Search Results
Overview
| Uniprot ID | Q5S007 |
|---|---|
| Protein Name | Leucine-rich repeat serine/threonine-protein kinase 2 |
| Gene Name | LRRK2 |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position | Flanking peptide |
|---|---|
| 1471 | ACMSKITKELLNKRG |
Function
Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking (PubMed:17114044, PubMed:20949042, PubMed:21850687, PubMed:22012985, PubMed:23395371, PubMed:24687852, PubMed:25201882, PubMed:26014385, PubMed:26824392, PubMed:27830463, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB29, RAB35, and RAB43 (PubMed:23395371, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421, PubMed:38127736). Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (PubMed:26824392). Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (PubMed:26824392). Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed:29125462, PubMed:30398148). Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose-6-phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner (PubMed:23395371). Regulates neuronal process morphology in the intact central nervous system (CNS) (PubMed:17114044). Plays a role in synaptic vesicle trafficking (PubMed:24687852). Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed:25201882). Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (PubMed:22012985). The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (PubMed:22012985). Phosphorylates PRDX3 (PubMed:21850687). By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis (PubMed:28720718). Acts as a positive regulator of innate immunity by mediating phosphorylation of RIPK2 downstream of NOD1 and NOD2, thereby enhancing RIPK2 activation (PubMed:27830463). Independent of its kinase activity, inhibits the proteasomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (PubMed:26014385). In addition, has GTPase activity via its Roc domain which regulates LRRK2 kinase activity (PubMed:18230735, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29212815). Recruited by RAB29/RAB7L1 to overloaded lysosomes where it phosphorylates and stabilizes RAB8A and RAB10 which promote lysosomal content release and suppress lysosomal enlargement through the EHBP1 and EHBP1L1 effector proteins (PubMed:30209220, PubMed:38227290)
Protein Sequence
10
MASGSCQGCE
20
EDEETLKKLI
30
VRLNNVQEGK
40
QIETLVQILE
50
DLLVFTYSER
60
ASKLFQGKNI
70
HVPLLIVLDS
80
YMRVASVQQV
90
GWSLLCKLIE
100
VCPGTMQSLM
110
GPQDVGNDWE
120
VLGVHQLILK
130
MLTVHNASVN
140
LSVIGLKTLD
150
LLLTSGKITL
160
LILDEESDIF
170
MLIFDAMHSF
180
PANDEVQKLG
190
CKALHVLFER
200
VSEEQLTEFV
210
ENKDYMILLS
220
ALTNFKDEEE
230
IVLHVLHCLH
240
SLAIPCNNVE
250
VLMSGNVRCY
260
NIVVEAMKAF
270
PMSERIQEVS
280
CCLLHRLTLG
290
NFFNILVLNE
300
VHEFVVKAVQ
310
QYPENAALQI
320
SALSCLALLT
330
ETIFLNQDLE
340
EKNENQENDD
350
EGEEDKLFWL
360
EACYKALTWH
370
RKNKHVQEAA
380
CWALNNLLMY
390
QNSLHEKIGD
400
EDGHFPAHRE
410
VMLSMLMHSS
420
SKEVFQASAN
430
ALSTLLEQNV
440
NFRKILLSKG
450
IHLNVLELMQ
460
KHIHSPEVAE
470
SGCKMLNHLF
480
EGSNTSLDIM
490
AAVVPKILTV
500
MKRHETSLPV
510
QLEALRAILH
520
FIVPGMPEES
530
REDTEFHHKL
540
NMVKKQCFKN
550
DIHKLVLAAL
560
NRFIGNPGIQ
570
KCGLKVISSI
580
VHFPDALEML
590
SLEGAMDSVL
600
HTLQMYPDDQ
610
EIQCLGLSLI
620
GYLITKKNVF
630
IGTGHLLAKI
640
LVSSLYRFKD
650
VAEIQTKGFQ
660
TILAILKLSA
670
SFSKLLVHHS
680
FDLVIFHQMS
690
SNIMEQKDQQ
700
FLNLCCKCFA
710
KVAMDDYLKN
720
VMLERACDQN
730
NSIMVECLLL
740
LGADANQAKE
750
GSSLICQVCE
760
KESSPKLVEL
770
LLNSGSREQD
