Q5S007 (LRRK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Leucine-rich repeat serine/threonine-protein kinase 2
EC=2.7.11.1

Alternative name(s):
Dardarin

Gene names

Name:	LRRK2
Synonyms:	PARK8

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	2527 AA.
Sequence status	Complete.
Protein existence	Evidence 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
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 process	Autophagy
Cellular component	Cytoplasm Membrane Mitochondrion
Coding sequence diversity	Polymorphism
Disease	Disease mutation Neurodegeneration Parkinson disease Parkinsonism
Domain	Coiled coil Leucine-rich repeat Repeat
Ligand	ATP-binding GTP-binding Nucleotide-binding
Molecular function	GTPase activation Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of MAPKK activity Inferred from direct assay PubMed 19302196. Source: BHF-UCL autophagy Inferred from electronic annotation. Source: UniProtKB-KW 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 PubMed 21168496. Source: BHF-UCL negative regulation of dendritic spine morphogenesis Inferred from mutant phenotype PubMed 21168496. Source: BHF-UCL negative regulation of neuroblast proliferation Inferred from mutant phenotype PubMed 21168496. Source: BHF-UCL negative regulation of neuron maturation Inferred from mutant phenotype PubMed 21168496. 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_component	dendrite cytoplasm Inferred from direct assay PubMed 21696411. Source: BHF-UCL external side of mitochondrial outer membrane Inferred from direct assay Ref.7. Source: UniProtKB membrane raft Inferred from electronic annotation. Source: Compara neuronal cell body Inferred from direct assay PubMed 21048939PubMed 21696411. Source: BHF-UCL plasma membrane Inferred from electronic annotation. Source: Compara synaptic vesicle Inferred from electronic annotation. Source: Compara trans-Golgi network Inferred from electronic annotation. Source: Compara
Molecular_function	ATP 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
itself		66	EBI-5323863,EBI-5323863
ARFGAP1	Q8N6T3-2	6	EBI-5323863,EBI-6288865
Arfgap1	Q62848	7	EBI-5323863,EBI-4398879	From a different organism.
ARHGEF7	Q14155	6	EBI-5323863,EBI-717515
CDC37	Q16543	6	EBI-5323863,EBI-295634
CDC42	P60953	3	EBI-5323863,EBI-81752
Ckmt1	P30275	2	EBI-5323863,EBI-773103	From a different organism.
DAPK1	P53355	2	EBI-5323863,EBI-358616
DNM1L	O00429	7	EBI-5323863,EBI-724571
DVL1	O14640-2	7	EBI-5323863,EBI-6504027
DVL2	O14641	3	EBI-5323863,EBI-740850
DVL3	Q92997	4	EBI-5323863,EBI-739789
LRP6	O75581	3	EBI-5323863,EBI-910915
LRRK1	Q38SD2	5	EBI-5323863,EBI-1050422
MAP2K3	P46734	3	EBI-5323863,EBI-602462
MAP2K6	P52564	4	EBI-5323863,EBI-448135
MAP2K7	O14733	3	EBI-5323863,EBI-492605
MSN	P26038	5	EBI-5323863,EBI-528768
NFATC2	Q13469	3	EBI-5323863,EBI-716258
PARK2	O60260	3	EBI-5323863,EBI-716346
RAC1	P63000	5	EBI-5323863,EBI-413628
SH3GL2	Q99962	2	EBI-5323863,EBI-77938
SNCA	P37840	6	EBI-5323863,EBI-985879
YWHAB	P31946	3	EBI-5323863,EBI-359815
YWHAE	P62258	3	EBI-5323863,EBI-356498
YWHAG	P61981	2	EBI-5323863,EBI-359832
YWHAH	Q04917	2	EBI-5323863,EBI-306940
YWHAQ	P27348	3	EBI-5323863,EBI-359854
YWHAZ	P63104	3	EBI-5323863,EBI-347088

