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Protein Page:
LRRK2 (human)
p Phosphorylation
a Acetylation
m Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
u Ubiquitination
s Sumoylation
n Neddylation
gl O-GlcNAc
ga O-GalNAc
h Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage

Overview
LRRK2 a large multidomain protein kinase with a TKL-type kinase domain, multiple protein-protein interaction domains and a mitochondrial Rho domain (MIRO). May play a role in the etiology of Parkinson disease. May also have GTPase activity. Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway. The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes. Interacts with PARK2, PRDX3 and TPCN2. Expressed throughout the adult brain, but at a lower level than in heart and liver. Expressed in the cerebellum, cerebral cortex, medulla, spinal cord occipital pole, frontal lobe, temporal lobe and putamen. Expression is particularly high in brain dopaminoceptive areas. Defects in LRRK2 are the cause of Parkinson disease type 8 (PARK8). A slowly progressive neurodegenerative disorder characterized by bradykinesia, rigidity, resting tremor, postural instability, neuronal loss in the substantia nigra, and the presence of neurofibrillary MAPT (tau)-positive and Lewy bodies in some patients. Note: This description may include information from UniProtKB.
Protein type: Kinase, protein; EC 2.7.11.1; Protein kinase, Ser/Thr (non-receptor); Protein kinase, TKL; TKL group; LRRK family
Cellular Component: dendrite cytoplasm; extracellular space; synaptic vesicle; neuron projection; mitochondrion; cell soma; axon; cytoplasm; plasma membrane; trans-Golgi network; lipid raft
Molecular Function: GTPase activity; MAP kinase kinase activity; tubulin binding; identical protein binding; protein serine/threonine kinase activity; protein binding; GTP-dependent protein kinase activity; Rho GTPase binding; protein homodimerization activity; GTP binding; GTPase activator activity; ATP binding; protein kinase activity
Biological Process: activation of MAPKK activity; activation of MAPK activity; protein amino acid autophosphorylation; determination of adult life span; tangential migration from the subventricular zone to the olfactory bulb; negative regulation of neuroblast proliferation; GTP catabolic process; small GTPase mediated signal transduction; positive regulation of autophagy; neuromuscular junction development; positive regulation of dopamine receptor signaling pathway; olfactory bulb development; MAPKKK cascade; peptidyl-threonine phosphorylation; regulation of locomotion; peptidyl-serine phosphorylation; positive regulation of programmed cell death; regulation of membrane potential; negative regulation of neuron maturation; positive regulation of protein ubiquitination; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; intracellular distribution of mitochondria; autophagy; response to oxidative stress; positive regulation of protein amino acid phosphorylation; positive regulation of GTPase activity
Reference #:  Q5S007 (UniProtKB)
Alt. Names/Synonyms: augmented in rheumatoid arthritis 17; AURA17; Dardarin; leucine-rich repeat kinase 2; Leucine-rich repeat serine/threonine-protein kinase 2; LRRK2; PARK8; RIPK7; ROCO2
Gene Symbols: LRRK2
Molecular weight: 286,103 Da
Basal Isoelectric point: 6.35  Predict pI for various phosphorylation states
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

LRRK2

Protein Structure Not Found.

Substrate Sequence Logo
Sequence Logo

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Sites Implicated In
enzymatic activity, induced: T1410‑p, S2032‑p, T2035‑p
intracellular localization: S910‑p, S935‑p
molecular association, regulation: S910‑p, S935‑p, T1410‑p
phosphorylation: S910‑p, S935‑p

Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

 
1 0 S3-p _____MAsGsCQGCE
1 0 S5-p ___MAsGsCQGCEED
1 0 T424-p ASANALStLLEQNVN
0 2 T489-p AVVPKILtVMKRHET
1 0 T524-p PEESREDtEFHHKLN
0 2 Y636-p KILVSSLyRFKDVAE
1 0 T776-p QDVRKALtISIGKGD
1 0 T826-p GPLFPDKtSNLRKQt
2 0 T833-p tSNLRKQtNIAstLA
0 2 S837-p RKQtNIAstLARMVI
1 3 T838-p KQtNIAstLARMVIR
1 1 S850-p VIRYQMKsAVEEGTA
1 1 S858-p AVEEGTAsGsDGNFs
3 2 S860-p EEGTAsGsDGNFsED
0 1 S865-p sGsDGNFsEDVLSKF
0 1 S895-p AQSDDLDsEGsEGSF
0 1 S898-p DDLDsEGsEGSFLVK
1 2 S908-p SFLVKKKsNsIsVGE
9 6 S910-p LVKKKsNsIsVGEFY
0 2 S912-p KKKsNsIsVGEFYRD
1 1 S926-p DAVLQRCsPNLQRHs
1 1 S933-p sPNLQRHsNsLGPIF
12 9 S935-p NLQRHsNsLGPIFDH
1 2 S954-p KRKRKILssDDsLRS
5 4 S955-p RKRKILssDDsLRSs
1 2 S958-p KILssDDsLRSsKLQ
1 0 S962-p sDDsLRSsKLQSHMR
1 1 S971-p LQSHMRHsDsIssLA
5 5 S973-p SHMRHsDsIssLAsE
0 1 S975-p MRHsDsIssLAsERE
3 3 S976-p RHsDsIssLAsEREY
1 1 S979-p DsIssLAsEREYITS
1 0 T1024-p ELHQNALtsFPQQLC
1 0 S1025-p LHQNALtsFPQQLCE
0 2 S1058-p PSYLLKMsCIANLDV
1 0 S1124-p NKISGICsPLRLKEL
1 0 S1253-p RVEKLHLsHNKLKEI
1 0 S1283-p SYNLELRsFPNEMGK
3 0 S1292-p PNEMGKLsKIWDLPL
1 0 Y1332-p RLKKAVPyNRMKLMI
6 0 T1343-p KLMIVGNtGsGKttL
3 0 S1345-p MIVGNtGsGKttLLQ
5 0 T1348-p GNtGsGKttLLQQLM
1 0 T1349-p NtGsGKttLLQQLMK
3 1 T1357-p LLQQLMKtKKSDLGM
4 0 T1368-p DLGMQSAtVGIDVKD
1 0 Y1402-p FAGREEFystHPHFM
3 0 S1403-p AGREEFystHPHFMt
3 0 T1404-p GREEFystHPHFMtQ
4 0 T1410-p stHPHFMtQRALYLA
2 0 S1443-p FNIKARAsssPVILV
2 0 S1444-p NIKARAsssPVILVG
1 0 S1445-p IKARAsssPVILVGt
3 0 T1452-p sPVILVGtHLDVsDE
1 0 S1457-p VGtHLDVsDEKQRKA
1 1 S1467-p KQRKACMsKItKELL
1 0 T1470-p KACMsKItKELLNKR
1 0 Y1485-p GFPAIRDyHFVNAtE
7 0 T1491-p DyHFVNAtEESDALA
5 0 T1503-p ALAKLRKtIINEsLN
1 0 S1508-p RKtIINEsLNFKIRD
1 0 S1536-p ELEKIILsERKNVPI
1 0 T1612-p KIMAQILtVKVEGCP
1 0 S1647-p KFPKNYMsQYFKLLE
0 1 K1833 LLDDLMKKAEEGDLL
2 0 T1849-p NPDQPRLtIPIsQIA
1 0 S1853-p PRLtIPIsQIAPDLI
1 0 T1912-p VKIFNKHtsLRLLRQ
1 0 S1913-p KIFNKHtsLRLLRQE
0 1 K1963 DRLLQQDKASLtRtL
2 0 T1967-p QQDKASLtRtLQHRI
2 0 T1969-p DKASLtRtLQHRIAL
0 8 Y2023-p ADYGIAQyCCRMGIK
4 0 T2031-p CCRMGIKtsEGtPGF
4 0 S2032-p CRMGIKtsEGtPGFR
4 0 T2035-p GIKtsEGtPGFRAPE
0 1 K2091 DELEIQGKLPDPVKE
1 0 S2166-p HHNSRNAsIWLGCGH
1 0 S2257-p CNSFSKQsKQKNFLL
1 0 T2483-p NRKNTEGtQKQKEIQ
1 0 T2524-p LAEKMRRtSVE____
  mouse

