LRK1_CAEEL
ID LRK1_CAEEL Reviewed; 2393 AA.
AC Q9TZM3; A3KFB1;
DT 22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 05-FEB-2008, sequence version 6.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Leucine-rich repeat serine/threonine-protein kinase 1 {ECO:0000250|UniProtKB:Q38SD2};
DE EC=2.7.11.1;
DE AltName: Full=Leucine-rich repeats, ras-like domain, kinase protein 1;
DE AltName: Full=PARK8-related kinase;
GN Name=lrk-1; ORFNames=T27C10.6;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1] {ECO:0000305, ECO:0000312|EMBL:BAF48647.1}
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP MUTAGENESIS OF LYS-1726 AND ILE-1877.
RX PubMed=17346966; DOI=10.1016/j.cub.2007.01.074;
RA Sakaguchi-Nakashima A., Meir J.Y., Jin Y., Matsumoto K., Hisamoto N.;
RT "LRK-1, a C. elegans PARK8-related kinase, regulates axonal-dendritic
RT polarity of SV proteins.";
RL Curr. Biol. 17:592-598(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=19251702; DOI=10.1074/jbc.m808255200;
RA Saemann J., Hegermann J., von Gromoff E., Eimer S., Baumeister R.,
RA Schmidt E.;
RT "Caenorhabditits elegans LRK-1 and PINK-1 Act Antagonistically in Stress
RT Response and Neurite Outgrowth.";
RL J. Biol. Chem. 284:16482-16491(2009).
CC -!- FUNCTION: Determines polarized sorting of synaptic vesicle (SV)
CC proteins to the axons by excluding SV proteins from the dendrite-
CC specific transport machinery in the Golgi. Role in stress response.
CC Appears to antagonize the effects of pink-1 both in the regulation of
CC axon guidance and stress response. {ECO:0000269|PubMed:17346966,
CC ECO:0000269|PubMed:19251702}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:Q38SD2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:Q38SD2};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q38SD2};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q38SD2};
CC -!- SUBCELLULAR LOCATION: Golgi apparatus {ECO:0000269|PubMed:17346966}.
CC -!- TISSUE SPECIFICITY: Expressed in cell bodies, but not in dendritic or
CC axonal processes, of adult head neurons. Also present in non-neuronal
CC tissues, such as the body wall musculature and the epithelial cells of
CC the nematode vulva. {ECO:0000269|PubMed:17346966,
CC ECO:0000269|PubMed:19251702}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. ROCO subfamily. {ECO:0000250|UniProtKB:Q38SD2}.
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DR EMBL; AB297384; BAF48647.1; -; mRNA.
DR EMBL; FO081425; CCD71547.1; -; Genomic_DNA.
DR RefSeq; NP_492839.4; NM_060438.6.
DR AlphaFoldDB; Q9TZM3; -.
DR SMR; Q9TZM3; -.
DR BioGRID; 38404; 2.
DR STRING; 6239.T27C10.6; -.
DR EPD; Q9TZM3; -.
DR PaxDb; Q9TZM3; -.
DR PeptideAtlas; Q9TZM3; -.
DR EnsemblMetazoa; T27C10.6.1; T27C10.6.1; WBGene00003068.
DR GeneID; 172995; -.
DR KEGG; cel:CELE_T27C10.6; -.
DR UCSC; T27C10.6; c. elegans.
DR CTD; 172995; -.
DR WormBase; T27C10.6; CE41939; WBGene00003068; lrk-1.
DR eggNOG; KOG0192; Eukaryota.
DR eggNOG; KOG0504; Eukaryota.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000165193; -.
DR HOGENOM; CLU_000987_0_0_1; -.
DR InParanoid; Q9TZM3; -.
DR OMA; TMDVIGY; -.
DR OrthoDB; 14978at2759; -.
DR PhylomeDB; Q9TZM3; -.
DR PRO; PR:Q9TZM3; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00003068; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005794; C:Golgi apparatus; IDA:WormBase.
DR GO; GO:0043025; C:neuronal cell body; IDA:WormBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0048846; P:axon extension involved in axon guidance; IGI:WormBase.
DR GO; GO:1901215; P:negative regulation of neuron death; IMP:ParkinsonsUK-UCL.
DR GO; GO:0008104; P:protein localization; IMP:WormBase.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IMP:WormBase.
DR GO; GO:0006979; P:response to oxidative stress; IGI:WormBase.
DR GO; GO:0048489; P:synaptic vesicle transport; IMP:WormBase.
DR Gene3D; 1.25.40.20; -; 3.
DR Gene3D; 3.40.50.300; -; 1.
DR Gene3D; 3.80.10.10; -; 3.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR032171; COR.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR020859; ROC_dom.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR Pfam; PF12796; Ank_2; 2.
