturbs mitochondrial dynamics via Dynamin-like protein. |
| GO:0005515 protein binding | IPI PMID:22899650 LRRK2 functions as a Wnt signaling scaffold, bridging cytoso... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:22899650 Aug 16. LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6. |
| GO:0005515 protein binding | IPI PMID:22952686 Biochemical characterization of highly purified leucine-rich... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:22952686 Biochemical characterization of highly purified leucine-rich repeat kinases 1 and 2 demonstrates formation of homodimers. |
| GO:0005515 protein binding | IPI PMID:22998870 LRRK2 controls an EndoA phosphorylation cycle in synaptic en... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:22998870 LRRK2 controls an EndoA phosphorylation cycle in synaptic endocytosis. |
| GO:0005515 protein binding | IPI PMID:23075850 Progressive degeneration of human neural stem cells caused b... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:23075850 Progressive degeneration of human neural stem cells caused by pathogenic LRRK2. |
| GO:0005515 protein binding | IPI PMID:23183827 LRRK2 interactions with Ξ±-synuclein in Parkinson's disease b... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:23183827 2012 Nov 27. LRRK2 interactions with Ξ±-synuclein in Parkinson's disease brains and in cell models. |
| GO:0005515 protein binding | IPI PMID:23241358 GTPase activity regulates kinase activity and cellular pheno... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:23241358 Dec 13. GTPase activity regulates kinase activity and cellular phenotypes of Parkinson's disease-associated LRRK2. |
| GO:0005515 protein binding | IPI PMID:23395371 RAB7L1 interacts with LRRK2 to modify intraneuronal protein ... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:23395371 RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson's disease risk. |
| GO:0005515 protein binding | IPI PMID:23455607 Interplay of LRRK2 with chaperone-mediated autophagy. | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:23455607 Interplay of LRRK2 with chaperone-mediated autophagy. |
| GO:0005515 protein binding | IPI PMID:23813973 Inhibition of excessive mitochondrial fission reduced aberra... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:23813973 Jun 27. Inhibition of excessive mitochondrial fission reduced aberrant autophagy and neuronal damage caused by LRRK2 G2019S mutation. |
| GO:0005515 protein binding | IPI PMID:23937259 Identification of protein phosphatase 1 as a regulator of th... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:23937259 Identification of protein phosphatase 1 as a regulator of the LRRK2 phosphorylation cycle. |
| GO:0005515 protein binding | IPI PMID:23949442 LRRK2 phosphorylates Snapin and inhibits interaction of Snap... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:23949442 LRRK2 phosphorylates Snapin and inhibits interaction of Snapin with SNAP-25. |
| GO:0005515 protein binding | IPI PMID:24113872 LRRK2 phosphorylates novel tau epitopes and promotes tauopat... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:24113872 2013 Oct 11. LRRK2 phosphorylates novel tau epitopes and promotes tauopathy. |
| GO:0005515 protein binding | IPI PMID:24165324 Leucine-rich repeat kinaseΒ 2 regulates tau phosphorylation t... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:24165324 Leucine-rich repeat kinase 2 regulates tau phosphorylation through direct activation of glycogen synthase kinase-3Ξ². |
| GO:0005515 protein binding | IPI PMID:24275654 A direct interaction between leucine-rich repeat kinase 2 an... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:24275654 2013 Nov 25. A direct interaction between leucine-rich repeat kinase 2 and specific Ξ²-tubulin isoforms regulates tubulin acetylation. |
| GO:0005515 protein binding | IPI PMID:24282027 Functional interaction of Parkinson's disease-associated LRR... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:24282027 Nov 26. Functional interaction of Parkinson's disease-associated LRRK2 with members of the dynamin GTPase superfamily. |
| GO:0005515 protein binding | IPI PMID:24351927 Parkinson-related LRRK2 mutation R1441C/G/H impairs PKA phos... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:24351927 Parkinson-related LRRK2 mutation R1441C/G/H impairs PKA phosphorylation of LRRK2 and disrupts its interaction with 14-3-3. |
| GO:0005515 protein binding | IPI PMID:24459295 Thiol peroxidases ameliorate LRRK2 mutant-induced mitochondr... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:24459295 Jan 23. Thiol peroxidases ameliorate LRRK2 mutant-induced mitochondrial and dopaminergic neuronal degeneration in Drosophila. |
| GO:0005515 protein binding | IPI PMID:24464040 LRRK2 regulates synaptogenesis and dopamine receptor activat... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:24464040 LRRK2 regulates synaptogenesis and dopamine receptor activation through modulation of PKA activity. |
| GO:0005515 protein binding | IPI PMID:24510904 Unbiased screen for interactors of leucine-rich repeat kinas... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:24510904 Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease. |
| GO:0005515 protein binding | IPI PMID:24687852 Leucine-rich repeat kinase 2 binds to neuronal vesicles thro... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:24687852 Mar 31. Leucine-rich repeat kinase 2 binds to neuronal vesicles through protein interactions mediated by its C-terminal WD40 domain. |
| GO:0005515 protein binding | IPI PMID:24695735 The Parkinson disease-linked LRRK2 protein mutation I2020T s... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:24695735 2014 Apr 2. The Parkinson disease-linked LRRK2 protein mutation I2020T stabilizes an active state conformation leading to increased kinase activity. |
| GO:0005515 protein binding | IPI PMID:24725412 Ribosomal protein s15 phosphorylation mediates LRRK2 neurode... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:24725412 Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in Parkinson's disease. |
| GO:0005515 protein binding | IPI PMID:24754922 MAP1B rescues LRRK2 mutant-mediated cytotoxicity. | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:24754922 MAP1B rescues LRRK2 mutant-mediated cytotoxicity. |
| GO:0005515 protein binding | IPI PMID:24794857 A Parkinson's disease gene regulatory network identifies the... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:24794857 May 2. A Parkinson's disease gene regulatory network identifies the signaling protein RGS2 as a modulator of LRRK2 activity and neuronal toxicity. |
| GO:0005515 protein binding | IPI PMID:24904275 LRRK2 kinase activity regulates synaptic vesicle trafficking... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:24904275 eCollection 2014. LRRK2 kinase activity regulates synaptic vesicle trafficking and neurotransmitter release through modulation of LRRK2 macro-molecular complex. |
| GO:0005515 protein binding | IPI PMID:24947832 Differential protein-protein interactions of LRRK1 and LRRK2... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:24947832 Differential protein-protein interactions of LRRK1 and LRRK2 indicate roles in distinct cellular signaling pathways. |
| GO:0005515 protein binding | IPI PMID:25009464 LRRK2 kinase activity and biology are not uniformly predicte... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:25009464 eCollection 2014. LRRK2 kinase activity and biology are not uniformly predicted by its autophosphorylation and cellular phosphorylation site status. |
| GO:0005515 protein binding | IPI PMID:25201882 Leucine-rich repeat kinase 2 regulates Sec16A at ER exit sit... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:25201882 Sep 8. Leucine-rich repeat kinase 2 regulates Sec16A at ER exit sites to allow ER-Golgi export. |
| GO:0005515 protein binding | IPI PMID:25360523 LRRK2 transport is regulated by its novel interacting partne... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:25360523 eCollection 2014. LRRK2 transport is regulated by its novel interacting partner Rab32. |
| GO:0005515 protein binding | IPI PMID:25446991 Threonine 56 phosphorylation of Bcl-2 is required for LRRK2 ... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:25446991 Threonine 56 phosphorylation of Bcl-2 is required for LRRK2 G2019S-induced mitochondrial depolarization and autophagy. |
| GO:0005515 protein binding | IPI PMID:25500533 Phosphorylation of LRRK2 by casein kinase 1Ξ± regulates trans... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:25500533 Phosphorylation of LRRK2 by casein kinase 1Ξ± regulates trans-Golgi clustering via differential interaction with ARHGEF7. |
| GO:0005515 protein binding | IPI PMID:25501810 LRRK2 functions in synaptic vesicle endocytosis through a ki... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:25501810 LRRK2 functions in synaptic vesicle endocytosis through a kinase-dependent mechanism. |
| GO:0005515 protein binding | IPI PMID:25605758 An early endosome regulator, Rab5b, is an LRRK2 kinase subst... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:25605758 An early endosome regulator, Rab5b, is an LRRK2 kinase substrate. |
| GO:0005515 protein binding | IPI PMID:26824392 Phosphoproteomics reveals that Parkinson's disease kinase LR... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:26824392 Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases. |
| GO:0005515 protein binding | IPI PMID:26894577 Identification of protein phosphatase 2A as an interacting p... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:26894577 Identification of protein phosphatase 2A as an interacting protein of leucine-rich repeat kinase 2. |
| GO:0005515 protein binding | IPI PMID:27013965 Protective LRRK2 R1398H Variant Enhances GTPase and Wnt Sign... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:27013965 eCollection 2016. Protective LRRK2 R1398H Variant Enhances GTPase and Wnt Signaling Activity. |
| GO:0005515 protein binding | IPI PMID:27273569 Ubiqutination via K27 and K29 chains signals aggregation and... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:27273569 Ubiqutination via K27 and K29 chains signals aggregation and neuronal protection of LRRK2 by WSB1. |
| GO:0005515 protein binding | IPI PMID:27314038 G2385R and I2020T Mutations Increase LRRK2 GTPase Activity. | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:27314038 G2385R and I2020T Mutations Increase LRRK2 GTPase Activity. |
| GO:0005515 protein binding | IPI PMID:27357661 Structural model of the dimeric Parkinson's protein LRRK2 re... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:27357661 Structural model of the dimeric Parkinson's protein LRRK2 reveals a compact architecture involving distant interdomain contacts. |
| GO:0005515 protein binding | IPI PMID:27424887 LRRK2 and RAB7L1 coordinately regulate axonal morphology and... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:27424887 LRRK2 and RAB7L1 coordinately regulate axonal morphology and lysosome integrity in diverse cellular contexts. |
| GO:0005515 protein binding | IPI PMID:28202711 Structural interface between LRRK2 and 14-3-3 protein. | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:28202711 Structural interface between LRRK2 and 14-3-3 protein. |
| GO:0005515 protein binding | IPI PMID:29513927 Comparative Protein Interaction Network Analysis Identifies ... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:29513927 Apr 17. Comparative Protein Interaction Network Analysis Identifies Shared and Distinct Functions for the Human ROCO Proteins. |
| GO:0005515 protein binding | IPI PMID:29519959 P62/SQSTM1 is a novel leucine-rich repeat kinase 2 (LRRK2) s... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:29519959 P62/SQSTM1 is a novel leucine-rich repeat kinase 2 (LRRK2) substrate that enhances neuronal toxicity. |
| GO:0005515 protein binding | IPI PMID:29541021 The LRRK2 Variant E193K Prevents Mitochondrial Fission Upon ... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:29541021 eCollection 2018. The LRRK2 Variant E193K Prevents Mitochondrial Fission Upon MPP+ Treatment by Altering LRRK2 Binding to DRP1. |
| GO:0005515 protein binding | IPI PMID:31046837 Parkinson's disease-associated LRRK2-G2019S mutant acts thro... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:31046837 Parkinson's disease-associated LRRK2-G2019S mutant acts through regulation of SERCA activity to control ER stress in astrocytes. |
| GO:0005515 protein binding | IPI PMID:31552791 LRRK2 binds to the Rab32 subfamily in a GTP-dependent manner... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:31552791 Epub 2019 Sep 25. LRRK2 binds to the Rab32 subfamily in a GTP-dependent manner via its armadillo domain. |
| GO:0005515 protein binding | IPI PMID:32017888 Structural Basis for Rab8a Recruitment of RILPL2 via LRRK2 P... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:32017888 2020 Feb 3. Structural Basis for Rab8a Recruitment of RILPL2 via LRRK2 Phosphorylation of Switch 2. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. |
| GO:0005515 protein binding | IPI PMID:33938021 Genomewide Association Studies of LRRK2 Modifiers of Parkins... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:33938021 Genomewide Association Studies of LRRK2 Modifiers of Parkinson's Disease. |
