Descriptions

Leucine-rich repeat serine/threonine-protein kinase 1 (LRRK1) is a protein involved in the negative regulation of bone mass, acting through the maturation of osteoclasts. In contrast to the mechanism of autoinhibition that occurs in LRRK2, the autoinhibition of LRRK1 is mediated by a steric mechanism involving the ANK domain, which blocks access to the active site of the kinase domain in a dimer-dependent manner. In contrast, the interaction of the N-terminal LRR domain with the N-lobe of the kinase domain contributes to the alleviation of autoinhibition by changing its position relative to the WD40 domain, exposing the exposure of the active site of the kinase domain. The autoinhibited dimer of LRRK1 could be stabilized by a loop (1791-1907) in the WD40 domain. In addition, the kinase activity of LRRK1 is also regulated by the interaction of its COR-B loop with the kinase domain. Phosphorylation of three residues (S1064, T1074, and S1075) in the autoinhibitory COR-B loop significantly increases the kinase activity of LRRK1. Phosphorylation by Rab7a, resulting in the F1065A mutation, also alleviates the autoinhibited state of LRRK1.

Autoinhibitory domains (AIDs)

Target domain

1719-1721 (N-lobe of kinase domain)

Relief mechanism

Partner binding, Cleavage

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for Q9TZM3

Entry ID Method Resolution Chain Position Source
AF-Q9TZM3-F1 Predicted AlphaFoldDB

No variants for Q9TZM3

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q9TZM3

No associated diseases with Q9TZM3

7 regional properties for Q9TZM3

Type Name Position InterPro Accession
domain CARD domain 1087 - 1170 IPR001315
repeat Leucine-rich repeat 687 - 709 IPR001611
domain NACHT nucleoside triphosphatase 131 - 440 IPR007111
domain FIIND domain 794 - 1077 IPR025307
domain CARD8/ASC/NALP1, CARD domain 1087 - 1167 IPR033516
domain NOD2, winged helix domain 370 - 424 IPR041075
domain NACHT, LRR and PYD domains-containing protein, helical domain HD2 426 - 537 IPR041267

Functions

Description
EC Number 2.7.11.1 Protein-serine/threonine kinases
Subcellular Localization
  • Golgi apparatus
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

3 GO annotations of cellular component

Name Definition
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
Golgi apparatus A membrane-bound cytoplasmic organelle of the endomembrane system that further processes the core oligosaccharides (e.g. N-glycans) added to proteins in the endoplasmic reticulum and packages them into membrane-bound vesicles. The Golgi apparatus operates at the intersection of the secretory, lysosomal, and endocytic pathways.
neuronal cell body The portion of a neuron that includes the nucleus, but excludes cell projections such as axons and dendrites.

5 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
GTP binding Binding to GTP, guanosine triphosphate.
metal ion binding Binding to a metal ion.
protein serine kinase activity Catalysis of the reactions
protein serine/threonine kinase activity Catalysis of the reactions

7 GO annotations of biological process

Name Definition
axon extension involved in axon guidance The long distance growth of a single cell process, that is involved in the migration of an axon growth cone, where the migration is directed to a specific target site by a combination of attractive and repulsive cues.
negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway Any process that stops, prevents or reduces the frequency, rate or extent of an endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway.
phosphorylation The process of introducing a phosphate group into a molecule, usually with the formation of a phosphoric ester, a phosphoric anhydride or a phosphoric amide.
protein localization Any process in which a protein is transported to, or maintained in, a specific location.
response to endoplasmic reticulum stress Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stress acting at the endoplasmic reticulum. ER stress usually results from the accumulation of unfolded or misfolded proteins in the ER lumen.
response to oxidative stress Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of oxidative stress, a state often resulting from exposure to high levels of reactive oxygen species, e.g. superoxide anions, hydrogen peroxide (H2O2), and hydroxyl radicals.
synaptic vesicle transport The directed movement of synaptic vesicles.

