LRRK1
entrez
79705
canonical
uniprot
Q38SD2
canonical
ensembl
ENSG00000154237
resolver
ensp
ENSP00000373600
resolver
genesymbol
LRRK1
resolver
genesymbol_syn
KIAA1790
resolver
hgnc
HGNC:18608
resolver
uniprot
Q6NVH5
resolver
uniprot
Q6NYC0
resolver
uniprot
Q6ZNL9
resolver
uniprot
Q6ZNM9
resolver
uniprot
Q96JN5
resolver
uniprot
Q9H5S3
resolver
uniprot_entry
LRRK1_HUMAN
resolver
uniprot_sec
Q6NVH5
resolver
uniprot_sec
Q6NYC0
resolver
uniprot_sec
Q6ZNL9
resolver
uniprot_sec
Q6ZNM9
resolver
uniprot_sec
Q96JN5
resolver
uniprot_sec
Q9H5S3
resolver
activity_regulation
ACTIVITY REGULATION: Activated by phosphorylation by PKC (PubMed:36040231). Binds both GTP and GDP; binding of GTP stimulates kinase activity (PubMed:16243488). Sterically autoinhibited in its dimeric state (PubMed:37857821). {ECO:0000269|PubMed:16243488, ECO:0000269|PubMed:36040231, ECO:0000269|PubMed:37857821}.
uniprot
proteins
amino_acid_sequence
MAGMSQRPPSMYWCVGPEESAVCPERAMETLNGAGDTGGKPSTRGGDPAARSRRTEGIRAAYRRGDRGGARDLLEEACDQCASQLEKGQLLSIPAAYGDLEMVRYLLSKRLVELPTEPTDDNPAVVAAYFGHTAVVQELLESLPGPCSPQRLLNWMLALACQRGHLGVVKLLVLTHGADPESYAVRKNEFPVIVRLPLYAAIKSGNEDIAIFLLRHGAYFCSYILLDSPDPSKHLLRKYFIEASPLPSSYPGKTALRVKWSHLRLPWVDLDWLIDISCQITELDLSANCLATLPSVIPWGLINLRKLNLSDNHLGELPGVQSSDEIICSRLLEIDISSNKLSHLPPGFLHLSKLQKLTASKNCLEKLFEEENATNWIGLRKLQELDISDNKLTELPALFLHSFKSLNSLNVSRNNLKVFPDPWACPLKCCKASRNALECLPDKMAVFWKNHLKDVDFSENALKEVPLGLFQLDALMFLRLQGNQLAALPPQEKWTCRQLKTLDLSRNQLGKNEDGLKTKRIAFFTTRGRQRSGTEAASVLEFPAFLSESLEVLCLNDNHLDTVPPSVCLLKSLSELYLGNNPGLRELPPELGQLGNLWQLDTEDLTISNVPAEIQKEGPKAMLSYLRAQLRKAEKCKLMKMIIVGPPRQGKSTLLEILQTGRAPQVVHGEATIRTTKWELQRPAGSRAKVESVEFNVWDIGGPASMATVNQCFFTDKALYVVVWNLALGEEAVANLQFWLLNIEAKAPNAVVLVVGTHLDLIEAKFRVERIATLRAYVLALCRSPSGSRATGFPDITFKHLHEISCKSLEGQEGLRQLIFHVTCSMKDVGSTIGCQRLAGRLIPRSYLSLQEAVLAEQQRRSRDDDVQYLTDRQLEQLVEQTPDNDIKDYEDLQSAISFLIETGTLLHFPDTSHGLRNLYFLDPIWLSECLQRIFNIKGSRSVAKNGVIRAEDLRMLLVGTGFTQQTEEQYFQFLAKFEIALPVANDSYLLPHLLPSKPGLDTHGMRHPTANTIQRVFKMSFVPVGFWQRFIARMLISLAEMDLQLFENKKNTKSRNRKVTIYSFTGNQRNRCSTFRVKRNQTIYWQEGLLVTFDGGYLSVESSDVNWKKKKSGGMKIVCQSEVRDFSAMAFITDHVNSLIDQWFPALTATESDGTPLMEQYVPCPVCETAWAQHTDPSEKSEDVQYFDMEDCVLTAIERDFISCPRHPDLPVPLQELVPELFMTDFPARLFLENSKLEHSEDEGSVLGQGGSGTVIYRARYQGQPVAVKRFHIKKFKNFANVPADTMLRHLRATDAMKNFSEFRQEASMLHALQHPCIVALIGISIHPLCFALELAPLSSLNTVLSENARDSSFIPLGHMLTQKIAYQIASGLAYLHKKNIIFCDLKSDNILVWSLDVKEHINIKLSDYGISRQSFHEGALGVEGTPGYQAPEIRPRIVYDEKVDMFSYGMVLYELLSGQRPALGHHQLQIAKKLSKGIRPVLGQPEEVQFRRLQALMMECWDTKPEKRPLALSVVSQMKDPTFATFMYELCCGKQTAFFSSQGQEYTVVFWDGKEESRNYTVVNTEKGLMEVQRMCCPGMKVSCQLQVQRSLWTATEDQKIYIYTLKGMCPLNTPQQALDTPAVVTCFLAVPVIKKNSYLVLAGLADGLVAVFPVVRGTPKDSCSYLCSHTANRSKFSIADEDARQNPYPVKAMEVVNSGSEVWYSNGPGLLVIDCASLEICRRLEPYMAPSMVTSVVCSSEGRGEEVVWCLDDKANSLVMYHSTTYQLCARYFCGVPSPLRDMFPVRPLDTEPPAASHTANPKVPEGDSIADVSIMYSEELGTQILIHQESLTDYCSMSSYSSSPPRQAARSPSSLPSSPASSSSVPFSTDCEDSDMLHTPGAASDRSEHDLTPMDGETFSQHLQAVKILAVRDLIWVPRRGGDVIVIGLEKDSGAQRGRVIAVLKARELTPHGVLVDAAVVAKDTVVCTFENENTEWCLAVWRGWGAREFDIFYQSYEELGRLEACTRKRR
uniprot
proteins
disease_involvement
