Target Information
| Target General Information | Top | |||||
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| Target ID |
T09197
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| Target Name |
Leucine-rich repeat kinase 2 G2019S mutant (LRRK2 G2019S)
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| Synonyms |
PARK8 G2019S mutant; LRRK2 G2019S mutant; Dardarin G2019S mutant
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| Gene Name |
LRRK2
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| Target Type |
Patented-recorded target
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[1] | ||||
| Function |
The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes. 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. Regulates neuronal process morphology in the intact central nervous system (CNS). Plays a role in synaptic vesicle trafficking. Phosphorylates PRDX3. Has GTPase activity. May play a role in the phosphorylation of proteins central to Parkinson disease. Plays an important role in recuiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization. Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway.
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| BioChemical Class |
Kinase
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| UniProt ID | ||||||
| EC Number |
EC 2.7.11.1
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| Sequence |
MASGSCQGCEEDEETLKKLIVRLNNVQEGKQIETLVQILEDLLVFTYSERASKLFQGKNI
HVPLLIVLDSYMRVASVQQVGWSLLCKLIEVCPGTMQSLMGPQDVGNDWEVLGVHQLILK MLTVHNASVNLSVIGLKTLDLLLTSGKITLLILDEESDIFMLIFDAMHSFPANDEVQKLG CKALHVLFERVSEEQLTEFVENKDYMILLSALTNFKDEEEIVLHVLHCLHSLAIPCNNVE VLMSGNVRCYNIVVEAMKAFPMSERIQEVSCCLLHRLTLGNFFNILVLNEVHEFVVKAVQ QYPENAALQISALSCLALLTETIFLNQDLEEKNENQENDDEGEEDKLFWLEACYKALTWH RKNKHVQEAACWALNNLLMYQNSLHEKIGDEDGHFPAHREVMLSMLMHSSSKEVFQASAN ALSTLLEQNVNFRKILLSKGIHLNVLELMQKHIHSPEVAESGCKMLNHLFEGSNTSLDIM AAVVPKILTVMKRHETSLPVQLEALRAILHFIVPGMPEESREDTEFHHKLNMVKKQCFKN DIHKLVLAALNRFIGNPGIQKCGLKVISSIVHFPDALEMLSLEGAMDSVLHTLQMYPDDQ EIQCLGLSLIGYLITKKNVFIGTGHLLAKILVSSLYRFKDVAEIQTKGFQTILAILKLSA SFSKLLVHHSFDLVIFHQMSSNIMEQKDQQFLNLCCKCFAKVAMDDYLKNVMLERACDQN