91 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
A2VDU3 MAP3K7 Mitogen-activated protein kinase kinase kinase 7 Bos taurus (Bovine) SS
Q4TVR5 DSTYK Dual serine/threonine and tyrosine protein kinase Bos taurus (Bovine) PR
Q3SZJ2 RIPK2 Receptor-interacting serine/threonine-protein kinase 2 Bos taurus (Bovine) PR
Q3MHH9 ECM2 Extracellular matrix protein 2 Bos taurus (Bovine) PR
P58874 OPTC Opticin Bos taurus (Bovine) PR
Q24K06 LRRC10 Leucine-rich repeat-containing protein 10 Bos taurus (Bovine) PR
Q6XUX0 DSTYK Dual serine/threonine and tyrosine protein kinase Gallus gallus (Chicken) PR
Q04861 NFKB1 Nuclear factor NF-kappa-B p105 subunit Gallus gallus (Chicken) SS
P98150 NFKB2 Nuclear factor NF-kappa-B p100 subunit Gallus gallus (Chicken) SS
P83104 Takl1 Putative mitogen-activated protein kinase kinase kinase 7-like Drosophila melanogaster (Fruit fly) PR
Q95UN8 slpr Mitogen-activated protein kinase kinase kinase Drosophila melanogaster (Fruit fly) EV
Q94527 Rel Nuclear factor NF-kappa-B p110 subunit Drosophila melanogaster (Fruit fly) EV
Q9V780 Lap1 Protein lap1 Drosophila melanogaster (Fruit fly) PR
O43353 RIPK2 Receptor-interacting serine/threonine-protein kinase 2 Homo sapiens (Human) PR
Q02779 MAP3K10 Mitogen-activated protein kinase kinase kinase 10 Homo sapiens (Human) SS
Q8NB16 MLKL Mixed lineage kinase domain-like protein Homo sapiens (Human) EV
Q16584 MAP3K11 Mitogen-activated protein kinase kinase kinase 11 Homo sapiens (Human) EV
P00540 MOS Proto-oncogene serine/threonine-protein kinase mos Homo sapiens (Human) PR
Q5TCX8 MAP3K21 Mitogen-activated protein kinase kinase kinase 21 Homo sapiens (Human) PR
Q6XUX3 DSTYK Dual serine/threonine and tyrosine protein kinase Homo sapiens (Human) PR
O43318 MAP3K7 Mitogen-activated protein kinase kinase kinase 7 Homo sapiens (Human) SS
Q9NYL2 MAP3K20 Mitogen-activated protein kinase kinase kinase 20 Homo sapiens (Human) PR
P80192 MAP3K9 Mitogen-activated protein kinase kinase kinase 9 Homo sapiens (Human) SS
P19838 NFKB1 Nuclear factor NF-kappa-B p105 subunit Homo sapiens (Human) SS
Q99549 MPHOSPH8 M-phase phosphoprotein 8 Homo sapiens (Human) PR
Q00653 NFKB2 Nuclear factor NF-kappa-B p100 subunit Homo sapiens (Human) SS
Q8N9B4 ANKRD42 Ankyrin repeat domain-containing protein 42 Homo sapiens (Human) PR
Q6ZVZ8 ASB18 Ankyrin repeat and SOCS box protein 18 Homo sapiens (Human) PR
Q96NW7 LRRC7 Leucine-rich repeat-containing protein 7 Homo sapiens (Human) PR
Q8IWT6 LRRC8A Volume-regulated anion channel subunit LRRC8A Homo sapiens (Human) PR
Q9HCJ2 LRRC4C Leucine-rich repeat-containing protein 4C Homo sapiens (Human) PR
Q9UFC0 LRWD1 Leucine-rich repeat and WD repeat-containing protein 1 Homo sapiens (Human) PR
Q96L50 LRR1 Leucine-rich repeat protein 1 Homo sapiens (Human) PR
Q86UN2 RTN4RL1 Reticulon-4 receptor-like 1 Homo sapiens (Human) PR
Q8IWK6 ADGRA3 Adhesion G protein-coupled receptor A3 Homo sapiens (Human) PR
Q7L1W4 LRRC8D Volume-regulated anion channel subunit LRRC8D Homo sapiens (Human) PR