| GO:0042802 identical protein binding | IPI PMID:16321986 The Parkinson disease causing LRRK2 mutation I2020T is assoc... | ACCEPT | Summary: Identical protein binding - LRRK2 forms homodimers, important for regulation. Reason: Identical protein binding - LRRK2 forms homodimers, important for regulation. Supporting Evidence: PMID:16321986 Dec 1. The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity. |
| GO:0042802 identical protein binding | IPI PMID:18230735 Structure of the ROC domain from the Parkinson's disease-ass... | ACCEPT | Summary: Identical protein binding - LRRK2 forms homodimers, important for regulation. Reason: Identical protein binding - LRRK2 forms homodimers, important for regulation. Supporting Evidence: PMID:18230735 Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase. |
| GO:0042802 identical protein binding | IPI PMID:18397888 The Parkinson disease-associated leucine-rich repeat kinase ... | ACCEPT | Summary: Identical protein binding - LRRK2 forms homodimers, important for regulation. Reason: Identical protein binding - LRRK2 forms homodimers, important for regulation. Supporting Evidence: PMID:18397888 2008 Apr 8. The Parkinson disease-associated leucine-rich repeat kinase 2 (LRRK2) is a dimer that undergoes intramolecular autophosphorylation. |
| GO:0042802 identical protein binding | IPI PMID:19712061 Homo- and heterodimerization of ROCO kinases: LRRK2 kinase i... | ACCEPT | Summary: Identical protein binding - LRRK2 forms homodimers, important for regulation. Reason: Identical protein binding - LRRK2 forms homodimers, important for regulation. Supporting Evidence: PMID:19712061 Epub 2009 Aug 27. Homo- and heterodimerization of ROCO kinases: LRRK2 kinase inhibition by the LRRK2 ROCO fragment. |
| GO:0042802 identical protein binding | IPI PMID:19733152 The Parkinson's disease kinase LRRK2 autophosphorylates its ... | ACCEPT | Summary: Identical protein binding - LRRK2 forms homodimers, important for regulation. Reason: Identical protein binding - LRRK2 forms homodimers, important for regulation. Supporting Evidence: PMID:19733152 The Parkinson's disease kinase LRRK2 autophosphorylates its GTPase domain at multiple sites. |
| GO:0042802 identical protein binding | IPI PMID:20515039 Membrane localization of LRRK2 is associated with increased ... | ACCEPT | Summary: Identical protein binding - LRRK2 forms homodimers, important for regulation. Reason: Identical protein binding - LRRK2 forms homodimers, important for regulation. Supporting Evidence: PMID:20515039 Membrane localization of LRRK2 is associated with increased formation of the highly active LRRK2 dimer and changes in its phosphorylation. |
| GO:0042802 identical protein binding | IPI PMID:21073465 Insight into the mode of action of the LRRK2 Y1699C pathogen... | ACCEPT | Summary: Identical protein binding - LRRK2 forms homodimers, important for regulation. Reason: Identical protein binding - LRRK2 forms homodimers, important for regulation. Supporting Evidence: PMID:21073465 Insight into the mode of action of the LRRK2 Y1699C pathogenic mutant. |
| GO:0042802 identical protein binding | IPI PMID:22363216 GTPase activity and neuronal toxicity of Parkinson's disease... | ACCEPT | Summary: Identical protein binding - LRRK2 forms homodimers, important for regulation. Reason: Identical protein binding - LRRK2 forms homodimers, important for regulation. Supporting Evidence: PMID:22363216 Feb 9. GTPase activity and neuronal toxicity of Parkinson's disease-associated LRRK2 is regulated by ArfGAP1. |
| GO:0042802 identical protein binding | IPI PMID:22952686 Biochemical characterization of highly purified leucine-rich... | ACCEPT | Summary: Identical protein binding - LRRK2 forms homodimers, important for regulation. Reason: Identical protein binding - LRRK2 forms homodimers, important for regulation. Supporting Evidence: PMID:22952686 Biochemical characterization of highly purified leucine-rich repeat kinases 1 and 2 demonstrates formation of homodimers. |
| GO:0042802 identical protein binding | IPI PMID:23220480 Dominant-negative effects of LRRK2 heterodimers: a possible ... | ACCEPT | Summary: Identical protein binding - LRRK2 forms homodimers, important for regulation. Reason: Identical protein binding - LRRK2 forms homodimers, important for regulation. Supporting Evidence: PMID:23220480 Dominant-negative effects of LRRK2 heterodimers: a possible mechanism of neurodegeneration in Parkinson's disease caused by LRRK2 I2020T mutation. |
| GO:0042802 identical protein binding | IPI PMID:23241358 GTPase activity regulates kinase activity and cellular pheno... | ACCEPT | Summary: Identical protein binding - LRRK2 forms homodimers, important for regulation. Reason: Identical protein binding - LRRK2 forms homodimers, important for regulation. Supporting Evidence: PMID:23241358 Dec 13. GTPase activity regulates kinase activity and cellular phenotypes of Parkinson's disease-associated LRRK2. |
| GO:0042802 identical protein binding | IPI PMID:24275654 A direct interaction between leucine-rich repeat kinase 2 an... | ACCEPT | Summary: Identical protein binding - LRRK2 forms homodimers, important for regulation. Reason: Identical protein binding - LRRK2 forms homodimers, important for regulation. Supporting Evidence: PMID:24275654 2013 Nov 25. A direct interaction between leucine-rich repeat kinase 2 and specific Ξ²-tubulin isoforms regulates tubulin acetylation. |
| GO:0042802 identical protein binding | IPI PMID:24591621 Parkinson disease-associated mutation R1441H in LRRK2 prolon... | ACCEPT | Summary: Identical protein binding - LRRK2 forms homodimers, important for regulation. Reason: Identical protein binding - LRRK2 forms homodimers, important for regulation. Supporting Evidence: PMID:24591621 Parkinson disease-associated mutation R1441H in LRRK2 prolongs the "active state" of its GTPase domain. |
| GO:0042802 identical protein binding | IPI PMID:24904275 LRRK2 kinase activity regulates synaptic vesicle trafficking... | ACCEPT | Summary: Identical protein binding - LRRK2 forms homodimers, important for regulation. Reason: Identical protein binding - LRRK2 forms homodimers, important for regulation. Supporting Evidence: PMID:24904275 eCollection 2014. LRRK2 kinase activity regulates synaptic vesicle trafficking and neurotransmitter release through modulation of LRRK2 macro-molecular complex. |
| GO:0042802 identical protein binding | IPI PMID:26824392 Phosphoproteomics reveals that Parkinson's disease kinase LR... | ACCEPT | Summary: Identical protein binding - LRRK2 forms homodimers, important for regulation. Reason: Identical protein binding - LRRK2 forms homodimers, important for regulation. Supporting Evidence: PMID:26824392 Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases. |
| GO:0042802 identical protein binding | IPI PMID:27013965 Protective LRRK2 R1398H Variant Enhances GTPase and Wnt Sign... | ACCEPT | Summary: Identical protein binding - LRRK2 forms homodimers, important for regulation. Reason: Identical protein binding - LRRK2 forms homodimers, important for regulation. Supporting Evidence: PMID:27013965 eCollection 2016. Protective LRRK2 R1398H Variant Enhances GTPase and Wnt Signaling Activity. |
| GO:0042802 identical protein binding | IPI PMID:27357661 Structural model of the dimeric Parkinson's protein LRRK2 re... | ACCEPT | Summary: Identical protein binding - LRRK2 forms homodimers, important for regulation. Reason: Identical protein binding - LRRK2 forms homodimers, important for regulation. Supporting Evidence: PMID:27357661 Structural model of the dimeric Parkinson's protein LRRK2 reveals a compact architecture involving distant interdomain contacts. |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | ACCEPT | Summary: Cytoplasm is a major localization for LRRK2. Reason: Cytoplasm is a major localization for LRRK2. |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mitochondrial inner membrane - reported but may be minor. Reason: Mitochondrial inner membrane - reported but may be minor. |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mitochondrial matrix - reported but may be minor. Reason: Mitochondrial matrix - reported but may be minor. |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000107 | ACCEPT | Summary: Endoplasmic reticulum - documented localization at ER exit sites. Reason: Endoplasmic reticulum - documented localization at ER exit sites. |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000120 | ACCEPT | Summary: Golgi apparatus localization is supported - LRRK2 is recruited to Golgi by Rab29. Reason: Golgi apparatus localization is supported - LRRK2 is recruited to Golgi by Rab29. |
| GO:0005802 trans-Golgi network | IEA GO_REF:0000107 | ACCEPT | Summary: Trans-Golgi network localization is supported by Rab29-mediated recruitment studies. Reason: Trans-Golgi network localization is supported by Rab29-mediated recruitment studies. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Plasma membrane - LRRK2 can localize to membranes but cytosol is predominant. Reason: Plasma membrane - LRRK2 can localize to membranes but cytosol is predominant. |
| GO:0007029 endoplasmic reticulum organization | IEA GO_REF:0000120 | ACCEPT | Summary: ER organization is related to LRRK2 role in Sec16A regulation at ER exit sites. Reason: ER organization is related to LRRK2 role in Sec16A regulation at ER exit sites. |
| GO:0007283 spermatogenesis | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Spermatogenesis is tissue-specific. Reason: Spermatogenesis is tissue-specific. |
| GO:0008021 synaptic vesicle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Synaptic vesicle is tissue-specific in neurons. Reason: Synaptic vesicle is tissue-specific in neurons. |
| GO:0008104 intracellular protein localization | IEA GO_REF:0000107 | ACCEPT | Summary: Intracellular protein localization - broad but relevant to trafficking role. Reason: Intracellular protein localization - broad but relevant to trafficking role. |
| GO:0010508 positive regulation of autophagy | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | Summary: Positive regulation of autophagy is a downstream effect of trafficking disruption, not core function. Reason: Positive regulation of autophagy is a downstream effect of trafficking disruption, not core function. |
| GO:0010977 negative regulation of neuron projection development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of neuron projection development - neuronal. Reason: Negative regulation of neuron projection development - neuronal. |
| GO:0021756 striatum development | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Striatum development is tissue-specific developmental effect. Reason: Striatum development is tissue-specific developmental effect. |
| GO:0031267 small GTPase binding | IEA GO_REF:0000120 | ACCEPT | Summary: Small GTPase binding - LRRK2 binds Rab substrates and other small GTPases. Reason: Small GTPase binding - LRRK2 binds Rab substrates and other small GTPases. |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of proteasomal ubiquitin-dependent protein catabolic process - downstream. Reason: Positive regulation of proteasomal ubiquitin-dependent protein catabolic process - downstream. |
| GO:0032760 positive regulation of tumor necrosis factor production | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of TNF production is downstream immune effect. Reason: Positive regulation of TNF production is downstream immune effect. |
| GO:0035556 intracellular signal transduction | IEA GO_REF:0000120 | ACCEPT | Summary: Intracellular signal transduction - LRRK2 functions as a kinase that phosphorylates Rab GTPases. Reason: Intracellular signal transduction - LRRK2 functions as a kinase that phosphorylates Rab GTPases. |
| GO:0035564 regulation of kidney size | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Regulation of kidney size is tissue-specific. Reason: Regulation of kidney size is tissue-specific. |
| GO:0035641 locomotory exploration behavior | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Locomotory exploration behavior is organismal phenotype. Reason: Locomotory exploration behavior is organismal phenotype. |
| GO:0042802 identical protein binding | IEA GO_REF:0000120 | ACCEPT | Summary: Identical protein binding - LRRK2 forms homodimers, important for regulation. Reason: Identical protein binding - LRRK2 forms homodimers, important for regulation. |
| GO:0043025 neuronal cell body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neuronal cell body is tissue-specific localization. Reason: Neuronal cell body is tissue-specific localization. |
| GO:0045121 membrane raft | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Membrane raft - reported localization. Reason: Membrane raft - reported localization. |
| GO:0045202 synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Synapse is tissue-specific neuronal localization. Reason: Synapse is tissue-specific neuronal localization. |
| GO:0051018 protein kinase A binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Protein kinase A binding - interaction documented but not core. Reason: Protein kinase A binding - interaction documented but not core. |
| GO:0051966 regulation of synaptic transmission, glutamatergic | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Regulation of synaptic transmission, glutamatergic - tissue-specific. Reason: Regulation of synaptic transmission, glutamatergic - tissue-specific. |
| GO:0060079 excitatory postsynaptic potential | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Excitatory postsynaptic potential - tissue-specific. Reason: Excitatory postsynaptic potential - tissue-specific. |
