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Q5S007 (LRRK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Leucine-rich repeat serine/threonine-protein kinase 2

EC=2.7.11.1
Alternative name(s):
Dardarin
Gene names
Name:LRRK2
Synonyms:PARK8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length2527 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May play a role in the phosphorylation of proteins central to Parkinson disease. Phosphorylates PRDX3. 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. Ref.8 Ref.10 Ref.11 Ref.12

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Subunit structure

Homodimer. Interacts with PARK2. Interacts with PRDX3. Interacts with TPCN2. Ref.8 Ref.11 Ref.12 Ref.13

Subcellular location

Cytoplasm. Membrane; Peripheral membrane protein. Mitochondrion. Note: Localized in the cytoplasm and associated with cellular membrane structures. Associates with the mitochondrial outer membrane. Ref.5 Ref.7 Ref.8 Ref.11

Tissue specificity

Expressed throughout the adult brain, but at a lower level than in heart and liver. Also expressed in placenta, lung, skeletal muscle, kidney and pancreas. In the brain, 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. Ref.1 Ref.9 Ref.14

Post-translational modification

Autophosphorylated. Ref.13

Involvement in disease

Parkinson disease 8 (PARK8) [MIM:607060]: 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: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.4 Ref.5 Ref.6 Ref.7 Ref.11 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35 Ref.36 Ref.37 Ref.38 Ref.39 Ref.40 Ref.42 Ref.44 Ref.46

Sequence similarities

Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.

Contains 12 LRR (leucine-rich) repeats.

Contains 1 protein kinase domain.

Contains 1 Roc domain.

Ontologies

Keywords
   Biological processAutophagy
   Cellular componentCytoplasm
Membrane
Mitochondrion
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Neurodegeneration
Parkinson disease
Parkinsonism
   DomainCoiled coil
Leucine-rich repeat
Repeat
   LigandATP-binding
GTP-binding
Nucleotide-binding
   Molecular functionGTPase activation
Kinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of MAPKK activity

Inferred from direct assay PubMed 19302196. Source: BHF-UCL

autophagy

Inferred from electronic annotation. Source: UniProtKB-KW

cellular response to organic cyclic compound

Inferred from electronic annotation. Source: Ensembl

determination of adult lifespan

Inferred from mutant phenotype PubMed 19692353. Source: BHF-UCL

exploration behavior

Inferred from mutant phenotype PubMed 20659558. Source: BHF-UCL

intracellular distribution of mitochondria

Inferred from mutant phenotype PubMed 21159966. Source: BHF-UCL

negative regulation of GTPase activity

Inferred from direct assay PubMed 22423108. Source: MGI

negative regulation of branching morphogenesis of a nerve

Inferred from mutant phenotype. Source: BHF-UCL

negative regulation of dendritic spine morphogenesis

Inferred from mutant phenotype. Source: BHF-UCL

negative regulation of neuroblast proliferation

Inferred from mutant phenotype. Source: BHF-UCL

negative regulation of neuron maturation

Inferred from mutant phenotype. Source: BHF-UCL

neuromuscular junction development

Inferred from mutant phenotype PubMed 21159966. Source: BHF-UCL

neuron death

Inferred from mutant phenotype PubMed 19692353. Source: BHF-UCL

peptidyl-serine phosphorylation

Inferred from direct assay PubMed 19576176. Source: BHF-UCL

peptidyl-threonine phosphorylation

Inferred from direct assay PubMed 21048939. Source: BHF-UCL

positive regulation of autophagy

Inferred from mutant phenotype Ref.12. Source: UniProtKB

positive regulation of dopamine receptor signaling pathway

Inferred from mutant phenotype PubMed 20659558. Source: BHF-UCL

positive regulation of programmed cell death

Inferred from direct assay PubMed 17200152. Source: UniProtKB

positive regulation of proteasomal ubiquitin-dependent protein catabolic process

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of protein ubiquitination

Inferred from direct assay Ref.8. Source: UniProtKB

protein autophosphorylation

Inferred from direct assay Ref.7Ref.5PubMed 17200152PubMed 17442267. Source: UniProtKB