DR Pfam; PF13637; Ank_4; 1.
DR Pfam; PF16095; COR; 1.
DR Pfam; PF13855; LRR_8; 1.
DR Pfam; PF00069; Pkinase; 1.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 8.
DR SMART; SM00369; LRR_TYP; 7.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF48403; SSF48403; 2.
DR SUPFAM; SSF50978; SSF50978; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 3.
DR PROSITE; PS51450; LRR; 10.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS51424; ROC; 1.
PE 1: Evidence at protein level;
KW ANK repeat; ATP-binding; Golgi apparatus; GTP-binding; Kinase;
KW Leucine-rich repeat; Magnesium; Manganese; Metal-binding;
KW Nucleotide-binding; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Stress response; Transferase.
FT CHAIN 1..2393
FT /note="Leucine-rich repeat serine/threonine-protein kinase
FT 1"
FT /id="PRO_0000385373"
FT REPEAT 56..86
FT /note="ANK 1"
FT /evidence="ECO:0000255"
FT REPEAT 90..120
FT /note="ANK 2"
FT /evidence="ECO:0000255"
FT REPEAT 123..152
FT /note="ANK 3"
FT /evidence="ECO:0000255"
FT REPEAT 197..226
FT /note="ANK 4"
FT /evidence="ECO:0000255"
FT REPEAT 230..259
FT /note="ANK 5"
FT /evidence="ECO:0000255"
FT REPEAT 264..293
FT /note="ANK 6"
FT /evidence="ECO:0000255"
FT REPEAT 317..347
FT /note="ANK 7"
FT /evidence="ECO:0000255"
FT REPEAT 361..390
FT /note="ANK 8"
FT /evidence="ECO:0000255"
FT REPEAT 407..437
FT /note="ANK 9"
FT /evidence="ECO:0000255"
FT REPEAT 439..464
FT /note="ANK 10"
FT /evidence="ECO:0000255"
FT REPEAT 532..553
FT /note="LRR 1"
FT REPEAT 555..576
FT /note="LRR 2"
FT REPEAT 580..600
FT /note="LRR 3"
FT REPEAT 604..625
FT /note="LRR 4"
FT REPEAT 627..648
FT /note="LRR 5"
FT REPEAT 718..739
FT /note="LRR 6"
FT REPEAT 742..763
FT /note="LRR 7"
FT REPEAT 765..787
FT /note="LRR 8"
FT REPEAT 856..877
FT /note="LRR 9"
FT REPEAT 883..905
FT /note="LRR 10"
FT REPEAT 906..928
FT /note="LRR 11"
FT REPEAT 930..952
FT /note="LRR 12"
FT DOMAIN 969..1167
FT /note="Roc"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00758"
FT DOMAIN 1694..1992
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 649..675
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 797..844
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1361..1382
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1596..1633
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 652..675
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1617..1631
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1847
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 982..989
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255"
FT BINDING 1040..1044
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255"
FT BINDING 1098..1101
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255"
FT BINDING 1700..1708
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 1726
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q38SD2,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT MUTAGEN 1726
FT /note="K->A: Loss of ability to correctly sort SV proteins.
FT No loss of ability to correctly sort SV proteins; when
FT associated with T-1877."
FT /evidence="ECO:0000269|PubMed:17346966"
FT MUTAGEN 1877
FT /note="I->T: No loss of ability to correctly sort SV
FT proteins; when associated with A-1726."