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 2527

2527

Leucine-rich repeat serine/threonine-protein kinase 2

PRO_0000086238

Regions

Repeat

983 – 1004

22

LRR 1

Repeat

1012 – 1033

22

LRR 2

Repeat

1036 – 1057

22

LRR 3

Repeat

1059 – 1080

22

LRR 4

Repeat

1084 – 1105

22

LRR 5

Repeat

1108 – 1129

22

LRR 6

Repeat

1130 – 1150

21

LRR 7

Repeat

1174 – 1196

23

LRR 8

Repeat

1197 – 1218

22

LRR 9

Repeat

1221 – 1241

21

LRR 10

Repeat

1246 – 1267

22

LRR 11

Repeat

1269 – 1291

23

LRR 12

Domain

1328 – 1511

184

Roc

Domain

1879 – 2138

260

Protein kinase

Nucleotide binding

1341 – 1348

8

GTP Potential

Nucleotide binding

1885 – 1893

9

ATP By similarity

Nucleotide binding

2098 – 2121

24

GTP Potential

Nucleotide binding

2295 – 2298

4

GTP Potential

Coiled coil

319 – 348

30

Potential

Compositional bias

728 – 731

4

Poly-Leu

Sites

Active site

1994

1

Proton acceptor By similarity

Binding site

1906

1

ATP By similarity

Natural variations

Natural variant

50

1

R → H.
Corresponds to variant rs2256408 [ dbSNP | Ensembl ].

VAR_024931

Natural variant

119

1

L → P. Ref.31 Ref.41
Corresponds to variant rs33995463 [ dbSNP | Ensembl ].

VAR_024932

Natural variant

228

1

C → S. Ref.42
Corresponds to variant rs56108242 [ dbSNP | Ensembl ].

VAR_054740

Natural variant

419

1

A → V. Ref.41
Corresponds to variant rs34594498 [ dbSNP | Ensembl ].

VAR_033903

Natural variant

551

1

N → K. Ref.21 Ref.31 Ref.41 Ref.45
Corresponds to variant rs7308720 [ dbSNP | Ensembl ].

VAR_024933

Natural variant

712

1

M → V in PARK8. Ref.42

VAR_054741

Natural variant

716

1

A → V. Ref.42

VAR_054742

Natural variant

723

1

I → V. Ref.31 Ref.41 Ref.45
Corresponds to variant rs10878307 [ dbSNP | Ensembl ].

VAR_024934

Natural variant

755

1

P → L.
Corresponds to variant rs34410987 [ dbSNP | Ensembl ].

VAR_033904

Natural variant

793

1

R → M in PARK8; unknown pathological significance. Ref.21 Ref.31 Ref.34
Corresponds to variant rs35173587 [ dbSNP | Ensembl ].

VAR_024935

Natural variant

871

1

K → E. Ref.42

VAR_054743

Natural variant

930

1

Q → R in PARK8; unknown pathological significance. Ref.21

VAR_024936

Natural variant

944

1

D → Y.
Corresponds to variant rs17519916 [ dbSNP | Ensembl ].

VAR_024937

Natural variant

1067

1

R → Q in PARK8. Ref.33

VAR_024938

Natural variant

1096

1

S → C in PARK8; unknown pathological significance. Ref.21

VAR_024939

Natural variant

1122

1

I → V in PARK8. Ref.1 Ref.31
Corresponds to variant rs34805604 [ dbSNP | Ensembl ].

VAR_024940

Natural variant

1228

1

S → T in PARK8. Ref.21

VAR_024941

Natural variant

1262

1

P → A. Ref.31
Corresponds to variant rs4640000 [ dbSNP | Ensembl ].

VAR_024942

Natural variant

1359

1

K → I Found in a renal cell carcinoma sample; somatic mutation. Ref.43

VAR_064728

Natural variant

1371

1

I → V in PARK8; unknown pathological significance. Ref.23 Ref.32
Corresponds to variant rs17466213 [ dbSNP | Ensembl ].

