LRRK1

Protein identityUniProt · HPA

UniProt accession

Q38SD2

Gene

LRRK1

Ensembl

ENSG00000154237

Chromosome

15

Canonical length

2015 aa

Protein class

Disease related genes, Enzymes, Potential drug targets, Predicted intracellular proteins

Subcellular location

Mitochondria,Cytosol

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a multi-domain protein that is a leucine-rich repeat kinase and a GDP/GTP binding protein. The encoded protein is thought to play a role in the regulation of bone mass. Mice lacking a similar gene showed severe osteopetrosis, increased bone mineralization and decreased bone resorption. [provided by RefSeq, Jan 2017]

Canonical amino-acid sequenceUniProt

2015 residues, UniProt reviewed canonical sequence.

>Q38SD2|LRRK1
     1  MAGMSQRPPS MYWCVGPEES AVCPERAMET LNGAGDTGGK PSTRGGDPAA RSRRTEGIRA
    61  AYRRGDRGGA RDLLEEACDQ CASQLEKGQL LSIPAAYGDL EMVRYLLSKR LVELPTEPTD
   121  DNPAVVAAYF GHTAVVQELL ESLPGPCSPQ RLLNWMLALA CQRGHLGVVK LLVLTHGADP
   181  ESYAVRKNEF PVIVRLPLYA AIKSGNEDIA IFLLRHGAYF CSYILLDSPD PSKHLLRKYF
   241  IEASPLPSSY PGKTALRVKW SHLRLPWVDL DWLIDISCQI TELDLSANCL ATLPSVIPWG
   301  LINLRKLNLS DNHLGELPGV QSSDEIICSR LLEIDISSNK LSHLPPGFLH LSKLQKLTAS
   361  KNCLEKLFEE ENATNWIGLR KLQELDISDN KLTELPALFL HSFKSLNSLN VSRNNLKVFP
   421  DPWACPLKCC KASRNALECL PDKMAVFWKN HLKDVDFSEN ALKEVPLGLF QLDALMFLRL
   481  QGNQLAALPP QEKWTCRQLK TLDLSRNQLG KNEDGLKTKR IAFFTTRGRQ RSGTEAASVL
   541  EFPAFLSESL EVLCLNDNHL DTVPPSVCLL KSLSELYLGN NPGLRELPPE LGQLGNLWQL
   601  DTEDLTISNV PAEIQKEGPK AMLSYLRAQL RKAEKCKLMK MIIVGPPRQG KSTLLEILQT
   661  GRAPQVVHGE ATIRTTKWEL QRPAGSRAKV ESVEFNVWDI GGPASMATVN QCFFTDKALY
   721  VVVWNLALGE EAVANLQFWL LNIEAKAPNA VVLVVGTHLD LIEAKFRVER IATLRAYVLA
   781  LCRSPSGSRA TGFPDITFKH LHEISCKSLE GQEGLRQLIF HVTCSMKDVG STIGCQRLAG
   841  RLIPRSYLSL QEAVLAEQQR RSRDDDVQYL TDRQLEQLVE QTPDNDIKDY EDLQSAISFL
   901  IETGTLLHFP DTSHGLRNLY FLDPIWLSEC LQRIFNIKGS RSVAKNGVIR AEDLRMLLVG
   961  TGFTQQTEEQ YFQFLAKFEI ALPVANDSYL LPHLLPSKPG LDTHGMRHPT ANTIQRVFKM
  1021  SFVPVGFWQR FIARMLISLA EMDLQLFENK KNTKSRNRKV TIYSFTGNQR NRCSTFRVKR
  1081  NQTIYWQEGL LVTFDGGYLS VESSDVNWKK KKSGGMKIVC QSEVRDFSAM AFITDHVNSL
  1141  IDQWFPALTA TESDGTPLME QYVPCPVCET AWAQHTDPSE KSEDVQYFDM EDCVLTAIER
  1201  DFISCPRHPD LPVPLQELVP ELFMTDFPAR LFLENSKLEH SEDEGSVLGQ GGSGTVIYRA
  1261  RYQGQPVAVK RFHIKKFKNF ANVPADTMLR HLRATDAMKN FSEFRQEASM LHALQHPCIV
  1321  ALIGISIHPL CFALELAPLS SLNTVLSENA RDSSFIPLGH MLTQKIAYQI ASGLAYLHKK
  1381  NIIFCDLKSD NILVWSLDVK EHINIKLSDY GISRQSFHEG ALGVEGTPGY QAPEIRPRIV
  1441  YDEKVDMFSY GMVLYELLSG QRPALGHHQL QIAKKLSKGI RPVLGQPEEV QFRRLQALMM
  1501  ECWDTKPEKR PLALSVVSQM KDPTFATFMY ELCCGKQTAF FSSQGQEYTV VFWDGKEESR
  1561  NYTVVNTEKG LMEVQRMCCP GMKVSCQLQV QRSLWTATED QKIYIYTLKG MCPLNTPQQA
  1621  LDTPAVVTCF LAVPVIKKNS YLVLAGLADG LVAVFPVVRG TPKDSCSYLC SHTANRSKFS
  1681  IADEDARQNP YPVKAMEVVN SGSEVWYSNG PGLLVIDCAS LEICRRLEPY MAPSMVTSVV
  1741  CSSEGRGEEV VWCLDDKANS LVMYHSTTYQ LCARYFCGVP SPLRDMFPVR PLDTEPPAAS
  1801  HTANPKVPEG DSIADVSIMY SEELGTQILI HQESLTDYCS MSSYSSSPPR QAARSPSSLP
  1861  SSPASSSSVP FSTDCEDSDM LHTPGAASDR SEHDLTPMDG ETFSQHLQAV KILAVRDLIW
  1921  VPRRGGDVIV IGLEKDSGAQ RGRVIAVLKA RELTPHGVLV DAAVVAKDTV VCTFENENTE
  1981  WCLAVWRGWG AREFDIFYQS YEELGRLEAC TRKRR

