| + |
LRRK2 | down-regulates activity 
phosphorylation
|
SNCA |
0.645 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249690 |
Ser129 |
NEAYEMPsEEGYQDY |
Homo sapiens |
|
| pmid |
sentence |
| 19576176 |
Here we show that full-length Lrrk2 or fragments containing its kinase domain have a significant capacity to phosphorylate recombinant alpha synuclein (Asyn) at serine 129. Such phosphorylated Asyn is the major component of pathological deposits in PD. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Parkinson |
| + |
LRRK2 |
phosphorylation
|
LRRK2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-188429 |
Ser1403 |
AGREEFYsTHPHFMT |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 19824698 |
We identified ser1403, thr1404, thr1410, thr1491 located within the roc domain, as well as thr1967 and thr1969 in the kinase domain, as the autophosphorylation sites. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-188433 |
Thr1404 |
GREEFYStHPHFMTQ |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 19824698 |
We identified ser1403, thr1404, thr1410, thr1491 located within the roc domain, as well as thr1967 and thr1969 in the kinase domain, as the autophosphorylation sites. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-188437 |
Thr1410 |
STHPHFMtQRALYLA |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 19824698 |
We identified ser1403, thr1404, thr1410, thr1491 located within the roc domain, as well as thr1967 and thr1969 in the kinase domain, as the autophosphorylation sites. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| Pathways: | Parkinson |
| + |
PRKACA | down-regulates activity
phosphorylation
|
LRRK2 |
0.415 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-237444 |
Ser1444 |
NIKARASsSPVILVG |
in vitro |
|
| pmid |
sentence |
| 24351927 |
Furthermore, our work establishes S1444 as a PKA-regulated 14-3-3 docking site.Strikingly, 14-3-3 binding to phospho-S1444 decreased LRRK2 kinase activity in vitro. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
LRRK2 | up-regulates 
phosphorylation
|
LRRK2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-166466 |
Ser2032 |
CRMGIKTsEGTPGFR |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 20595391 |
Three putative autophosphorylation sites (thr-2031, ser-2032, and thr-2035) have been identified within the activation segment of the lrrk2 kinase domain based on sequence homology to mixed-lineage kinases. Phosphorylation at one or more of these sites is critical for the kinase activity of lrrk2. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-188417 |
Thr1967 |
QQDKASLtRTLQHRI |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 19824698 |
We identified ser1403, thr1404, thr1410, thr1491 located within the roc domain, as well as thr1967 and thr1969 in the kinase domain, as the autophosphorylation sites. substitution of thr1969 located in close proximity to thr1967 had little effect on its kinase activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-188421 |
Thr1969 |
DKASLTRtLQHRIAL |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 19824698 |
We identified ser1403, thr1404, thr1410, thr1491 located within the roc domain, as well as thr1967 and thr1969 in the kinase domain, as the autophosphorylation sites. Substitution of thr1967, an autophosphorylation site located within the kinase domain, to ala caused a significant decrease in the kinase activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-166470 |
Thr2031 |
CCRMGIKtSEGTPGF |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 20595391 |
Three putative autophosphorylation sites (thr-2031, ser-2032, and thr-2035) have been identified within the activation segment of the lrrk2 kinase domain based on sequence homology to mixed-lineage kinases. Phosphorylation at one or more of these sites is critical for the kinase activity of lrrk2. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-166474 |
Thr2035 |
GIKTSEGtPGFRAPE |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 20595391 |
Three putative autophosphorylation sites (thr-2031, ser-2032, and thr-2035) have been identified within the activation segment of the lrrk2 kinase domain based on sequence homology to mixed-lineage kinases. Phosphorylation at one or more of these sites is critical for the kinase activity of lrrk2. |
|
| Publications: |
5 |
Organism: |
Homo Sapiens |
| Pathways: | Parkinson |
| + |
LRRK2 | up-regulates
phosphorylation
|
AKT1 |
0.387 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-174044 |
Ser473 |
RPHFPQFsYSASGTA |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 21658387 |
A knockdown experiment using intact cells also demonstrated LRRK2-mediated phosphorylation of Akt1 (Ser473), suggesting that Akt1 is a convincing candidate for the physiological substrate of LRRK2. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252598 |
Ser473 |
RPHFPQFsYSASGTA |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 24916379 |