regulation of kidney size

Inferred from sequence or structural similarity. Source: BHF-UCL

regulation of locomotion

Inferred from mutant phenotype PubMed 19692353. Source: BHF-UCL

regulation of membrane potential

Inferred from mutant phenotype PubMed 21159966. Source: BHF-UCL

response to oxidative stress

Inferred from mutant phenotype PubMed 19692353. Source: BHF-UCL

small GTPase mediated signal transduction

Inferred from electronic annotation. Source: InterPro

tangential migration from the subventricular zone to the olfactory bulb

Inferred from mutant phenotype PubMed 21168496. Source: BHF-UCL

   Cellular_componentaxon

Inferred from electronic annotation. Source: Ensembl

cytoplasmic side of mitochondrial outer membrane

Inferred from direct assay Ref.7. Source: UniProtKB

dendrite cytoplasm

Inferred from direct assay PubMed 21696411. Source: BHF-UCL

extracellular space

Inferred from direct assay PubMed 22664934. Source: UniProt

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

membrane raft

Inferred from electronic annotation. Source: Ensembl

neuronal cell body

Inferred from direct assay PubMed 21048939PubMed 21696411. Source: BHF-UCL

plasma membrane

Inferred from electronic annotation. Source: Ensembl

synaptic vesicle

Inferred from electronic annotation. Source: Ensembl

trans-Golgi network

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

GTP binding

Inferred from direct assay PubMed 16980962PubMed 17442267. Source: UniProtKB

GTP-dependent protein kinase activity

Inferred from mutant phenotype PubMed 17200152. Source: UniProtKB

GTPase activator activity

Inferred from direct assay PubMed 17442267. Source: UniProtKB

GTPase activity

Inferred from direct assay PubMed 21048939. Source: BHF-UCL

MAP kinase kinase activity

Inferred from direct assay PubMed 19302196. Source: BHF-UCL

tubulin binding

Inferred from direct assay PubMed 21159966. Source: BHF-UCL

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself52EBI-5323863,EBI-5323863
AGO2Q9UKV83EBI-5323863,EBI-528269
AKT1P317496EBI-5323863,EBI-296087
ARFGAP1Q8N6T3-26EBI-5323863,EBI-6288865
Arfgap1Q628487EBI-5323863,EBI-4398879From a different organism.
ARHGEF7Q141556EBI-5323863,EBI-717515
CDC37Q165437EBI-5323863,EBI-295634
CDC42P609533EBI-5323863,EBI-81752
Ckmt1P302752EBI-5323863,EBI-773103From a different organism.
DAPK1P533552EBI-5323863,EBI-358616
DNM1Q051934EBI-5323863,EBI-713135
Dnm1P390532EBI-5323863,EBI-397785From a different organism.
DNM1LO0042911EBI-5323863,EBI-724571
DNM1LO00429-32EBI-5323863,EBI-6896746
DVL1O14640-27EBI-5323863,EBI-6504027
DVL2O146413EBI-5323863,EBI-740850
DVL3Q929974EBI-5323863,EBI-739789
FADDQ131584EBI-5323863,EBI-494804
GSK3BP498417EBI-5323863,EBI-373586
HSPA8P111423EBI-5323863,EBI-351896
LRP6O755813EBI-5323863,EBI-910915
LRRK1Q38SD25EBI-5323863,EBI-1050422
MAP2K3P467345EBI-5323863,EBI-602462
MAP2K6P525644EBI-5323863,EBI-448135
MAP2K7O147333EBI-5323863,EBI-492605
MAPTP10636-23EBI-5323863,EBI-7796412
MAPTP10636-89EBI-5323863,EBI-366233
MBPP026873EBI-5323863,EBI-908215From a different organism.
Mfn1Q811U43EBI-5323863,EBI-9029118From a different organism.
MFN2O951403EBI-5323863,EBI-3324756
MSNP260385EBI-5323863,EBI-528768
NFATC2Q134693EBI-5323863,EBI-716258
OPA1O603133EBI-5323863,EBI-1054131
PARK2O602603EBI-5323863,EBI-716346
PRDX3P3004810EBI-5323863,EBI-748336
RAB5BP610204EBI-5323863,EBI-399401
Rab5bP610212EBI-5323863,EBI-8320093From a different organism.
Rab7l1Q634813EBI-5323863,EBI-6513837From a different organism.
RAC1P630005EBI-5323863,EBI-413628
SH3GL2Q999622EBI-5323863,EBI-77938
SNAPINO952955EBI-5323863,EBI-296723
SNCAP378406EBI-5323863,EBI-985879
Spag9Q58A652EBI-5323863,EBI-6530207From a different organism.
TUBBP074373EBI-5323863,EBI-350864
TUBB4AP043504EBI-5323863,EBI-355007
YWHABP319463EBI-5323863,EBI-359815
YWHAEP622584EBI-5323863,EBI-356498
YWHAGP619813EBI-5323863,EBI-359832
YWHAHQ049173EBI-5323863,EBI-306940
YWHAQP273484EBI-5323863,EBI-359854
YWHAZP631044EBI-5323863,EBI-347088

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 25272527Leucine-rich repeat serine/threonine-protein kinase 2
PRO_0000086238

Regions

Repeat983 – 100422LRR 1
Repeat1012 – 103322LRR 2
Repeat1036 – 105722LRR 3
Repeat1059 – 108022LRR 4
Repeat1084 – 110522LRR 5
Repeat1108 – 112922LRR 6
Repeat1130 – 115021LRR 7
Repeat1174 – 119623LRR 8
Repeat1197 – 121822LRR 9
Repeat1221 – 124121LRR 10
Repeat1246 – 126722LRR 11
Repeat1269 – 129123LRR 12
Domain1328 – 1511184Roc
Domain1879 – 2138260Protein kinase
Nucleotide binding1341 – 13488GTP Potential
Nucleotide binding1885 – 18939ATP By similarity
Nucleotide binding2098 – 212124GTP Potential
Nucleotide binding2295 – 22984GTP Potential
Coiled coil319 – 34830 Potential
Compositional bias728 – 7314Poly-Leu