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against LRRK1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.29

Highest tissue expression

7.5 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about LRRK1.

Disease | AllUniProt

Conditions LRRK1 is implicated in, by any mechanism.

• Osteosclerotic metaphyseal dysplasia (OSMD) MIM:615198

Disease | GeneticClinVar

26 pathogenic / likely-pathogenic of 1,114 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Osteosclerotic metaphyseal dysplasia
• Ovarian serous cystadenocarcinoma

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.49

gnomAD pLI

0

gnomAD missense Z

2.72

DepMap mean gene effect

0.03

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• bone resorption
• intracellular signal transduction
• osteoclast development
• positive regulation of canonical Wnt signaling pathway
• positive regulation of intracellular signal transduction

Molecular functions

• ATP binding
• GTP binding
• identical protein binding
• metal ion binding
• protein serine kinase activity
• protein serine/threonine kinase activity

Cellular components

• cytosol
• mitochondrion
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Protein kinase domain
• Leucine-rich repeat
• Ankyrin repeat
• Leucine-rich repeat, typical subtype
• Protein kinase-like domain superfamily
• Roc domain
• P-loop containing nucleoside triphosphate hydrolase
• C-terminal of Roc, COR-A domain
• Leucine-rich repeat domain superfamily
• WD40-repeat-containing domain superfamily
• Ankyrin repeat-containing domain superfamily
• C-terminal of Roc, COR-B domain
• Protein kinase domain
• Leucine Rich Repeat
• Ras of Complex, Roc, domain of DAPkinase
• C-terminal of Roc, COR-A domain
• C-terminal of Roc, COR-B domain
• Plant LRR receptor-like serine/threonine-protein kinases

KeywordsUniProt

• ANK repeat
• ATP-binding
• Cell membrane
• Cytoplasm
• GTP-binding
• Kinase
• Leucine-rich repeat
• Magnesium
• Manganese
• Membrane
• Metal-binding
• Nucleotide-binding
• Phosphoprotein
• Repeat
• Serine/threonine-protein kinase
• Transferase
• WD repeat

InteractionsUniProt · HPA

Protein binding partners of LRRK1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CSK
• ABL1
• BAG5
• EGFR
• LRRK2