NSIMVECLLLLGADANQAKEGSSLICQVCEKESSPKLVELLLNSGSREQDVRKALTISIG KGDSQIISLLLRRLALDVANNSICLGGFCIGKVEPSWLGPLFPDKTSNLRKQTNIASTLA RMVIRYQMKSAVEEGTASGSDGNFSEDVLSKFDEWTFIPDSSMDSVFAQSDDLDSEGSEG SFLVKKKSNSISVGEFYRDAVLQRCSPNLQRHSNSLGPIFDHEDLLKRKRKILSSDDSLR SSKLQSHMRHSDSISSLASEREYITSLDLSANELRDIDALSQKCCISVHLEHLEKLELHQ NALTSFPQQLCETLKSLTHLDLHSNKFTSFPSYLLKMSCIANLDVSRNDIGPSVVLDPTV KCPTLKQFNLSYNQLSFVPENLTDVVEKLEQLILEGNKISGICSPLRLKELKILNLSKNH ISSLSENFLEACPKVESFSARMNFLAAMPFLPPSMTILKLSQNKFSCIPEAILNLPHLRS LDMSSNDIQYLPGPAHWKSLNLRELLFSHNQISILDLSEKAYLWSRVEKLHLSHNKLKEI PPEIGCLENLTSLDVSYNLELRSFPNEMGKLSKIWDLPLDELHLNFDFKHIGCKAKDIIR FLQQRLKKAVPYNRMKLMIVGNTGSGKTTLLQQLMKTKKSDLGMQSATVGIDVKDWPIQI RDKRKRDLVLNVWDFAGREEFYSTHPHFMTQRALYLAVYDLSKGQAEVDAMKPWLFNIKA RASSSPVILVGTHLDVSDEKQRKACMSKITKELLNKRGFPAIRDYHFVNATEESDALAKL RKTIINESLNFKIRDQLVVGQLIPDCYVELEKIILSERKNVPIEFPVIDRKRLLQLVREN QLQLDENELPHAVHFLNESGVLLHFQDPALQLSDLYFVEPKWLCKIMAQILTVKVEGCPK HPKGIISRRDVEKFLSKKRKFPKNYMSQYFKLLEKFQIALPIGEEYLLVPSSLSDHRPVI ELPHCENSEIIIRLYEMPYFPMGFWSRLINRLLEISPYMLSGRERALRPNRMYWRQGIYL NWSPEAYCLVGSEVLDNHPESFLKITVPSCRKGCILLGQVVDHIDSLMEEWFPGLLEIDI CGEGETLLKKWALYSFNDGEEHQKILLDDLMKKAEEGDLLVNPDQPRLTIPISQIAPDLI LADLPRNIMLNNDELEFEQAPEFLLGDGSFGSVYRAAYEGEEVAVKIFNKHTSLRLLRQE LVVLCHLHHPSLISLLAAGIRPRMLVMELASKGSLDRLLQQDKASLTRTLQHRIALHVAD GLRYLHSAMIIYRDLKPHNVLLFTLYPNAAIIAKIADYGIAQYCCRMGIKTSEGTPGFRA PEVARGNVIYNQQADVYSFGLLLYDILTTGGRIVEGLKFPNEFDELEIQGKLPDPVKEYG CAPWPMVEKLIKQCLKENPQERPTSAQVFDILNSAELVCLTRRILLPKNVIVECMVATHH NSRNASIWLGCGHTDRGQLSFLDLNTEGYTSEEVADSRILCLALVHLPVEKESWIVSGTQ SGTLLVINTEDGKKRHTLEKMTDSVTCLYCNSFSKQSKQKNFLLVGTADGKLAIFEDKTV KLKGAAPLKILNIGNVSTPLMCLSESTNSTERNVMWGGCGTKIFSFSNDFTIQKLIETRT SQLFSYAAFSDSNIITVVVDTALYIAKQNSPVVEVWDKKTEKLCGLIDCVHFLREVMVKE NKESKHKMSYSGRVKTLCLQKNTALWIGTGGGHILLLDLSTRRLIRVIYNFCNSVRVMMT AQLGSLKNVMLVLGYNRKNTEGTQKQKEIQSCLTVWDINLPHEVQNLEKHIEVRKELAEK MRRTSVE Click to Show/Hide
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| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Adenosine triphosphate | Ligand Info | |||||
| Structure Description | Structure of the LRRK2 G2019S mutant | PDB:7LI3 | ||||
| Method | Electron microscopy | Resolution | 3.80 Å | Mutation | Yes | [2] |
