LMTK3_MOUSE
ID LMTK3_MOUSE Reviewed; 1424 AA.
AC Q5XJV6; A6BLZ0; Q52KF1;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Serine/threonine-protein kinase LMTK3;
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q96Q04};
DE AltName: Full=Apoptosis-associated tyrosine kinase 3;
DE AltName: Full=Lemur tyrosine kinase 3;
DE Flags: Precursor;
GN Name=Lmtk3; Synonyms=Aatyk3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, PHOSPHORYLATION, AND MUTAGENESIS OF ASP-266.
RC TISSUE=Brain;
RX PubMed=17651901; DOI=10.1016/j.neuroscience.2007.05.048;
RA Tomomura M., Morita N., Yoshikawa F., Konishi A., Akiyama H., Furuichi T.,
RA Kamiguchi H.;
RT "Structural and functional analysis of the apoptosis-associated tyrosine
RT kinase (AATYK) family.";
RL Neuroscience 148:510-521(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-947, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain cortex;
RX PubMed=17114649; DOI=10.1074/mcp.m600046-mcp200;
RA Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F.,
RA Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B.,
RA Panse C., Schlapbach R., Mansuy I.M.;
RT "Qualitative and quantitative analyses of protein phosphorylation in naive
RT and stimulated mouse synaptosomal preparations.";
RL Mol. Cell. Proteomics 6:283-293(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-232; SER-531; SER-535;
RP SER-947; SER-962 AND SER-977, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, INTERACTION WITH AP-2 COMPLEX SUBUNIT ALPHA, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=24760852; DOI=10.1523/jneurosci.1621-13.2014;
RA Inoue T., Hoshina N., Nakazawa T., Kiyama Y., Kobayashi S., Abe T.,
RA Yamamoto T., Manabe T., Yamamoto T.;
RT "LMTK3 deficiency causes pronounced locomotor hyperactivity and impairs
RT endocytic trafficking.";
RL J. Neurosci. 34:5927-5937(2014).
RN [7]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-490, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- FUNCTION: Protein kinase which phosphorylates ESR1 (in vitro) and
CC protects it against proteasomal degradation. May also regulate ESR1
CC levels indirectly via a PKC-AKT-FOXO3 pathway where it decreases the
CC activity of PKC and the phosphorylation of AKT, thereby increasing
CC binding of transcriptional activator FOXO3 to the ESR1 promoter and
CC increasing ESR1 transcription (By similarity). Involved in endocytic
CC trafficking of N-methyl-D-aspartate receptors (NMDAR) in neurons
CC (PubMed:24760852). {ECO:0000250|UniProtKB:Q96Q04,
CC ECO:0000269|PubMed:24760852}.
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:Q96Q04};
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:Q96Q04};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q96Q04};
CC -!- SUBUNIT: Interacts with ESR1 (By similarity). Interacts with AP-2
CC complex subunit alpha (PubMed:24760852). {ECO:0000250|UniProtKB:Q96Q04,
CC ECO:0000269|PubMed:24760852}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305|PubMed:17651901}; Single-
CC pass membrane protein {ECO:0000305|PubMed:17651901}. Cell projection,
CC axon {ECO:0000269|PubMed:17651901}. Cell projection, dendrite
CC {ECO:0000269|PubMed:17651901}. Golgi apparatus membrane
CC {ECO:0000269|PubMed:24760852}. Note=Punctate pattern in cell
CC projections.
CC -!- TISSUE SPECIFICITY: Expressed in brain. Predominantly expressed in
CC cerebral cortex, thalamus, the cerebellum and hippocampal formation (at
CC protein level). {ECO:0000269|PubMed:17651901,
CC ECO:0000269|PubMed:24760852}.
CC -!- DEVELOPMENTAL STAGE: Up-regulated during postnatal development, and
CC expressed in adult stage. {ECO:0000269|PubMed:17651901}.
CC -!- PTM: Autophosphorylated. {ECO:0000269|PubMed:17651901}.
CC -!- DISRUPTION PHENOTYPE: Viable and grossly normal. Mice exhibit prominent
CC behavioral abnormalities, including locomotor hyperactivity, reduced
CC anxiety, and decreased depression-like behavior.
CC {ECO:0000269|PubMed:24760852}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; AB288873; BAF64834.1; -; mRNA.
DR EMBL; BC083185; AAH83185.1; -; mRNA.
DR EMBL; BC094377; AAH94377.1; -; mRNA.
DR CCDS; CCDS39961.1; -.
DR RefSeq; NP_001005511.2; NM_001005511.3.
DR RefSeq; NP_001277919.1; NM_001290990.1.
DR RefSeq; XP_006541027.1; XM_006540964.3.
DR RefSeq; XP_017177816.1; XM_017322327.1.
DR AlphaFoldDB; Q5XJV6; -.
DR SMR; Q5XJV6; -.
DR BioGRID; 238177; 4.
DR IntAct; Q5XJV6; 6.
