ID F6URV2_XENTR Unreviewed; 2514 AA.
AC F6URV2;
DT 27-JUL-2011, integrated into UniProtKB/TrEMBL.
DT 02-JUN-2021, sequence version 4.
DT 27-MAR-2024, entry version 78.
DE RecName: Full=non-specific serine/threonine protein kinase {ECO:0000256|ARBA:ARBA00012513};
DE EC=2.7.11.1 {ECO:0000256|ARBA:ARBA00012513};
GN Name=lrrk2 {ECO:0000313|Ensembl:ENSXETP00000033900,
GN ECO:0000313|RefSeq:XP_002932250.3, ECO:0000313|RefSeq:XP_012815439.2,
GN ECO:0000313|RefSeq:XP_012815440.2,
GN ECO:0000313|Xenbase:XB-GENE-5768572};
OS Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX NCBI_TaxID=8364 {ECO:0000313|Ensembl:ENSXETP00000033900};
RN [1] {ECO:0000313|Ensembl:ENSXETP00000033900}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Nigerian {ECO:0000313|Ensembl:ENSXETP00000033900};
RX PubMed=20431018; DOI=10.1126/science.1183670;
RA Hellsten U., Harland R.M., Gilchrist M.J., Hendrix D., Jurka J.,
RA Kapitonov V., Ovcharenko I., Putnam N.H., Shu S., Taher L., Blitz I.L.,
RA Blumberg B., Dichmann D.S., Dubchak I., Amaya E., Detter J.C., Fletcher R.,
RA Gerhard D.S., Goodstein D., Graves T., Grigoriev I.V., Grimwood J.,
RA Kawashima T., Lindquist E., Lucas S.M., Mead P.E., Mitros T., Ogino H.,
RA Ohta Y., Poliakov A.V., Pollet N., Robert J., Salamov A., Sater A.K.,
RA Schmutz J., Terry A., Vize P.D., Warren W.C., Wells D., Wills A.,
RA Wilson R.K., Zimmerman L.B., Zorn A.M., Grainger R., Grammer T.,
RA Khokha M.K., Richardson P.M., Rokhsar D.S.;
RT "The genome of the Western clawed frog Xenopus tropicalis.";
RL Science 328:633-636(2010).
RN [2] {ECO:0000313|Ensembl:ENSXETP00000033900}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (JUN-2011) to UniProtKB.
RN [3] {ECO:0000313|RefSeq:XP_002932250.3, ECO:0000313|RefSeq:XP_012815439.2}
RP IDENTIFICATION.
RC STRAIN=Nigerian {ECO:0000313|RefSeq:XP_002932250.3,
RC ECO:0000313|RefSeq:XP_012815439.2};
RC TISSUE=Liver and blood {ECO:0000313|RefSeq:XP_002932250.3,
RC ECO:0000313|RefSeq:XP_012815439.2};
RG RefSeq;
RL Submitted (NOV-2023) to UniProtKB.
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:0000256|ARBA:ARBA00001433};
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:0000256|ARBA:ARBA00000775};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000256|ARBA:ARBA00001946};
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DR RefSeq; XP_002932250.3; XM_002932204.5.
DR RefSeq; XP_012815439.2; XM_012959985.3.
DR RefSeq; XP_012815440.2; XM_012959986.3.
DR Ensembl; ENSXETT00000033900; ENSXETP00000033900; ENSXETG00000015544.
DR KEGG; xtr:100145062; -.
DR AGR; Xenbase:XB-GENE-5768572; -.
DR Xenbase; XB-GENE-5768572; lrrk2.
DR eggNOG; KOG0192; Eukaryota.
DR eggNOG; KOG0619; Eukaryota.
DR HOGENOM; CLU_000815_0_0_1; -.
DR OMA; FIVECMV; -.
DR OrthoDB; 148126at2759; -.
DR TreeFam; TF313679; -.
DR Proteomes; UP000008143; Chromosome 3.
DR Bgee; ENSXETG00000015544; Expressed in testis and 14 other cell types or tissues.
DR GO; GO:0005829; C:cytosol; IEA:UniProt.
DR GO; GO:0043226; C:organelle; IEA:UniProt.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0009966; P:regulation of signal transduction; IEA:UniProt.
DR CDD; cd14068; STKc_LRRK2; 1.
DR Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 1.
DR Gene3D; 1.25.10.10; Leucine-rich Repeat Variant; 2.
DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 3.
DR Gene3D; 3.30.70.1390; ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2; 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1.
DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
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; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR020859; ROC_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR NCBIfam; TIGR00231; small_GTP; 1.
DR PANTHER; PTHR48005; LEUCINE RICH REPEAT KINASE 2; 1.
DR PANTHER; PTHR48005:SF13; SERINE_THREONINE-PROTEIN KINASE DDB_G0278509-RELATED; 1.
DR Pfam; PF16095; COR; 1.
DR Pfam; PF00560; LRR_1; 2.
DR Pfam; PF13855; LRR_8; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF08477; Roc; 1.
DR Pfam; PF19056; WD40_2; 1.
DR PRINTS; PR00449; RASTRNSFRMNG.
DR SMART; SM00364; LRR_BAC; 6.
DR SMART; SM00369; LRR_TYP; 6.
DR SMART; SM00175; RAB; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF48371; ARM repeat; 2.
DR SUPFAM; SSF52058; L domain-like; 1.
DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR SUPFAM; SSF50978; WD40 repeat-like; 1.
DR PROSITE; PS51450; LRR; 3.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS51419; RAB; 1.
DR PROSITE; PS51424; ROC; 1.
PE 4: Predicted;
KW ATP-binding {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|PROSITE-
KW ProRule:PRU10141}; Differentiation {ECO:0000256|ARBA:ARBA00022782};
KW GTP-binding {ECO:0000256|ARBA:ARBA00023134};
KW Kinase {ECO:0000256|ARBA:ARBA00022777, ECO:0000313|RefSeq:XP_002932250.3};
KW Leucine-rich repeat {ECO:0000256|ARBA:ARBA00022614};
KW Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741, ECO:0000256|PROSITE-
KW ProRule:PRU10141}; Reference proteome {ECO:0000313|Proteomes:UP000008143};
KW Repeat {ECO:0000256|ARBA:ARBA00022737};
KW Serine/threonine-protein kinase {ECO:0000256|ARBA:ARBA00022527};
KW Transferase {ECO:0000256|ARBA:ARBA00022777,
KW ECO:0000313|RefSeq:XP_002932250.3}.
FT DOMAIN 1320..1503
FT /note="Roc"
FT /evidence="ECO:0000259|PROSITE:PS51424"
FT DOMAIN 1871..2130
FT /note="Protein kinase"
FT /evidence="ECO:0000259|PROSITE:PS50011"
FT BINDING 1898
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU10141"
SQ SEQUENCE 2514 AA; 284722 MW; 0CE8025898D36AC9 CRC64;
MSNREELEEN VRKLVVRLKN IEEGKQIETL VQILDDLYAH TLYDCAPEVF HDNNVLLPLL
LVLESYGKVA VIQQAGWSLL CRLIEVCPET LHRLQTPIDL GREWDVLGVH QQILKILSIY
LTNIAILTTG LKTLTALLAS DVMHFLLLDH EVDIFMLIFD AMRAFPNKEE IQMYGCKALY
LLLIKVPEEQ LSEFVESKDH FILLQVLRDF KEKESVVLPA LQVLLPLAGP SSNVEVLMSG