| GO:0060159 regulation of dopamine receptor signaling pathway | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Regulation of dopamine receptor signaling pathway - tissue-specific. Reason: Regulation of dopamine receptor signaling pathway - tissue-specific. |
| GO:0060628 regulation of ER to Golgi vesicle-mediated transport | IEA GO_REF:0000107 | ACCEPT | Summary: Regulation of ER to Golgi vesicle-mediated transport - via Sec16A regulation. Reason: Regulation of ER to Golgi vesicle-mediated transport - via Sec16A regulation. |
| GO:0060828 regulation of canonical Wnt signaling pathway | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Regulation of canonical Wnt signaling pathway - LRRK2 acts as scaffold but not core function. Reason: Regulation of canonical Wnt signaling pathway - LRRK2 acts as scaffold but not core function. |
| GO:0061001 regulation of dendritic spine morphogenesis | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Regulation of dendritic spine morphogenesis - neuronal effect. Reason: Regulation of dendritic spine morphogenesis - neuronal effect. |
| GO:0070971 endoplasmic reticulum exit site | IEA GO_REF:0000120 | ACCEPT | Summary: ER exit site localization - LRRK2 regulates Sec16A at ER exit sites. Reason: ER exit site localization - LRRK2 regulates Sec16A at ER exit sites. |
| GO:0070973 protein localization to endoplasmic reticulum exit site | IEA GO_REF:0000120 | MODIFY | Summary: Protein localization to ER exit site - LRRK2 regulates Sec16A; the annotated term is now obsolete. Reason: GO:0070973 protein localization to endoplasmic reticulum exit site was obsoleted (GO release 2026-07-26) because it conflated distinct processes; GO suggests context-specific replacements. PMID:25201882 shows LRRK2 anchors Sec16A at ER exit sites and that this regulates anterograde ER-to-Golgi export (LRRK2 depletion disperses Sec16A and impairs ER export), so the finding is best captured by GO:0060628 regulation of ER to Golgi vesicle-mediated transport. Proposed replacements: regulation of ER to Golgi vesicle-mediated transport Supporting Evidence: PMID:25201882 LRRK2 regulates the anterograde ER-Golgi transport through anchoring Sec16A at the endoplasmic reticulum exit sites |
| GO:0090394 negative regulation of excitatory postsynaptic potential | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of excitatory postsynaptic potential - tissue-specific. Reason: Negative regulation of excitatory postsynaptic potential - tissue-specific. |
| GO:0098978 glutamatergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Glutamatergic synapse is tissue-specific. Reason: Glutamatergic synapse is tissue-specific. |
| GO:0099523 presynaptic cytosol | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Presynaptic cytosol is tissue-specific. Reason: Presynaptic cytosol is tissue-specific. |
| GO:0140058 neuron projection arborization | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Neuron projection arborization is developmental. Reason: Neuron projection arborization is developmental. |
| GO:0141161 regulation of cAMP/PKA signal transduction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Regulation of cAMP/PKA signal transduction - related to dopamine signaling. Reason: Regulation of cAMP/PKA signal transduction - related to dopamine signaling. |
| GO:1900242 regulation of synaptic vesicle endocytosis | IEA GO_REF:0000107 | ACCEPT | Summary: Regulation of synaptic vesicle endocytosis - well-documented LRRK2 function. Reason: Regulation of synaptic vesicle endocytosis - well-documented LRRK2 function. |
| GO:1900244 positive regulation of synaptic vesicle endocytosis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of synaptic vesicle endocytosis - tissue-specific. Reason: Positive regulation of synaptic vesicle endocytosis - tissue-specific. |
| GO:1902803 regulation of synaptic vesicle transport | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Regulation of synaptic vesicle transport - tissue-specific. Reason: Regulation of synaptic vesicle transport - tissue-specific. |
| GO:1903980 positive regulation of microglial cell activation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of microglial cell activation is downstream immune effect. Reason: Positive regulation of microglial cell activation is downstream immune effect. |
| GO:1904644 cellular response to curcumin | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Cellular response to curcumin is an experimental condition response. Reason: Cellular response to curcumin is an experimental condition response. |
| GO:1904713 beta-catenin destruction complex binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Beta-catenin destruction complex binding - scaffold role. Reason: Beta-catenin destruction complex binding - scaffold role. |
| GO:1990904 ribonucleoprotein complex | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ribonucleoprotein complex - specific interaction. Reason: Ribonucleoprotein complex - specific interaction. |
| GO:1990909 Wnt signalosome | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Wnt signalosome localization - scaffold role. Reason: Wnt signalosome localization - scaffold role. |
| GO:0004674 protein serine/threonine kinase activity | EXP PMID:26751287 The LINK-A lncRNA activates normoxic HIF1Ξ± signalling in tri... | ACCEPT | Summary: Protein serine/threonine kinase activity is a core enzymatic function of LRRK2. The kinase domain phosphorylates Rab GTPases at their switch II regions. Reason: Protein serine/threonine kinase activity is a core enzymatic function of LRRK2. The kinase domain phosphorylates Rab GTPases at their switch II regions. Supporting Evidence: PMID:26751287 The LINK-A lncRNA activates normoxic HIF1Ξ± signalling in triple-negative breast cancer. |
| GO:1905504 negative regulation of motile cilium assembly | TAS PMID:30398148 A pathway for Parkinson's Disease LRRK2 kinase to block prim... | ACCEPT | Summary: Negative regulation of motile cilium assembly - core function via Rab8/Rab10/RILPL1 axis. Reason: Negative regulation of motile cilium assembly - core function via Rab8/Rab10/RILPL1 axis. Supporting Evidence: PMID:30398148 A pathway for Parkinson's Disease LRRK2 kinase to block primary cilia and Sonic hedgehog signaling in the brain. |
| GO:0035542 regulation of SNARE complex assembly | IMP PMID:23949442 LRRK2 phosphorylates Snapin and inhibits interaction of Snap... | KEEP AS NON CORE | Summary: Regulation of SNARE complex assembly - related to vesicle function. Reason: Regulation of SNARE complex assembly - related to vesicle function. Supporting Evidence: PMID:23949442 LRRK2 phosphorylates Snapin and inhibits interaction of Snapin with SNAP-25. |
| GO:0043410 positive regulation of MAPK cascade | IMP PMID:21857923 Dysregulated LRRK2 signaling in response to endoplasmic reti... | UNDECIDED | Summary: Positive regulation of MAPK cascade - may be indirect. Reason: Positive regulation of MAPK cascade - may be indirect. Supporting Evidence: PMID:21857923 Dysregulated LRRK2 signaling in response to endoplasmic reticulum stress leads to dopaminergic neuron degeneration in C. |
| GO:0043410 positive regulation of MAPK cascade | IMP PMID:23628791 Down-regulation of LRRK2 in control and DAT transfected HEK ... | UNDECIDED | Summary: Positive regulation of MAPK cascade - may be indirect. Reason: Positive regulation of MAPK cascade - may be indirect. Supporting Evidence: PMID:23628791 2013 Apr 27. Down-regulation of LRRK2 in control and DAT transfected HEK cells increases manganese-induced oxidative stress and cell toxicity. |
| GO:1901030 positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway | IDA PMID:21370995 Expression of leucine-rich repeat kinase 2 (LRRK2) inhibits ... | MARK AS OVER ANNOTATED | Summary: Positive regulation of mitochondrial outer membrane permeabilization in apoptotic signaling is disease-related. Reason: Positive regulation of mitochondrial outer membrane permeabilization in apoptotic signaling is disease-related. Supporting Evidence: PMID:21370995 Expression of leucine-rich repeat kinase 2 (LRRK2) inhibits the processing of uMtCK to induce cell death in a cell culture model system. |
| GO:0042802 identical protein binding | IPI PMID:38127736 Rab29-dependent asymmetrical activation of leucine-rich repe... | ACCEPT | Summary: Identical protein binding - LRRK2 forms homodimers, important for regulation. Reason: Identical protein binding - LRRK2 forms homodimers, important for regulation. Supporting Evidence: PMID:38127736 2023 Dec 21. Rab29-dependent asymmetrical activation of leucine-rich repeat kinase 2. |
| GO:0005515 protein binding | IPI PMID:38858457 Systematic rare variant analyses identify RAB32 as a suscept... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:38858457 2024 Jun 10. Systematic rare variant analyses identify RAB32 as a susceptibility gene for familial Parkinson's disease. |
| GO:0141161 regulation of cAMP/PKA signal transduction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Regulation of cAMP/PKA signal transduction - related to dopamine signaling. Reason: Regulation of cAMP/PKA signal transduction - related to dopamine signaling. |
| GO:0007266 Rho protein signal transduction | IDA PMID:25500533 Phosphorylation of LRRK2 by casein kinase 1Ξ± regulates trans... | UNDECIDED | Summary: Rho protein signal transduction - may be downstream effect. Reason: Rho protein signal transduction - may be downstream effect. Supporting Evidence: PMID:25500533 Phosphorylation of LRRK2 by casein kinase 1Ξ± regulates trans-Golgi clustering via differential interaction with ARHGEF7. |
| GO:0034614 cellular response to reactive oxygen species | IMP PMID:24576675 LRRK2, but not pathogenic mutants, protects against H2O2 str... | MARK AS OVER ANNOTATED | Summary: Cellular response to reactive oxygen species is disease-related. Reason: Cellular response to reactive oxygen species is disease-related. Supporting Evidence: PMID:24576675 LRRK2, but not pathogenic mutants, protects against H2O2 stress depending on mitochondrial function and endocytosis in a yeast model. |
| GO:2000377 regulation of reactive oxygen species metabolic process | IMP PMID:24576675 LRRK2, but not pathogenic mutants, protects against H2O2 str... | MARK AS OVER ANNOTATED | Summary: Regulation of ROS metabolic process is downstream. Reason: Regulation of ROS metabolic process is downstream. Supporting Evidence: PMID:24576675 LRRK2, but not pathogenic mutants, protects against H2O2 stress depending on mitochondrial function and endocytosis in a yeast model. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:27830463 LRRK2 enhances Nod1/2-mediated inflammatory cytokine product... | ACCEPT | Summary: Protein serine/threonine kinase activity is a core enzymatic function of LRRK2. The kinase domain phosphorylates Rab GTPases at their switch II regions. Reason: Protein serine/threonine kinase activity is a core enzymatic function of LRRK2. The kinase domain phosphorylates Rab GTPases at their switch II regions. Supporting Evidence: PMID:27830463 Nov 9. LRRK2 enhances Nod1/2-mediated inflammatory cytokine production by promoting Rip2 phosphorylation. |
| GO:0030159 signaling receptor complex adaptor activity | IDA PMID:22899650 LRRK2 functions as a Wnt signaling scaffold, bridging cytoso... | UNDECIDED | Summary: Signaling receptor complex adaptor activity - Wnt scaffold role. Reason: Signaling receptor complex adaptor activity - Wnt scaffold role. Supporting Evidence: PMID:22899650 Aug 16. LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6. |
| GO:0039706 co-receptor binding | TAS PMID:24115276 The regulation and deregulation of Wnt signaling by PARK gen... | UNDECIDED | Summary: Co-receptor binding - Wnt-related, needs verification. Reason: Co-receptor binding - Wnt-related, needs verification. Supporting Evidence: PMID:24115276 The regulation and deregulation of Wnt signaling by PARK genes in health and disease. |
| GO:0090263 positive regulation of canonical Wnt signaling pathway | IGI PMID:22899650 LRRK2 functions as a Wnt signaling scaffold, bridging cytoso... | KEEP AS NON CORE | Summary: Positive regulation of canonical Wnt signaling pathway - scaffold role. Reason: Positive regulation of canonical Wnt signaling pathway - scaffold role. Supporting Evidence: PMID:22899650 Aug 16. LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6. |
| GO:0097413 Lewy body | IDA PMID:27273569 Ubiqutination via K27 and K29 chains signals aggregation and... | KEEP AS NON CORE | Summary: Lewy body - disease-specific pathological structure. Reason: Lewy body - disease-specific pathological structure. Supporting Evidence: PMID:27273569 Ubiqutination via K27 and K29 chains signals aggregation and neuronal protection of LRRK2 by WSB1. |
| GO:0004706 JUN kinase kinase kinase activity | IDA PMID:19302196 The Parkinson disease-associated protein kinase LRRK2 exhibi... | UNDECIDED | Summary: JUN kinase kinase kinase activity - reported but may not be physiological core function. Reason: JUN kinase kinase kinase activity - reported but may not be physiological core function. Supporting Evidence: PMID:19302196 Epub 2009 Mar 3. The Parkinson disease-associated protein kinase LRRK2 exhibits MAPKKK activity and phosphorylates MKK3/6 and MKK4/7, in vitro. |