780
VRKALTISIG
790
KGDSQIISLL
800
LRRLALDVAN
810
NSICLGGFCI
820
GKVEPSWLGP
830
LFPDKTSNLR
840
KQTNIASTLA
850
RMVIRYQMKS
860
AVEEGTASGS
870
DGNFSEDVLS
880
KFDEWTFIPD
890
SSMDSVFAQS
900
DDLDSEGSEG
910
SFLVKKKSNS
920
ISVGEFYRDA
930
VLQRCSPNLQ
940
RHSNSLGPIF
950
DHEDLLKRKR
960
KILSSDDSLR
970
SSKLQSHMRH
980
SDSISSLASE
990
REYITSLDLS
1000
ANELRDIDAL
1010
SQKCCISVHL
1020
EHLEKLELHQ
1030
NALTSFPQQL
1040
CETLKSLTHL
1050
DLHSNKFTSF
1060
PSYLLKMSCI
1070
ANLDVSRNDI
1080
GPSVVLDPTV
1090
KCPTLKQFNL
1100
SYNQLSFVPE
1110
NLTDVVEKLE
1120
QLILEGNKIS
1130
GICSPLRLKE
1140
LKILNLSKNH
1150
ISSLSENFLE
1160
ACPKVESFSA
1170
RMNFLAAMPF
1180
LPPSMTILKL
1190
SQNKFSCIPE
1200
AILNLPHLRS
1210
LDMSSNDIQY
1220
LPGPAHWKSL
1230
NLRELLFSHN
1240
QISILDLSEK
1250
AYLWSRVEKL
1260
HLSHNKLKEI
1270
PPEIGCLENL
1280
TSLDVSYNLE
1290
LRSFPNEMGK
1300
LSKIWDLPLD
1310
ELHLNFDFKH
1320
IGCKAKDIIR
1330
FLQQRLKKAV
1340
PYNRMKLMIV
1350
GNTGSGKTTL
1360
LQQLMKTKKS
1370
DLGMQSATVG
1380
IDVKDWPIQI
1390
RDKRKRDLVL
1400
NVWDFAGREE
1410
FYSTHPHFMT
1420
QRALYLAVYD
1430
LSKGQAEVDA
1440
MKPWLFNIKA
1450
RASSSPVILV
1460
GTHLDVSDEK
1470
QRKACMSKIT
1480
KELLNKRGFP
1490
AIRDYHFVNA
1500
TEESDALAKL
1510
RKTIINESLN
1520
FKIRDQLVVG
1530
QLIPDCYVEL
1540
EKIILSERKN
1550
VPIEFPVIDR
1560
KRLLQLVREN
1570
QLQLDENELP
1580
HAVHFLNESG
1590
VLLHFQDPAL
1600
QLSDLYFVEP
1610
KWLCKIMAQI
1620
LTVKVEGCPK
1630
HPKGIISRRD
1640
VEKFLSKKRK
1650
FPKNYMSQYF
1660
KLLEKFQIAL
1670
PIGEEYLLVP
1680
SSLSDHRPVI
1690
ELPHCENSEI
1700
IIRLYEMPYF
1710
PMGFWSRLIN
1720
RLLEISPYML
1730
SGRERALRPN
1740
RMYWRQGIYL
1750
NWSPEAYCLV
1760
GSEVLDNHPE
1770
SFLKITVPSC
1780
RKGCILLGQV
1790
VDHIDSLMEE
1800
WFPGLLEIDI
1810
CGEGETLLKK
1820
WALYSFNDGE
1830
EHQKILLDDL
1840
MKKAEEGDLL
1850
VNPDQPRLTI
1860
PISQIAPDLI
1870
LADLPRNIML
1880
NNDELEFEQA
1890
PEFLLGDGSF
1900
GSVYRAAYEG
1910
EEVAVKIFNK
1920
HTSLRLLRQE
1930
LVVLCHLHHP
1940
SLISLLAAGI
1950
RPRMLVMELA
1960
SKGSLDRLLQ
1970
QDKASLTRTL
1980
QHRIALHVAD
1990
GLRYLHSAMI
2000
IYRDLKPHNV
2010
LLFTLYPNAA
2020
IIAKIADYGI
2030
AQYCCRMGIK
2040
TSEGTPGFRA
2050
PEVARGNVIY
2060
NQQADVYSFG
2070
LLLYDILTTG
2080
GRIVEGLKFP
2090
NEFDELEIQG
2100
KLPDPVKEYG
2110
CAPWPMVEKL
2120
IKQCLKENPQ
2130
ERPTSAQVFD
2140
ILNSAELVCL
2150
TRRILLPKNV
2160
IVECMVATHH
2170
NSRNASIWLG
2180
CGHTDRGQLS
2190
FLDLNTEGYT
2200
SEEVADSRIL
2210
CLALVHLPVE
2220
KESWIVSGTQ
2230
SGTLLVINTE
2240
DGKKRHTLEK
2250
MTDSVTCLYC
2260
NSFSKQSKQK
2270
NFLLVGTADG
2280
KLAIFEDKTV
2290
KLKGAAPLKI
2300
LNIGNVSTPL
2310
MCLSESTNST
2320
ERNVMWGGCG
2330
TKIFSFSNDF
2340
TIQKLIETRT
2350
SQLFSYAAFS
2360
DSNIITVVVD
2370
TALYIAKQNS
2380
PVVEVWDKKT
2390
EKLCGLIDCV
2400
HFLREVMVKE
2410
NKESKHKMSY
2420
SGRVKTLCLQ
2430
KNTALWIGTG
2440
GGHILLLDLS
2450
TRRLIRVIYN
2460
FCNSVRVMMT
2470
AQLGSLKNVM
2480
LVLGYNRKNT
2490
EGTQKQKEIQ
2500
SCLTVWDINL
2510
PHEVQNLEKH
2520
IEVRKELAEK
MRRTSVE
Gene Ontology
| Classification | GO ID | Description |
|---|---|---|
| Cellular Component | GO:0044753 | amphisome |
| Cellular Component | GO:0044754 | autolysosome |
| Biological Process | GO:0071287 | cellular response to manganese ion |
| Biological Process | GO:0034599 | cellular response to oxidative stress |
| Biological Process | GO:0034614 | cellular response to reactive oxygen species |
| Biological Process | GO:0009267 | cellular response to starvation |
| Biological Process | GO:0008340 | determination of adult lifespan |
| Biological Process | GO:0006897 | endocytosis |
| Biological Process | GO:0007029 | endoplasmic reticulum organization |