Sites

Active site19941Proton acceptor By similarity
Binding site19061ATP By similarity

Natural variations

Natural variant501R → H.
Corresponds to variant rs2256408 [ dbSNP | Ensembl ].
VAR_024931
Natural variant1191L → P. Ref.31 Ref.41
Corresponds to variant rs33995463 [ dbSNP | Ensembl ].
VAR_024932
Natural variant2281C → S. Ref.42
Corresponds to variant rs56108242 [ dbSNP | Ensembl ].
VAR_054740
Natural variant4191A → V. Ref.41
Corresponds to variant rs34594498 [ dbSNP | Ensembl ].
VAR_033903
Natural variant5511N → K. Ref.21 Ref.31 Ref.41 Ref.45
Corresponds to variant rs7308720 [ dbSNP | Ensembl ].
VAR_024933
Natural variant7121M → V in PARK8. Ref.42
VAR_054741
Natural variant7161A → V. Ref.42
VAR_054742
Natural variant7231I → V. Ref.31 Ref.41 Ref.45
Corresponds to variant rs10878307 [ dbSNP | Ensembl ].
VAR_024934
Natural variant7551P → L.
Corresponds to variant rs34410987 [ dbSNP | Ensembl ].
VAR_033904
Natural variant7931R → M in PARK8; unknown pathological significance. Ref.21 Ref.31 Ref.34
Corresponds to variant rs35173587 [ dbSNP | Ensembl ].
VAR_024935
Natural variant8711K → E. Ref.42
VAR_054743
Natural variant9301Q → R in PARK8; unknown pathological significance. Ref.21
VAR_024936
Natural variant9441D → Y.
Corresponds to variant rs17519916 [ dbSNP | Ensembl ].
VAR_024937
Natural variant10671R → Q in PARK8. Ref.33
VAR_024938
Natural variant10961S → C in PARK8; unknown pathological significance. Ref.21
VAR_024939
Natural variant11221I → V in PARK8. Ref.1 Ref.31
Corresponds to variant rs34805604 [ dbSNP | Ensembl ].
VAR_024940
Natural variant12281S → T in PARK8. Ref.21
VAR_024941
Natural variant12621P → A. Ref.31
Corresponds to variant rs4640000 [ dbSNP | Ensembl ].
VAR_024942
Natural variant13591K → I Found in a renal cell carcinoma sample; somatic mutation. Ref.43
VAR_064728
Natural variant13711I → V in PARK8; unknown pathological significance. Ref.23 Ref.32
Corresponds to variant rs17466213 [ dbSNP | Ensembl ].
VAR_024943
Natural variant13751D → E.
Corresponds to variant rs28365226 [ dbSNP | Ensembl ].
VAR_047022
Natural variant13981R → H. Ref.31 Ref.32 Ref.41 Ref.45
Corresponds to variant rs7133914 [ dbSNP | Ensembl ].
VAR_024944
Natural variant14411R → C in PARK; shows an increase in activity in both autophosphorylation and phosphorylation of a generic substrate. Ref.1 Ref.7 Ref.23 Ref.31 Ref.35 Ref.39
VAR_024945
Natural variant14411R → G in PARK8. Ref.14 Ref.31 Ref.36 Ref.39
Corresponds to variant rs33939927 [ dbSNP | Ensembl ].
VAR_024946
Natural variant14411R → H in PARK8; pathogenicity has yet to be confirmed. Ref.31 Ref.35
Corresponds to variant rs34995376 [ dbSNP | Ensembl ].
VAR_024947
Natural variant15141R → Q in PARK8; pathogenicity has yet to be confirmed; might have an effect on protein structure. Ref.31 Ref.41 Ref.45
Corresponds to variant rs35507033 [ dbSNP | Ensembl ].
VAR_024948
Natural variant15421P → S in PARK8; pathogenicity has yet to be confirmed; might have an effect on protein structure. Ref.31 Ref.41 Ref.45
Corresponds to variant rs33958906 [ dbSNP | Ensembl ].
VAR_024949
Natural variant15501R → Q in an ovarian mucinous carcinoma sample; somatic mutation. Ref.41
VAR_040678
Natural variant15981V → E in PARK8; pathogenicity has yet to be confirmed; might have an effect on protein structure. Ref.31
Corresponds to variant rs721710 [ dbSNP | Ensembl ].
VAR_024950
Natural variant16281R → P May be associated with Parkinson disease in some populations. Ref.31 Ref.44 Ref.45
Corresponds to variant rs33949390 [ dbSNP | Ensembl ].
VAR_024951
Natural variant16461M → T. Ref.31 Ref.45
Corresponds to variant rs35303786 [ dbSNP | Ensembl ].
VAR_024952
Natural variant16471S → T. Ref.31 Ref.45
Corresponds to variant rs11564148 [ dbSNP | Ensembl ].
VAR_024953
Natural variant16991Y → C in PARK8. Ref.1 Ref.14 Ref.22 Ref.31
Corresponds to variant rs35801418 [ dbSNP | Ensembl ].
VAR_024954
Natural variant17231R → P in an ovarian serous carcinoma sample; somatic mutation. Ref.41
VAR_040679
Natural variant17281R → H in PARK8. Ref.42
VAR_054744
Natural variant17281R → L in PARK8. Ref.42
VAR_054745
Natural variant18691M → T in PARK8; pathogenicity has yet to be confirmed. Ref.31 Ref.34
Corresponds to variant rs35602796 [ dbSNP | Ensembl ].
VAR_024955
Natural variant18701L → F. Ref.42
VAR_054746
Natural variant19411R → H in PARK8. Ref.22
VAR_024956
Natural variant20121I → T in PARK8; pathogenicity uncertain. Ref.31
Corresponds to variant rs34015634 [ dbSNP | Ensembl ].
VAR_024957
Natural variant20191G → S in PARK8; shows an increase in activity in both autophosphorylation and phosphorylation of a generic substrate; results in increased PRDX3 phosphorylation promoting dysregulation of mitochondrial function and oxidative damage. Ref.7 Ref.11 Ref.15 Ref.16 Ref.17 Ref.18 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.34 Ref.35 Ref.37 Ref.38 Ref.39 Ref.42 Ref.46
Corresponds to variant rs34637584 [ dbSNP | Ensembl ].
VAR_024958
Natural variant20201I → T in PARK8; significant increase in autophosphorylation of about 40% in comparison to wild-type protein in vitro. Ref.1 Ref.5 Ref.19 Ref.21 Ref.31
Corresponds to variant rs35870237 [ dbSNP | Ensembl ].
VAR_024959
Natural variant20811N → D. Ref.31 Ref.45
Corresponds to variant rs33995883 [ dbSNP | Ensembl ].
VAR_024960
Natural variant21191P → L. Ref.31
Corresponds to variant rs12423862 [ dbSNP | Ensembl ].
VAR_024961
Natural variant21411T → M in PARK8. Ref.42
VAR_054747
Natural variant21431R → H in PARK8. Ref.42
VAR_054748
Natural variant22611N → I. Ref.31
Corresponds to variant rs12581902 [ dbSNP | Ensembl ].
VAR_024962
Natural variant23561T → I in PARK8. Ref.22
VAR_024963
Natural variant23851G → R Associated with Parkinson disease; under conditions of oxidative stress the variant protein is more toxic and is associated with a higher rate of apoptosis. Ref.31 Ref.40 Ref.44
Corresponds to variant rs34778348 [ dbSNP | Ensembl ].
VAR_024964
Natural variant23951E → K. Ref.42
VAR_054749
Natural variant23971M → T. Ref.31 Ref.32 Ref.45
Corresponds to variant rs3761863 [ dbSNP | Ensembl ].
VAR_024965
Natural variant24661L → H in PARK8. Ref.42
VAR_054750

Experimental info

Sequence conflict2121L → S in AAV63975. Ref.1

Secondary structure

.............................. 2527
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q5S007 [UniParc].