FT /evidence="ECO:0000269|PubMed:17346966"
SQ SEQUENCE 2393 AA; 266322 MW; C0E6BB5780DC9C85 CRC64;
MDLSSGGPSS SSDVASELDN SDAMQLVRQA VLFENVELLA DLFKVNPWVW NRVDRHGRTP
LMLAAHNGKL DSLRTILMLS PNSLNLVNDR GKTALHMAAE SGETSIVLEL VELGSDPMKS
DNEGHCALEL AQMAGHNEVA AKLIDAIQKE SEDLNEAHTM IISACISGSA DVVYEISRRF
MEKKQSREIL FNGRNEEDET ALLIACTNGH IEIVRHLLQF EEHLLQSHVS KDTVIHAAVS
SQNVEVLQLC LEKFPQLVKS TNNEGSTCLH WAARCGSSEC VSTILNFPFP SEFIIEIDTV
GAPAYQLALD VNEVDGECRT AMYLAVAEGH LEVVKAMTDF KCTSIDGRQR CPFQLDVYCT
RGRTPFMLAA FNQNLPLMTL LLDAGADVNL PLAVLDTEYS VEEGRCIGSG ALVEAVRSDG
LHIVHFLLDR GALDTDNKAL RLAAQGKNEK LIRVFLVRLV FADPEYKINK KNIDVGQIQV
GQSLLPSSLC PSKAAQLNWN SANLEQLQSD WFVAAALHVN PRLRTTRLSL AAITRVDLSD
NRLNTFPSIL FQMPSLRSLN LADNSIRKIE IPTYYISSTS LEILNLRNNQ LECIAIQFLS
SLPQLQQLDV SKNELSQLPE YIWLCPALKE LNASYNRLST LPMVARASRG ERPRLNNSNN
NFNTQSPTQE SNPIVVDDPP NVTSNPLRRQ NVWQASINLS KVDDDSLFPD FPVTSSNTLT
TINLSFNKFH TFPFCLACTC PRLLILNMSN NSMTSLPPMA CVPAHLRTLD LSYNKIQESF
IEASPLHVVC HAVPPTTSNG SMLPKRRNSP ARQHRSRSKS AVRSQRSLSV SRHHALIDPQ
KEEESCVHKR HDSLEWLKTL QLAGNRLRSI SVTNAASKVL LPALNVMDIS DNKLLQAPPD
VARLTLLSML NLSGNTAIKE LPPDYGMLSR LWSLSLKGCS LKEPLESMVN VENCKTVEIV
AYLKTILEES KTYHHLRLMI LGSDGVGKSV IWDALCKEAV QKRQPIHSET GVIRQAEWKF
EAKRSKGDKN LGPVGFSVID FGGQREYHST HQYFLSKRSL NLVLWKITDG DEALAQLDTW
LVNIHARAPN STVILVGTNL DQVASNSSKF GPGYIDIMEQ KVRTRYMVAD ADKSGLPRIV
DVILINSTSR NDVKALLNTI YRTAWEVRMG KERAMEQQIP SSYIALMKVT KELGVEFRKE
GQPAVMTVEA YRERVKKRMI SKFGRPFRDD IEFYAACTFL HDCGELVRFE DATLRDLIFV
DPLWLAEFLT SVVILRSPNL PAGLLSTDAI NPHTRSFKSG ALLMLKTQLL DLLHKFELAL
ATQPRQLLIP SLLPDEYRLR SDFLASAVKI RMKMSQWNVR CPSPAGSPTK SPLRRTSPTD
QNGVGSEDVM LQFTYDDDQL LRRIYALAYI PSGFWSRLVT RIVGDKNVCA AIESIFMTTS
ADRAKIADIA TKHAKAEWVV WQTGIELHVK GHSLFTLKQF LPLAEVRDID YSAIDMRAKD
EQKRWRTWNQ PSHRPIVEMV VNSLSISAAS QHGRKLSMKT DVEGRSRLLA MISDLLDTLL
EDWYPALGTR FVHSSEGDLL VSRYVLCPQC VRDAERNGSR SRTSSSASHR RSQDDGELPI
TSSSHMKGSR TTGDISKCRG GVVHCFVIEE CMLAGREYNW VECPSHGGLH MRELAPDTVF
ADIENALTIH PDQLKRSRML GRGAFGFVFR ATVRQPNGEL CEVAQKMLEP VDPGPGGRPS
ALAAYKAAAD KWKRDSMEFA CRAYCTSRQE LSLLSRMKHP NVIGLVGVCT FPLSLVVELA
PLGALNQLLG SHRKAGTKLS LGVIKESAVQ VARALEYLHS AHIIYRDLKS ENVLGWRFPA
PFSPQTDVLL KLGDYGISRS VLPSGGAKGF GGTEGFMAPE IVRFNGEEEY TQKVDCFSFG
MFLYELLTLK FPFESEEHVK ERMLDGARPV LLPHELLLPT PMLDLLVHCW SAHPESRPSS
SQLVGFCAAP EFTHLLDVCE LGEALPPTQL MAVGITDEID DPDDFEAQLW LSGREMVVMG
CTQYGFVDQK SIELPHRGKY VSKVRDSVWS CDECGQVTVY GISLHETGHL QLPSLNGTLI
CAPELISNDV LILISDKQIV LLKLSESNSV SHLGTIDSPY EIRTATFLGN GSTRQIWAGH
SEGRISIHHI ASNDSFSFSS SLYLPDDKCI VRQLVGSKDA QKVWIALEKS SKVQMVEVEK
RQVTGSLDIR KVMPGSETIH TIDMEMASQN YVTCIGLLER NDGDQLYIGT SKGLLVIAHA
TTLQPLSACR PFEGDITSIC ILEEPSREEE NTRGKATTLS TASSESGLGW VRERVSETVD
RFRSSPATVE TQGAALVVCI GRQFRSLSHR FVAEEKLADV YSIAVWRTEE WAL