Q96FE5 LINGO1 Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 1 Homo sapiens (Human) PR
Q8TDW0 LRRC8C Volume-regulated anion channel subunit LRRC8C Homo sapiens (Human) PR
Q38SD2 LRRK1 Leucine-rich repeat serine/threonine-protein kinase 1 Homo sapiens (Human) EV
Q80XI6 Map3k11 Mitogen-activated protein kinase kinase kinase 11 Mus musculus (Mouse) PR
Q8VDG6 Map3k21 Mitogen-activated protein kinase kinase kinase 21 Mus musculus (Mouse) PR
P58801 Ripk2 Receptor-interacting serine/threonine-protein kinase 2 Mus musculus (Mouse) PR
Q62073 Map3k7 Mitogen-activated protein kinase kinase kinase 7 Mus musculus (Mouse) EV
Q3U1V8 Map3k9 Mitogen-activated protein kinase kinase kinase 9 Mus musculus (Mouse) SS
Q9D2Y4 Mlkl Mixed lineage kinase domain-like protein Mus musculus (Mouse) SS
Q9ESL4 Map3k20 Mitogen-activated protein kinase kinase kinase 20 Mus musculus (Mouse) PR
P00536 Mos Proto-oncogene serine/threonine-protein kinase mos Mus musculus (Mouse) PR
Q66L42 Map3k10 Mitogen-activated protein kinase kinase kinase 10 Mus musculus (Mouse) SS
Q9CZK6 Anks3 Ankyrin repeat and SAM domain-containing protein 3 Mus musculus (Mouse) PR
P25799 Nfkb1 Nuclear factor NF-kappa-B p105 subunit [Cleaved into: Nuclear factor NF-kappa-B p50 subunit] Mus musculus (Mouse) EV
Q8VHA6 Asb18 Ankyrin repeat and SOCS box protein 18 Mus musculus (Mouse) PR
Q9WTK5 Nfkb2 Nuclear factor NF-kappa-B p100 subunit [Cleaved into: Nuclear factor NF-kappa-B p52 subunit] Mus musculus (Mouse) EV
A6H694 Lrrc63 Leucine-rich repeat-containing protein 63 Mus musculus (Mouse) PR
Q9D9Q0 Lrrc69 Leucine-rich repeat-containing protein 69 Mus musculus (Mouse) PR
Q8BGI7 Lrrc39 Leucine-rich repeat-containing protein 39 Mus musculus (Mouse) PR
Q7TT36 Adgra3 Adhesion G protein-coupled receptor A3 Mus musculus (Mouse) PR
P59383 Lrrn4 Leucine-rich repeat neuronal protein 4 Mus musculus (Mouse) PR
Q9D1T0 Lingo1 Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 1 Mus musculus (Mouse) PR
Q8R502 Lrrc8c Volume-regulated anion channel subunit LRRC8C Mus musculus (Mouse) PR
Q80WG5 Lrrc8a Volume-regulated anion channel subunit LRRC8A Mus musculus (Mouse) PR
Q8K0S5 Rtn4rl1 Reticulon-4 receptor-like 1 Mus musculus (Mouse) PR
Q80TE7 Lrrc7 Leucine-rich repeat-containing protein 7 Mus musculus (Mouse) PR
Q5DU41 Lrrc8b Volume-regulated anion channel subunit LRRC8B Mus musculus (Mouse) PR
Q5RKR3 Islr2 Immunoglobulin superfamily containing leucine-rich repeat protein 2 Mus musculus (Mouse) PR
Q8C031 Lrrc4c Leucine-rich repeat-containing protein 4C Mus musculus (Mouse) PR
P0C8E4 Map3k7 Mitogen-activated protein kinase kinase kinase 7 Rattus norvegicus (Rat) SS
Q66HA1 Map3k11 Mitogen-activated protein kinase kinase kinase 11 Rattus norvegicus (Rat) PR
D3ZG83 Map3k10 Mitogen-activated protein kinase kinase kinase 10 Rattus norvegicus (Rat) SS
P00539 Mos Proto-oncogene serine/threonine-protein kinase mos Rattus norvegicus (Rat) PR