Last modified April 20, 2010. Version 2.
Checksum: 26142A0CECBBC3F4

FASTA2,527286,103
        10         20         30         40         50         60 
MASGSCQGCE EDEETLKKLI VRLNNVQEGK QIETLVQILE DLLVFTYSER ASKLFQGKNI 

        70         80         90        100        110        120 
HVPLLIVLDS YMRVASVQQV GWSLLCKLIE VCPGTMQSLM GPQDVGNDWE VLGVHQLILK 

       130        140        150        160        170        180 
MLTVHNASVN LSVIGLKTLD LLLTSGKITL LILDEESDIF MLIFDAMHSF PANDEVQKLG 

       190        200        210        220        230        240 
CKALHVLFER VSEEQLTEFV ENKDYMILLS ALTNFKDEEE IVLHVLHCLH SLAIPCNNVE 

       250        260        270        280        290        300 
VLMSGNVRCY NIVVEAMKAF PMSERIQEVS CCLLHRLTLG NFFNILVLNE VHEFVVKAVQ 

       310        320        330        340        350        360 
QYPENAALQI SALSCLALLT ETIFLNQDLE EKNENQENDD EGEEDKLFWL EACYKALTWH 

       370        380        390        400        410        420 
RKNKHVQEAA CWALNNLLMY QNSLHEKIGD EDGHFPAHRE VMLSMLMHSS SKEVFQASAN 

       430        440        450        460        470        480 
ALSTLLEQNV NFRKILLSKG IHLNVLELMQ KHIHSPEVAE SGCKMLNHLF EGSNTSLDIM 

       490        500        510        520        530        540 
AAVVPKILTV MKRHETSLPV QLEALRAILH FIVPGMPEES REDTEFHHKL NMVKKQCFKN 

       550        560        570        580        590        600 
DIHKLVLAAL NRFIGNPGIQ KCGLKVISSI VHFPDALEML SLEGAMDSVL HTLQMYPDDQ 

       610        620        630        640        650        660 
EIQCLGLSLI GYLITKKNVF IGTGHLLAKI LVSSLYRFKD VAEIQTKGFQ TILAILKLSA 

       670        680        690        700        710        720 
SFSKLLVHHS FDLVIFHQMS SNIMEQKDQQ FLNLCCKCFA KVAMDDYLKN VMLERACDQN 

       730        740        750        760        770        780 
NSIMVECLLL LGADANQAKE GSSLICQVCE KESSPKLVEL LLNSGSREQD VRKALTISIG 

       790        800        810        820        830        840 
KGDSQIISLL LRRLALDVAN NSICLGGFCI GKVEPSWLGP LFPDKTSNLR KQTNIASTLA 

       850        860        870        880        890        900 
RMVIRYQMKS AVEEGTASGS DGNFSEDVLS KFDEWTFIPD SSMDSVFAQS DDLDSEGSEG 

       910        920        930        940        950        960 
SFLVKKKSNS ISVGEFYRDA VLQRCSPNLQ RHSNSLGPIF DHEDLLKRKR KILSSDDSLR 

       970        980        990       1000       1010       1020 
SSKLQSHMRH SDSISSLASE REYITSLDLS ANELRDIDAL SQKCCISVHL EHLEKLELHQ 

      1030       1040       1050       1060       1070       1080 
NALTSFPQQL CETLKSLTHL DLHSNKFTSF PSYLLKMSCI ANLDVSRNDI GPSVVLDPTV 

      1090       1100       1110       1120       1130       1140 
KCPTLKQFNL SYNQLSFVPE NLTDVVEKLE QLILEGNKIS GICSPLRLKE LKILNLSKNH 

      1150       1160       1170       1180       1190       1200 
ISSLSENFLE ACPKVESFSA RMNFLAAMPF LPPSMTILKL SQNKFSCIPE AILNLPHLRS 

      1210       1220       1230       1240       1250       1260 
LDMSSNDIQY LPGPAHWKSL NLRELLFSHN QISILDLSEK AYLWSRVEKL HLSHNKLKEI 

      1270       1280       1290       1300       1310       1320 
PPEIGCLENL TSLDVSYNLE LRSFPNEMGK LSKIWDLPLD ELHLNFDFKH IGCKAKDIIR 

      1330       1340       1350       1360       1370       1380 
FLQQRLKKAV PYNRMKLMIV GNTGSGKTTL LQQLMKTKKS DLGMQSATVG IDVKDWPIQI 

      1390       1400       1410       1420       1430       1440 
RDKRKRDLVL NVWDFAGREE FYSTHPHFMT QRALYLAVYD LSKGQAEVDA MKPWLFNIKA 

      1450       1460       1470       1480       1490       1500 
RASSSPVILV GTHLDVSDEK QRKACMSKIT KELLNKRGFP AIRDYHFVNA TEESDALAKL 

      1510       1520       1530       1540       1550       1560 
RKTIINESLN FKIRDQLVVG QLIPDCYVEL EKIILSERKN VPIEFPVIDR KRLLQLVREN 

      1570       1580       1590       1600       1610       1620 
QLQLDENELP HAVHFLNESG VLLHFQDPAL QLSDLYFVEP KWLCKIMAQI LTVKVEGCPK 

      1630       1640       1650       1660       1670       1680 
HPKGIISRRD VEKFLSKKRK FPKNYMSQYF KLLEKFQIAL PIGEEYLLVP SSLSDHRPVI 

      1690       1700       1710       1720       1730       1740 
ELPHCENSEI IIRLYEMPYF PMGFWSRLIN RLLEISPYML SGRERALRPN RMYWRQGIYL 

      1750       1760       1770       1780       1790       1800 
NWSPEAYCLV GSEVLDNHPE SFLKITVPSC RKGCILLGQV VDHIDSLMEE WFPGLLEIDI 

      1810       1820       1830       1840       1850       1860 
CGEGETLLKK WALYSFNDGE EHQKILLDDL MKKAEEGDLL VNPDQPRLTI PISQIAPDLI 

      1870       1880       1890       1900       1910       1920 
LADLPRNIML NNDELEFEQA PEFLLGDGSF GSVYRAAYEG EEVAVKIFNK HTSLRLLRQE 

