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IID00844
 UniprotQ5S007
ProteinLeucine-rich repeat serine/threonine-protein kinase 2
GeneLRRK2
OrganismHomo sapiens
Sequence LLPS PhaSepDB
PhaSePro
LLPSDB
DrLLPS Network xml rdf
Structure
Experiment
  :order   disorder   conflict   PDB cluster   ProS   Pfam Domain   SEG
2527
 order/disorder by at least rule
     disorder by at least rule
     order by at least rule
 order/disorder by majority rule
Seq 904-941 Hetero dimer : IID00301Complex
 Evidence X-RAY 5myc P Reference
       Region 5myc P 904-906 disorder
       Region 5myc P 907-918 order
       Region 5myc P 919-941 disorder
Seq 929-941 Hetero tetramer : IID00301Complex
 Evidence X-RAY 5my9 P Reference
       Region 5my9 P 929-932 disorder
       Region 5my9 P 933-936 order
       Region 5my9 P 937-941 disorder
Seq 1329-1520 Homo dimer :
 Evidence X-RAY 2zej A Reference
       Region 2zej A 1333-1334 disorder
       Region 2zej A 1335-1356 order
       Region 2zej A 1357-1367 disorder
       Region 2zej A 1368-1378 order
       Region 2zej A 1379-1387 disorder
       Region 2zej A 1388-1511 order
       Region 2zej A 1512-1516 disorder
 Evidence X-RAY 2zej B Reference
       Region 2zej B 1333-1334 disorder
       Region 2zej B 1335-1357 order
       Region 2zej B 1358-1364 disorder
       Region 2zej B 1365-1378 order
       Region 2zej B 1379-1387 disorder
       Region 2zej B 1388-1512 order
       Region 2zej B 1513-1516 disorder
 Evidence X-RAY 6oje A Reference
       Region 6oje A 1329-1332 disorder
       Region 6oje A 1333-1518 order
       Region 6oje A 1519-1520 disorder
 Evidence X-RAY 6oje B Reference
       Region 6oje B 1329-1332 disorder
       Region 6oje B 1333-1519 order
       Region 6oje B 1520-1520 disorder
 Evidence X-RAY 6ojf A Reference
       Region 6ojf A 1329-1331 disorder
       Region 6ojf A 1332-1519 order
       Region 6ojf A 1520-1520 disorder
 Evidence X-RAY 6ojf B Reference
       Region 6ojf B 1329-1331 disorder
       Region 6ojf B 1332-1517 order
       Region 6ojf B 1518-1520 disorder
 Evidence X-RAY 6xaf A Reference
       Region 6xaf A 1329-1334 disorder
       Region 6xaf A 1335-1356 order
       Region 6xaf A 1357-1364 disorder
       Region 6xaf A 1365-1514 order
       Region 6xaf A 1515-1520 disorder
 Evidence X-RAY 6xaf B Reference
       Region 6xaf B 1329-1333 disorder
       Region 6xaf B 1334-1356 order
       Region 6xaf B 1357-1364 disorder
       Region 6xaf B 1365-1515 order
       Region 6xaf B 1516-1520 disorder
Seq 1335-1505 Monomer :
 Evidence X-RAY 3d6t B Reference
       Region 3d6t B 1335-1351 order
       Region 3d6t B 1352-1352 disorder
       Region 3d6t B 1353-1355 order
       Region 3d6t B 1356-1369 disorder
       Region 3d6t B 1370-1377 order
       Region 3d6t B 1378-1387 disorder
       Region 3d6t B 1388-1390 order
       Region 3d6t B 1391-1391 disorder
       Region 3d6t B 1392-1458 order
       Region 3d6t B 1459-1467 disorder
       Region 3d6t B 1468-1469 order
       Region 3d6t B 1470-1472 disorder
       Region 3d6t B 1473-1474 order
       Region 3d6t B 1475-1477 disorder
       Region 3d6t B 1478-1494 order
       Region 3d6t B 1495-1499 disorder
       Region 3d6t B 1500-1505 order
Seq 2142-2527 Homo dimer :
 Evidence X-RAY 6dlo B Reference
       Region 6dlo B 2142-2159 order
       Region 6dlo B 2160-2164 disorder
       Region 6dlo B 2165-2251 order
       Region 6dlo B 2252-2259 disorder
       Region 6dlo B 2260-2304 order
       Region 6dlo B 2305-2313 disorder
       Region 6dlo B 2314-2395 order
       Region 6dlo B 2396-2407 disorder
       Region 6dlo B 2408-2420 order
       Region 6dlo B 2421-2423 disorder
       Region 6dlo B 2424-2476 order
       Region 6dlo B 2477-2487 disorder
       Region 6dlo B 2488-2498 order
       Region 6dlo B 2499-2527 disorder
 Evidence X-RAY 6dlo A Reference
       Region 6dlo A 2142-2158 order
       Region 6dlo A 2159-2163 disorder
       Region 6dlo A 2164-2253 order
       Region 6dlo A 2254-2258 disorder
       Region 6dlo A 2259-2305 order
       Region 6dlo A 2306-2313 disorder
       Region 6dlo A 2314-2395 order
       Region 6dlo A 2396-2407 disorder
       Region 6dlo A 2408-2462 order
       Region 6dlo A 2463-2467 disorder
       Region 6dlo A 2468-2477 order
       Region 6dlo A 2478-2487 disorder
       Region 6dlo A 2488-2496 order
       Region 6dlo A 2497-2527 disorder
 Evidence X-RAY 6dlp B Reference
       Region 6dlp B 2142-2159 order
       Region 6dlp B 2160-2164 disorder
       Region 6dlp B 2165-2251 order
       Region 6dlp B 2252-2259 disorder
       Region 6dlp B 2260-2304 order
       Region 6dlp B 2305-2313 disorder
       Region 6dlp B 2314-2395 order
       Region 6dlp B 2396-2407 disorder