VAR_024943

Natural variant

1375

1

D → E.
Corresponds to variant rs28365226 [ dbSNP | Ensembl ].

VAR_047022

Natural variant

1398

1

R → H. Ref.31 Ref.32 Ref.41 Ref.45
Corresponds to variant rs7133914 [ dbSNP | Ensembl ].

VAR_024944

Natural variant

1441

1

R → 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 variant

1441

1

R → G in PARK8. Ref.14 Ref.31 Ref.36 Ref.39
Corresponds to variant rs33939927 [ dbSNP | Ensembl ].

VAR_024946

Natural variant

1441

1

R → H in PARK8; pathogenicity has yet to be confirmed. Ref.31 Ref.35
Corresponds to variant rs34995376 [ dbSNP | Ensembl ].

VAR_024947

Natural variant

1514

1

R → 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 variant

1542

1

P → 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 variant

1550

1

R → Q in an ovarian mucinous carcinoma sample; somatic mutation. Ref.41

VAR_040678

Natural variant

1598

1

V → 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 variant

1628

1

R → 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 variant

1646

1

M → T. Ref.31 Ref.45
Corresponds to variant rs35303786 [ dbSNP | Ensembl ].

VAR_024952

Natural variant

1647

1

S → T. Ref.31 Ref.45
Corresponds to variant rs11564148 [ dbSNP | Ensembl ].

VAR_024953

Natural variant

1699

1

Y → C in PARK8. Ref.1 Ref.14 Ref.22 Ref.31
Corresponds to variant rs35801418 [ dbSNP | Ensembl ].

VAR_024954

Natural variant

1723

1

R → P in an ovarian serous carcinoma sample; somatic mutation. Ref.41

VAR_040679

Natural variant

1728

1

R → H in PARK8. Ref.42

VAR_054744

Natural variant

1728

1

R → L in PARK8. Ref.42

VAR_054745

Natural variant

1869

1

M → T in PARK8; pathogenicity has yet to be confirmed. Ref.31 Ref.34
Corresponds to variant rs35602796 [ dbSNP | Ensembl ].

VAR_024955

Natural variant

1870

1

L → F. Ref.42

VAR_054746

Natural variant

1941

1

R → H in PARK8. Ref.22

VAR_024956

Natural variant

2012

1

I → T in PARK8; pathogenicity uncertain. Ref.31
Corresponds to variant rs34015634 [ dbSNP | Ensembl ].

VAR_024957

Natural variant

2019

1

G → 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
Corresponds to variant rs34637584 [ dbSNP | Ensembl ].

VAR_024958

Natural variant

2020

1

I → 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 variant

2081

1

N → D. Ref.31 Ref.45
Corresponds to variant rs33995883 [ dbSNP | Ensembl ].

VAR_024960

Natural variant

2119

1

P → L. Ref.31
Corresponds to variant rs12423862 [ dbSNP | Ensembl ].

VAR_024961

Natural variant

2141

1

T → M in PARK8. Ref.42

VAR_054747

Natural variant

2143

1

R → H in PARK8. Ref.42

VAR_054748

Natural variant

2261

1

N → I. Ref.31
Corresponds to variant rs12581902 [ dbSNP | Ensembl ].

VAR_024962

Natural variant

2356

1

T → I in PARK8. Ref.22

VAR_024963

Natural variant

2385

1

G → 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 variant

2395

1

E → K. Ref.42

VAR_054749

Natural variant

2397

1

M → T. Ref.31 Ref.32 Ref.45
Corresponds to variant rs3761863 [ dbSNP | Ensembl ].

VAR_024965

Natural variant

2466

1

L → H in PARK8. Ref.42

VAR_054750

Experimental info

Sequence conflict

212

1

L → S in AAV63975. Ref.1

Secondary structure

1

.