NVRCYNLITE AMQAFPDNEE IQEVCCCLFQ KLTFGSFYNI LVLNEAHEVI IKALTKYYSN
TTIQAATLSC LALLTETIFL NKDLEDGDNV EEIKGQTYWF QQSFKALKSH KKNTEVQEAA
CWALNNLFMY HPELHDKVGD EDTQYPVHKE VMLSMLMHSS SKDVFQASTA ALATLSEHNV
NIRKLLLEKG VHINVIEIMK KHLCCPEAAE SACRVLQHLF NGSSFNLDIM VGAFTVVLSA
AKKHKNIPSV QLEALRVLLQ MVYEDEELNL QNSTPISEET LFLNLPQKVI KNQCLLEGTH
NLVLQAMNKF IGHRAIQECG LKVLRCLSEC SGALEILSQQ GALDTILHTL QMYPGDSEIQ
YVGLFLLANL VTRKNLCIAT MHLLSTHLVS TLQRYKDDVR IQEEGFLTAL TLMKLSHSFA
KLLDLEEFEK VLFYQISMCL ANKRSMKFQK LCCGCFAEMT SKDELKNTLL VKACADNYIV
IAECLLLLGA DVNTKTKHTT LIIQVCEKGN NPKMVELLLN NGVREQDARK ALNVSIKKCD
NEIISLLLKK LGLDAANNSI CLGGFHIGRT EPSWLIPLFT EKQPLLKQPS VDQEGKKGSI
LARMVLRYHR KNSEIERCRS SGDLSFTEEI HEKSEDSLPH LDVFEEAGIS YSDVDSEGSG
GSLRIRKSNS IGNLEIHKLD HVKLWRRHCN SLGTWADEPT VHRKKDFPQM DYPGAKLSLN
IKRADSLSSL AEKDHIKSLD LSTNDLENIN LIVKKGSLTN HLERLEKLEL QHNSLSSFPK
SLCEALRSLT YLDLRGNSFK SFPHYILEIS SLVFLDVSRN EIGPNLDWNS TKMCPNLKQL
NLSYNQLMSF PENIGNITQN LEELIMEGNN ISEIHIPLCL PELHTINLNK NSIHFLATDF
LKDCVKLETF SATTNLLSIA PNLPQKISAV KLSHNKVTNI PTEILQLSHL RSIDLSNNQI
AHLPGPLEWT SLNLREIILN HNHISVLNLS KDACRWSRLE KLHLSYNKIK EIPPEIGFLE
NITSFDISYN PDLRTFPDEM GKLTKIWDLP LDGLCLDIDL KHIGCKAKDL IRFLQQRLKK
AVPYNRMKVL IVGNTGSGKT TLVQQLMKCR RLEHGAEKAT VGIDVKDWPI LIRGKIKKEI
TLNVWDFAGQ EEFYCSHPHF MTPQALYLVV YDLSKGVSEV DAIKPWLFNI KARASSSPVI
LVGTHLDVSD EKCQKACISK IKQELCNQRG LPSIREYHFV NASEESDLLA KLRKTIIREC
LNFKIREQPV LGQLIPDSYL ELEKKILNER KNVPLEFPVI SHERMLEIVE ESQLHLDENE
LTHAVHFLNE SGVLLHFEDP ALQLRDLYFV DPQWLCKIIA QILTVRADGC QKYPKGIIHC
NDVERFLEKK KKFPKNYMSQ YFKLLEKFQI ALPLGEDQLL IPSSLSDHRP VIELPHCENS
EVIIRLYEMS YFPMGFWSRL INRLLEVSTY MLSGRERAQR PNRMYWRQGI YLNWSPEAYC
LVESTKLDRN PNSFLKVTVP SCRKGCILLG QVVDHIDSLM EEWFPGLLES DICEEGEALL
KKWVLYSFDD GQEHKKILLS DLQAKAEEGD LLVNPEDPRQ TIPVSQIAPD IVLADLPRNI
MLNAEELEFD QAPEFLLGDG GFGSVYRASY KGEDVAVKIF NKHTSSRLLR QELTVLSHLH
HPSLVCLLAA GVHPRMLVME LAPKGSLDHL LQQDCASLTR TLQHRIALHV ADGLRYLHSA
MIIYRDLKPH NVLLFTLYPN SAIIAKIADY GIAQYCCRMG IKTSEGTPGF RAPEVARGNV
IYNQQADVYS FGLLLYDILT GGARMVEGLK FPNEFDELAI HGRLPDPVKE YNCAPWPEVE
VLIKKCLKEN PQQRPTSATV YEILNSAELL CLMRNIVIFS MLTAECMVAA SPLVKKHAVW
VGNGSTRKGQ MCCIDFNKGG QTCEDFSDSR ILCLTLVTLP GEKQSWILAG TQSGEIIAAD
SEDLKIKHTL HKLTDSVTCL LFSCIQGESP KKYYILAGTA NGRVAVFENT AVKCTDAAPM
KVINIGDSST PVMHLCESTY SPEKKSVWGI CGTKIFSLSS EFTVQKTIDT RVATLYSHGS
YSESNITCIA IDKYIYVAKK ISPYVEIWDK KAEKICEVLD CVQFLKEDTV KRRKCKQEEA
YTARVKALYL QKNTALWVGT GGGHILLIDL STRQPIRIIT SFCDSIRSMV PAQLDRGSIK
NVVLVLGCRC TPQKDIQSFL SVWDTNLAHE VQNLKKHNEI RQELADKLRG LSMD
//