| PDB Sequence |
GIQKCGLKVI
567 SSIVHFPDAL577 GAMDSVLHTL593 QMYPDDQEIQ603 CLGLSLIGYG624 HLLAKILVSS 634 LYRFKDVAEI644 QTKGFQTILA654 ILKLSASFSK664 LLVHHSFDLV674 IFHQMSSNIM 684 EQKDQQFLNL694 CCKCFAKVAM704 DDYLKNVMLE714 RACDQNNSIM724 VECLLLLGAD 734 ANQAKEGSSL744 ICQVCEKESS754 PKLVELLLNS764 GSREQDVRKA774 LTISIGKGDS 784 QIISLLLRRL794 ALDVANNSIC804 LGGFCIGKVE814 PSWLGPLFPD824 KTSNLRKQTN 834 IASTLARMVI844 RYQMKSAVEE854 REYITSLDLS990 ANELRDIDAL1000 SQKCCISVHL 1010 EHLEKLELHQ1020 NALTSFPQQL1030 CETLKSLTHL1040 DLHSNKFTSF1050 PSYLLKMSCI 1060 ANLDVSRNDI1070 GPSVVLDPTV1080 KCPTLKQFNL1090 SYNQLSFVPE1100 NLTDVVEKLE 1110 QLILEGNKIS1120 GICSPLRLKE1130 LKILNLSKNH1140 ISSLSENFLE1150 ACPKVESFSA 1160 RMNFLAAMPF1170 LPPSMTILKL1180 SQNKFSCIPE1190 AILNLPHLRS1200 LDMSSNDIQY 1210 LPGPAHWKSL1220 NLRELLFSHN1230 QISILDLSEK1240 AYLWSRVEKL1250 HLSHNKLKEI 1260 PPEIGCLENL1270 TSLDVSYNLE1280 LRSFPNEMGK1290 LSKIWDLPLD1300 ELHLNFDFKH 1310 IGCKAKDIIR1320 FLQQRLKKAV1330 PYNRMKLMIV1340 GNTGSGKTTL1350 LQQLMKTKKS 1360 DLGMQSATVG1370 IDVKDWPIQI1380 RDKRKRDLVL1390 NVWDFAGREE1400 FYSTHPHFMT 1410 QRALYLAVYD1420 LSKGQAEVDA1430 MKPWLFNIKA1440 RASSSPVILV1450 GTHLDVSKAC 1465 MSKITKELLN1475 KRGFPAIRDY1485 HFVNATEESD1495 ALAKLRKTII1505 NESLNFKIRD 1515 QLVVGQLIPD1525 CYVELEKIIL1535 SERKNVPIEF1545 PVIDRKRLLQ1555 LVRENQLQLD 1565 ENELPHAVHF1575 LNESGVLLHF1585 QDPALQLSDL1595 YFVEPKWLCK1605 IMAQILTVKV 1615 EGCPKHPKGI1625 ISRRDPKNYM1646 TQYFKLLEKF1656 QIALVPSSLS1674 DHRPVIELPH 1684 CENSEIIIRL1694 YEMPYFPMGF1704 WSRLINRLLE1714 ISPYMLALRP1729 NRMYWRQGIY 1739 LNWSPEAYCL1749 VGSEVLDNHP1759 ESFLKITVPS1769 CRKGCILLGQ1779 VVDHIDSLME 1789 EWFPGLLEID1799 ICGEGETLLK1809 KWALYSFNDG1819 EEHQKILLDD1829 LMKKAEEGDL 1839 LVNPDQPRLT1849 IPISQIAPDL1859 ILADLPRNIM1869 LNNDELEFEQ1879 APEFLLGDGS 1889 FGSVYRAAYE1899 GEEVAVKIFN1909 KHTSLRLLRQ1919 ELVVLCHLHH1929 PSLISLLAAG 1939 IRPRMLVMEL1949 ASKGSLDRLL1959 QQDKASLTRT1969 LQHRIALHVA1979 DGLRYLHSAM 1989 IIYRDLKPHN1999 VLLFTLYPNA2009 AIIAKIADYS2019 IAQYCCRMTS2032 EGTPGFRAPE 2042 VARGNVIYNQ2052 QADVYSFGLL2062 LYDILTTGGR2072 IVEGLKFPNE2082 FDELEIQGKL 2092 PDPVKEYGCA2102 PWPMVEKLIK2112 QCLKENPQER2122 PTSAQVFDIL2132 NSAELVCLTR 