 
S3 _____MASGACQGCE
A5 ___MASGACQGCEEE
T426 AAAHALSTLLEQNVN
T491 AVVPKILTVMKAHGT
S526 LEESREDSQCRPNVL
Q636 KILASTLQRFKDVAE
T776 QDVRKALTVSIQKGD
S826 GPLFPDKSSNLRKQT
T833 SSNLRKQTNTGSVLA
S837 RKQTNTGSVLARKVL
V838 KQTNTGSVLARKVLR
N850 VLRYQMRNTLQEGVA
S858 TLQEGVASGsDGKFS
S860-p QEGVASGsDGKFSED
S865 SGsDGKFSEDALAKF
S895 GQSDDLDSEGSESSF
S898 DDLDSEGSESSFLVK
S908-p SFLVKRKsNsIsVGE
S910-p LVKRKsNsIsVGEVY
S912-p KRKsNsIsVGEVYRD
S926 DLALQRCSPNAQRHS
S933 SPNAQRHSNsLGPVF
S935-p NAQRHSNsLGPVFDH
S954-p RRKRKILssDEsLRS
S955-p RKRKILssDEsLRSS
S958-p KILssDEsLRSSRLP
S962 sDEsLRSSRLPSHMR
S971 LPSHMRQSDsSSsLA
S973-p SHMRQSDsSSsLASE
S975 MRQSDsSSsLASERE
S976-p RQSDsSSsLASEREH
S979 DsSSsLASEREHITS
T1024 ELHQNSLTSFPQQLC
S1025 LHQNSLTSFPQQLCE
P1058 PSFVLKMPRITNLDA
S1124 NKISGICSPLSLKEL
S1253 RVEKLHLSHNKLKEI
S1283 SYNLELRSFPNEMGK
S1292-p PNEMGKLsKIWDLPL
Y1332 RLKKAVPYNRMKLMI
T1343 KLMIVGNTGSGKTTL
S1345 MIVGNTGSGKTTLLQ
T1348 GNTGSGKTTLLQQLM
T1349 NTGSGKTTLLQQLMK
M1357 LLQQLMKMKKPELGM
T1368 ELGMQGATVGIDVRD
Y1402 FAGREEFYSTHPHFM
S1403 AGREEFYSTHPHFMT
T1404 GREEFYSTHPHFMTQ
T1410 STHPHFMTQRALYLA
S1443 FNIKARASSSPVILV
S1444 NIKARASSSPVILVG
S1445 IKARASSSPVILVGT
T1452 SPVILVGTHLDVSDE
S1457 VGTHLDVSDEKQRKA
S1467 KQRKACISKITKELL
T1470 KACISKITKELLNKR
Y1485 GFPTIRDYHFVNATE
T1491 DYHFVNATEESDALA
T1503 ALAKLRKTIINESLN
S1508 RKTIINESLNFKIRD
S1536 ELEKIILSERKAVPT
T1612 KVMAQILTVKVDGCL
M1647 RFPKNYMMQYFKLLE
K1833-u LLDELMKkAEEGDLL
T1849 NPDQPRLTIPISQIA
S1853 PRLTIPISQIAPDLI
T1912 VKIFNKHTSLRLLRQ
S1913 KIFNKHTSLRLLRQE
K1963-u DRLLQQDkASLTRTL
T1967 QQDkASLTRTLQHRI
T1969 DkASLTRTLQHRIAL
Y2023 ADYGIAQYCCRMGIK
T2031 CCRMGIKTSEGTPGF
S2032 CRMGIKTSEGTPGFR
T2035 GIKTSEGTPGFRAPE
K2091-u DELAIQGkLPDPVKE
T2166 NLNSKSATLWLGCGN
S2257 CNSLAKQSKQSNFLL
I2483 KRKSTEGIQEQKEIQ
T2524 LADKMRKTSVE____
  rat

 
S3 _____MASGACQGCD
A5 ___MASGACQGCDEE
T425 AAAHALSTLLEQNVN
T490 AVIPKILTVMRTHGT
S525 SEDSRDDSRCQPNVL
Q635 KILASTLQRFKDVAE
T775 QDVRKALTVSIQKGD
S825 GPLFPDKSSNLRKQT
T832 SSNLRKQTNAGSVLA
S836 RKQTNAGSVLARKVL
V837 KQTNAGSVLARKVLR
N849 VLRYQMRNTLQEGVA
S857 TLQEGVASGSEGNFS
S859 QEGVASGSEGNFSED
S864 SGSEGNFSEDALAKF
S894 GQSDDLDSEGSESSF
S897 DDLDSEGSESSFLVK
S907 SFLVKKKSNSVSVGE
S909 LVKKKSNSVSVGEVY
S911 KKKSNSVSVGEVYRD
S925 DLALQRCSPNAQRHS
S932 SPNAQRHSSSLGPVF
S934 NAQRHSSSLGPVFDH
S953 RRKRKILSSDESLRS
S954 RKRKILSSDESLRSS
S957 KILSSDESLRSSRLQ
S961 SDESLRSSRLQSHTR
S970 LQSHTRQSDSSSSLA
S972 SHTRQSDSSSSLASE
S974 TRQSDSSSSLASERE
S975 RQSDSSSSLASEREH
S978 DSSSSLASEREHITS
T1023 ELHQNSLTSFPQQLC
S1024 LHQNSLTSFPQQLCE
P1057 PSFMLKMPSVIHLDA
S1123 NKISGICSPLSLKEL
S1252 RVEKLHLSHNKLKEI
S1282 SYNLELRSFPNEMGK
S1291 PNEMGKLSKIWDLPL
Y1331 RLKKAVPYNRMKLMI
T1342 KLMIVGNTGSGKTTL
S1344 MIVGNTGSGKTTLLQ
T1347 GNTGSGKTTLLQQLM
T1348 NTGSGKTTLLQQLMK
M1356 LLQQLMKMKKSELGM
T1367 ELGMQGATVGIDVRD
Y1401 FAGREEFYSTHPHFM
S1402 AGREEFYSTHPHFMT
T1403 GREEFYSTHPHFMTQ
T1409 STHPHFMTQRALYLA
S1442 FNIKARASSSPVILV
S1443 NIKARASSSPVILVG
S1444 IKARASSSPVILVGT
T1451 SPVILVGTHLDVSDE
S1456 VGTHLDVSDEKQRKA
G1466 KQRKACIGKITKELL
T1469 KACIGKITKELLNKR
Y1484 GFPTIRDYHFVNATE
T1490 DYHFVNATEESDALA
T1502 ALAKLRKTIINESLN
S1507 RKTIINESLNFKIRD
S1535 ELEKIILSERKAVPT
T1611 KVMAQILTVKVDGCL
A1646 RFPKNYMAQYFKLLE
K1832 LLDELMKKAEEGDLL
T1848 NPDQPRLTIPISQIA
S1852 PRLTIPISQIAPDLI
T1911 VKIFNKHTSLRLLRQ
S1912 KIFNKHTSLRLLRQE
K1962 DRLLQQDKASLTRTL
T1966 QQDKASLTRTLQHRI
T1968 DKASLTRTLQHRIAL
Y2022 ADYGIAQYCCRMGIK
T2030 CCRMGIKTSEGTPGF
S2031 CRMGIKTSEGTPGFR
T2034 GIKTSEGTPGFRAPE
K2090 DELAIQGKLPDPVKE
T2165 NLNSKRATLWLGCGN
S2256 CNSFAKQSKQSHFLL
T2482 KRKSTEGTQEQKEIQ
T2523 LADKMRKTSVE____
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