Expression of wild-type LRRK2 promoted neuronal survival against apoptosis through activation of the downstream effector, Akt by phosphorylation of Ser473. Phosphorylated Akt in turn inhibited FOXO 1 signaling |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Parkinson |
| + |
LRRK2 | up-regulates
phosphorylation
|
AKT |
0.387 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-205115 |
Ser473 |
RPHFPQFsYSASGTA |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 24916379 |
Expression of wild-type LRRK2 promoted neuronal survival against apoptosis through activation of the downstream effector, Akt by phosphorylation of Ser473. Phosphorylated Akt in turn inhibited FOXO 1 signaling |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244410 |
|
|
Homo sapiens |
Neuron |
| pmid |
sentence |
| 21658387 |
Lrrk2 directly phosphorylates akt1 as a possible physiological substrate. These data establish that lrrk2 can protect neurons from apoptotic insult through a survival pathway in which lrrk2 signals to activate akt. Lrrk2-mediated phosphorylation of akt1 (ser473) |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
LRRK2 | down-regulates
phosphorylation
|
SH3GL2 |
0.484 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-192072 |
Ser75 |
LSMINTMsKIRGQEK |
Homo sapiens |
|
| pmid |
sentence |
| 22998870 |
We show that lrrk2 affects synaptic endocytosis by phosphorylating endophilin-a1 at s75. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-192075 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22998870 |
We show that lrrk2 affects synaptic endocytosis by phosphorylating endoa at s75, a residue in the bar domain / our work uncovers a regulatory mechanism that indicates that reduced lrrk2 kinase activity facilitates endoa membrane association, while increased kinase activity inhibits membrane association. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
LRRK2 | down-regulates
phosphorylation
|
SNAPIN |
0.53 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-202436 |
Thr117 |
NHSVAKEtARRRAML |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 23949442 |
Lrrk2 phosphorylates snapin and inhibits interaction of snapin with snap-25. these data suggest that lrrk2 may regulate neurotransmitter release via control of snapin function by inhibitory phosphorylation. hreonine 117 of snapin is one of the sites phosphorylated by lrrk2 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Brain |
| + |
LRRK2 | up-regulates
phosphorylation
|
ARHGEF7 |
0.468 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-169221 |
Thr127 |
KVLSSLVtLNKVTAD |
Homo sapiens |
|
| pmid |
sentence |
| 21048939 |
Arhgef7 is interacting with lrrk2 in vitro and in vivo. Lrrk2 phosphorylates arhgef7 in vitro.Two Threonine residues, t107 and t143, within the arhgef7 n-terminus were identified with high confidence |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-169225 |
Thr164 |
LGSQSLHtRTSKLFQ |
Homo sapiens |
|
| pmid |
sentence |
| 21048939 |
Arhgef7 is interacting with lrrk2 in vitro and in vivo. Lrrk2 phosphorylates arhgef7 in vitro.Two Threonine residues, t107 and t143, within the arhgef7 n-terminus were identified with high confidence |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
LRRK2 | down-regulates activity
phosphorylation
|
PRDX3 |
0.423 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262891 |
Thr146 |
SHLAWINtPRKNGGL |
Homo sapiens |
SH-SY5Y Cell |
| pmid |
sentence |
| 21850687 |
Here, we show that LRRK2 interacts with human peroxiredoxin 3 (PRDX3), a mitochondrial member of the antioxidant family of thioredoxin (Trx) peroxidases. Importantly, mutations in the LRRK2 kinase domain significantly increased phosphorylation of PRDX3 compared to wild-type. The increase in PRDX3 phosphorylation was associated with decreased peroxidase activity and increased death in LRRK2-expressing but not in LRRK2-depleted or vector-transfected neuronal cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
LRRK2 | down-regulates
phosphorylation
|
LRRK2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-188425 |
Thr1491 |
DYHFVNAtEESDALA |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 19824698 |
We identified ser1403, thr1404, thr1410, thr1491 located within the roc domain, as well as thr1967 and thr1969 in the kinase domain, as the autophosphorylation sites. eduction in the gtp-bound form of lrrk2 caused by t1491d mutation might have lowered the kinase activity, implicating the autophosphorylation of the roc domain in a negative feedback regulation of the kinase activity of lrrk2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Parkinson |
| + |
LRRK2 | down-regulates activity
phosphorylation
|
LARS1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277417 |
Thr293 |
NIFLVAAtLRPETMF |
in vitro |
|
| pmid |
sentence |
| 30411383 |