       Region 6dlp B 2408-2420 order
       Region 6dlp B 2421-2423 disorder
       Region 6dlp B 2424-2476 order
       Region 6dlp B 2477-2487 disorder
       Region 6dlp B 2488-2498 order
       Region 6dlp B 2499-2527 disorder
 Evidence X-RAY 6dlp A Reference
       Region 6dlp A 2142-2158 order
       Region 6dlp A 2159-2163 disorder
       Region 6dlp A 2164-2253 order
       Region 6dlp A 2254-2258 disorder
       Region 6dlp A 2259-2305 order
       Region 6dlp A 2306-2313 disorder
       Region 6dlp A 2314-2395 order
       Region 6dlp A 2396-2407 disorder
       Region 6dlp A 2408-2462 order
       Region 6dlp A 2463-2467 disorder
       Region 6dlp A 2468-2477 order
       Region 6dlp A 2478-2487 disorder
       Region 6dlp A 2488-2496 order
       Region 6dlp A 2497-2527 disorder
SeqProS predicted 907-918 This region is predicted to be disordered by NeProc and AlphaFold (pLDDT < 68.5). Hetero dimer : IID00301Complex
       Region 5myc P 907-918 order
SeqProS predicted 933-936 This region is predicted to be disordered by NeProc and AlphaFold (pLDDT < 68.5). Hetero tetramer : IID00301Complex
       Region 5my9 P 933-936 order
Seqphosphorylation
    910-910 Phosphoserine
    935-935 Phosphoserine
    955-955 Phosphoserine
    973-973 Phosphoserine
    1292-1292 Phosphoserine
    1444-1444 Phosphoserine
 
Prediction
NeProc
Disorder 1-10,332-343,855-862,893-940,2481-2485,2522-2527
Order 11-331,344-849,863-892,941-2397,2408-2480,2486-2521
ProS 5-10,858-862,893-940,2481-2485
AlphaFold
Disorder 1-12,26-30,96-114,146-146,156-157,245-247,280-280,327-348,393-393,473-475,514-527,529-529,574-574,616-622,686-687,738-742,752-753,765-766,768-768,795-800,807-807,821-834,849-982,1003-1005,1306-1314,1320-1320,1324-1329,1357-1369,1380-1386,1397-1401,1403-1403,1440-1440,1475-1478,1513-1516,1565-1568,1586-1593,1611-1623,1639-1639,1718-1727,1756-1757,1790-1790,1793-1794,1797-1807,1837-1838,1888-1890,1909-1913,1926-1926,2019-2019,2023-2034,2045-2049,2071-2071,2073-2090,2159-2164,2251-2260,2308-2310,2312-2312,2395-2411,2464-2465,2477-2489,2523-2527
Order 13-25,31-95,115-145,147-155,158-244,248-279,281-326,349-392,394-472,476-513,528-528,530-573,575-615,623-685,688-737,743-751,754-764,767-767,769-794,801-806,808-820,835-848,983-1002,1006-1305,1315-1319,1321-1323,1330-1356,1370-1379,1387-1396,1402-1402,1404-1439,1441-1474,1479-1512,1517-1564,1569-1585,1594-1610,1624-1638,1640-1717,1728-1755,1758-1789,1791-1792,1795-1796,1808-1836,1839-1887,1891-1908,1914-1925,1927-2018,2020-2022,2035-2044,2050-2070,2072-2072,2091-2158,2165-2250,2261-2307,2311-2311,2313-2394,2412-2463,2466-2476,2490-2522
Pfam Hmmer
PF08477 1336-1455 1.5e-34
PF00069 1879-2132 1.5e-35
SEG 325-346 ,890-901 ,950-966 ,1009-1019
Function
Function in SwissProt
Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking (PubMed:20949042, PubMed:22012985, PubMed:26824392, PubMed:27830463, PubMed:29125462, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:30635421, PubMed:21850687, PubMed:23395371, PubMed:17114044, PubMed:24687852, PubMed:26014385, PubMed:25201882). Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed:26824392, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:29125462, PubMed:30635421). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB35, and RAB43 (PubMed:26824392, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:29125462, PubMed:30635421, PubMed:23395371). Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (PubMed:26824392). Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (PubMed:26824392). Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed:29125462, PubMed:30398148). Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose-6-phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner (PubMed:23395371). Regulates neuronal process morphology in the intact central nervous system (CNS) (PubMed:17114044). Plays a role in synaptic vesicle trafficking (PubMed:24687852). Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed:25201882). Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (PubMed:22012985). The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (PubMed:22012985). Phosphorylates PRDX3 (PubMed:21850687). By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis (PubMed:28720718). Acts as a positive regulator of innate immunity by mediating phosphorylation of RIPK2 downstream of NOD1 and NOD2, thereby enhancing RIPK2 activation (PubMed:27830463). Independent of its kinase activity, inhibits the proteasomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (PubMed:26014385). In addition, has GTPase activity via its Roc domain which regulates LRRK2 kinase activity (PubMed:18230735, PubMed:26824392, PubMed:29125462, PubMed:28720718, PubMed:29212815).