DISEASE: Osteosclerotic metaphyseal dysplasia (OSMD) [MIM:615198]: An autosomal recessive skeletal dysplasia characterized by osteosclerosis at multiple skeletal sites, predominantly at the metaphyses of the long bones and vertebral bodies. {ECO:0000269|PubMed:27055475, ECO:0000269|PubMed:27829680, ECO:0000269|PubMed:31571209, ECO:0000269|PubMed:32119750}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
FUNCTION: Serine/threonine-protein kinase which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). Phosphorylates RAB7A; this activity is dependent on protein kinase C (PKC) activation (PubMed:36040231, PubMed:37558661, PubMed:37857821). Plays a role in the negative regulation of bone mass, acting through the maturation of osteoclasts (By similarity). {ECO:0000250|UniProtKB:Q3UHC2, ECO:0000269|PubMed:36040231, ECO:0000269|PubMed:37558661, ECO:0000269|PubMed:37857821}.
uniprot
proteins
mass_dalton
225393
uniprot
proteins
mutagenesis
MUTAGEN 1..48; /note="Missing: Enhances phosphorylation of RAB7A, likely by destabilizing the dimer."; /evidence="ECO:0000269|PubMed:37857821"; MUTAGEN 1..25; /note="Missing: Enhances phosphorylation of RAB7A, likely by destabilizing the dimer."; /evidence="ECO:0000269|PubMed:37857821"; MUTAGEN 651; /note="K->A: Loss of GTP/GDP-binding."; /evidence="ECO:0000269|PubMed:16243488"; MUTAGEN 746; /note="K->G: No effect on GTP-binding. Increases phosphorylation of RAB7A."; /evidence="ECO:0000269|PubMed:16243488, ECO:0000269|PubMed:37558661, ECO:0000269|PubMed:37857821"; MUTAGEN 971; /note="Y->F: Increases RAB7A phosphorylation, likely by blocking EGF-mediated inactivation."; /evidence="ECO:0000269|PubMed:37558661"; MUTAGEN 1022; /note="F->C: No effect on GTP-binding but loss of subsequent stimulation of kinase activity."; /evidence="ECO:0000269|PubMed:16243488"; MUTAGEN 1034; /note="R->A: Abolishes phosphorylation of RAB7A."; /evidence="ECO:0000269|PubMed:37558661"; MUTAGEN 1061; /note="T->A: Slightly increases phosphorylation of RAB7A."; /evidence="ECO:0000269|PubMed:36040231"; MUTAGEN 1064; /note="S->A: Inhibits phosphorylation activity and blocks activation by phorbol ester; when associated with A-1074 and A-1075."; /evidence="ECO:0000269|PubMed:36040231"; MUTAGEN 1064; /note="S->E: Phosphomimetic mutant which increases phosphorylation of RAB7A by 2-6 fold; when associated with E-1074 and E-1075."; /evidence="ECO:0000269|PubMed:36040231, ECO:0000269|PubMed:37558661, ECO:0000269|PubMed:37857821"; MUTAGEN 1074; /note="S->A: Inhibits phosphorylation activity and blocks activation by phorbol ester; when associated with A-1064 and A-1075."; /evidence="ECO:0000269|PubMed:36040231"; MUTAGEN 1074; /note="S->E: Phosphomimetic mutant which increases phosphorylation of RAB7A by 2 fold when activated by phorbol ester. Phosphomimetic mutant which increases phosphorylation of RAB7A by 2 fold; when associated with E-1064 and E-1075."; /evidence="ECO:0000269|PubMed:36040231, ECO:0000269|PubMed:37558661, ECO:0000269|PubMed:37857821"; MUTAGEN 