2142 RILLPKNVIV2152 ECMVATHHNS2162 RNASIWLGCG2172 HTDRGQLSFL2182 DLNTEGYTSE 2192 EVADSRILCL2202 ALVHLPVEKE2212 SWIVSGTQSG2222 TLLVINTEDG2232 KKRHTLEKMT 2242 DSVTCLYCNS2252 FSKQSKQKNF2262 LLVGTADGKL2272 AIFEDKTVKL2282 KGAAPLKILN 2292 IGNVSTPLMC2302 LSESTNSTER2312 NVMWGGCGTK2322 IFSFSNDFTI2332 QKLIETRTSQ 2342 LFSYAAFSDS2352 NIITVVVDTA2362 LYIAKQNSPV2372 VEVWDKKTEK2382 LCGLIDCVHF 2392 LREVTVKENK2402 ESKHKMSYSG2412 RVKTLCLQKN2422 TALWIGTGGG2432 HILLLDLSTR 2442 RLIRVIYNFC2452 NSVRVMMTAQ2462 LGSLKNVMLV2472 LGYNRKNTEG2482 TQKQKEIQSC 2492 LTVWDINLPH2502 EVQNLEKHIE2512 VRKELAEKMR2522 RTSVE
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| Ligand Name: Guanosine-5'-Diphosphate | Ligand Info | |||||
| Structure Description | Structure of the LRRK2 G2019S mutant | PDB:7LI3 | ||||
| Method | Electron microscopy | Resolution | 3.80 Å | Mutation | Yes | [2] |
| PDB Sequence |
GIQKCGLKVI
567 SSIVHFPDAL577 GAMDSVLHTL593 QMYPDDQEIQ603 CLGLSLIGYG624 HLLAKILVSS 634 LYRFKDVAEI644 QTKGFQTILA654 ILKLSASFSK664 LLVHHSFDLV674 IFHQMSSNIM 684 EQKDQQFLNL694 CCKCFAKVAM704 DDYLKNVMLE714 RACDQNNSIM724 VECLLLLGAD 734 ANQAKEGSSL744 ICQVCEKESS754 PKLVELLLNS764 GSREQDVRKA774 LTISIGKGDS 784 QIISLLLRRL794 ALDVANNSIC804 LGGFCIGKVE814 PSWLGPLFPD824 KTSNLRKQTN 834 IASTLARMVI844 RYQMKSAVEE854 REYITSLDLS990 ANELRDIDAL1000 SQKCCISVHL 1010 EHLEKLELHQ1020 NALTSFPQQL1030 CETLKSLTHL1040 DLHSNKFTSF1050 PSYLLKMSCI 1060 ANLDVSRNDI1070 GPSVVLDPTV1080 KCPTLKQFNL1090 SYNQLSFVPE1100 NLTDVVEKLE 1110 QLILEGNKIS1120 GICSPLRLKE1130 LKILNLSKNH1140 ISSLSENFLE1150 ACPKVESFSA 1160 RMNFLAAMPF1170 LPPSMTILKL1180 SQNKFSCIPE1190 AILNLPHLRS1200 LDMSSNDIQY 1210 LPGPAHWKSL1220 NLRELLFSHN1230 QISILDLSEK1240 AYLWSRVEKL1250 HLSHNKLKEI 1260 PPEIGCLENL1270 TSLDVSYNLE1280 LRSFPNEMGK1290 LSKIWDLPLD1300 ELHLNFDFKH 1310 IGCKAKDIIR1320 FLQQRLKKAV1330 PYNRMKLMIV1340 GNTGSGKTTL1350 LQQLMKTKKS 1360 DLGMQSATVG1370 IDVKDWPIQI1380 RDKRKRDLVL1390 NVWDFAGREE1400 FYSTHPHFMT 1410 QRALYLAVYD1420 LSKGQAEVDA1430 MKPWLFNIKA1440 RASSSPVILV1450 GTHLDVSKAC 1465 MSKITKELLN1475 KRGFPAIRDY1485 HFVNATEESD1495 ALAKLRKTII1505 NESLNFKIRD 1515 QLVVGQLIPD1525 CYVELEKIIL1535 SERKNVPIEF1545 PVIDRKRLLQ1555 