      1930       1940       1950       1960       1970       1980 
LVVLCHLHHP SLISLLAAGI RPRMLVMELA SKGSLDRLLQ QDKASLTRTL QHRIALHVAD 

      1990       2000       2010       2020       2030       2040 
GLRYLHSAMI IYRDLKPHNV LLFTLYPNAA IIAKIADYGI AQYCCRMGIK TSEGTPGFRA 

      2050       2060       2070       2080       2090       2100 
PEVARGNVIY NQQADVYSFG LLLYDILTTG GRIVEGLKFP NEFDELEIQG KLPDPVKEYG 

      2110       2120       2130       2140       2150       2160 
CAPWPMVEKL IKQCLKENPQ ERPTSAQVFD ILNSAELVCL TRRILLPKNV IVECMVATHH 

      2170       2180       2190       2200       2210       2220 
NSRNASIWLG CGHTDRGQLS FLDLNTEGYT SEEVADSRIL CLALVHLPVE KESWIVSGTQ 

      2230       2240       2250       2260       2270       2280 
SGTLLVINTE DGKKRHTLEK MTDSVTCLYC NSFSKQSKQK NFLLVGTADG KLAIFEDKTV 

      2290       2300       2310       2320       2330       2340 
KLKGAAPLKI LNIGNVSTPL MCLSESTNST ERNVMWGGCG TKIFSFSNDF TIQKLIETRT 

      2350       2360       2370       2380       2390       2400 
SQLFSYAAFS DSNIITVVVD TALYIAKQNS PVVEVWDKKT EKLCGLIDCV HFLREVMVKE 

      2410       2420       2430       2440       2450       2460 
NKESKHKMSY SGRVKTLCLQ KNTALWIGTG GGHILLLDLS TRRLIRVIYN FCNSVRVMMT 

      2470       2480       2490       2500       2510       2520 
AQLGSLKNVM LVLGYNRKNT EGTQKQKEIQ SCLTVWDINL PHEVQNLEKH IEVRKELAEK 


