Q5S006

※ Protein Information

Tag	Content
UniProt Accession	LRRK2_MOUSE; Q5S006;
Entrez ID	66725
GenBank Protein ID
GenBank Nucleotide ID
Protein Name	Leucine-rich repeat serine/threonine-protein kinase 2 (EC 2.7.11.1)
Gene Name	Lrrk2
Organism	Mus musculus
NCBI Taxa ID	10090
Functional Description	Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway. The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes. Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose 6 phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner. Regulates neuronal process morphology in the intact central nervous system (CNS). Phosphorylates PRDX3. Has GTPase activity (By similarity). Functional Description Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway. The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes. Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose 6 phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner. Regulates neuronal process morphology in the intact central nervous system (CNS). Phosphorylates PRDX3. Has GTPase activity (By similarity).
Sequence (Fasta)	MASGACQGCE EEEEEEALKK LIVRLNNVQE GKQIETLLQL LEDMLVFTYS DRASKLFEDK 60 NFHVPLLIVL DSYMRVASVQ QAGWSLLCKL IEVCPGTLQS LIGPQDIGND WEVLGIHRLI 120 LKMLTVHHAN VNLSIVGLKA LDLLLDSGKL TLLILDEECD IFLLIFDAMH RYSANDEVQK 180 LGCKALHVLF ERVSEEQLTE FVENKDYTIL LSTFGSFRRD KEIVYHVLCC LHSLAVTCSN 240 VEVLMSGNVR CYNLVVEAMK AFPTNENIQE VSCSLFQKLT LGNFFNILVL NEVHVFVVKA 300 VRQYPENAAL QISALSCLAL LTETIFLNQD LEERSETQEQ SEEEDSEKLF WLEPCYKALV 360 RHRKDKHVQE AACWALNNLL MYQNSLHEKI GDEDGQFPAH REVMLSMLMH SSSKDVFQAA 420 AHALSTLLEQ NVNFRKILLA KGVYLNVLEL MQKHAHAPEV AESGCKMLSH LFEGSNPSLD 480 TMAAVVPKIL TVMKAHGTSL SVQLEALRAI LHFVVPGLLE ESREDSQCRP NVLRKQCFRT 540 DIHKLVLVAL NRFIGNPGIQ KCGLKVISSL AHLPDATETL SLQGAVDSVL HTLQMYPDDQ 600 EIQCLGLHLM GCLMTKKNFC IGTGHLLAKI LASTLQRFKD VAEVQTTGLQ TTLSILELSV 660 SFSKLLVHYS FDVVIFHQMS SSVVEQKDEQ FLNLCCKCFA KVAVDDELKN TMLERACDQN 720 NSIMVECLLL LGADANQVKG ATSLIYQVCE KESSPKLVEL LLNGGCREQD VRKALTVSIQ 780 KGDSQVISLL LRKLALDLAN NSICLGGFGI GKIDPSWLGP LFPDKSSNLR KQTNTGSVLA 840 RKVLRYQMRN TLQEGVASGS DGKFSEDALA KFGEWTFIPD SSMDSVFGQS DDLDSEGSES 900 SFLVKRKSNS ISVGEVYRDL ALQRCSPNAQ RHSNSLGPVF DHEDLLRRKR KILSSDESLR 960 