LVRENQLQLD 1565 ENELPHAVHF1575 LNESGVLLHF1585 QDPALQLSDL1595 YFVEPKWLCK1605 IMAQILTVKV 1615 EGCPKHPKGI1625 ISRRDPKNYM1646 TQYFKLLEKF1656 QIALVPSSLS1674 DHRPVIELPH 1684 CENSEIIIRL1694 YEMPYFPMGF1704 WSRLINRLLE1714 ISPYMLALRP1729 NRMYWRQGIY 1739 LNWSPEAYCL1749 VGSEVLDNHP1759 ESFLKITVPS1769 CRKGCILLGQ1779 VVDHIDSLME 1789 EWFPGLLEID1799 ICGEGETLLK1809 KWALYSFNDG1819 EEHQKILLDD1829 LMKKAEEGDL 1839 LVNPDQPRLT1849 IPISQIAPDL1859 ILADLPRNIM1869 LNNDELEFEQ1879 APEFLLGDGS 1889 FGSVYRAAYE1899 GEEVAVKIFN1909 KHTSLRLLRQ1919 ELVVLCHLHH1929 PSLISLLAAG 1939 IRPRMLVMEL1949 ASKGSLDRLL1959 QQDKASLTRT1969 LQHRIALHVA1979 DGLRYLHSAM 1989 IIYRDLKPHN1999 VLLFTLYPNA2009 AIIAKIADYS2019 IAQYCCRMTS2032 EGTPGFRAPE 2042 VARGNVIYNQ2052 QADVYSFGLL2062 LYDILTTGGR2072 IVEGLKFPNE2082 FDELEIQGKL 2092 PDPVKEYGCA2102 PWPMVEKLIK2112 QCLKENPQER2122 PTSAQVFDIL2132 NSAELVCLTR 2142 RILLPKNVIV2152 ECMVATHHNS2162 RNASIWLGCG2172 HTDRGQLSFL2182 DLNTEGYTSE 2192 EVADSRILCL2202 ALVHLPVEKE2212 SWIVSGTQSG2222 TLLVINTEDG2232 KKRHTLEKMT 2242 DSVTCLYCNS2252 FSKQSKQKNF2262 LLVGTADGKL2272 AIFEDKTVKL2282 KGAAPLKILN 2292 IGNVSTPLMC2302 LSESTNSTER2312 NVMWGGCGTK2322 IFSFSNDFTI2332 QKLIETRTSQ 2342 LFSYAAFSDS2352 NIITVVVDTA2362 LYIAKQNSPV2372 VEVWDKKTEK2382 LCGLIDCVHF 2392 LREVTVKENK2402 ESKHKMSYSG2412 RVKTLCLQKN2422 TALWIGTGGG2432 HILLLDLSTR 2442 RLIRVIYNFC2452 NSVRVMMTAQ2462 LGSLKNVMLV2472 LGYNRKNTEG2482 TQKQKEIQSC 2492 LTVWDINLPH2502 EVQNLEKHIE2512 VRKELAEKMR2522 RTSVE
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THR1343
3.874
GLY1344
3.342
SER1345
2.683
GLY1346
3.946
LYS1347
3.077
THR1348
3.185
THR1349
3.189
MET1364
3.848
GLN1365
3.499
SER1366
4.713
ALA1367
4.274
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Similarity Proteins
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| References | Top | |||||
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| REF 1 | Leucine-rich repeat kinase 2 inhibitors: a patent review (2014-2016).Expert Opin Ther Pat. 2017 Jun;27(6):667-676. | |||||
| REF 2 | Structural analysis of the full-length human LRRK2. Cell. 2021 Jun 24;184(13):3519-3527.e10. | |||||
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