MRRTSVE 

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References

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[1]"Mutations in a large multifunctional protein (LRRK2) cause autosomal dominant parkinsonism with pleiomorphic a-synuclein and tau-pathology (PARK8)."
Zimprich A., Biskup S., Leitner P., Lichtner P., Farrer M., Lincoln S.J., Kachergus J.M., Hulihan M.M., Uitti R.J., Calne D.B., Stoessl A.J., Pfeiffer R.F., Patenge N., Carballo Carbajal I., Vieregge P., Asmus F., Mueller-Myhsok B., Dickson D.W. expand/collapse author list , Meitinger T., Strom T.M., Wszolek Z.K., Gasser T.
Neuron 44:601-607(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANTS PARK8 VAL-1122; CYS-1441; CYS-1699 AND THR-2020.
Tissue: Brain.
[2]"The finished DNA sequence of human chromosome 12."
Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. expand/collapse author list , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2128-2527.
Tissue: Testis.
[4]"PET in LRRK2 mutations: comparison to sporadic Parkinson's disease and evidence for presymptomatic compensation."
Adams J.R., van Netten H., Schulzer M., Mak E., McKenzie J., Strongosky A., Sossi V., Ruth T.J., Lee C.S., Farrer M., Gasser T., Uitti R.J., Calne D.B., Wszolek Z.K., Stoessl A.J.
Brain 128:2777-2785(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: DISEASE.
[5]"The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity."
Gloeckner C.J., Kinkl N., Schumacher A., Braun R.J., O'Neill E., Meitinger T., Kolch W., Prokisch H., Ueffing M.
Hum. Mol. Genet. 15:223-232(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PARK8 THR-2020.
[6]"LRRK2 mutations are not common in Alzheimer's disease."
Toft M., Sando S.B., Melquist S., Ross O.A., White L.R., Aasly J.O., Farrer M.J.
Mech. Ageing Dev. 126:1201-1205(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: DISEASE.
[7]"Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity."
West A.B., Moore D.J., Biskup S., Bugayenko A., Smith W.W., Ross C.A., Dawson V.L., Dawson T.M.
Proc. Natl. Acad. Sci. U.S.A. 102:16842-16847(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS PARK8 CYS-1441 AND SER-2019.
[8]"Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin and mutant LRRK2 induces neuronal degeneration."
Smith W.W., Pei Z., Jiang H., Moore D.J., Liang Y., West A.B., Dawson V.L., Dawson T.M., Ross C.A.
Proc. Natl. Acad. Sci. U.S.A. 102:18676-18681(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PARK2, POSSIBLE FUNCTION.
[9]"LRRK2 expression linked to dopamine-innervated areas."
Galter D., Westerlund M., Carmine A., Lindqvist E., Sydow O., Olson L.
Ann. Neurol. 59:714-719(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[10]"Signal transduction protein array analysis links LRRK2 to Ste20 kinases and PKC zeta that modulate neuronal plasticity."
Zach S., Felk S., Gillardon F.
PLoS ONE 5:E13191-E13191(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3 exacerbating oxidative stress-induced neuronal death."
Angeles D.C., Gan B.H., Onstead L., Zhao Y., Lim K.L., Dachsel J., Melrose H., Farrer M., Wszolek Z.K., Dickson D.W., Tan E.K.
Hum. Mutat. 32:1390-1397(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PRDX3, CHARACTERIZATION OF VARIANT PARK8 SER-2019.
[12]"Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP."
Gomez-Suaga P., Luzon-Toro B., Churamani D., Zhang L., Bloor-Young D., Patel S., Woodman P.G., Churchill G.C., Hilfiker S.
Hum. Mol. Genet. 21:511-525(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH TPCN2.
[13]"Biochemical characterization of highly purified leucine-rich repeat kinases 1 and 2 demonstrates formation of homodimers."
Civiero L., Vancraenenbroeck R., Belluzzi E., Beilina A., Lobbestael E., Reyniers L., Gao F., Micetic I., De Maeyer M., Bubacco L., Baekelandt V., Cookson M.R., Greggio E., Taymans J.M.
PLoS ONE 7:E43472-E43472(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, AUTOPHOSPHORYLATION.
[14]"Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease."
Paisan-Ruiz C., Jain S., Evans E.W., Gilks W.P., Simon J., van der Brug M., Lopez de Munain A., Aparicio S., Gil A.M., Khan N.L., Johnson J., Martinez J.R., Nicholl D., Carrera I.M., Pena A.S., de Silva R., Lees A.J., Marti-Masso J.F. expand/collapse author list , Perez-Tur J., Wood N.W., Singleton A.B.
Neuron 44:595-600(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK8 GLY-1441 AND CYS-1699, TISSUE SPECIFICITY.
[15]"Identification of a novel LRRK2 mutation linked to autosomal dominant parkinsonism: evidence of a common founder across European populations."
Kachergus J.M., Mata I.F., Hulihan M., Taylor J.P., Lincoln S., Aasly J.O., Gibson J.M., Ross O.A., Lynch T., Wiley J., Payami H., Nutt J., Maraganore D.M., Czyzewski K., Styczynska M., Wszolek Z.K., Farrer M.J., Toft M.
Am. J. Hum. Genet. 76:672-680(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 SER-2019.
[16]"Clinical and positron emission tomography of Parkinson's disease caused by LRRK2."
Hernandez D.G., Paisan-Ruiz C., McInerney-Leo A., Jain S., Meyer-Lindenberg A., Evans E.W., Berman K.F., Johnson J., Auburger G., Schaeffer A.A., Lopez G.J., Nussbaum R.L., Singleton A.B.
Ann. Neurol. 57:453-456(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 SER-2019.
[17]"Clinical features of LRRK2-associated Parkinson's disease in central Norway."
Aasly J.O., Toft M., Fernandez-Mata I., Kachergus J.M., Hulihan M., White L.R., Farrer M.J.
Ann. Neurol. 57:762-765(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8/PD SER-2019.
[18]"G2019S LRRK2 mutation in French and North African families with Parkinson's disease."
French Parkinson's disease genetics study group
Lesage S., Ibanez P., Lohmann E., Pollak P., Tison F., Tazir M., Leutenegger A.-L., Guimaraes J., Bonnet A.-M., Agid Y., Duerr A., Brice A.
Ann. Neurol. 58:784-787(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 SER-2019.
[19]"An LRRK2 mutation as a cause for the parkinsonism in the original PARK8 family."
Funayama M., Hasegawa K., Ohta E., Kawashima N., Komiyama M., Kowa H., Tsuji S., Obata F.
Ann. Neurol. 57:918-921(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 THR-2020.
[20]"Genetic and clinical identification of Parkinson's disease patients with LRRK2 G2019S mutation."
Deng H., Le W., Guo Y., Hunter C.B., Xie W., Jankovic J.
Ann. Neurol. 57:933-934(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 SER-2019.
[21]"Type and frequency of mutations in the LRRK2 gene in familial and sporadic Parkinson's disease."
Berg D., Schweitzer K., Leitner P., Zimprich A., Lichtner P., Belcredi P., Bruessel T., Schulte C., Maass S., Naegele T.
Brain 128:3000-3011(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK8 MET-793; ARG-930; CYS-1096 THR-1228; SER-2019 AND THR-2020, VARIANT LYS-551.
[22]"Mutations in the gene LRRK2 encoding dardarin (PARK8) cause familial Parkinson's disease: clinical, pathological, olfactory and functional imaging and genetic data."
Khan N.L., Jain S., Lynch J.M., Pavese N., Abou-Sleiman P.M., Holton J.L., Healy D.G., Gilks W.P., Sweeney M.G., Ganguly M., Gibbons V., Gandhi S., Vaughan J., Eunson L.H., Katzenschlager R., Gayton J., Lennox G., Revesz T. expand/collapse author list , Nicholl D., Bhatia K.P., Quinn N., Brooks D., Lees A.J., Davis M.B., Piccini P., Singleton A.B., Wood N.W.
Brain 128:2786-2796(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK8 CYS-1699; HIS-1941; SER-2019 AND ILE-2356.
[23]"Comprehensive analysis of the LRRK2 gene in sixty families with Parkinson's disease."
Di Fonzo A., Tassorelli C., De Mari M., Chien H.F., Ferreira J., Rohe C.F., Riboldazzi G., Antonini A., Albani G., Mauro A., Marconi R., Abbruzzese G., Lopiano L., Fincati E., Guidi M., Marini P., Stocchi F., Onofrj M. expand/collapse author list , Toni V., Tinazzi M., Fabbrini G., Lamberti P., Vanacore N., Meco G., Leitner P., Uitti R.J., Wszolek Z.K., Gasser T., Simons E.J., Breedveld G.J., Goldwurm S., Pezzoli G., Sampaio C., Barbosa E., Martignoni E., Oostra B.A., Bonifati V.
Eur. J. Hum. Genet. 14:322-331(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK8 VAL-1371; CYS-1441 AND SER-2019.
[24]"The G6055A (G2019S) mutation in LRRK2 is frequent in both early and late onset Parkinson's disease and originates from a common ancestor."
Goldwurm S., Di Fonzo A., Simons E.J., Rohe C.F., Zini M., Canesi M., Tesei S., Zecchinelli A., Antonini A., Mariani C., Meucci N., Sacilotto G., Sironi F., Salani G., Ferreira J., Chien H.F., Fabrizio E., Vanacore N. expand/collapse author list , Dalla Libera A., Stocchi F., Diroma C., Lamberti P., Sampaio C., Meco G., Barbosa E., Bertoli-Avella A.M., Breedveld G.J., Oostra B.A., Pezzoli G., Bonifati V.