| GO:0004709 MAP kinase kinase kinase activity | IDA PMID:19302196 The Parkinson disease-associated protein kinase LRRK2 exhibi... | UNDECIDED | Summary: MAP kinase kinase kinase activity - reported in vitro but physiological relevance unclear. Reason: MAP kinase kinase kinase activity - reported in vitro but physiological relevance unclear. Supporting Evidence: PMID:19302196 Epub 2009 Mar 3. The Parkinson disease-associated protein kinase LRRK2 exhibits MAPKKK activity and phosphorylates MKK3/6 and MKK4/7, in vitro. |
| GO:0007254 JNK cascade | IDA PMID:19302196 The Parkinson disease-associated protein kinase LRRK2 exhibi... | UNDECIDED | Summary: JNK cascade - reported but physiological relevance as direct function unclear. Reason: JNK cascade - reported but physiological relevance as direct function unclear. Supporting Evidence: PMID:19302196 Epub 2009 Mar 3. The Parkinson disease-associated protein kinase LRRK2 exhibits MAPKKK activity and phosphorylates MKK3/6 and MKK4/7, in vitro. |
| GO:0000287 magnesium ion binding | IMP PMID:28720718 Phosphorylation of amyloid precursor protein by mutant LRRK2... | UNDECIDED | Summary: GO term GO:0000287 requires further review - no pre-defined decision available. Reason: Term not in curated decision list, requires manual review. Supporting Evidence: PMID:28720718 Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD activity and neurotoxicity in Parkinson's disease. |
| GO:0004674 protein serine/threonine kinase activity | IMP PMID:28720718 Phosphorylation of amyloid precursor protein by mutant LRRK2... | ACCEPT | Summary: Protein serine/threonine kinase activity is a core enzymatic function of LRRK2. The kinase domain phosphorylates Rab GTPases at their switch II regions. Reason: Protein serine/threonine kinase activity is a core enzymatic function of LRRK2. The kinase domain phosphorylates Rab GTPases at their switch II regions. Supporting Evidence: PMID:28720718 Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD activity and neurotoxicity in Parkinson's disease. |
| GO:0005515 protein binding | IPI PMID:26014385 LRRK2 Promotes Tau Accumulation, Aggregation and Release. | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:26014385 2015 May 27. LRRK2 Promotes Tau Accumulation, Aggregation and Release. |
| GO:0005515 protein binding | IPI PMID:28720718 Phosphorylation of amyloid precursor protein by mutant LRRK2... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:28720718 Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD activity and neurotoxicity in Parkinson's disease. |
| GO:0005737 cytoplasm | IMP PMID:26014385 LRRK2 Promotes Tau Accumulation, Aggregation and Release. | ACCEPT | Summary: Cytoplasm is a major localization for LRRK2. Reason: Cytoplasm is a major localization for LRRK2. Supporting Evidence: PMID:26014385 2015 May 27. LRRK2 Promotes Tau Accumulation, Aggregation and Release. |
| GO:0006468 protein phosphorylation | IMP PMID:28720718 Phosphorylation of amyloid precursor protein by mutant LRRK2... | ACCEPT | Summary: Protein phosphorylation - core enzymatic function of LRRK2 kinase domain. Reason: Protein phosphorylation - core enzymatic function of LRRK2 kinase domain. Supporting Evidence: PMID:28720718 Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD activity and neurotoxicity in Parkinson's disease. |
| GO:0031647 regulation of protein stability | IMP PMID:26014385 LRRK2 Promotes Tau Accumulation, Aggregation and Release. | KEEP AS NON CORE | Summary: Regulation of protein stability - tau-related. Reason: Regulation of protein stability - tau-related. Supporting Evidence: PMID:26014385 2015 May 27. LRRK2 Promotes Tau Accumulation, Aggregation and Release. |
| GO:0007029 endoplasmic reticulum organization | IMP PMID:25201882 Leucine-rich repeat kinase 2 regulates Sec16A at ER exit sit... | ACCEPT | Summary: ER organization is related to LRRK2 role in Sec16A regulation at ER exit sites. Reason: ER organization is related to LRRK2 role in Sec16A regulation at ER exit sites. Supporting Evidence: PMID:25201882 Sep 8. Leucine-rich repeat kinase 2 regulates Sec16A at ER exit sites to allow ER-Golgi export. |
| GO:0060628 regulation of ER to Golgi vesicle-mediated transport | ISS GO_REF:0000024 | ACCEPT | Summary: Regulation of ER to Golgi vesicle-mediated transport - via Sec16A regulation. Reason: Regulation of ER to Golgi vesicle-mediated transport - via Sec16A regulation. |
| GO:0070971 endoplasmic reticulum exit site | IDA PMID:25201882 Leucine-rich repeat kinase 2 regulates Sec16A at ER exit sit... | ACCEPT | Summary: ER exit site localization - LRRK2 regulates Sec16A at ER exit sites. Reason: ER exit site localization - LRRK2 regulates Sec16A at ER exit sites. Supporting Evidence: PMID:25201882 Sep 8. Leucine-rich repeat kinase 2 regulates Sec16A at ER exit sites to allow ER-Golgi export. |
| GO:0070973 protein localization to endoplasmic reticulum exit site | IMP PMID:25201882 Leucine-rich repeat kinase 2 regulates Sec16A at ER exit sit... | MODIFY | Summary: Protein localization to ER exit site - LRRK2 regulates Sec16A; the annotated term is now obsolete. Reason: GO:0070973 protein localization to endoplasmic reticulum exit site was obsoleted (GO release 2026-07-26) because it conflated distinct processes; GO suggests context-specific replacements. PMID:25201882 shows LRRK2 anchors Sec16A at ER exit sites and that this regulates anterograde ER-to-Golgi export (LRRK2 depletion disperses Sec16A and impairs ER export), so the finding is best captured by GO:0060628 regulation of ER to Golgi vesicle-mediated transport. Proposed replacements: regulation of ER to Golgi vesicle-mediated transport Supporting Evidence: PMID:25201882 LRRK2 regulates the anterograde ER-Golgi transport through anchoring Sec16A at the endoplasmic reticulum exit sites |
| GO:0099400 caveola neck | IDA PMID:19640926 LRRK2 regulates autophagic activity and localizes to specifi... | KEEP AS NON CORE | Summary: Caveola neck - specific localization. Reason: Caveola neck - specific localization. Supporting Evidence: PMID:19640926 Jul 29. LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model. |
| GO:1905289 regulation of CAMKK-AMPK signaling cascade | IMP PMID:22012985 Leucine-rich repeat kinase 2 regulates autophagy through a c... | KEEP AS NON CORE | Summary: Regulation of CAMKK-AMPK signaling cascade - downstream effect. Reason: Regulation of CAMKK-AMPK signaling cascade - downstream effect. Supporting Evidence: PMID:22012985 Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP. |
| GO:0005794 Golgi apparatus | IDA PMID:23395371 RAB7L1 interacts with LRRK2 to modify intraneuronal protein ... | ACCEPT | Summary: Golgi apparatus localization is supported - LRRK2 is recruited to Golgi by Rab29. Reason: Golgi apparatus localization is supported - LRRK2 is recruited to Golgi by Rab29. Supporting Evidence: PMID:23395371 RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson's disease risk. |
| GO:1905279 regulation of retrograde transport, endosome to Golgi | IGI PMID:23395371 RAB7L1 interacts with LRRK2 to modify intraneuronal protein ... | ACCEPT | Summary: Regulation of retrograde transport, endosome to Golgi - via Rab29/RAB7L1 interaction. Reason: Regulation of retrograde transport, endosome to Golgi - via Rab29/RAB7L1 interaction. Supporting Evidence: PMID:23395371 RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson's disease risk. |
| GO:0060828 regulation of canonical Wnt signaling pathway | TAS PMID:22988876 The importance of Wnt signalling for neurodegeneration in Pa... | KEEP AS NON CORE | Summary: Regulation of canonical Wnt signaling pathway - LRRK2 acts as scaffold but not core function. Reason: Regulation of canonical Wnt signaling pathway - LRRK2 acts as scaffold but not core function. Supporting Evidence: PMID:22988876 The importance of Wnt signalling for neurodegeneration in Parkinson's disease. |
| GO:0008017 microtubule binding | TAS PMID:24115276 The regulation and deregulation of Wnt signaling by PARK gen... | KEEP AS NON CORE | Summary: Microtubule binding - documented but significance unclear. Reason: Microtubule binding - documented but significance unclear. Supporting Evidence: PMID:24115276 The regulation and deregulation of Wnt signaling by PARK genes in health and disease. |
| GO:0060070 canonical Wnt signaling pathway | TAS PMID:24115276 The regulation and deregulation of Wnt signaling by PARK gen... | KEEP AS NON CORE | Summary: Canonical Wnt signaling pathway - scaffold role. Reason: Canonical Wnt signaling pathway - scaffold role. Supporting Evidence: PMID:24115276 The regulation and deregulation of Wnt signaling by PARK genes in health and disease. |
| GO:1904713 beta-catenin destruction complex binding | NAS PMID:24115276 The regulation and deregulation of Wnt signaling by PARK gen... | KEEP AS NON CORE | Summary: Beta-catenin destruction complex binding - scaffold role. Reason: Beta-catenin destruction complex binding - scaffold role. Supporting Evidence: PMID:24115276 The regulation and deregulation of Wnt signaling by PARK genes in health and disease. |
| GO:1904887 Wnt signalosome assembly | TAS PMID:24115276 The regulation and deregulation of Wnt signaling by PARK gen... | KEEP AS NON CORE | Summary: Wnt signalosome assembly - via LRP6 bridging. Reason: Wnt signalosome assembly - via LRP6 bridging. Supporting Evidence: PMID:24115276 The regulation and deregulation of Wnt signaling by PARK genes in health and disease. |
| GO:1990909 Wnt signalosome | NAS PMID:24115276 The regulation and deregulation of Wnt signaling by PARK gen... | KEEP AS NON CORE | Summary: Wnt signalosome localization - scaffold role. Reason: Wnt signalosome localization - scaffold role. Supporting Evidence: PMID:24115276 The regulation and deregulation of Wnt signaling by PARK genes in health and disease. |
| GO:1904887 Wnt signalosome assembly | IPI PMID:22899650 LRRK2 functions as a Wnt signaling scaffold, bridging cytoso... | KEEP AS NON CORE | Summary: Wnt signalosome assembly - via LRP6 bridging. Reason: Wnt signalosome assembly - via LRP6 bridging. Supporting Evidence: PMID:22899650 Aug 16. LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6. |
| GO:0035751 regulation of lysosomal lumen pH | IMP PMID:22012985 Leucine-rich repeat kinase 2 regulates autophagy through a c... | ACCEPT | Summary: Regulation of lysosomal lumen pH - via effects on lysosomal function. Reason: Regulation of lysosomal lumen pH - via effects on lysosomal function. Supporting Evidence: PMID:22012985 Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP. |
| GO:1990909 Wnt signalosome | IDA PMID:22899650 LRRK2 functions as a Wnt signaling scaffold, bridging cytoso... | KEEP AS NON CORE | Summary: Wnt signalosome localization - scaffold role. Reason: Wnt signalosome localization - scaffold role. Supporting Evidence: PMID:22899650 Aug 16. LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6. |
| GO:0005783 endoplasmic reticulum | IDA PMID:19640926 LRRK2 regulates autophagic activity and localizes to specifi... | ACCEPT | Summary: Endoplasmic reticulum - documented localization at ER exit sites. Reason: Endoplasmic reticulum - documented localization at ER exit sites. Supporting Evidence: PMID:19640926 Jul 29. LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model. |
| GO:0005902 microvillus | IDA PMID:19640926 LRRK2 regulates autophagic activity and localizes to specifi... | KEEP AS NON CORE | Summary: Microvillus - specific localization. Reason: Microvillus - specific localization. Supporting Evidence: PMID:19640926 Jul 29. LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model. |
| GO:0016242 negative regulation of macroautophagy | IMP PMID:19640926 LRRK2 regulates autophagic activity and localizes to specifi... | MARK AS OVER ANNOTATED | Summary: Negative regulation of macroautophagy is downstream of trafficking effects. Reason: Negative regulation of macroautophagy is downstream of trafficking effects. Supporting Evidence: PMID:19640926 Jul 29. LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model. |
| GO:0044753 amphisome | IDA PMID:19640926 LRRK2 regulates autophagic activity and localizes to specifi... | KEEP AS NON CORE | Summary: Amphisome - autophagy-related. Reason: Amphisome - autophagy-related. Supporting Evidence: PMID:19640926 Jul 29. LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model. |
| GO:0044754 autolysosome | IDA PMID:19640926 LRRK2 regulates autophagic activity and localizes to specifi... | KEEP AS NON CORE | Summary: Autolysosome - autophagy-related. Reason: Autolysosome - autophagy-related. Supporting Evidence: PMID:19640926 Jul 29. LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model. |
| GO:0097487 multivesicular body, internal vesicle | IDA PMID:19640926 LRRK2 regulates autophagic activity and localizes to specifi... | KEEP AS NON CORE | Summary: Multivesicular body, internal vesicle - endosomal. Reason: Multivesicular body, internal vesicle - endosomal. Supporting Evidence: PMID:19640926 Jul 29. LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model. |
| GO:0005886 plasma membrane | IDA PMID:22899650 LRRK2 functions as a Wnt signaling scaffold, bridging cytoso... | KEEP AS NON CORE | Summary: Plasma membrane - LRRK2 can localize to membranes but cytosol is predominant. Reason: Plasma membrane - LRRK2 can localize to membranes but cytosol is predominant. Supporting Evidence: PMID:22899650 Aug 16. LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6. |
| GO:0016301 kinase activity | IMP PMID:23916833 Inhibition of LRRK2 kinase activity stimulates macroautophag... | ACCEPT | Summary: Kinase activity is a core function - LRRK2 is a dual-function kinase/GTPase. Reason: Kinase activity is a core function - LRRK2 is a dual-function kinase/GTPase. Supporting Evidence: PMID:23916833 Inhibition of LRRK2 kinase activity stimulates macroautophagy. |