In this study, we elucidated that leucyl-tRNA synthetase (LRS) was an LRRK2 kinase substrate and identified T293 as an LRRK2 phosphorylation site. LRRK2-meidated LRS phosphorylation or G2019S can lead to impairment of LRS editing, increased ER stress, and accumulation of autophagy markers. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
LRRK2 | up-regulates activity
phosphorylation
|
MSN |
0.569 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-154498 |
Thr558 |
LGRDKYKtLRQIRQG |
Homo sapiens |
|
| pmid |
sentence |
| 17447891 |
This led to the discovery that moesin, a protein which anchors the actin cytoskeleton to the plasma membrane, is efficiently phosphorylated by lrrk2, at thr558. Moesin phosphorylation could be essential to support the cytoskeletal changes accompanying this process. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-39433 |
Thr558 |
LGRDKYKtLRQIRQG |
Homo sapiens |
|
| pmid |
sentence |
| 8537411 |
This led to the discovery that moesin, a protein which anchors the actin cytoskeleton to the plasma membrane, is efficiently phosphorylated by lrrk2, at thr558. Moesin phosphorylation could be essential to support the cytoskeletal changes accompanying this process. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
LRRK2 | up-regulates activity
phosphorylation
|
DNM1L |
0.586 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276495 |
Thr595 |
NWRGMLKtSKAEELL |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 23813973 |
LRRK2 G2019S directly bound to and phosphorylated Drp1 at Threonine595, whereas P110 treatment abolished this phosphorylation.Threonine595 phosphorylation of Drp1 by LRRK2 G2019S is required for Drp1-mediated mitochondrial fragmentation and excessive autophagy |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
LRRK2 | up-regulates activity
phosphorylation
|
RAB5B |
0.618 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276873 |
Thr6 |
tARPNGQP |
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 25605758 |
Using recombinant proteins, we show here that LRRK2 phosphorylates Rab5b at its Thr6 residue in in vitro kinase assays with mass spectrophotometry analysis. Phosphorylation of Rab5b by LRRK2 on the threonine residue was confirmed by western analysis using cells stably expressing LRRK2 G2019S. The phosphomimetic T6D mutant exhibited stronger GTPase activity than that of the wild-type Rab5b. In addition, phosphorylation of Rab5b by LRRK2 also exhibited GTPase activity stronger than that of the unphosphorylated Rab5b protein. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
LRRK2 | up-regulates activity
phosphorylation
|
NSF |
0.375 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277196 |
Thr645 |
RKLLIIGtTSRKDVL |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 26758690 |
LRRK2 phosphorylates full-length NSF at threonine 645 in the ATP binding pocket of D2 domain. Functionally, NSF phosphorylated by LRRK2 displays enhanced ATPase activity and increased rate of SNARE complex disassembling. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
LRRK2 | up-regulates activity
phosphorylation
|
RAB8A |
0.337 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260267 |
Thr72 |
AGQERFRtITTAYYR |
in vitro |
|
| pmid |
sentence |
| 32227113 |
In a screen for Rab8A kinases we identify TAK1 and MST3 kinases that can efficiently phosphorylate the Switch II residue Threonine72 (Thr72) in a similar manner as LRRK2 in vitro. |Overall our data suggests that the phosphorylation of Rab8A at Ser111 may influence Switch II-binding by regulators, thus disrupting interactions with its cognate GEF and moderately impairs its interaction with GAPs.|The antagonistic interplay between Ser111 phosphorylation and Thr72 phosphorylation is genetically concordant with how respective mutations in PINK1 and LRRK2 cause Parkinson’s disease |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
LRRK2 | down-regulates activity
phosphorylation
|
RAB10 |
0.337 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261277 |
Thr73 |
AGQERFHtITTSYYR |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 26824392 |
To investigate whether the phosphorylation of Rab10 by LRRK2 is direct, we performed an in vitro kinase assay using recombinant components. Notably, we found that both wt and LRRK2-G2019S, but neither kinase inactive D1994A mutant nor small molecule-inhibited LRRK2, efficiently phosphorylated Rab10, proving a direct kinase-substrate relationship (Figure 2C). Furthermore, incubation of Rab10 with LRRK2 followed by tryptic digestion and MS analysis unambiguously identified T73 as the major phosphorylation site (Figure 2—figure supplement 1B)|In pathogenic conditions, in which LRRK2 is hyperactive, RabGTPases have strongly diminished affinities for GDIs. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
LRRK2 | up-regulates activity
phosphorylation
|
MAP3K5 |
0.331 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277251 |
Thr825 |
LKISDFGtSKRLAGI |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 28888991 |