J. Med. Genet. 42:E65-E65(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 SER-2019.
[25]"Genetic screening for a single common LRRK2 mutation in familial Parkinson's disease."
The Parkinson study group-PROGENI investigators
Nichols W.C., Pankratz N., Hernandez D., Paisan-Ruiz C., Jain S., Halter C.A., Michaels V.E., Reed T., Rudolph A., Shults C.W., Singleton A., Foroud T.
Lancet 365:410-412(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 SER-2019.
[26]"A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson's disease."
The Italian Parkinson genetics network
Di Fonzo A., Rohe C.F., Ferreira J., Chien H.F., Vacca L., Stocchi F., Guedes L., Fabrizio E., Manfredi M., Vanacore N., Goldwurm S., Breedveld G.J., Sampaio C., Meco G., Barbosa E., Oostra B.A., Bonifati V.
Lancet 365:412-415(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 SER-2019.
[27]"A common LRRK2 mutation in idiopathic Parkinson's disease."
Gilks W.P., Abou-Sleiman P.M., Gandhi S., Jain S., Singleton A., Lees A.J., Shaw K., Bhatia K.P., Bonifati V., Quinn N.P., Lynch J.M., Healy D.G., Holton J.L., Revesz T., Wood N.W.
Lancet 365:415-416(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 SER-2019.
[28]"LRRK2 mutations and Parkinsonism."
Toft M., Mata I.F., Kachergus J.M., Ross O.A., Farrer M.J.
Lancet 365:1229-1230(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 SER-2019.
[29]"Escaping Parkinson's disease: a neurologically healthy octogenarian with the LRRK2 G2019S mutation."
Kay D.M., Kramer P., Higgins D.S., Zabetian C.P., Payami H.
Mov. Disord. 20:1077-1078(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SER-2019.
[30]"Parkinson's disease and LRRK2: frequency of a common mutation in U.S. movement disorder clinics."
Kay D.M., Zabetian C.P., Factor S.A., Nutt J.G., Samii A., Griffith A., Bird T.D., Kramer P., Higgins D.S., Payami H.
Mov. Disord. 21:519-523(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 SER-2019.
[31]"Lrrk2 pathogenic substitutions in Parkinson's disease."
Mata I.F., Kachergus J.M., Taylor J.P., Lincoln S., Aasly J., Lynch T., Hulihan M.M., Cobb S.A., Wu R.-M., Lu C.-S., Lahoz C., Wszolek Z.K., Farrer M.J.
Neurogenetics 6:171-177(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK8 CYS-1441; GLY-1441; HIS-1441; GLN-1514; SER-1542; GLU-1598; CYS-1699; THR-1869; THR-2012; SER-2019; THR-2020 AND ARG-2385, VARIANTS PRO-119; LYS-551; VAL-723; MET-793; VAL-1122; ALA-1262; HIS-1398; PRO-1628; THR-1646; THR-1647; ASP-2081; LEU-2119; ILE-2261 AND THR-2397.
[32]"LRRK2 gene in Parkinson disease: mutation analysis and case control association study."
Paisan-Ruiz C., Lang A.E., Kawarai T., Sato C., Salehi-Rad S., Fisman G.K., Al-Khairallah T., St George-Hyslop P.H., Singleton A., Rogaeva E.
Neurology 65:696-700(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK8 VAL-1371 AND SER-2019, VARIANTS HIS-1398 AND THR-2397.
[33]"Analysis of LRRK2 functional domains in nondominant Parkinson disease."
Skipper L., Shen H., Chua E., Bonnard C., Kolatkar P., Tan L.C.S., Jamora R.D., Puvan K., Puong K.Y., Zhao Y., Pavanni R., Wong M.C., Yuen Y., Farrer M., Liu J.J., Tan E.K.
Neurology 65:1319-1321(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 GLN-1067.
[34]"LRRK2 mutations in Parkinson disease."
Farrer M., Stone J., Mata I.F., Lincoln S., Kachergus J., Hulihan M., Strain K.J., Maraganore D.M.
Neurology 65:738-740(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK8 MET-793; THR-1869 AND SER-2019.
[35]"A clinic-based study of the LRRK2 gene in Parkinson disease yields new mutations."
Zabetian C.P., Samii A., Mosley A.D., Roberts J.W., Leis B.C., Yearout D., Raskind W.H., Griffith A.
Neurology 65:741-744(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK8 CYS-1441; HIS-1441 AND SER-2019.
[36]"LRRK2 R1441G in Spanish patients with Parkinson's disease."
Mata I.F., Taylor J.P., Kachergus J., Hulihan M., Huerta C., Lahoz C., Blazquez M., Guisasola L.M., Salvador C., Ribacoba R., Martinez C., Farrer M., Alvarez V.
Neurosci. Lett. 382:309-311(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 GLY-1441.
[37]"LRRK2 G2019S is a common mutation in Spanish patients with late-onset Parkinson's disease."
Infante J., Rodriguez E., Combarros O., Mateo I., Fontalba A., Pascual J., Oterino A., Polo J.M., Leno C., Berciano J.
Neurosci. Lett. 395:224-226(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 SER-2019.
[38]"Clinical traits of LRRK2-associated Parkinson's disease in Ireland: a link between familial and idiopathic PD."
Gosal D., Ross O.A., Wiley J., Irvine G.B., Johnston J.A., Toft M., Mata I.F., Kachergus J., Hulihan M., Taylor J.P., Lincoln S.J., Farrer M.J., Lynch T., Mark Gibson J.
Parkinsonism Relat. Disord. 11:349-352(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 SER-2019.
[39]"LRRK2 mutations in Spanish patients with Parkinson disease: frequency, clinical features, and incomplete penetrance."
Gaig C., Ezquerra M., Marti M.J., Munoz E., Valldeoriola F., Tolosa E.
Arch. Neurol. 63:377-382(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK8 CYS-1441; GLY-1441 AND SER-2019.
[40]"The LRRK2 Gly2385Arg variant is associated with Parkinson's disease: genetic and functional evidence."
Tan E.K., Zhao Y., Skipper L., Tan M.G., Di Fonzo A., Sun L., Fook-Chong S., Tang S., Chua E., Yuen Y., Tan L., Pavanni R., Wong M.C., Kolatkar P., Lu C.S., Bonifati V., Liu J.J.
Hum. Genet. 120:857-863(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT ARG-2385, ASSOCIATION WITH PARKINSON DISEASE.
[41]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] PRO-119; VAL-419; LYS-551; VAL-723; HIS-1398; GLN-1514; SER-1542; GLN-1550 AND PRO-1723.
[42]"Comprehensive analysis of LRRK2 in publicly available Parkinson's disease cases and neurologically normal controls."
Paisan-Ruiz C., Nath P., Washecka N., Gibbs J.R., Singleton A.B.
Hum. Mutat. 29:485-490(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK8 VAL-712; LEU-1728; HIS-1728; SER-2019; MET-2141; HIS-2143 AND HIS-2466, VARIANTS SER-228; VAL-716; GLU-871; PHE-1870 AND LYS-2395.
[43]"Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma."
Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H., Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J., Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M. expand/collapse author list , Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L., Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J., Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A., Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K., Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.
Nature 469:539-542(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ILE-1359.
[44]"Genetic characteristics of leucine-rich repeat kinase 2 (LRRK2) associated Parkinson's disease."
Bardien S., Lesage S., Brice A., Carr J.
Parkinsonism Relat. Disord. 17:501-508(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION OF VARIANTS PRO-1628 AND ARG-2385 WITH PARKINSON DISEASE.
[45]"Deep sequencing of the LRRK2 gene in 14,002 individuals reveals evidence of purifying selection and independent origin of the p.Arg1628Pro mutation in Europe."
Rubio J.P., Topp S., Warren L., St Jean P.L., Wegmann D., Kessner D., Novembre J., Shen J., Fraser D., Aponte J., Nangle K., Cardon L.R., Ehm M.G., Chissoe S.L., Whittaker J.C., Nelson M.R., Mooser V.E.
Hum. Mutat. 33:1087-1098(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LYS-551; VAL-723; HIS-1398; GLN-1514; SER-1542; PRO-1628; THR-1646; THR-1647; ASP-2081 AND THR-2397.
[46]"Systematic review and UK-based study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in early-onset Parkinson's disease."
Kilarski L.L., Pearson J.P., Newsway V., Majounie E., Knipe M.D., Misbahuddin A., Chinnery P.F., Burn D.J., Clarke C.E., Marion M.H., Lewthwaite A.J., Nicholl D.J., Wood N.W., Morrison K.E., Williams-Gray C.H., Evans J.R., Sawcer S.J., Barker R.A. expand/collapse author list , Wickremaratchi M.M., Ben-Shlomo Y., Williams N.M., Morris H.R.
Mov. Disord. 27:1522-1529(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 SER-2019.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY792511 mRNA. Translation: AAV63975.1.
AC079630 Genomic DNA. No translation available.
AC084290 Genomic DNA. No translation available.
AC107023 Genomic DNA. No translation available.
AL834529 mRNA. Translation: CAD39185.1.
RefSeqNP_940980.3. NM_198578.3.
UniGeneHs.187636.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2ZEJX-ray2.00A/B1333-1516[»]
3D6TX-ray2.43B1336-1505[»]
ProteinModelPortalQ5S007.
SMRQ5S007. Positions 1335-1512.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid125700. 139 interactions.
DIPDIP-29684N.
IntActQ5S007. 157 interactions.
MINTMINT-7997594.
STRING9606.ENSP00000298910.