| GO:1902902 negative regulation of autophagosome assembly | IMP PMID:23916833 Inhibition of LRRK2 kinase activity stimulates macroautophag... | MARK AS OVER ANNOTATED | Summary: Negative regulation of autophagosome assembly is downstream effect. Reason: Negative regulation of autophagosome assembly is downstream effect. Supporting Evidence: PMID:23916833 Inhibition of LRRK2 kinase activity stimulates macroautophagy. |
| GO:0009267 cellular response to starvation | IMP PMID:24211199 Pathogenic Parkinson's disease mutations across the function... | MARK AS OVER ANNOTATED | Summary: Cellular response to starvation is experimental condition. Reason: Cellular response to starvation is experimental condition. Supporting Evidence: PMID:24211199 Pathogenic Parkinson's disease mutations across the functional domains of LRRK2 alter the autophagic/lysosomal response to starvation. |
| GO:0010506 regulation of autophagy | IMP PMID:24211199 Pathogenic Parkinson's disease mutations across the function... | MARK AS OVER ANNOTATED | Summary: Regulation of autophagy is downstream of trafficking/lysosomal effects. Reason: Regulation of autophagy is downstream of trafficking/lysosomal effects. Supporting Evidence: PMID:24211199 Pathogenic Parkinson's disease mutations across the functional domains of LRRK2 alter the autophagic/lysosomal response to starvation. |
| GO:0004674 protein serine/threonine kinase activity | TAS PMID:22899650 LRRK2 functions as a Wnt signaling scaffold, bridging cytoso... | ACCEPT | Summary: Protein serine/threonine kinase activity is a core enzymatic function of LRRK2. The kinase domain phosphorylates Rab GTPases at their switch II regions. Reason: Protein serine/threonine kinase activity is a core enzymatic function of LRRK2. The kinase domain phosphorylates Rab GTPases at their switch II regions. Supporting Evidence: PMID:22899650 Aug 16. LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6. |
| GO:0005525 GTP binding | TAS PMID:22899650 LRRK2 functions as a Wnt signaling scaffold, bridging cytoso... | ACCEPT | Summary: GTP binding is essential for LRRK2 ROC domain function and regulates kinase activity. Reason: GTP binding is essential for LRRK2 ROC domain function and regulates kinase activity. Supporting Evidence: PMID:22899650 Aug 16. LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6. |
| GO:0005829 cytosol | IDA PMID:22899650 LRRK2 functions as a Wnt signaling scaffold, bridging cytoso... | ACCEPT | Summary: Cytosol is the predominant localization of LRRK2, from which it is recruited to membranes. Reason: Cytosol is the predominant localization of LRRK2, from which it is recruited to membranes. Supporting Evidence: PMID:22899650 Aug 16. LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6. |
| GO:0004672 protein kinase activity | IDA PMID:25500533 Phosphorylation of LRRK2 by casein kinase 1Ξ± regulates trans... | ACCEPT | Summary: Protein kinase activity is a core function of LRRK2, phosphorylating Rab GTPases and other substrates. Reason: Protein kinase activity is a core function of LRRK2, phosphorylating Rab GTPases and other substrates. Supporting Evidence: PMID:25500533 Phosphorylation of LRRK2 by casein kinase 1Ξ± regulates trans-Golgi clustering via differential interaction with ARHGEF7. |
| GO:0005798 Golgi-associated vesicle | IDA PMID:24510904 Unbiased screen for interactors of leucine-rich repeat kinas... | ACCEPT | Summary: Golgi-associated vesicle - consistent with trafficking role. Reason: Golgi-associated vesicle - consistent with trafficking role. Supporting Evidence: PMID:24510904 Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease. |
| GO:0007030 Golgi organization | IMP PMID:24510904 Unbiased screen for interactors of leucine-rich repeat kinas... | ACCEPT | Summary: Golgi organization - LRRK2 regulates Golgi-related trafficking through Rab phosphorylation. Reason: Golgi organization - LRRK2 regulates Golgi-related trafficking through Rab phosphorylation. Supporting Evidence: PMID:24510904 Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease. |
| GO:0005737 cytoplasm | IDA PMID:19625296 Mutations in the LRRK2 Roc-COR tandem domain link Parkinson'... | ACCEPT | Summary: Cytoplasm is a major localization for LRRK2. Reason: Cytoplasm is a major localization for LRRK2. Supporting Evidence: PMID:19625296 Jul 22. Mutations in the LRRK2 Roc-COR tandem domain link Parkinson's disease to Wnt signalling pathways. |
| GO:0030426 growth cone | IDA PMID:19625296 Mutations in the LRRK2 Roc-COR tandem domain link Parkinson'... | KEEP AS NON CORE | Summary: Growth cone is tissue-specific neuronal structure. Reason: Growth cone is tissue-specific neuronal structure. Supporting Evidence: PMID:19625296 Jul 22. Mutations in the LRRK2 Roc-COR tandem domain link Parkinson's disease to Wnt signalling pathways. |
| GO:0043005 neuron projection | IDA PMID:19625296 Mutations in the LRRK2 Roc-COR tandem domain link Parkinson'... | KEEP AS NON CORE | Summary: Neuron projection is tissue-specific in neurons. Reason: Neuron projection is tissue-specific in neurons. Supporting Evidence: PMID:19625296 Jul 22. Mutations in the LRRK2 Roc-COR tandem domain link Parkinson's disease to Wnt signalling pathways. |
| GO:0090394 negative regulation of excitatory postsynaptic potential | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Negative regulation of excitatory postsynaptic potential - tissue-specific. Reason: Negative regulation of excitatory postsynaptic potential - tissue-specific. |
| GO:0007040 lysosome organization | IMP PMID:25416817 Dysregulation of lysosomal morphology by pathogenic LRRK2 is... | ACCEPT | Summary: Lysosome organization - consistent with endolysosomal trafficking role. Reason: Lysosome organization - consistent with endolysosomal trafficking role. Supporting Evidence: PMID:25416817 Dysregulation of lysosomal morphology by pathogenic LRRK2 is corrected by TPC2 inhibition. |
| GO:0019722 calcium-mediated signaling | IMP PMID:25416817 Dysregulation of lysosomal morphology by pathogenic LRRK2 is... | KEEP AS NON CORE | Summary: Calcium-mediated signaling - via NAADP pathway. Reason: Calcium-mediated signaling - via NAADP pathway. Supporting Evidence: PMID:25416817 Dysregulation of lysosomal morphology by pathogenic LRRK2 is corrected by TPC2 inhibition. |
| GO:0046039 GTP metabolic process | IDA PMID:21048939 ARHGEF7 (Beta-PIX) acts as guanine nucleotide exchange facto... | ACCEPT | Summary: GTP metabolic process - related to GTPase activity. Reason: GTP metabolic process - related to GTPase activity. Supporting Evidence: PMID:21048939 ARHGEF7 (Beta-PIX) acts as guanine nucleotide exchange factor for leucine-rich repeat kinase 2. |
| GO:0007005 mitochondrion organization | IMP PMID:22764206 Pharmacological rescue of mitochondrial deficits in iPSC-der... | MARK AS OVER ANNOTATED | Summary: Mitochondrion organization effects are likely secondary. Reason: Mitochondrion organization effects are likely secondary. Supporting Evidence: PMID:22764206 Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson's disease. |
| GO:0034599 cellular response to oxidative stress | IMP PMID:22764206 Pharmacological rescue of mitochondrial deficits in iPSC-der... | MARK AS OVER ANNOTATED | Summary: Cellular response to oxidative stress is a pleiotropic disease-related effect. Reason: Cellular response to oxidative stress is a pleiotropic disease-related effect. Supporting Evidence: PMID:22764206 Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson's disease. |
| GO:0051646 mitochondrion localization | IMP PMID:22764206 Pharmacological rescue of mitochondrial deficits in iPSC-der... | MARK AS OVER ANNOTATED | Summary: Mitochondrion localization effects are secondary. Reason: Mitochondrion localization effects are secondary. Supporting Evidence: PMID:22764206 Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson's disease. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8857565 | ACCEPT | Summary: Cytosol is the predominant localization of LRRK2, from which it is recruited to membranes. Reason: Cytosol is the predominant localization of LRRK2, from which it is recruited to membranes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8857577 | ACCEPT | Summary: Cytosol is the predominant localization of LRRK2, from which it is recruited to membranes. Reason: Cytosol is the predominant localization of LRRK2, from which it is recruited to membranes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8857583 | ACCEPT | Summary: Cytosol is the predominant localization of LRRK2, from which it is recruited to membranes. Reason: Cytosol is the predominant localization of LRRK2, from which it is recruited to membranes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9634702 | ACCEPT | Summary: Cytosol is the predominant localization of LRRK2, from which it is recruited to membranes. Reason: Cytosol is the predominant localization of LRRK2, from which it is recruited to membranes. |
| GO:0034599 cellular response to oxidative stress | IMP PMID:21857923 Dysregulated LRRK2 signaling in response to endoplasmic reti... | MARK AS OVER ANNOTATED | Summary: Cellular response to oxidative stress is a pleiotropic disease-related effect. Reason: Cellular response to oxidative stress is a pleiotropic disease-related effect. Supporting Evidence: PMID:21857923 Dysregulated LRRK2 signaling in response to endoplasmic reticulum stress leads to dopaminergic neuron degeneration in C. |
| GO:1902236 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway | IMP PMID:21857923 Dysregulated LRRK2 signaling in response to endoplasmic reti... | MARK AS OVER ANNOTATED | Summary: Negative regulation of ER stress-induced intrinsic apoptotic signaling pathway is disease-related. Reason: Negative regulation of ER stress-induced intrinsic apoptotic signaling pathway is disease-related. Supporting Evidence: PMID:21857923 Dysregulated LRRK2 signaling in response to endoplasmic reticulum stress leads to dopaminergic neuron degeneration in C. |
| GO:0014041 regulation of neuron maturation | IMP PMID:21168496 Adult neurogenesis and neurite outgrowth are impaired in LRR... | MARK AS OVER ANNOTATED | Summary: Regulation of neuron maturation is developmental. Reason: Regulation of neuron maturation is developmental. Supporting Evidence: PMID:21168496 2010 Dec 16. Adult neurogenesis and neurite outgrowth are impaired in LRRK2 G2019S mice. |
| GO:0021772 olfactory bulb development | IMP PMID:21168496 Adult neurogenesis and neurite outgrowth are impaired in LRR... | MARK AS OVER ANNOTATED | Summary: Olfactory bulb development is tissue-specific. Reason: Olfactory bulb development is tissue-specific. Supporting Evidence: PMID:21168496 2010 Dec 16. Adult neurogenesis and neurite outgrowth are impaired in LRRK2 G2019S mice. |
| GO:0022028 tangential migration from the subventricular zone to the olfactory bulb | IMP PMID:21168496 Adult neurogenesis and neurite outgrowth are impaired in LRR... | MARK AS OVER ANNOTATED | Summary: Tangential migration from subventricular zone is developmental. Reason: Tangential migration from subventricular zone is developmental. Supporting Evidence: PMID:21168496 2010 Dec 16. Adult neurogenesis and neurite outgrowth are impaired in LRRK2 G2019S mice. |
| GO:0061001 regulation of dendritic spine morphogenesis | IMP PMID:21168496 Adult neurogenesis and neurite outgrowth are impaired in LRR... | KEEP AS NON CORE | Summary: Regulation of dendritic spine morphogenesis - neuronal effect. Reason: Regulation of dendritic spine morphogenesis - neuronal effect. Supporting Evidence: PMID:21168496 2010 Dec 16. Adult neurogenesis and neurite outgrowth are impaired in LRRK2 G2019S mice. |
| GO:2000172 regulation of branching morphogenesis of a nerve | IMP PMID:21168496 Adult neurogenesis and neurite outgrowth are impaired in LRR... | MARK AS OVER ANNOTATED | Summary: Regulation of branching morphogenesis of a nerve is developmental. Reason: Regulation of branching morphogenesis of a nerve is developmental. Supporting Evidence: PMID:21168496 2010 Dec 16. Adult neurogenesis and neurite outgrowth are impaired in LRRK2 G2019S mice. |
| GO:0061001 regulation of dendritic spine morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Regulation of dendritic spine morphogenesis - neuronal effect. Reason: Regulation of dendritic spine morphogenesis - neuronal effect. |
| GO:0070585 protein localization to mitochondrion | TAS PMID:24252804 The role of oxidative stress in Parkinson's disease. | MARK AS OVER ANNOTATED | Summary: Protein localization to mitochondrion is secondary. Reason: Protein localization to mitochondrion is secondary. Supporting Evidence: PMID:24252804 The role of oxidative stress in Parkinson's disease. |
| GO:0090140 regulation of mitochondrial fission | TAS PMID:24252804 The role of oxidative stress in Parkinson's disease. | MARK AS OVER ANNOTATED | Summary: Regulation of mitochondrial fission is secondary effect. Reason: Regulation of mitochondrial fission is secondary effect. Supporting Evidence: PMID:24252804 The role of oxidative stress in Parkinson's disease. |
| GO:0043195 terminal bouton | TAS PMID:21563316 Synaptic vesicle trafficking and Parkinson's disease. | KEEP AS NON CORE | Summary: Terminal bouton is tissue-specific neuronal localization. Reason: Terminal bouton is tissue-specific neuronal localization. Supporting Evidence: PMID:21563316 Synaptic vesicle trafficking and Parkinson's disease. |