SSRLPSHMRQ SDSSSSLASE REHITSLDLS ANELKDIDAL SQKCCLSSHL EHLTKLELHQ 1020 NSLTSFPQQL CETLKCLIHL DLHSNKFTSF PSFVLKMPRI TNLDASRNDI GPTVVLDPAM 1080 KCPSLKQLNL SYNQLSSIPE NLAQVVEKLE QLLLEGNKIS GICSPLSLKE LKILNLSKNH 1140 IPSLPGDFLE ACSKVESFSA RMNFLAAMPA LPSSITSLKL SQNSFTCIPE AIFSLPHLRS 1200 LDMSHNNIEC LPGPAHWKSL NLRELIFSKN QISTLDFSEN PHVWSRVEKL HLSHNKLKEI 1260 PPEIGCLENL TSLDVSYNLE LRSFPNEMGK LSKIWDLPLD GLHLNFDFKH VGCKAKDIIR 1320 FLQQRLKKAV PYNRMKLMIV GNTGSGKTTL LQQLMKMKKP ELGMQGATVG IDVRDWSIQI 1380 RGKRRKDLVL NVWDFAGREE FYSTHPHFMT QRALYLAVYD LSKGQAEVDA MKPWLFNIKA 1440 RASSSPVILV GTHLDVSDEK QRKACISKIT KELLNKRGFP TIRDYHFVNA TEESDALAKL 1500 RKTIINESLN FKIRDQPVVG QLIPDCYVEL EKIILSERKA VPTEFPVINR KHLLQLVNEH 1560 QLQLDENELP HAVHFLNESG VLLHFQDPAL QLSDLYFVEP KWLCKVMAQI LTVKVDGCLK 1620 HPKGIISRRD VEKFLSKKKR FPKNYMMQYF KLLEKFQIAL PIGEEYLLVP SSLSDHRPVI 1680 ELPHCENSEI IIRLYEMPYF PMGFWSRLIN RLLEISPFML SGRERALRPN RMYWRQGIYL 1740 NWSPEAYCLV GSEVLDNRPE SFLKITVPSC RKGCILLGRV VDHIDSLMEE WFPGLLEIDI 1800 CGEGETLLKK WALYSFNDGE EHQKILLDEL MKKAEEGDLL INPDQPRLTI PISQIAPDLI 1860 LADLPRNIML NNDELEFEEA PEFLLGDGSF GSVYRAAYEG EEVAVKIFNK HTSLRLLRQE 1920 LVVLCHLHHP SLISLLAAGI RPRMLVMELA SKGSLDRLLQ QDKASLTRTL QHRIALHVAD 1980 GLRYLHSAMI IYRDLKPHNV LLFTLYPNAA IIAKIADYGI AQYCCRMGIK TSEGTPGFRA 2040 PEVARGNVIY NQQADVYSFG LLLHDIWTTG SRIMEGLRFP NEFDELAIQG KLPDPVKEYG 2100 CAPWPMVEKL ITKCLKENPQ ERPTSAQVFD ILNSAELICL MRHILIPKNI IVECMVATNL 2160 NSKSATLWLG CGNTEKGQLS LFDLNTERYS YEEVADSRIL CLALVHLAAE KESWVVCGTQ 2220 SGALLVINVE EETKRHTLEK MTDSVTCLHC NSLAKQSKQS NFLLVGTADG NLMIFEDKAV 2280 KCKGAAPLKT LHIGDVSTPL MCLSESLNSS ERHITWGGCG TKVFSFSNDF TIQKLIETKT 2340 NQLFSYAAFS DSNIIALAVD TALYIAKKNS PVVEVWDKKT EKLCELIDCV HFLKEVMVKL 2400 NKESKHQLSY SGRVKALCLQ KNTALWIGTG GGHILLLDLS TRRVIRTIHN FCDSVRAMAT 2460 AQLGSLKNVM LVLGYKRKST EGIQEQKEIQ SCLSIWDLNL PHEVQNLEKH IEVRTELADK 2520 MRKTSVE 2528 Fasta Sequence >Q5S006\|Lrrk2\|Mus musculus (Mouse) MASGACQGCEEEEEEEALKKLIVRLNNVQEGKQIETLLQLLEDMLVFTYSDRASKLFEDKNFHVPLLIVLDSYMRVASVQQAGWSLLCKLIEVCPGTLQSLIGPQDIGNDWEVLGIHRLILKMLTVHHANVNLSIVGLKALDLLLDSGKLTLLILDEECDIFLLIFDAMHRYSANDEVQKLGCKALHVLFERVSEEQLTEFVENKDYTILLSTFGSFRRDKEIVYHVLCCLHSLAVTCSNVEVLMSGNVRCYNLVVEAMKAFPTNENIQEVSCSLFQKLTLGNFFNILVLNEVHVFVVKAVRQYPENAALQISALSCLALLTETIFLNQDLEERSETQEQSEEEDSEKLFWLEPCYKALVRHRKDKHVQEAACWALNNLLMYQNSLHEKIGDEDGQFPAHREVMLSMLMHSSSKDVFQAAAHALSTLLEQNVNFRKILLAKGVYLNVLELMQKHAHAPEVAESGCKMLSHLFEGSNPSLDTMAAVVPKILTVMKAHGTSLSVQLEALRAILHFVVPGLLEESREDSQCRPNVLRKQCFRTDIHKLVLVALNRFIGNPGIQKCGLKVISSLAHLPDATETLSLQGAVDSVLHTLQMYPDDQEIQCLGLHLMGCLMTKKNFCIGTGHLLAKILASTLQRFKDVAEVQTTGLQTTLSILELSVSFSKLLVHYSFDVVIFHQMSSSVVEQKDEQFLNLCCKCFAKVAVDDELKNTMLERACDQNNSIMVECLLLLGADANQVKGATSLIYQVCEKESSPKLVELLLNGGCREQDVRKALTVSIQKGDSQVISLLLRKLALDLANNSICLGGFGIGKIDPSWLGPLFPDKSSNLRKQTNTGSVLARKVLRYQMRNTLQEGVASGSDGKFSEDALAKFGEWTFIPDSSMDSVFGQSDDLDSEGSESSFLVKRKSNSISVGEVYRDLALQRCSPNAQRHSNSLGPVFDHEDLLRRKRKILSSDESLRSSRLPSHMRQSDSSSSLASEREHITSLDLSANELKDIDALSQKCCLSSHLEHLTKLELHQNSLTSFPQQLCETLKCLIHLDLHSNKFTSFPSFVLKMPRITNLDASRNDIGPTVVLDPAMKCPSLKQLNLSYNQLSSIPENLAQVVEKLEQLLLEGNKISGICSPLSLKELKILNLSKNHIPSLPGDFLEACSKVESFSARMNFLAAMPALPSSITSLKLSQNSFTCIPEAIFSLPHLRSLDMSHNNIECLPGPAHWKSLNLRELIFSKNQISTLDFSENPHVWSRVEKLHLSHNKLKEIPPEIGCLENLTSLDVSYNLELRSFPNEMGKLSKIWDLPLDGLHLNFDFKHVGCKAKDIIRFLQQRLKKAVPYNRMKLMIVGNTGSGKTTLLQQLMKMKKPELGMQGATVGIDVRDWSIQIRGKRRKDLVLNVWDFAGREEFYSTHPHFMTQRALYLAVYDLSKGQAEVDAMKPWLFNIKARASSSPVILVGTHLDVSDEKQRKACISKITKELLNKRGFPTIRDYHFVNATEESDALAKLRKTIINESLNFKIRDQPVVGQLIPDCYVELEKIILSERKAVPTEFPVINRKHLLQLVNEHQLQLDENELPHAVHFLNESGVLLHFQDPALQLSDLYFVEPKWLCKVMAQILTVKVDGCLKHPKGIISRRDVEKFLSKKKRFPKNYMMQYFKLLEKFQIALPIGEEYLLVPSSLSDHRPVIELPHCENSEIIIRLYEMPYFPMGFWSRLINRLLEISPFMLSGRERALRPNRMYWRQGIYLNWSPEAYCLVGSEVLDNRPESFLKITVPSCRKGCILLGRVVDHIDSLMEEWFPGLLEIDICGEGETLLKKWALYSFNDGEEHQKILLDELMKKAEEGDLLINPDQPRLTIPISQIAPDLILADLPRNIMLNNDELEFEEAPEFLLGDGSFGSVYRAAYEGEEVAVKIFNKHTSLRLLRQELVVLCHLHHPSLISLLAAGIRPRMLVMELASKGSLDRLLQQDKASLTRTLQHRIALHVADGLRYLHSAMIIYRDLKPHNVLLFTLYPNAAIIAKIADYGIAQYCCRMGIKTSEGTPGFRAPEVARGNVIYNQQADVYSFGLLLHDIWTTGSRIMEGLRFPNEFDELAIQGKLPDPVKEYGCAPWPMVEKLITKCLKENPQERPTSAQVFDILNSAELICLMRHILIPKNIIVECMVATNLNSKSATLWLGCGNTEKGQLSLFDLNTERYSYEEVADSRILCLALVHLAAEKESWVVCGTQSGALLVINVEEETKRHTLEKMTDSVTCLHCNSLAKQSKQSNFLLVGTADGNLMIFEDKAVKCKGAAPLKTLHIGDVSTPLMCLSESLNSSERHITWGGCGTKVFSFSNDFTIQKLIETKTNQLFSYAAFSDSNIIALAVDTALYIAKKNSPVVEVWDKKTEKLCELIDCVHFLKEVMVKLNKESKHQLSYSGRVKALCLQKNTALWIGTGGGHILLLDLSTRRVIRTIHNFCDSVRAMATAQLGSLKNVMLVLGYKRKSTEGIQEQKEIQSCLSIWDLNLPHEVQNLEKHIEVRTELADKMRKTSVE