| Biological Process | GO:0060079 | excitatory postsynaptic potential |
| Biological Process | GO:0035640 | exploration behavior |
| Biological Process | GO:0007030 | Golgi organization |
| Biological Process | GO:0046039 | GTP metabolic process |
| Biological Process | GO:0048312 | intracellular distribution of mitochondria |
| Biological Process | GO:0008104 | intracellular protein localization |
| Biological Process | GO:0035556 | intracellular signal transduction |
| Biological Process | GO:0007254 | JNK cascade |
| Biological Process | GO:0035641 | locomotory exploration behavior |
| Biological Process | GO:0007040 | lysosome organization |
| Biological Process | GO:0000165 | MAPK cascade |
| Biological Process | GO:0051646 | mitochondrion localization |
| Biological Process | GO:0007005 | mitochondrion organization |
| Biological Process | GO:1902902 | negative regulation of autophagosome assembly |
| Biological Process | GO:1902236 | negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway |
| Biological Process | GO:0090394 | negative regulation of excitatory postsynaptic potential |
| Biological Process | GO:0034260 | negative regulation of GTPase activity |
| Biological Process | GO:1902823 | negative regulation of late endosome to lysosome transport |
| Biological Process | GO:0016242 | negative regulation of macroautophagy |
| Biological Process | GO:1905504 | negative regulation of motile cilium assembly |
| Biological Process | GO:0010977 | negative regulation of neuron projection development |
| Biological Process | GO:0010955 | negative regulation of protein processing |
| Biological Process | GO:1903217 | negative regulation of protein processing involved in protein targeting to mitochondrion |
| Biological Process | GO:1903215 | negative regulation of protein targeting to mitochondrion |
| Biological Process | GO:0007528 | neuromuscular junction development |
| Biological Process | GO:0140058 | neuron projection arborization |
| Biological Process | GO:0048812 | neuron projection morphogenesis |
| Biological Process | GO:0021772 | olfactory bulb development |
| Biological Process | GO:0010508 | positive regulation of autophagy |
| Biological Process | GO:0090263 | positive regulation of canonical Wnt signaling pathway |
| Biological Process | GO:0060161 | positive regulation of dopamine receptor signaling pathway |
| Biological Process | GO:0043410 | positive regulation of MAPK cascade |
| Biological Process | GO:1903980 | positive regulation of microglial cell activation |
| Biological Process | GO:1901030 | positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway |
| Biological Process | GO:0043068 | positive regulation of programmed cell death |
| Biological Process | GO:0032436 | positive regulation of proteasomal ubiquitin-dependent protein catabolic process |
| Biological Process | GO:1902499 | positive regulation of protein autoubiquitination |
| Biological Process | GO:0031398 | positive regulation of protein ubiquitination |
| Biological Process | GO:1900244 | positive regulation of synaptic vesicle endocytosis |
| Biological Process | GO:0032760 | positive regulation of tumor necrosis factor production |
| Biological Process | GO:0046777 | protein autophosphorylation |
| Biological Process | GO:0070973 | protein localization to endoplasmic reticulum exit site |
| Biological Process | GO:0070585 | protein localization to mitochondrion |