| GO:0071287 cellular response to manganese ion | IMP PMID:23628791 Down-regulation of LRRK2 in control and DAT transfected HEK ... | MARK AS OVER ANNOTATED | Summary: Cellular response to manganese ion is experimental. Reason: Cellular response to manganese ion is experimental. Supporting Evidence: PMID:23628791 2013 Apr 27. Down-regulation of LRRK2 in control and DAT transfected HEK cells increases manganese-induced oxidative stress and cell toxicity. |
| GO:1902803 regulation of synaptic vesicle transport | TAS PMID:21563316 Synaptic vesicle trafficking and Parkinson's disease. | KEEP AS NON CORE | Summary: Regulation of synaptic vesicle transport - tissue-specific. Reason: Regulation of synaptic vesicle transport - tissue-specific. Supporting Evidence: PMID:21563316 Synaptic vesicle trafficking and Parkinson's disease. |
| GO:1903351 cellular response to dopamine | IMP PMID:23628791 Down-regulation of LRRK2 in control and DAT transfected HEK ... | MARK AS OVER ANNOTATED | Summary: Cellular response to dopamine is tissue-specific. Reason: Cellular response to dopamine is tissue-specific. Supporting Evidence: PMID:23628791 2013 Apr 27. Down-regulation of LRRK2 in control and DAT transfected HEK cells increases manganese-induced oxidative stress and cell toxicity. |
| GO:0006897 endocytosis | IMP PMID:24576675 LRRK2, but not pathogenic mutants, protects against H2O2 str... | KEEP AS NON CORE | Summary: Endocytosis - related to synaptic vesicle endocytosis role. Reason: Endocytosis - related to synaptic vesicle endocytosis role. Supporting Evidence: PMID:24576675 LRRK2, but not pathogenic mutants, protects against H2O2 stress depending on mitochondrial function and endocytosis in a yeast model. |
| GO:0006897 endocytosis | IGI PMID:24576675 LRRK2, but not pathogenic mutants, protects against H2O2 str... | KEEP AS NON CORE | Summary: Endocytosis - related to synaptic vesicle endocytosis role. Reason: Endocytosis - related to synaptic vesicle endocytosis role. Supporting Evidence: PMID:24576675 LRRK2, but not pathogenic mutants, protects against H2O2 stress depending on mitochondrial function and endocytosis in a yeast model. |
| GO:0034599 cellular response to oxidative stress | IMP PMID:21362567 LRRK2 mutant iPSC-derived DA neurons demonstrate increased s... | MARK AS OVER ANNOTATED | Summary: Cellular response to oxidative stress is a pleiotropic disease-related effect. Reason: Cellular response to oxidative stress is a pleiotropic disease-related effect. Supporting Evidence: PMID:21362567 LRRK2 mutant iPSC-derived DA neurons demonstrate increased susceptibility to oxidative stress. |
| GO:0036479 peroxidase inhibitor activity | IDA PMID:21850687 Mutations in LRRK2 increase phosphorylation of peroxiredoxin... | UNDECIDED | Summary: Peroxidase inhibitor activity - reported but unclear if core function. Reason: Peroxidase inhibitor activity - reported but unclear if core function. Supporting Evidence: PMID:21850687 Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3 exacerbating oxidative stress-induced neuronal death. |
| GO:1903748 negative regulation of protein localization to mitochondrion | IDA PMID:21370995 Expression of leucine-rich repeat kinase 2 (LRRK2) inhibits ... | UNDECIDED | Summary: GO term GO:1903748 requires further review - no pre-defined decision available. Reason: Term not in curated decision list, requires manual review. Supporting Evidence: PMID:21370995 Expression of leucine-rich repeat kinase 2 (LRRK2) inhibits the processing of uMtCK to induce cell death in a cell culture model system. |
| GO:1902499 positive regulation of protein autoubiquitination | IDA PMID:16352719 Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, ... | KEEP AS NON CORE | Summary: Positive regulation of protein autoubiquitination - parkin-related. Reason: Positive regulation of protein autoubiquitination - parkin-related. Supporting Evidence: PMID:16352719 Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, and mutant LRRK2 induces neuronal degeneration. |
| GO:0044325 transmembrane transporter binding | IPI PMID:21370995 Expression of leucine-rich repeat kinase 2 (LRRK2) inhibits ... | KEEP AS NON CORE | Summary: Transmembrane transporter binding - various interactions. Reason: Transmembrane transporter binding - various interactions. Supporting Evidence: PMID:21370995 Expression of leucine-rich repeat kinase 2 (LRRK2) inhibits the processing of uMtCK to induce cell death in a cell culture model system. |
| GO:0010955 negative regulation of protein processing | IDA PMID:21370995 Expression of leucine-rich repeat kinase 2 (LRRK2) inhibits ... | KEEP AS NON CORE | Summary: Negative regulation of protein processing - specific effect. Reason: Negative regulation of protein processing - specific effect. Supporting Evidence: PMID:21370995 Expression of leucine-rich repeat kinase 2 (LRRK2) inhibits the processing of uMtCK to induce cell death in a cell culture model system. |
| GO:1903748 negative regulation of protein localization to mitochondrion | IC PMID:21370995 Expression of leucine-rich repeat kinase 2 (LRRK2) inhibits ... | UNDECIDED | Summary: GO term GO:1903748 requires further review - no pre-defined decision available. Reason: Term not in curated decision list, requires manual review. Supporting Evidence: PMID:21370995 Expression of leucine-rich repeat kinase 2 (LRRK2) inhibits the processing of uMtCK to induce cell death in a cell culture model system. |
| GO:0008104 intracellular protein localization | ISS GO_REF:0000024 | ACCEPT | Summary: Intracellular protein localization - broad but relevant to trafficking role. Reason: Intracellular protein localization - broad but relevant to trafficking role. |
| GO:0031398 positive regulation of protein ubiquitination | IDA PMID:20173330 LRRK2 and the stress response: interaction with MKKs and JNK... | KEEP AS NON CORE | Summary: Positive regulation of protein ubiquitination - related to parkin interaction. Reason: Positive regulation of protein ubiquitination - related to parkin interaction. Supporting Evidence: PMID:20173330 LRRK2 and the stress response: interaction with MKKs and JNK-interacting proteins. |
| GO:0035556 intracellular signal transduction | ISS GO_REF:0000024 | ACCEPT | Summary: Intracellular signal transduction - LRRK2 functions as a kinase that phosphorylates Rab GTPases. Reason: Intracellular signal transduction - LRRK2 functions as a kinase that phosphorylates Rab GTPases. |
| GO:0051966 regulation of synaptic transmission, glutamatergic | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Regulation of synaptic transmission, glutamatergic - tissue-specific. Reason: Regulation of synaptic transmission, glutamatergic - tissue-specific. |
| GO:0060079 excitatory postsynaptic potential | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Excitatory postsynaptic potential - tissue-specific. Reason: Excitatory postsynaptic potential - tissue-specific. |
| GO:0060159 regulation of dopamine receptor signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Regulation of dopamine receptor signaling pathway - tissue-specific. Reason: Regulation of dopamine receptor signaling pathway - tissue-specific. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:21850687 Mutations in LRRK2 increase phosphorylation of peroxiredoxin... | ACCEPT | Summary: Protein serine/threonine kinase activity is a core enzymatic function of LRRK2. The kinase domain phosphorylates Rab GTPases at their switch II regions. Reason: Protein serine/threonine kinase activity is a core enzymatic function of LRRK2. The kinase domain phosphorylates Rab GTPases at their switch II regions. Supporting Evidence: PMID:21850687 Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3 exacerbating oxidative stress-induced neuronal death. |
| GO:0005829 cytosol | IDA PMID:21850687 Mutations in LRRK2 increase phosphorylation of peroxiredoxin... | ACCEPT | Summary: Cytosol is the predominant localization of LRRK2, from which it is recruited to membranes. Reason: Cytosol is the predominant localization of LRRK2, from which it is recruited to membranes. Supporting Evidence: PMID:21850687 Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3 exacerbating oxidative stress-induced neuronal death. |
| GO:0005741 mitochondrial outer membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mitochondrial outer membrane - reported but may be minor. Reason: Mitochondrial outer membrane - reported but may be minor. |
| GO:0005743 mitochondrial inner membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mitochondrial inner membrane - reported but may be minor. Reason: Mitochondrial inner membrane - reported but may be minor. |
| GO:0005759 mitochondrial matrix | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mitochondrial matrix - reported but may be minor. Reason: Mitochondrial matrix - reported but may be minor. |
| GO:0005764 lysosome | ISS GO_REF:0000024 | ACCEPT | Summary: Lysosome localization is consistent with LRRK2 role in endolysosomal trafficking. Reason: Lysosome localization is consistent with LRRK2 role in endolysosomal trafficking. |
| GO:0005768 endosome | ISS GO_REF:0000024 | ACCEPT | Summary: Endosome localization is consistent with LRRK2 role in regulating Rab-dependent trafficking. Reason: Endosome localization is consistent with LRRK2 role in regulating Rab-dependent trafficking. |
| GO:0005783 endoplasmic reticulum | ISS GO_REF:0000024 | ACCEPT | Summary: Endoplasmic reticulum - documented localization at ER exit sites. Reason: Endoplasmic reticulum - documented localization at ER exit sites. |
| GO:0005794 Golgi apparatus | ISS GO_REF:0000024 | ACCEPT | Summary: Golgi apparatus localization is supported - LRRK2 is recruited to Golgi by Rab29. Reason: Golgi apparatus localization is supported - LRRK2 is recruited to Golgi by Rab29. |
| GO:0030424 axon | IDA PMID:17120249 Localization of LRRK2 to membranous and vesicular structures... | KEEP AS NON CORE | Summary: Axon localization is tissue-specific in neurons. Reason: Axon localization is tissue-specific in neurons. Supporting Evidence: PMID:17120249 Localization of LRRK2 to membranous and vesicular structures in mammalian brain. |
| GO:0030425 dendrite | IDA PMID:17120249 Localization of LRRK2 to membranous and vesicular structures... | KEEP AS NON CORE | Summary: Dendrite localization is tissue-specific in neurons, not a core localization. Reason: Dendrite localization is tissue-specific in neurons, not a core localization. Supporting Evidence: PMID:17120249 Localization of LRRK2 to membranous and vesicular structures in mammalian brain. |
| GO:0031410 cytoplasmic vesicle | ISS GO_REF:0000024 | ACCEPT | Summary: Cytoplasmic vesicle - consistent with trafficking role. Reason: Cytoplasmic vesicle - consistent with trafficking role. |
| GO:0043204 perikaryon | IDA PMID:17120249 Localization of LRRK2 to membranous and vesicular structures... | KEEP AS NON CORE | Summary: Perikaryon (neuronal cell body) is tissue-specific localization. Reason: Perikaryon (neuronal cell body) is tissue-specific localization. Supporting Evidence: PMID:17120249 Localization of LRRK2 to membranous and vesicular structures in mammalian brain. |
| GO:0016301 kinase activity | IDA PMID:17114044 The familial Parkinsonism gene LRRK2 regulates neurite proce... | ACCEPT | Summary: Kinase activity is a core function - LRRK2 is a dual-function kinase/GTPase. Reason: Kinase activity is a core function - LRRK2 is a dual-function kinase/GTPase. Supporting Evidence: PMID:17114044 The familial Parkinsonism gene LRRK2 regulates neurite process morphology. |
| GO:0030424 axon | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Axon localization is tissue-specific in neurons. Reason: Axon localization is tissue-specific in neurons. |
| GO:0030425 dendrite | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Dendrite localization is tissue-specific in neurons, not a core localization. Reason: Dendrite localization is tissue-specific in neurons, not a core localization. |
| GO:0043204 perikaryon | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Perikaryon (neuronal cell body) is tissue-specific localization. Reason: Perikaryon (neuronal cell body) is tissue-specific localization. |
| GO:0048812 neuron projection morphogenesis | IMP PMID:17114044 The familial Parkinsonism gene LRRK2 regulates neurite proce... | MARK AS OVER ANNOTATED | Summary: Neuron projection morphogenesis is developmental. Reason: Neuron projection morphogenesis is developmental. Supporting Evidence: PMID:17114044 The familial Parkinsonism gene LRRK2 regulates neurite process morphology. |
| GO:0000149 SNARE binding | IPI PMID:21307259 LRRK2 controls synaptic vesicle storage and mobilization wit... | KEEP AS NON CORE | Summary: SNARE binding - related to vesicle function. Reason: SNARE binding - related to vesicle function. Supporting Evidence: PMID:21307259 LRRK2 controls synaptic vesicle storage and mobilization within the recycling pool. |
| GO:0003779 actin binding | IPI PMID:21307259 LRRK2 controls synaptic vesicle storage and mobilization wit... | KEEP AS NON CORE | Summary: Actin binding - documented interaction. Reason: Actin binding - documented interaction. Supporting Evidence: PMID:21307259 LRRK2 controls synaptic vesicle storage and mobilization within the recycling pool. |