※ PTM-Disease Association

Num	PTM	Disease	Cell Type	Type	PTM Site	PMID
1	Serine Phosphorylation	Parkinson's disease	cell line	D	S910	20642453
1	[Reference]: We have also demonstrated that Ser910/Ser935 phosphorylation and 14-3-3 binding to endogenous LRRK2 is significantly reduced in tissues of homozygous LRRK2(R1441C) knock-in mice.?
2	Serine Phosphorylation	Parkinson's disease		D	S935	20642453
2	[Reference]: Strikingly, we found that five of the six most common pathogenic mutations (R1441C, R1441G, R1441H, Y1699C and I2020T) display markedly reduced phosphorylation of Ser910/Ser935 thereby disrupting interaction with 14-3-3.

※ Disease Cross-ref Annotation

Database	Annotation
CTD (Curated) (count: 6)	MESH:D002292 ; Carcinoma, Renal Cell MESH:D004715 ; Endometriosis MESH:D009410 ; Nerve Degeneration MESH:D010300 ; Parkinson Disease OMIM:607060 ; PARKINSON DISEASE 8, AUTOSOMAL DOMINANT MESH:D020734 ; Parkinsonian Disorders

※ PTM Sites

PTM	Modification Sites
Phosphorylation (count: 15) (view all)	1292 PNEMGKLSKIWDLPL dbPAF 1721 EISPFMLSGRERALR dbPAF 860 QEGVASGSDGKFSED dbPAF 908 SFLVKRKSNSISVGE dbPAF 910 LVKRKSNSISVGEVY dbPAF 912 KRKSNSISVGEVYRD dbPAF 933 SPNAQRHSNSLGPVF dbPAF 935 NAQRHSNSLGPVFDH dbPAF 954 RRKRKILSSDESLRS dbPAF 955 RKRKILSSDESLRSS dbPAF 958 KILSSDESLRSSRLP dbPAF 971 LPSHMRQSDSSSSLA dbPAF 973 SHMRQSDSSSSLASE dbPAF 974 HMRQSDSSSSLASER dbPAF 976 RQSDSSSSLASEREH dbPAF
Ubiquitination (count: 3)	1833 LLDELMKKAEEGDLL PLMD 1963 DRLLQQDKASLTRTL PLMD 2091 DELAIQGKLPDPVKE PLMD

PTM

Modification Sites

Phosphorylation
(count: 15)
(view all)

1292      PNEMGKLSKIWDLPL     dbPAF
1721      EISPFMLSGRERALR     dbPAF
860       QEGVASGSDGKFSED     dbPAF
908       SFLVKRKSNSISVGE     dbPAF
910       LVKRKSNSISVGEVY     dbPAF
912       KRKSNSISVGEVYRD     dbPAF

Ubiquitination
(count: 3)

1833      LLDELMKKAEEGDLL     PLMD
1963      DRLLQQDKASLTRTL     PLMD
2091      DELAIQGKLPDPVKE     PLMD

PTMD Annotation Information

※ Protein Information

Functional Description

Fasta Sequence

※ PTM-Disease Association

※ Disease Cross-ref Annotation

※ PTM Sites