LRRK2 phosphorylated ASK1 at Thr832 that is adjacent to Thr845, which serves as an autophosphorylation site. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
LRRK2 | up-regulates quantity 
transcriptional regulation
|
CADPS2 |
0.297 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268928 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 28647363 |
This approach enabled us to disclose a differential effect of high levels of LRRK2 and aSyn on CADPS2 promoter activity. Specifically, CADPS2 transcriptional activity was enhanced by high cellular levels of LRRK2 and reduced by overexpression of aSyn. Consistently, CADPS2 mRNA levels were diminished in aSyn overexpressing cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
LRRK2 | up-regulates
binding
|
DVL3 |
0.493 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-202187 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23754980 |
Subsequent assays confirmed a direct interaction between the lrrk2 roccor domain and all three human dvl proteins, these data are consistent with a role for lrrk2 in the activation of canonical wnt signaling bringing dvl proteins to cellular membranes. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ARHGEF7 | up-regulates
binding
|
LRRK2 |
0.468 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-169217 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21048939 |
Arhgef7 is interacting with lrrk2 in vitro and in vivo. Gtpase activity of full-length lrrk2 increases in the presence of recombinant arhgef7. Arhgef7 might act as a guanine nucleotide exchange factor for lrrk2 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ARFGAP1 | up-regulates
binding
|
LRRK2 |
0.598 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-196264 |
|
|
Homo sapiens |
Neuron |
| pmid |
sentence |
| 22363216 |
The gtp hydrolysis activity of lrrk2 is markedly enhanced by arfgap1 supporting a role for arfgap1 as a gtpase-activating protein for lrrk2.Lrrk2 and arfgap1 interact in vitro in mammalian cells and in vivo in brain, and co-localize in the cytoplasm and at golgi membranes |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Brain |
| + |
LRRK2 | down-regulates
phosphorylation
|
SH3GL1 |
0.479 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-192068 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22998870 |
We show that lrrk2 affects synaptic endocytosis by phosphorylating endoa at s75, a residue in the bar domain / our work uncovers a regulatory mechanism that indicates that reduced lrrk2 kinase activity facilitates endoa membrane association, while increased kinase activity inhibits membrane association. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
LRRK2 | down-regulates
phosphorylation
|
MAPT |
0.545 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-195756 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22303461 |
Lrrk2 directly phosphorylates tubulin-associated tau, but not free tau;(iii) lrrk2 phosphorylates tau at thr181 as one of the target sites;. furthermore, we revealed that lrrk2-mediated phosphorylation of tau reduces its tubulin-binding ability. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
LRRK2 | down-regulates
phosphorylation
|
ARFGAP1 |
0.598 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-196732 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22423108 |
Arfgap1 is an lrrk2 kinase substrate whose gap activity is inhibited by lrrk2. The phosphorylation of arfgap1 by lrrk2 was subjected to mass spectrometry to determine the sites of phosphorylation. There was 95.3% coverage and serines(s155, s246, s284) and threonine (t189, t216, t292) are phosphorylated by lrrk2. Mutational analysis of these serine and threonine amino acids to alanine reveals that no single amino acid is the predominant phospho-amino acid. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-196267 |
|
|
Homo sapiens |
Neuron |
| pmid |
sentence |
| 22363216 |
Arfgap1 is an lrrk2 kinase substrate whose gap activity is inhibited by lrrk2. The phosphorylation of arfgap1 by lrrk2 was subjected to mass spectrometry to determine the sites of phosphorylation. There was 95.3% coverage and serines(s155, s246, s284) and threonine (t189, t216, t292) are phosphorylated by lrrk2. Mutational analysis of these serine and threonine amino acids to alanine reveals that no single amino acid is the predominant phospho-amino acid. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Tissue: |
Brain |
| + |
LRRK2 | up-regulates
|
Autophagy |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-237005 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 22012985 |
We report that LRRK2 activates a calcium-dependent protein kinase kinase-² (CaMKK-²)/adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway which is followed by a persistent increase in autophagosome formation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
3.0
LRRK2
- 
- 