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2527

Helix Strand Turn

Details...

Beta strand

1336 – 1341

6

Helix

1347 – 1354

8

Beta strand

1370 – 1377

8

Beta strand

1389 – 1395

7

Helix

1398 – 1402

5

Helix

1406 – 1411

6

Beta strand

1412 – 1420

9

Helix

1421 – 1423

3

Helix

1425 – 1429

5

Helix

1431 – 1441

11

Beta strand

1446 – 1452

7

Helix

1454 – 1456

3

Helix

1459 – 1472

14

Turn

1473 – 1475

3

Beta strand

1481 – 1487

7

Helix

1495 – 1509

15

Sequences

	Sequence		Length	Mass (Da)
	Q5S007 [UniParc]. Last modified April 20, 2010. Version 2. Checksum: 26142A0CECBBC3F4	FASTA	2,527	286,103
	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

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. , 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. , 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. , 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. , 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. , 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. , 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. , 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. , 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.
+	Additional computationally mapped references.

Web resources

GeneReviews

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.

IPI

IPI00175649.

RefSeq

NP_940980.3. NM_198578.3.

UniGene

Hs.187636.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ZEJ	X-ray	2.00	A/B	1333-1516	[»]
3D6T	X-ray	2.43	B	1336-1505	[»]

ProteinModelPortal

Q5S007.

SMR

Q5S007. Positions 1335-1512.

ModBase

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Protein-protein interaction databases

DIP

DIP-29684N.

IntAct

Q5S007. 75 interactions.

STRING

9606.ENSP00000298910.

PTM databases

PhosphoSite

Q5S007.

Polymorphism databases

DMDM

294862450.

Proteomic databases

PaxDb

Q5S007.

PRIDE

Q5S007.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000298910; ENSP00000298910; ENSG00000188906.

GeneID

120892.

KEGG

hsa:120892.

UCSC

uc001rmg.4. human.

Organism-specific databases

CTD

120892.

GeneCards

GC12P040590.

HGNC

HGNC:18618. LRRK2.

HPA

HPA014293.

MIM

168600. phenotype.
607060. phenotype.
609007. gene.

neXtProt

NX_Q5S007.

Orphanet

2828. Young adult-onset Parkinsonism.

PharmGKB

PA134968052.

GenAtlas

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Phylogenomic databases

eggNOG

COG4886.

HOGENOM

HOG000293315.

HOVERGEN

HBG081937.

InParanoid

Q5S007.

KO

K08844.

OMA

VMLSMLM.

Gene expression databases

ArrayExpress

Q5S007.

Bgee

Q5S007.

CleanEx

HS_LRRK2.

Genevestigator

Q5S007.

GermOnline

ENSG00000188906. Homo sapiens.

Family and domain databases

Gene3D

1.25.10.10. 2 hits.
1.25.40.20. 1 hit.
2.130.10.10. 1 hit.

InterPro

IPR020683. 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.
IPR000719. Prot_kinase_cat_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]

Pfam

PF00560. LRR_1. 1 hit.
PF12799. LRR_4. 1 hit.
PF08477. Miro. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]

PRINTS

PR00449. RASTRNSFRMNG.

SMART

SM00369. LRR_TYP. 1 hit.
SM00320. WD40. 1 hit.
[Graphical view]

SUPFAM

SSF48371. ARM-type_fold. 1 hit.
SSF56112. Kinase_like. 1 hit.
SSF50978. WD40_like. 1 hit.

TIGRFAMs

TIGR00231. small_GTP. 1 hit.

PROSITE

PS51450. 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]

ProtoNet

Search...

Other

BindingDB

Q5S007.

ChEMBL

CHEMBL1075104.

EvolutionaryTrace

Q5S007.

GenomeRNAi

120892.

NextBio

80641.

SOURCE

Search...

Entry information

Entry name

LRRK2_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 99 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.