| Biological Process | GO:0006468 | protein phosphorylation |
| Biological Process | GO:0010506 | regulation of autophagy |
| Biological Process | GO:2000172 | regulation of branching morphogenesis of a nerve |
| Biological Process | GO:1905289 | regulation of CAMKK-AMPK signaling cascade |
| Biological Process | GO:0141161 | regulation of cAMP/PKA signal transduction |
| Biological Process | GO:0060828 | regulation of canonical Wnt signaling pathway |
| Biological Process | GO:0031344 | regulation of cell projection organization |
| Biological Process | GO:0061001 | regulation of dendritic spine morphogenesis |
| Biological Process | GO:0060159 | regulation of dopamine receptor signaling pathway |
| Biological Process | GO:0060628 | regulation of ER to Golgi vesicle-mediated transport |
| Biological Process | GO:0035564 | regulation of kidney size |
| Biological Process | GO:0040012 | regulation of locomotion |
| Biological Process | GO:0035751 | regulation of lysosomal lumen pH |
| Biological Process | GO:0042391 | regulation of membrane potential |
| Biological Process | GO:0051900 | regulation of mitochondrial depolarization |
| Biological Process | GO:0090140 | regulation of mitochondrial fission |
| Biological Process | GO:1902692 | regulation of neuroblast proliferation |
| Biological Process | GO:0014041 | regulation of neuron maturation |
| Biological Process | GO:0031647 | regulation of protein stability |
| Biological Process | GO:2000377 | regulation of reactive oxygen species metabolic process |
| Biological Process | GO:1905279 | regulation of retrograde transport, endosome to Golgi |
| Biological Process | GO:0035542 | regulation of SNARE complex assembly |
| Biological Process | GO:0051966 | regulation of synaptic transmission, glutamatergic |
| Biological Process | GO:1900242 | regulation of synaptic vesicle endocytosis |
| Biological Process | GO:2000300 | regulation of synaptic vesicle exocytosis |
| Biological Process | GO:1902803 | regulation of synaptic vesicle transport |
| Biological Process | GO:0006979 | response to oxidative stress |
| Biological Process | GO:0007266 | Rho protein signal transduction |
| Biological Process | GO:0007283 | spermatogenesis |
| Biological Process | GO:0021756 | striatum development |
| Biological Process | GO:0022028 | tangential migration from the subventricular zone to the olfactory bulb |
| Biological Process | GO:1904887 | Wnt signalosome assembly |
| Cellular Component | GO:0030424 | axon |
| Cellular Component | GO:0099400 | caveola neck |
| Cellular Component | GO:0005737 | cytoplasm |
| Cellular Component | GO:0032473 | cytoplasmic side of mitochondrial outer membrane |
| Cellular Component | GO:0031410 | cytoplasmic vesicle |
| Cellular Component | GO:0005856 | cytoskeleton |
| Cellular Component | GO:0005829 | cytosol |
| Cellular Component | GO:0030425 | dendrite |
| Cellular Component | GO:0032839 | dendrite cytoplasm |
| Cellular Component | GO:0005783 | endoplasmic reticulum |
| Cellular Component | GO:0070971 | endoplasmic reticulum exit site |
| Cellular Component | GO:0005789 | endoplasmic reticulum membrane |
| Cellular Component | GO:0005768 | endosome |
| Cellular Component | GO:0070062 | extracellular exosome |
| Cellular Component | GO:0005615 | extracellular space |
| Cellular Component | GO:0098978 | glutamatergic synapse |
| Cellular Component | GO:0005794 | Golgi apparatus |