P70587 Lrrc7 Leucine-rich repeat-containing protein 7 Rattus norvegicus (Rat) PR
Q4V8G0 Lrrc63 Leucine-rich repeat-containing protein 63 Rattus norvegicus (Rat) PR
Q80WD0 Rtn4rl1 Reticulon-4 receptor-like 1 Rattus norvegicus (Rat) PR
Q9FPR3 EDR1 Serine/threonine-protein kinase EDR1 Arabidopsis thaliana (Mouse-ear cress) PR
Q2MHE4 HT1 Serine/threonine/tyrosine-protein kinase HT1 Arabidopsis thaliana (Mouse-ear cress) PR
O22558 STY8 Serine/threonine-protein kinase STY8 Arabidopsis thaliana (Mouse-ear cress) PR
Q8RWL6 STY17 Serine/threonine-protein kinase STY17 Arabidopsis thaliana (Mouse-ear cress) PR
F4JTP5 STY46 Serine/threonine-protein kinase STY46 Arabidopsis thaliana (Mouse-ear cress) PR
Q05609 CTR1 Serine/threonine-protein kinase CTR1 Arabidopsis thaliana (Mouse-ear cress) PR
O22265 CAO Signal recognition particle 43 kDa protein, chloroplastic Arabidopsis thaliana (Mouse-ear cress) PR
Q9SZI3 NPR2 Regulatory protein NPR2 Arabidopsis thaliana (Mouse-ear cress) PR
Q9SHI4 RLP3 Receptor-like protein 3 Arabidopsis thaliana (Mouse-ear cress) SS
Q5G5E0 PIRL5 Plant intracellular Ras-group-related LRR protein 5 Arabidopsis thaliana (Mouse-ear cress) PR
P43298 TMK1 Receptor protein kinase TMK1 Arabidopsis thaliana (Mouse-ear cress) PR
C0LGE4 At1g12460 Probable LRR receptor-like serine/threonine-protein kinase At1g12460 Arabidopsis thaliana (Mouse-ear cress) PR
C0LGJ1 At1g74360 Probable LRR receptor-like serine/threonine-protein kinase At1g74360 Arabidopsis thaliana (Mouse-ear cress) PR
Q0WR59 At5g10020 Probable inactive receptor kinase At5g10020 Arabidopsis thaliana (Mouse-ear cress) PR
Q9LFG1 At3g53590 Putative leucine-rich repeat receptor-like serine/threonine-protein kinase At3g53590 Arabidopsis thaliana (Mouse-ear cress) PR
Q67E00 dstyk Dual serine/threonine and tyrosine protein kinase Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) PR
B0JZ65 lrwd1 Leucine-rich repeat and WD repeat-containing protein 1 Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) PR
Q68F79 lrrc8e Volume-regulated anion channel subunit LRRC8E Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) PR
B0R160 lrwd1 Leucine-rich repeat and WD repeat-containing protein 1 Danio rerio (Zebrafish) (Brachydanio rerio) PR
10 20 30 40 50 60
MDLSSGGPSS SSDVASELDN SDAMQLVRQA VLFENVELLA DLFKVNPWVW NRVDRHGRTP
70 80 90 100 110 120
LMLAAHNGKL DSLRTILMLS PNSLNLVNDR GKTALHMAAE SGETSIVLEL VELGSDPMKS
130 140 150 160 170 180
DNEGHCALEL AQMAGHNEVA AKLIDAIQKE SEDLNEAHTM IISACISGSA DVVYEISRRF
190 200 210 220 230 240
MEKKQSREIL FNGRNEEDET ALLIACTNGH IEIVRHLLQF EEHLLQSHVS KDTVIHAAVS
250 260 270 280 290 300
SQNVEVLQLC LEKFPQLVKS TNNEGSTCLH WAARCGSSEC VSTILNFPFP SEFIIEIDTV
310 320 330 340 350 360
GAPAYQLALD VNEVDGECRT AMYLAVAEGH LEVVKAMTDF KCTSIDGRQR CPFQLDVYCT
370 380 390 400 410 420
RGRTPFMLAA FNQNLPLMTL LLDAGADVNL PLAVLDTEYS VEEGRCIGSG ALVEAVRSDG
430 440 450 460 470 480
LHIVHFLLDR GALDTDNKAL RLAAQGKNEK LIRVFLVRLV FADPEYKINK KNIDVGQIQV
490 500 510 520 530 540