1075; /note="T->A: Inhibits phosphorylation activity and blocks activation by phorbol ester. Inhibits phosphorylation activity and blocks activation by phorbol ester; when associated with A-1064 and A-1074."; /evidence="ECO:0000269|PubMed:36040231"; MUTAGEN 1075; /note="T->E: Phosphomimetic mutant which abolishes phosphorylation of RAB7A and blocks activation by phorbol ester. Increases phosphorylation of RAB7A by 2-6 fold; when associated with E-1064 and E-1074."; /evidence="ECO:0000269|PubMed:36040231, ECO:0000269|PubMed:37558661, ECO:0000269|PubMed:37857821"; MUTAGEN 1144; /note="W->A: Abolishes phosphorylation of RAB7A."; /evidence="ECO:0000269|PubMed:37558661"; MUTAGEN 1270; /note="K->M: Abolishes phosphorylation of RAB7A."; /evidence="ECO:0000269|PubMed:37558661"; MUTAGEN 1270; /note="K->W: Loss of autophosphorylation."; /evidence="ECO:0000269|PubMed:16243488"; MUTAGEN 1298; /note="M->K: Enhances phosphorylation of RAB7A."; /evidence="ECO:0000269|PubMed:37558661"; MUTAGEN 1305; /note="R->A: Abolishes phosphorylation of RAB7A."; /evidence="ECO:0000269|PubMed:37558661"; MUTAGEN 1409; /note="D->A: Abolishes phosphorylation of RAB7A."; /evidence="ECO:0000269|PubMed:37857821"; MUTAGEN 1412; /note="I->T: No effect on GTP-binding but reduction in subsequent stimulation of kinase activity."; /evidence="ECO:0000269|PubMed:16243488"; MUTAGEN 1798..1885; /note="Missing: Increases phosphorylation of RAB7A; the truncated WD40 loop likely destabilizes the dimer."; /evidence="ECO:0000269|PubMed:37857821
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated (PubMed:16243488). Autophosphorylation is inhibited in its dimeric state (PubMed:22952686, PubMed:37857821). Phosphorylated by protein kinase C isozymes PRKCA, PRKCB, PRKCG, PRKCE, PRKCZ and PRKCT at Thr-1061, Ser-1064, Ser-1074 and Thr-1075 (PubMed:36040231). Phosphorylation at these Ser-1064, Ser-1074 and Thr-1075 activates the kinase activity of LRRK1 to phosphorylate RAB7A (PubMed:36040231). {ECO:0000269|PubMed:16243488, ECO:0000269|PubMed:22952686, ECO:0000269|PubMed:36040231, ECO:0000269|PubMed:37857821}.
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
ROCO subfamily
uniprot
proteins
protein_family
TKL Ser/Thr protein kinase family
uniprot
proteins
pubmed
11347906
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16243488
uniprot
proteins
pubmed
16572171
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
22952686
uniprot
proteins
pubmed
23526378
uniprot
proteins
pubmed
27055475
uniprot
proteins
pubmed
27829680
uniprot
proteins
pubmed
31571209
uniprot
proteins
pubmed
32119750
uniprot
proteins
pubmed
36040231
uniprot
proteins
pubmed
37558661
uniprot
proteins
pubmed
37857821
uniprot
proteins
sequence_length
2015
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16243488, ECO:0000269|PubMed:36040231}. Cell membrane {ECO:0000269|PubMed:36040231}; Peripheral membrane protein {ECO:0000305|PubMed:36040231}.
uniprot
proteins