| Cellular Component | GO:0000139 | Golgi membrane |
| Cellular Component | GO:0005798 | Golgi-associated vesicle |
| Cellular Component | GO:0030426 | growth cone |
| Cellular Component | GO:0097413 | Lewy body |
| Cellular Component | GO:0005764 | lysosome |
| Cellular Component | GO:0005902 | microvillus |
| Cellular Component | GO:0005743 | mitochondrial inner membrane |
| Cellular Component | GO:0005759 | mitochondrial matrix |
| Cellular Component | GO:0031966 | mitochondrial membrane |
| Cellular Component | GO:0005741 | mitochondrial outer membrane |
| Cellular Component | GO:0005739 | mitochondrion |
| Cellular Component | GO:0097487 | multivesicular body, internal vesicle |
| Cellular Component | GO:0043005 | neuron projection |
| Cellular Component | GO:0043025 | neuronal cell body |
| Cellular Component | GO:0043204 | perikaryon |
| Cellular Component | GO:0045335 | phagocytic vesicle |
| Cellular Component | GO:0005886 | plasma membrane |
| Cellular Component | GO:0098794 | postsynapse |
| Cellular Component | GO:0099523 | presynaptic cytosol |
| Cellular Component | GO:1990904 | ribonucleoprotein complex |
| Cellular Component | GO:0030672 | synaptic vesicle membrane |
| Cellular Component | GO:0043195 | terminal bouton |
| Cellular Component | GO:0005802 | trans-Golgi network |
| Cellular Component | GO:1990909 | Wnt signalosome |
| Molecular Function | GO:0003779 | actin binding |
| Molecular Function | GO:0005524 | ATP binding |
| Molecular Function | GO:1904713 | beta-catenin destruction complex binding |
| Molecular Function | GO:0030276 | clathrin binding |
| Molecular Function | GO:0039706 | co-receptor binding |
| Molecular Function | GO:0005525 | GTP binding |
| Molecular Function | GO:0034211 | GTP-dependent protein kinase activity |
| Molecular Function | GO:0005096 | GTPase activator activity |
| Molecular Function | GO:0003924 | GTPase activity |
| Molecular Function | GO:0042802 | identical protein binding |
| Molecular Function | GO:0004706 | JUN kinase kinase kinase activity |
| Molecular Function | GO:0016301 | kinase activity |
| Molecular Function | GO:0000287 | magnesium ion binding |
| Molecular Function | GO:0004709 | MAP kinase kinase kinase activity |
| Molecular Function | GO:0008017 | microtubule binding |
| Molecular Function | GO:0036479 | peroxidase inhibitor activity |
| Molecular Function | GO:0042803 | protein homodimerization activity |
| Molecular Function | GO:0051018 | protein kinase A binding |
| Molecular Function | GO:0004672 | protein kinase activity |
| Molecular Function | GO:0106310 | protein serine kinase activity |
| Molecular Function | GO:0004674 | protein serine/threonine kinase activity |
| Molecular Function | GO:0030159 | signaling receptor complex adaptor activity |
| Molecular Function | GO:0031267 | small GTPase binding |
| Molecular Function | GO:0000149 | SNARE binding |
| Molecular Function | GO:0017075 | syntaxin-1 binding |
| Molecular Function | GO:0044325 | transmembrane transporter binding |
| Molecular Function | GO:0015631 | tubulin binding |
| Biological Process | GO:0006914 | autophagy |
| Biological Process | GO:0019722 | calcium-mediated signaling |
| Biological Process | GO:0060070 | canonical Wnt signaling pathway |
| Biological Process | GO:1904644 | cellular response to curcumin |
| Biological Process | GO:1903351 | cellular response to dopamine |
Reference
PMID: N/A