GQSLLPSSLC PSKAAQLNWN SANLEQLQSD WFVAAALHVN PRLRTTRLSL AAITRVDLSD
550 560 570 580 590 600
NRLNTFPSIL FQMPSLRSLN LADNSIRKIE IPTYYISSTS LEILNLRNNQ LECIAIQFLS
610 620 630 640 650 660
SLPQLQQLDV SKNELSQLPE YIWLCPALKE LNASYNRLST LPMVARASRG ERPRLNNSNN
670 680 690 700 710 720
NFNTQSPTQE SNPIVVDDPP NVTSNPLRRQ NVWQASINLS KVDDDSLFPD FPVTSSNTLT
730 740 750 760 770 780
TINLSFNKFH TFPFCLACTC PRLLILNMSN NSMTSLPPMA CVPAHLRTLD LSYNKIQESF
790 800 810 820 830 840
IEASPLHVVC HAVPPTTSNG SMLPKRRNSP ARQHRSRSKS AVRSQRSLSV SRHHALIDPQ
850 860 870 880 890 900
KEEESCVHKR HDSLEWLKTL QLAGNRLRSI SVTNAASKVL LPALNVMDIS DNKLLQAPPD
910 920 930 940 950 960
VARLTLLSML NLSGNTAIKE LPPDYGMLSR LWSLSLKGCS LKEPLESMVN VENCKTVEIV
970 980 990 1000 1010 1020
AYLKTILEES KTYHHLRLMI LGSDGVGKSV IWDALCKEAV QKRQPIHSET GVIRQAEWKF
1030 1040 1050 1060 1070 1080
EAKRSKGDKN LGPVGFSVID FGGQREYHST HQYFLSKRSL NLVLWKITDG DEALAQLDTW
1090 1100 1110 1120 1130 1140
LVNIHARAPN STVILVGTNL DQVASNSSKF GPGYIDIMEQ KVRTRYMVAD ADKSGLPRIV
1150 1160 1170 1180 1190 1200
DVILINSTSR NDVKALLNTI YRTAWEVRMG KERAMEQQIP SSYIALMKVT KELGVEFRKE
1210 1220 1230 1240 1250 1260
GQPAVMTVEA YRERVKKRMI SKFGRPFRDD IEFYAACTFL HDCGELVRFE DATLRDLIFV
1270 1280 1290 1300 1310 1320
DPLWLAEFLT SVVILRSPNL PAGLLSTDAI NPHTRSFKSG ALLMLKTQLL DLLHKFELAL
1330 1340 1350 1360 1370 1380
ATQPRQLLIP SLLPDEYRLR SDFLASAVKI RMKMSQWNVR CPSPAGSPTK SPLRRTSPTD
1390 1400 1410 1420 1430 1440
QNGVGSEDVM LQFTYDDDQL LRRIYALAYI PSGFWSRLVT RIVGDKNVCA AIESIFMTTS
1450 1460 1470 1480 1490 1500
ADRAKIADIA TKHAKAEWVV WQTGIELHVK GHSLFTLKQF LPLAEVRDID YSAIDMRAKD
1510 1520 1530 1540 1550 1560
EQKRWRTWNQ PSHRPIVEMV VNSLSISAAS QHGRKLSMKT DVEGRSRLLA MISDLLDTLL
1570 1580 1590 1600 1610 1620
EDWYPALGTR FVHSSEGDLL VSRYVLCPQC VRDAERNGSR SRTSSSASHR RSQDDGELPI
1630 1640 1650 1660 1670 1680
TSSSHMKGSR TTGDISKCRG GVVHCFVIEE CMLAGREYNW VECPSHGGLH MRELAPDTVF
1690 1700 1710 1720 1730 1740
ADIENALTIH PDQLKRSRML GRGAFGFVFR ATVRQPNGEL CEVAQKMLEP VDPGPGGRPS
1750 1760 1770 1780 1790 1800
ALAAYKAAAD KWKRDSMEFA CRAYCTSRQE LSLLSRMKHP NVIGLVGVCT FPLSLVVELA
1810 1820 1830 1840 1850 1860
PLGALNQLLG SHRKAGTKLS LGVIKESAVQ VARALEYLHS AHIIYRDLKS ENVLGWRFPA
1870 1880 1890 1900 1910 1920
PFSPQTDVLL KLGDYGISRS VLPSGGAKGF GGTEGFMAPE IVRFNGEEEY TQKVDCFSFG
1930 1940 1950 1960 1970 1980
MFLYELLTLK FPFESEEHVK ERMLDGARPV LLPHELLLPT PMLDLLVHCW SAHPESRPSS
1990 2000 2010 2020 2030 2040
SQLVGFCAAP EFTHLLDVCE LGEALPPTQL MAVGITDEID DPDDFEAQLW LSGREMVVMG
2050 2060 2070 2080 2090 2100
CTQYGFVDQK SIELPHRGKY VSKVRDSVWS CDECGQVTVY GISLHETGHL QLPSLNGTLI
2110 2120 2130 2140 2150 2160
CAPELISNDV LILISDKQIV LLKLSESNSV SHLGTIDSPY EIRTATFLGN GSTRQIWAGH
2170 2180 2190 2200 2210 2220
SEGRISIHHI ASNDSFSFSS SLYLPDDKCI VRQLVGSKDA QKVWIALEKS SKVQMVEVEK
2230 2240 2250 2260 2270 2280
RQVTGSLDIR KVMPGSETIH TIDMEMASQN YVTCIGLLER NDGDQLYIGT SKGLLVIAHA
2290 2300 2310 2320 2330 2340
TTLQPLSACR PFEGDITSIC ILEEPSREEE NTRGKATTLS TASSESGLGW VRERVSETVD
2350 2360 2370 2380 2390
RFRSSPATVE TQGAALVVCI GRQFRSLSHR FVAEEKLADV YSIAVWRTEE WAL