Chemistry

BindingDBQ5S007.
ChEMBLCHEMBL1075104.
GuidetoPHARMACOLOGY2059.

PTM databases

PhosphoSiteQ5S007.

Polymorphism databases

DMDM294862450.

Proteomic databases

PaxDbQ5S007.
PRIDEQ5S007.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000298910; ENSP00000298910; ENSG00000188906.
GeneID120892.
KEGGhsa:120892.
UCSCuc001rmg.4. human.

Organism-specific databases

CTD120892.
GeneCardsGC12P040590.
HGNCHGNC:18618. LRRK2.
HPACAB037160.
HPA014293.
MIM168600. phenotype.
607060. phenotype.
609007. gene.
neXtProtNX_Q5S007.
Orphanet2828. Young adult-onset Parkinsonism.
PharmGKBPA134968052.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG4886.
HOGENOMHOG000293315.
HOVERGENHBG081937.
InParanoidQ5S007.
KOK08844.
OMAFKIRDQP.
TreeFamTF313679.

Enzyme and pathway databases

SignaLinkQ5S007.

Gene expression databases

ArrayExpressQ5S007.
BgeeQ5S007.
CleanExHS_LRRK2.
GenevestigatorQ5S007.

Family and domain databases

Gene3D1.25.10.10. 2 hits.
1.25.40.20. 1 hit.
2.130.10.10. 1 hit.
InterProIPR020683. Ankyrin_rpt-contain_dom.
IPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR011009. Kinase-like_dom.
IPR001611. Leu-rich_rpt.
IPR025875. Leu-rich_rpt_4.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR013684. MIRO-like.
IPR027417. P-loop_NTPase.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR020859. ROC_GTPase.
IPR008271. Ser/Thr_kinase_AS.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamPF00560. LRR_1. 1 hit.
PF12799. LRR_4. 1 hit.
PF08477. Miro. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSPR00449. RASTRNSFRMNG.
SMARTSM00369. LRR_TYP. 1 hit.
SM00320. WD40. 1 hit.
[Graphical view]
SUPFAMSSF48371. SSF48371. 2 hits.
SSF50978. SSF50978. 1 hit.
SSF52540. SSF52540. 1 hit.
SSF56112. SSF56112. 1 hit.
TIGRFAMsTIGR00231. small_GTP. 1 hit.
PROSITEPS51450. LRR. 11 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS51424. ROC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ5S007.
GeneWikiLRRK2.
GenomeRNAi120892.
NextBio80641.
PROQ5S007.
SOURCESearch...

Entry information

Entry nameLRRK2_HUMAN
AccessionPrimary (citable) accession number: Q5S007
Secondary accession number(s): A6NJU2, Q6ZS50, Q8NCX9
Entry history
Integrated into UniProtKB/Swiss-Prot: January 24, 2006
Last sequence update: April 20, 2010
Last modified: March 19, 2014
This is version 109 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM