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Protein Page:
LRRK2 (mouse)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitylation
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

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; Protein kinase, TKL; EC 2.7.11.1; Protein kinase, Ser/Thr (non-receptor); TKL group; LRRK family
Cellular Component: axon; caveola; cell soma; cytoplasm; cytoplasmic vesicle; cytosol; dendrite; dendrite cytoplasm; endoplasmic reticulum; endosome; extracellular space; Golgi apparatus; Golgi-associated vesicle; growth cone; inclusion body; intracellular; intracellular membrane-bound organelle; lipid raft; lysosome; membrane; microvillus; mitochondrial inner membrane; mitochondrial matrix; mitochondrial membrane; mitochondrial outer membrane; mitochondrion; neuron projection; perikaryon; plasma membrane; ribonucleoprotein complex; synapse; synaptic vesicle; terminal button; trans-Golgi network
Molecular Function: actin binding; clathrin binding; glycoprotein binding; GTP binding; GTP-dependent protein kinase activity; GTPase activator activity; GTPase activity; identical protein binding; kinase activity; MAP kinase kinase activity; protein binding; protein homodimerization activity; protein kinase A binding; protein kinase activity; protein serine/threonine kinase activity; receptor signaling complex scaffold activity; Rho GTPase binding; SNARE binding; syntaxin-1 binding; tubulin binding
Biological Process: activation of MAPK activity; activation of MAPKK activity; calcium-mediated signaling; cellular response to starvation; determination of adult life span; endocytosis; Golgi organization and biogenesis; GTP metabolic process; intracellular distribution of mitochondria; lysosome organization and biogenesis; MAPKKK cascade; mitochondrion localization; mitochondrion organization and biogenesis; negative regulation of macroautophagy; negative regulation of protein amino acid phosphorylation; negative regulation of protein binding; neurite morphogenesis; neuromuscular junction development; olfactory bulb development; peptidyl-serine phosphorylation; peptidyl-threonine phosphorylation; phosphorylation; positive regulation of autophagy; positive regulation of dopamine receptor signaling pathway; positive regulation of programmed cell death; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; positive regulation of protein amino acid phosphorylation; positive regulation of protein binding; positive regulation of protein ubiquitination; protein amino acid autophosphorylation; protein amino acid phosphorylation; regulation of autophagy; regulation of calcium-mediated signaling; regulation of dopamine receptor signaling pathway; regulation of excitatory postsynaptic membrane potential; regulation of locomotion; regulation of membrane potential; regulation of mitochondrial depolarization; regulation of neuron maturation; regulation of synaptic transmission, glutamatergic; response to oxidative stress; tangential migration from the subventricular zone to the olfactory bulb
Reference #:  Q5S006 (UniProtKB)
Alt. Names/Synonyms: 4921513O20Rik; 9330188B09Rik; AW561911; cI-46; D630001M17Rik; Gm927; leucine-rich repeat kinase 2; Leucine-rich repeat serine/threonine-protein kinase 2; Lrrk2; OTTMUSP00000022827
Gene Symbols: Lrrk2
Molecular weight: 284,732 Da
Basal Isoelectric point: 6.38  Predict pI for various phosphorylation states
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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LRRK2

Protein Structure Not Found.
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Substrate Sequence Logo
Sequence Logo

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Sites Implicated In
molecular association, regulation: 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



 LTP 

LTP: 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.


 HTP 

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


       mouse

 
1 0 S3 _____MASGACQGCE
1 0 A5 ___MASGACQGCEEE
0 1 V360 EPCYKALVRHRKDKH
1 0 T426 AAAHALSTLLEQNVN
0 2 T491 AVVPKILTVMKAHGT
0 1 T498 TVMKAHGTSLSVQLE
1 0 S526 LEESREDSQCRPNVL
0 1 S633 LLAKILASTLQRFKD
0 1 T634 LAKILASTLQRFKDV
0 1 Q636 KILASTLQRFKDVAE
0 1 E707 AKVAVDDELKNTMLE
1 0 T776 QDVRKALTVSIQKGD
0 1 S784 VSIQKGDSQVISLLL
0 1 S788 KGDSQVISLLLRKLA
1 0 S826 GPLFPDKSSNLRKQT
2 0 T833 SSNLRKQTNTGSVLA
0 2 S837 RKQTNTGSVLARKVL
1 3 V838 KQTNTGSVLARKVLR
1 1 N850 VLRYQMRNTLQEGVA
1 1 S858 TLQEGVASGsDGKFS
3 2 S860‑p QEGVASGsDGKFSED
0 1 S865 SGsDGKFSEDALAKF
0 1 S895 GQSDDLDSEGSESSF
0 1 S898 DDLDSEGSESSFLVK
1 3 S908 SFLVKRKSNsIsVGE
12 12 S910‑p LVKRKSNsIsVGEVY
0 2 S912‑p KRKSNsIsVGEVYRD
1 1 S926 DLALQRCSPNAQRHS
1 1 S933 SPNAQRHSNsLGPVF
17 15 S935‑p NAQRHSNsLGPVFDH
1 3 S954‑p RRKRKILssDEsLRS
7 5 S955‑p RKRKILssDEsLRSS
1 3 S958‑p KILssDEsLRSSRLP
1 0 S962 sDEsLRSSRLPSHMR
1 2 S971 LPSHMRQSDsSSsLA
7 9 S973‑p SHMRQSDsSSsLASE
0 2 S975 MRQSDsSSsLASERE
3 5 S976‑p RQSDsSSsLASEREH
1 1 S979 DsSSsLASEREHITS
1 0 T1024 ELHQNSLTSFPQQLC
1 0 S1025 LHQNSLTSFPQQLCE
0 2 P1058 PSFVLKMPRITNLDA
0 1 K1118 QLLLEGNKISGICSP
1 0 S1124 NKISGICSPLSLKEL
0 1 K1129 ICSPLSLKELKILNL
0 1 S1157 EACSKVESFSARMNF
0 1 S1159 CSKVESFSARMNFLA
0 1 T1176 PALPSSITSLKLSQN
0 1 S1219 PGPAHWKSLNLRELI
0 1 S1228 NLRELIFSKNQISTL
1 0 S1253 RVEKLHLSHNKLKEI
1 0 S1283 SYNLELRSFPNEMGK
4 0 S1292‑p PNEMGKLsKIWDLPL
1 0 Y1332 RLKKAVPYNRMKLMI
6 0 T1343 KLMIVGNTGSGKTTL
3 0 S1345 MIVGNTGSGKTTLLQ
5 0 T1348 GNTGSGKTTLLQQLM
1 0 T1349 NTGSGKTTLLQQLMK
4 1 M1357 LLQQLMKMKKPELGM
4 0 T1368 ELGMQGATVGIDVRD
1 0 Y1402 FAGREEFYSTHPHFM
3 0 S1403 AGREEFYSTHPHFMT
3 0 T1404 GREEFYSTHPHFMTQ
6 0 T1410 STHPHFMTQRALYLA
2 0 S1443 FNIKARASSSPVILV
2 0 S1444 NIKARASSSPVILVG
1 0 S1445 IKARASSSPVILVGT
3 0 T1452 SPVILVGTHLDVSDE
1 0 S1457 VGTHLDVSDEKQRKA
1 1 S1467 KQRKACISKITKELL
1 0 T1470 KACISKITKELLNKR
1 0 Y1485 GFPTIRDYHFVNATE
9 0 T1491 DYHFVNATEESDALA
8 0 T1503 ALAKLRKTIINESLN
1 0 S1508 RKTIINESLNFKIRD
1 0 S1536 ELEKIILSERKAVPT
1 1 T1612 KVMAQILTVKVDGCL
1 0 S1627 KHPKGIISRRDVEKF
1 0 M1647 RFPKNYMMQYFKLLE
0 1 S1716‑p INRLLEIsPFMLSGR
0 1 F1718 RLLEIsPFMLSGRER
0 1 S1721 EIsPFMLSGRERALR
0 1 K1833‑ub LLDELMKkAEEGDLL
2 0 T1849 NPDQPRLTIPISQIA
1 0 S1853 PRLTIPISQIAPDLI
1 0 T1912 VKIFNKHTSLRLLRQ
1 0 S1913 KIFNKHTSLRLLRQE
0 1 K1963‑ub DRLLQQDkASLTRTL
2 0 T1967 QQDkASLTRTLQHRI
2 0 T1969 DkASLTRTLQHRIAL
0 7 Y2023 ADYGIAQYCCRMGIK
5 0 T2031 CCRMGIKTSEGTPGF
6 0 S2032 CRMGIKTSEGTPGFR
5 0 T2035 GIKTSEGTPGFRAPE
0 1 K2091‑ub DELAIQGkLPDPVKE
1 0 T2166 NLNSKSATLWLGCGN
0 1 T2237 EEETKRHTLEKMTDS
1 0 S2257 CNSLAKQSKQSNFLL
0 1 H2449 RRVIRTIHNFCDSVR
0 1 T2460 DSVRAMATAQLGSLK
2 0 I2483 KRKSTEGIQEQKEIQ
1 0 T2524 LADKMRKTSVE____
  human

 
S3‑p _____MAsGsCQGCE
S5‑p ___MAsGsCQGCEED
T358‑p EACYKALtWHRKNKH
T424‑p ASANALStLLEQNVN
T489‑p AVVPKILtVMKRHEt
T496‑p tVMKRHEtSLPVQLE
T524‑p PEESREDtEFHHKLN
S633‑p LLAKILVssLyRFKD
S634‑p LAKILVssLyRFKDV
Y636‑p KILVssLyRFKDVAE
Y707‑p AKVAMDDyLKNVMLE
T776‑p QDVRKALtISIGKGD
S784‑p ISIGKGDsQIIsLLL
S788‑p KGDsQIIsLLLRRLA
T826‑p GPLFPDKtSNLRKQt
T833‑p tSNLRKQtNIAstLA
S837‑p RKQtNIAstLARMVI
T838‑p KQtNIAstLARMVIR
S850‑p VIRYQMKsAVEEGTA
S858‑p AVEEGTAsGsDGNFs
S860‑p EEGTAsGsDGNFsED
S865‑p sGsDGNFsEDVLSKF
S895‑p AQSDDLDsEGsEGSF
S898‑p DDLDsEGsEGSFLVK
S908‑p SFLVKKKsNsIsVGE
S910‑p LVKKKsNsIsVGEFY
S912‑p KKKsNsIsVGEFYRD
S926‑p DAVLQRCsPNLQRHs
S933‑p sPNLQRHsNsLGPIF
S935‑p NLQRHsNsLGPIFDH
S954‑p KRKRKILssDDsLRS
S955‑p RKRKILssDDsLRSs
S958‑p KILssDDsLRSsKLQ
S962‑p sDDsLRSsKLQSHMR
S971‑p LQSHMRHsDsIssLA
S973‑p SHMRHsDsIssLAsE
S975‑p MRHsDsIssLAsERE
S976‑p RHsDsIssLAsEREY
S979‑p DsIssLAsEREYITS
T1024‑p ELHQNALtsFPQQLC
S1025‑p LHQNALtsFPQQLCE
S1058‑p PSYLLKMsCIANLDV
K1118‑ub QLILEGNkISGICsP
S1124‑p NkISGICsPLRLkEL
K1129‑ub ICsPLRLkELKILNL
S1157‑p EACPKVEsFsARMNF
S1159‑p CPKVEsFsARMNFLA
T1176‑p PFLPPSMtILKLSQN
S1219‑p PGPAHWKsLNLRELL
S1228‑p NLRELLFsHNQISIL
S1253‑p RVEKLHLsHNKLKEI
S1283‑p SYNLELRsFPNEMGK
S1292‑p PNEMGKLsKIWDLPL
Y1332‑p RLKKAVPyNRMKLMI
T1343‑p KLMIVGNtGsGKttL
S1345‑p MIVGNtGsGKttLLQ
T1348‑p GNtGsGKttLLQQLM
T1349‑p NtGsGKttLLQQLMK
T1357‑p LLQQLMKtKKSDLGM
T1368‑p DLGMQSAtVGIDVKD
Y1402‑p FAGREEFystHPHFM
S1403‑p AGREEFystHPHFMt
T1404‑p GREEFystHPHFMtQ
T1410‑p stHPHFMtQRALYLA
S1443‑p FNIKARAsssPVILV
S1444‑p NIKARAsssPVILVG
S1445‑p IKARAsssPVILVGt
T1452‑p sPVILVGtHLDVsDE
S1457‑p VGtHLDVsDEKQRKA
S1467‑p KQRKACMsKItKELL
T1470‑p KACMsKItKELLNKR
Y1485‑p GFPAIRDyHFVNAtE
T1491‑p DyHFVNAtEESDALA
T1503‑p ALAKLRKtIINEsLN
S1508‑p RKtIINEsLNFKIRD
S1536‑p ELEKIILsERKNVPI
T1612‑p KIMAQILtVKVEGCP
S1627‑p KHPKGIIsRRDVEKF
S1647‑p KFPKNYMsQYFKLLE
S1716 INRLLEISPyMLsGR
Y1718‑p RLLEISPyMLsGRER
S1721‑p EISPyMLsGRERALR
K1833 LLDDLMKKAEEGDLL
T1849‑p NPDQPRLtIPIsQIA
S1853‑p PRLtIPIsQIAPDLI
T1912‑p VKIFNKHtsLRLLRQ
S1913‑p KIFNKHtsLRLLRQE
K1963 DRLLQQDKASLtRtL
T1967‑p QQDKASLtRtLQHRI
T1969‑p DKASLtRtLQHRIAL
Y2023‑p ADYGIAQyCCRMGIK
T2031‑p CCRMGIKtsEGtPGF
S2032‑p CRMGIKtsEGtPGFR
T2035‑p GIKtsEGtPGFRAPE
K2091 DELEIQGKLPDPVKE
S2166‑p HHNSRNAsIWLGCGH
T2237‑p EDGKKRHtLEKMTDS
S2257‑p CNSFSKQsKQKNFLL
Y2449‑p RRLIRVIyNFCNSVR
T2460‑p NSVRVMMtAQLGSLK
T2483‑p NRKNTEGtQKQKEIQ
T2524‑p LAEKMRRtSVE____
  rat

 
S3 _____MASGACQGCD
A5 ___MASGACQGCDEE
M359 EPCYKALMRHRKNKH
T425 AAAHALSTLLEQNVN
T490 AVIPKILTVMRTHGT
T497 TVMRTHGTSLSVQLE
S525 SEDSRDDSRCQPNVL
S632 LLAKILASTLQRFKD
T633 LAKILASTLQRFKDV
Q635 KILASTLQRFKDVAE
E706 AKVAVDDELKSKMLE
T775 QDVRKALTVSIQKGD
N783 VSIQKGDNQVISLLL
S787 KGDNQVISLLLRRLA
S825 GPLFPDKSSNLRKQT
T832 SSNLRKQTNAGSVLA
S836 RKQTNAGSVLARKVL
V837 KQTNAGSVLARKVLR
N849 VLRYQMRNTLQEGVA
S857 TLQEGVASGSEGNFS
S859 QEGVASGSEGNFSED
S864 SGSEGNFSEDALAKF
S894 GQSDDLDSEGSESSF
S897 DDLDSEGSESSFLVK
S907 SFLVKKKSNsVSVGE
S909‑p 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
K1117 QLLLEGNKISGICSP
S1123 NKISGICSPLSLKEL
K1128 ICSPLSLKELKILNL
S1156 EACPKVESFSARMNF
S1158 CPKVESFSARMNFLA
T1175 PALPSSITSLKLSQN
S1218 PGPAHWKSLNLRELI
S1227 NLRELIFSKNQISTL
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
S1626 KHPKGIISRRDVEKF
A1646 RFPKNYMAQYFKLLE
S1715 INRLLEISPFMLSGR
F1717 RLLEISPFMLSGRER
S1720 EISPFMLSGRERALR
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
T2236 EDETRRHTLDKMTDS
S2256 CNSFAKQSKQSHFLL
H2448 RRVIRTIHNFCDSVR
T2459 DSVRAMATAQLGNLK
T2482 KRKSTEGTQEQKEIQ
T2523 LADKMRKTSVE____
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