| GO:0017075 syntaxin-1 binding | IPI PMID:21307259 LRRK2 controls synaptic vesicle storage and mobilization wit... | KEEP AS NON CORE | Summary: Syntaxin-1 binding - vesicle-related. Reason: Syntaxin-1 binding - vesicle-related. Supporting Evidence: PMID:21307259 LRRK2 controls synaptic vesicle storage and mobilization within the recycling pool. |
| GO:0030276 clathrin binding | IPI PMID:21307259 LRRK2 controls synaptic vesicle storage and mobilization wit... | KEEP AS NON CORE | Summary: Clathrin binding - endocytosis-related. Reason: Clathrin binding - endocytosis-related. Supporting Evidence: PMID:21307259 LRRK2 controls synaptic vesicle storage and mobilization within the recycling pool. |
| GO:1902803 regulation of synaptic vesicle transport | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Regulation of synaptic vesicle transport - tissue-specific. Reason: Regulation of synaptic vesicle transport - tissue-specific. |
| GO:1902823 negative regulation of late endosome to lysosome transport | TAS PMID:23949442 LRRK2 phosphorylates Snapin and inhibits interaction of Snap... | KEEP AS NON CORE | Summary: Negative regulation of late endosome to lysosome transport - downstream effect. Reason: Negative regulation of late endosome to lysosome transport - downstream effect. Supporting Evidence: PMID:23949442 LRRK2 phosphorylates Snapin and inhibits interaction of Snapin with SNAP-25. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:23949442 LRRK2 phosphorylates Snapin and inhibits interaction of Snap... | ACCEPT | Summary: Protein serine/threonine kinase activity is a core enzymatic function of LRRK2. The kinase domain phosphorylates Rab GTPases at their switch II regions. Reason: Protein serine/threonine kinase activity is a core enzymatic function of LRRK2. The kinase domain phosphorylates Rab GTPases at their switch II regions. Supporting Evidence: PMID:23949442 LRRK2 phosphorylates Snapin and inhibits interaction of Snapin with SNAP-25. |
| GO:2000300 regulation of synaptic vesicle exocytosis | IMP PMID:23949442 LRRK2 phosphorylates Snapin and inhibits interaction of Snap... | KEEP AS NON CORE | Summary: Regulation of synaptic vesicle exocytosis - tissue-specific. Reason: Regulation of synaptic vesicle exocytosis - tissue-specific. Supporting Evidence: PMID:23949442 LRRK2 phosphorylates Snapin and inhibits interaction of Snapin with SNAP-25. |
| GO:0051900 regulation of mitochondrial depolarization | IMP PMID:22736029 G2019S leucine-rich repeat kinase 2 causes uncoupling protei... | MARK AS OVER ANNOTATED | Summary: Regulation of mitochondrial depolarization is disease-related. Reason: Regulation of mitochondrial depolarization is disease-related. Supporting Evidence: PMID:22736029 Jun 26. G2019S leucine-rich repeat kinase 2 causes uncoupling protein-mediated mitochondrial depolarization. |
| GO:0005829 cytosol | IDA PMID:24403142 Mutant LRRK2 toxicity in neurons depends on LRRK2 levels and... | ACCEPT | Summary: Cytosol is the predominant localization of LRRK2, from which it is recruited to membranes. Reason: Cytosol is the predominant localization of LRRK2, from which it is recruited to membranes. Supporting Evidence: PMID:24403142 Mutant LRRK2 toxicity in neurons depends on LRRK2 levels and synuclein but not kinase activity or inclusion bodies. |
| GO:0051018 protein kinase A binding | IPI PMID:24464040 LRRK2 regulates synaptogenesis and dopamine receptor activat... | KEEP AS NON CORE | Summary: Protein kinase A binding - interaction documented but not core. Reason: Protein kinase A binding - interaction documented but not core. Supporting Evidence: PMID:24464040 LRRK2 regulates synaptogenesis and dopamine receptor activation through modulation of PKA activity. |
| GO:0005829 cytosol | IDA PMID:22736029 G2019S leucine-rich repeat kinase 2 causes uncoupling protei... | ACCEPT | Summary: Cytosol is the predominant localization of LRRK2, from which it is recruited to membranes. Reason: Cytosol is the predominant localization of LRRK2, from which it is recruited to membranes. Supporting Evidence: PMID:22736029 Jun 26. G2019S leucine-rich repeat kinase 2 causes uncoupling protein-mediated mitochondrial depolarization. |
| GO:0031966 mitochondrial membrane | IDA PMID:22736029 G2019S leucine-rich repeat kinase 2 causes uncoupling protei... | KEEP AS NON CORE | Summary: Mitochondrial membrane - reported. Reason: Mitochondrial membrane - reported. Supporting Evidence: PMID:22736029 Jun 26. G2019S leucine-rich repeat kinase 2 causes uncoupling protein-mediated mitochondrial depolarization. |
| GO:1902692 regulation of neuroblast proliferation | IMP PMID:21168496 Adult neurogenesis and neurite outgrowth are impaired in LRR... | MARK AS OVER ANNOTATED | Summary: Regulation of neuroblast proliferation is developmental. Reason: Regulation of neuroblast proliferation is developmental. Supporting Evidence: PMID:21168496 2010 Dec 16. Adult neurogenesis and neurite outgrowth are impaired in LRRK2 G2019S mice. |
| GO:0005615 extracellular space | HDA PMID:22664934 Comparison of tear protein levels in breast cancer patients ... | KEEP AS NON CORE | Summary: Extracellular space - exosome secretion. Reason: Extracellular space - exosome secretion. Supporting Evidence: PMID:22664934 Comparison of tear protein levels in breast cancer patients and healthy controls using a de novo proteomic approach. |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: Extracellular exosome - secreted in exosomes. Reason: Extracellular exosome - secreted in exosomes. Supporting Evidence: PMID:19056867 2008 Dec 3. Large-scale proteomics and phosphoproteomics of urinary exosomes. |
| GO:0032839 dendrite cytoplasm | IDA PMID:21696411 LRRK2 expression in idiopathic and G2019S positive Parkinson... | KEEP AS NON CORE | Summary: Dendrite cytoplasm is tissue-specific. Reason: Dendrite cytoplasm is tissue-specific. Supporting Evidence: PMID:21696411 LRRK2 expression in idiopathic and G2019S positive Parkinson's disease subjects: a morphological and quantitative study. |
| GO:0043025 neuronal cell body | IDA PMID:21696411 LRRK2 expression in idiopathic and G2019S positive Parkinson... | KEEP AS NON CORE | Summary: Neuronal cell body is tissue-specific localization. Reason: Neuronal cell body is tissue-specific localization. Supporting Evidence: PMID:21696411 LRRK2 expression in idiopathic and G2019S positive Parkinson's disease subjects: a morphological and quantitative study. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:22423108 ArfGAP1 is a GTPase activating protein for LRRK2: reciprocal... | ACCEPT | Summary: Protein serine/threonine kinase activity is a core enzymatic function of LRRK2. The kinase domain phosphorylates Rab GTPases at their switch II regions. Reason: Protein serine/threonine kinase activity is a core enzymatic function of LRRK2. The kinase domain phosphorylates Rab GTPases at their switch II regions. Supporting Evidence: PMID:22423108 ArfGAP1 is a GTPase activating protein for LRRK2: reciprocal regulation of ArfGAP1 by LRRK2. |
| GO:0034260 negative regulation of GTPase activity | IDA PMID:22423108 ArfGAP1 is a GTPase activating protein for LRRK2: reciprocal... | UNDECIDED | Summary: Negative regulation of GTPase activity - needs verification. Reason: Negative regulation of GTPase activity - needs verification. Supporting Evidence: PMID:22423108 ArfGAP1 is a GTPase activating protein for LRRK2: reciprocal regulation of ArfGAP1 by LRRK2. |
| GO:0010508 positive regulation of autophagy | IMP PMID:22012985 Leucine-rich repeat kinase 2 regulates autophagy through a c... | MARK AS OVER ANNOTATED | Summary: Positive regulation of autophagy is a downstream effect of trafficking disruption, not core function. Reason: Positive regulation of autophagy is a downstream effect of trafficking disruption, not core function. Supporting Evidence: PMID:22012985 Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP. |
| GO:0044325 transmembrane transporter binding | IPI PMID:22012985 Leucine-rich repeat kinase 2 regulates autophagy through a c... | KEEP AS NON CORE | Summary: Transmembrane transporter binding - various interactions. Reason: Transmembrane transporter binding - various interactions. Supporting Evidence: PMID:22012985 Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP. |
| GO:0003924 GTPase activity | IDA PMID:21048939 ARHGEF7 (Beta-PIX) acts as guanine nucleotide exchange facto... | ACCEPT | Summary: GTPase activity is a core function of LRRK2 ROC domain. The ROC domain binds and hydrolyzes GTP. Reason: GTPase activity is a core function of LRRK2 ROC domain. The ROC domain binds and hydrolyzes GTP. Supporting Evidence: PMID:21048939 ARHGEF7 (Beta-PIX) acts as guanine nucleotide exchange factor for leucine-rich repeat kinase 2. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:21048939 ARHGEF7 (Beta-PIX) acts as guanine nucleotide exchange facto... | ACCEPT | Summary: Protein serine/threonine kinase activity is a core enzymatic function of LRRK2. The kinase domain phosphorylates Rab GTPases at their switch II regions. Reason: Protein serine/threonine kinase activity is a core enzymatic function of LRRK2. The kinase domain phosphorylates Rab GTPases at their switch II regions. Supporting Evidence: PMID:21048939 ARHGEF7 (Beta-PIX) acts as guanine nucleotide exchange factor for leucine-rich repeat kinase 2. |
| GO:0031267 small GTPase binding | IPI PMID:21048939 ARHGEF7 (Beta-PIX) acts as guanine nucleotide exchange facto... | ACCEPT | Summary: Small GTPase binding - LRRK2 binds Rab substrates and other small GTPases. Reason: Small GTPase binding - LRRK2 binds Rab substrates and other small GTPases. Supporting Evidence: PMID:21048939 ARHGEF7 (Beta-PIX) acts as guanine nucleotide exchange factor for leucine-rich repeat kinase 2. |
| GO:0043005 neuron projection | IDA PMID:21048939 ARHGEF7 (Beta-PIX) acts as guanine nucleotide exchange facto... | KEEP AS NON CORE | Summary: Neuron projection is tissue-specific in neurons. Reason: Neuron projection is tissue-specific in neurons. Supporting Evidence: PMID:21048939 ARHGEF7 (Beta-PIX) acts as guanine nucleotide exchange factor for leucine-rich repeat kinase 2. |
| GO:0043025 neuronal cell body | IDA PMID:21048939 ARHGEF7 (Beta-PIX) acts as guanine nucleotide exchange facto... | KEEP AS NON CORE | Summary: Neuronal cell body is tissue-specific localization. Reason: Neuronal cell body is tissue-specific localization. Supporting Evidence: PMID:21048939 ARHGEF7 (Beta-PIX) acts as guanine nucleotide exchange factor for leucine-rich repeat kinase 2. |
| GO:0004672 protein kinase activity | IDA PMID:21850687 Mutations in LRRK2 increase phosphorylation of peroxiredoxin... | ACCEPT | Summary: Protein kinase activity is a core function of LRRK2, phosphorylating Rab GTPases and other substrates. Reason: Protein kinase activity is a core function of LRRK2, phosphorylating Rab GTPases and other substrates. Supporting Evidence: PMID:21850687 Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3 exacerbating oxidative stress-induced neuronal death. |
| GO:0005739 mitochondrion | IDA PMID:21850687 Mutations in LRRK2 increase phosphorylation of peroxiredoxin... | KEEP AS NON CORE | Summary: Mitochondrion - reported but not primary localization. Reason: Mitochondrion - reported but not primary localization. Supporting Evidence: PMID:21850687 Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3 exacerbating oxidative stress-induced neuronal death. |
| GO:0035640 exploration behavior | IMP PMID:20659558 Impaired dopaminergic neurotransmission and microtubule-asso... | MARK AS OVER ANNOTATED | Summary: Exploration behavior is a high-level organismal phenotype. Reason: Exploration behavior is a high-level organismal phenotype. Supporting Evidence: PMID:20659558 2010 Jul 24. Impaired dopaminergic neurotransmission and microtubule-associated protein tau alterations in human LRRK2 transgenic mice. |
| GO:0060161 positive regulation of dopamine receptor signaling pathway | IMP PMID:20659558 Impaired dopaminergic neurotransmission and microtubule-asso... | KEEP AS NON CORE | Summary: Positive regulation of dopamine receptor signaling pathway - tissue-specific. Reason: Positive regulation of dopamine receptor signaling pathway - tissue-specific. Supporting Evidence: PMID:20659558 2010 Jul 24. Impaired dopaminergic neurotransmission and microtubule-associated protein tau alterations in human LRRK2 transgenic mice. |
| GO:0010508 positive regulation of autophagy | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Positive regulation of autophagy is a downstream effect of trafficking disruption, not core function. Reason: Positive regulation of autophagy is a downstream effect of trafficking disruption, not core function. |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of proteasomal ubiquitin-dependent protein catabolic process - downstream. Reason: Positive regulation of proteasomal ubiquitin-dependent protein catabolic process - downstream. |
| GO:0035564 regulation of kidney size | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Regulation of kidney size is tissue-specific. Reason: Regulation of kidney size is tissue-specific. |
| GO:0005515 protein binding | IPI PMID:21159966 LRRK2 kinase regulates synaptic morphology through distinct ... | KEEP AS NON CORE | Summary: Protein binding is uninformative - LRRK2 has many documented interactors. Reason: Protein binding is uninformative - LRRK2 has many documented interactors. Supporting Evidence: PMID:21159966 LRRK2 kinase regulates synaptic morphology through distinct substrates at the presynaptic and postsynaptic compartments of the Drosophila neuromuscular junction. |
| GO:0015631 tubulin binding | IDA PMID:21159966 LRRK2 kinase regulates synaptic morphology through distinct ... | KEEP AS NON CORE | Summary: Tubulin binding - documented but not core function. Reason: Tubulin binding - documented but not core function. Supporting Evidence: PMID:21159966 LRRK2 kinase regulates synaptic morphology through distinct substrates at the presynaptic and postsynaptic compartments of the Drosophila neuromuscular junction. |
| GO:0042391 regulation of membrane potential | IMP PMID:21159966 LRRK2 kinase regulates synaptic morphology through distinct ... | KEEP AS NON CORE | Summary: Regulation of membrane potential - neuronal effect. Reason: Regulation of membrane potential - neuronal effect. Supporting Evidence: PMID:21159966 LRRK2 kinase regulates synaptic morphology through distinct substrates at the presynaptic and postsynaptic compartments of the Drosophila neuromuscular junction. |
| GO:0048312 intracellular distribution of mitochondria | IMP PMID:21159966 LRRK2 kinase regulates synaptic morphology through distinct ... | MARK AS OVER ANNOTATED | Summary: Intracellular distribution of mitochondria is secondary. Reason: Intracellular distribution of mitochondria is secondary. Supporting Evidence: PMID:21159966 LRRK2 kinase regulates synaptic morphology through distinct substrates at the presynaptic and postsynaptic compartments of the Drosophila neuromuscular junction. |
| GO:0007528 neuromuscular junction development | IMP PMID:21159966 LRRK2 kinase regulates synaptic morphology through distinct ... | MARK AS OVER ANNOTATED | Summary: Neuromuscular junction development is tissue-specific. Reason: Neuromuscular junction development is tissue-specific. Supporting Evidence: PMID:21159966 LRRK2 kinase regulates synaptic morphology through distinct substrates at the presynaptic and postsynaptic compartments of the Drosophila neuromuscular junction. |
| GO:0005525 GTP binding | IDA PMID:17260967 GTP binding is essential to the protein kinase activity of L... | ACCEPT | Summary: GTP binding is essential for LRRK2 ROC domain function and regulates kinase activity. Reason: GTP binding is essential for LRRK2 ROC domain function and regulates kinase activity. Supporting Evidence: PMID:17260967 GTP binding is essential to the protein kinase activity of LRRK2, a causative gene product for familial Parkinson's disease. |
| GO:0034211 GTP-dependent protein kinase activity | IDA PMID:17260967 GTP binding is essential to the protein kinase activity of L... | ACCEPT | Summary: GTP-dependent protein kinase activity reflects the intramolecular regulation between ROC GTPase and kinase domains. Reason: GTP-dependent protein kinase activity reflects the intramolecular regulation between ROC GTPase and kinase domains. Supporting Evidence: PMID:17260967 GTP binding is essential to the protein kinase activity of LRRK2, a causative gene product for familial Parkinson's disease. |
| GO:0006979 response to oxidative stress | IMP PMID:19692353 Leucine-Rich Repeat Kinase 2 interacts with Parkin, DJ-1 and... | MARK AS OVER ANNOTATED | Summary: Response to oxidative stress is pleiotropic/disease-related. Reason: Response to oxidative stress is pleiotropic/disease-related. Supporting Evidence: PMID:19692353 Aug 19. Leucine-Rich Repeat Kinase 2 interacts with Parkin, DJ-1 and PINK-1 in a Drosophila melanogaster model of Parkinson's disease. |
| GO:0008340 determination of adult lifespan | IMP PMID:19692353 Leucine-Rich Repeat Kinase 2 interacts with Parkin, DJ-1 and... | MARK AS OVER ANNOTATED | Summary: Determination of adult lifespan is pleiotropic. Reason: Determination of adult lifespan is pleiotropic. Supporting Evidence: PMID:19692353 Aug 19. Leucine-Rich Repeat Kinase 2 interacts with Parkin, DJ-1 and PINK-1 in a Drosophila melanogaster model of Parkinson's disease. |
| GO:0040012 regulation of locomotion | IMP PMID:19692353 Leucine-Rich Repeat Kinase 2 interacts with Parkin, DJ-1 and... | MARK AS OVER ANNOTATED | Summary: Regulation of locomotion is high-level organismal phenotype. Reason: Regulation of locomotion is high-level organismal phenotype. Supporting Evidence: PMID:19692353 Aug 19. Leucine-Rich Repeat Kinase 2 interacts with Parkin, DJ-1 and PINK-1 in a Drosophila melanogaster model of Parkinson's disease. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:19576176 Lrrk2 phosphorylates alpha synuclein at serine 129: Parkinso... | ACCEPT | Summary: Protein serine/threonine kinase activity is a core enzymatic function of LRRK2. The kinase domain phosphorylates Rab GTPases at their switch II regions. Reason: Protein serine/threonine kinase activity is a core enzymatic function of LRRK2. The kinase domain phosphorylates Rab GTPases at their switch II regions. Supporting Evidence: PMID:19576176 Lrrk2 phosphorylates alpha synuclein at serine 129: Parkinson disease implications. |
| GO:0034211 GTP-dependent protein kinase activity | IMP PMID:17200152 Parkinson's disease-associated mutations in LRRK2 link enhan... | ACCEPT | Summary: GTP-dependent protein kinase activity reflects the intramolecular regulation between ROC GTPase and kinase domains. Reason: GTP-dependent protein kinase activity reflects the intramolecular regulation between ROC GTPase and kinase domains. Supporting Evidence: PMID:17200152 Jan 2. Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity. |
| GO:0000165 MAPK cascade | IDA PMID:17200152 Parkinson's disease-associated mutations in LRRK2 link enhan... | UNDECIDED | Summary: MAPK cascade - reported but may be downstream effect. Reason: MAPK cascade - reported but may be downstream effect. Supporting Evidence: PMID:17200152 Jan 2. Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity. |
| GO:0004672 protein kinase activity | IDA PMID:16269541 Parkinson's disease-associated mutations in leucine-rich rep... | ACCEPT | Summary: Protein kinase activity is a core function of LRRK2, phosphorylating Rab GTPases and other substrates. Reason: Protein kinase activity is a core function of LRRK2, phosphorylating Rab GTPases and other substrates. Supporting Evidence: PMID:16269541 Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. |
| GO:0004672 protein kinase activity | IDA PMID:17442267 The R1441C mutation of LRRK2 disrupts GTP hydrolysis. | ACCEPT | Summary: Protein kinase activity is a core function of LRRK2, phosphorylating Rab GTPases and other substrates. Reason: Protein kinase activity is a core function of LRRK2, phosphorylating Rab GTPases and other substrates. Supporting Evidence: PMID:17442267 The R1441C mutation of LRRK2 disrupts GTP hydrolysis. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:17200152 Parkinson's disease-associated mutations in LRRK2 link enhan... | ACCEPT | Summary: Protein serine/threonine kinase activity is a core enzymatic function of LRRK2. The kinase domain phosphorylates Rab GTPases at their switch II regions. Reason: Protein serine/threonine kinase activity is a core enzymatic function of LRRK2. The kinase domain phosphorylates Rab GTPases at their switch II regions. Supporting Evidence: PMID:17200152 Jan 2. Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity. |
| GO:0005096 GTPase activator activity | IDA PMID:17442267 The R1441C mutation of LRRK2 disrupts GTP hydrolysis. | UNDECIDED | Summary: GTPase activator activity - LRRK2 has intrinsic GTPase activity but GAP activity on other GTPases is unclear. Reason: GTPase activator activity - LRRK2 has intrinsic GTPase activity but GAP activity on other GTPases is unclear. Supporting Evidence: PMID:17442267 The R1441C mutation of LRRK2 disrupts GTP hydrolysis. |
| GO:0005525 GTP binding | IDA PMID:16980962 Kinase activity of mutant LRRK2 mediates neuronal toxicity. | ACCEPT | Summary: GTP binding is essential for LRRK2 ROC domain function and regulates kinase activity. Reason: GTP binding is essential for LRRK2 ROC domain function and regulates kinase activity. Supporting Evidence: PMID:16980962 Kinase activity of mutant LRRK2 mediates neuronal toxicity. |
| GO:0005525 GTP binding | IDA PMID:17442267 The R1441C mutation of LRRK2 disrupts GTP hydrolysis. | ACCEPT | Summary: GTP binding is essential for LRRK2 ROC domain function and regulates kinase activity. Reason: GTP binding is essential for LRRK2 ROC domain function and regulates kinase activity. Supporting Evidence: PMID:17442267 The R1441C mutation of LRRK2 disrupts GTP hydrolysis. |
| GO:0032473 cytoplasmic side of mitochondrial outer membrane | IDA PMID:16269541 Parkinson's disease-associated mutations in leucine-rich rep... | KEEP AS NON CORE | Summary: Cytoplasmic side of mitochondrial outer membrane - reported. Reason: Cytoplasmic side of mitochondrial outer membrane - reported. Supporting Evidence: PMID:16269541 Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. |
| GO:0043068 positive regulation of programmed cell death | IDA PMID:17200152 Parkinson's disease-associated mutations in LRRK2 link enhan... | MARK AS OVER ANNOTATED | Summary: Positive regulation of programmed cell death is disease-related. Reason: Positive regulation of programmed cell death is disease-related. Supporting Evidence: PMID:17200152 Jan 2. Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity. |
| GO:0046777 protein autophosphorylation | IDA PMID:16269541 Parkinson's disease-associated mutations in leucine-rich rep... | ACCEPT | Summary: Protein autophosphorylation is well-documented for LRRK2, including Ser1292 as an activity marker. Reason: Protein autophosphorylation is well-documented for LRRK2, including Ser1292 as an activity marker. Supporting Evidence: PMID:16269541 Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. |
| GO:0046777 protein autophosphorylation | IMP PMID:16980962 Kinase activity of mutant LRRK2 mediates neuronal toxicity. | ACCEPT | Summary: Protein autophosphorylation is well-documented for LRRK2, including Ser1292 as an activity marker. Reason: Protein autophosphorylation is well-documented for LRRK2, including Ser1292 as an activity marker. Supporting Evidence: PMID:16980962 Kinase activity of mutant LRRK2 mediates neuronal toxicity. |
| GO:0046777 protein autophosphorylation | IDA PMID:17200152 Parkinson's disease-associated mutations in LRRK2 link enhan... | ACCEPT | Summary: Protein autophosphorylation is well-documented for LRRK2, including Ser1292 as an activity marker. Reason: Protein autophosphorylation is well-documented for LRRK2, including Ser1292 as an activity marker. Supporting Evidence: PMID:17200152 Jan 2. Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity. |
| GO:0046777 protein autophosphorylation | IDA PMID:17442267 The R1441C mutation of LRRK2 disrupts GTP hydrolysis. | ACCEPT | Summary: Protein autophosphorylation is well-documented for LRRK2, including Ser1292 as an activity marker. Reason: Protein autophosphorylation is well-documented for LRRK2, including Ser1292 as an activity marker. Supporting Evidence: PMID:17442267 The R1441C mutation of LRRK2 disrupts GTP hydrolysis. |
| GO:0004672 protein kinase activity | IDA PMID:16321986 The Parkinson disease causing LRRK2 mutation I2020T is assoc... | ACCEPT | Summary: Protein kinase activity is a core function of LRRK2, phosphorylating Rab GTPases and other substrates. Reason: Protein kinase activity is a core function of LRRK2, phosphorylating Rab GTPases and other substrates. Supporting Evidence: PMID:16321986 Dec 1. The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity. |
| GO:0005737 cytoplasm | IDA PMID:16321986 The Parkinson disease causing LRRK2 mutation I2020T is assoc... | ACCEPT | Summary: Cytoplasm is a major localization for LRRK2. Reason: Cytoplasm is a major localization for LRRK2. Supporting Evidence: PMID:16321986 Dec 1. The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity. |
| GO:0005737 cytoplasm | IDA PMID:16352719 Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, ... | ACCEPT | Summary: Cytoplasm is a major localization for LRRK2. Reason: Cytoplasm is a major localization for LRRK2. Supporting Evidence: PMID:16352719 Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, and mutant LRRK2 induces neuronal degeneration. |
| GO:0031398 positive regulation of protein ubiquitination | IDA PMID:16352719 Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, ... | KEEP AS NON CORE | Summary: Positive regulation of protein ubiquitination - related to parkin interaction. Reason: Positive regulation of protein ubiquitination - related to parkin interaction. Supporting Evidence: PMID:16352719 Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, and mutant LRRK2 induces neuronal degeneration. |
| GO:0042803 protein homodimerization activity | IPI PMID:16321986 The Parkinson disease causing LRRK2 mutation I2020T is assoc... | ACCEPT | Summary: Protein homodimerization activity - LRRK2 dimerization is well-documented. Reason: Protein homodimerization activity - LRRK2 dimerization is well-documented. Supporting Evidence: PMID:16321986 Dec 1. The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity. |
| GO:0046777 protein autophosphorylation | IDA PMID:16321986 The Parkinson disease causing LRRK2 mutation I2020T is assoc... | ACCEPT | Summary: Protein autophosphorylation is well-documented for LRRK2, including Ser1292 as an activity marker. Reason: Protein autophosphorylation is well-documented for LRRK2, including Ser1292 as an activity marker. Supporting Evidence: PMID:16321986 Dec 1. The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity. |
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)