DR MINT; Q5XJV6; -.
DR STRING; 10090.ENSMUSP00000112592; -.
DR iPTMnet; Q5XJV6; -.
DR PhosphoSitePlus; Q5XJV6; -.
DR MaxQB; Q5XJV6; -.
DR PaxDb; Q5XJV6; -.
DR PRIDE; Q5XJV6; -.
DR ProteomicsDB; 292344; -.
DR DNASU; 381983; -.
DR GeneID; 381983; -.
DR KEGG; mmu:381983; -.
DR CTD; 114783; -.
DR MGI; MGI:3039582; Lmtk3.
DR eggNOG; ENOG502R1RA; Eukaryota.
DR InParanoid; Q5XJV6; -.
DR PhylomeDB; Q5XJV6; -.
DR TreeFam; TF332280; -.
DR BioGRID-ORCS; 381983; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Lmtk3; mouse.
DR PRO; PR:Q5XJV6; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q5XJV6; protein.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IBA:GO_Central.
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:0006468; P:protein phosphorylation; IBA:GO_Central.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell projection; Golgi apparatus; Kinase; Magnesium; Membrane;
KW Metal-binding; Methylation; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Signal; Transferase;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..1424
FT /note="Serine/threonine-protein kinase LMTK3"
FT /id="PRO_0000259461"
FT TRANSMEM 40..60
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 133..411
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 74..95
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 413..465
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 486..516
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 544..666
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 680..964
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 976..1024
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1041..1313
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1325..1424
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 414..441
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 552..572
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 741..764
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 820..843
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 848..863
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 932..957
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1115..1129
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1135..1153
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1165..1179
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1245..1261
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1295..1313
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1326..1345
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1346..1363
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 266
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 139..147
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 164
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 232
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 490
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 531
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 535
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 947
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16452087,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 962
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 977
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MUTAGEN 266
FT /note="D->V: Significant decrease in autophosphorylation."
FT /evidence="ECO:0000269|PubMed:17651901"
FT CONFLICT 691
FT /note="D -> G (in Ref. 1; BAF64834)"
FT /evidence="ECO:0000305"
FT CONFLICT 811
FT /note="K -> E (in Ref. 1; BAF64834 and 2; AAH94377)"
FT /evidence="ECO:0000305"
FT CONFLICT 941
FT /note="A -> E (in Ref. 1; BAF64834)"
FT /evidence="ECO:0000305"
FT CONFLICT 950
FT /note="K -> R (in Ref. 1; BAF64834)"
FT /evidence="ECO:0000305"
FT CONFLICT 1266
FT /note="D -> G (in Ref. 1; BAF64834)"
FT /evidence="ECO:0000305"
FT CONFLICT 1287
FT /note="V -> A (in Ref. 1; BAF64834)"
FT /evidence="ECO:0000305"
FT CONFLICT 1369
FT /note="S -> N (in Ref. 1; BAF64834)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1424 AA; 150891 MW; 86A0BACC47909C91 CRC64;
MPAPGALILL AAVSASGCLA SPAHPDGFAL SRAPLAPPYA VVLISCSGLL AFIFLLLTCL
CCKRGDVRFK EFENPEGEDC SGEYTPPAEE TSSSQSLPDV YILPLAEVSL PMPAPQPPHS
DISTPLGLSR QHLSYLQEIG SGWFGKVILG EVFSDYSPAQ VVVKELRASA GPLEQRKFIS
EAQPYRSLQH PNVLQCLGVC VETLPFLLIM EFCQLGDLKR YLRAQRPPEG MSPELPPRDL
RTLQRMGLEI ARGLAHLHSH NYVHSDLALR NCLLTSDLTV RIGDYGLAHS NYKEDYYLTP
ERLWVPLRWA APELLGELHG SFVLVDQSRE SNVWSLGVTL WELFEFGAQP YRHLSDEEVL
AFVVRQQHVK LARPRLKLPY ADYWYDILQS CWRPPAQRPS ASDLQLQLTY LLSERPPRPP
PPPPPPRDGP FPWPWPPSHS APRPGTLSSQ FPLLDGFPGA DPDDVLTVTE SSRGLNLECL
WEKARRGAGR GGGAPPWQPA SAPPAPHTNP SNPFYEALST PSVLPVISAR SPSVSSEYYI
RLEEHGSPPE PLFPNDWDPL DPGVPGPQAP QTPSEVPQLV SETWASPLFP APRPFPAQSS
GSGGFLLSGW DPEGRGAGET LAGDPAEVLG EQGTAPWAEE EEEESSPGED SSSLGGGPSR
RGPLPCPLCS REGPCSCLPL ERGDAVAGWG DHPALGCPHP PEDDSSLRAE RGSLADLPLV
PPTSAPLEFL DPLMGAAAPQ YPGRGPPPAP PPPPPPPRAS AEPAASPDPP SALASPGSGL
SSPGPKPGDS GYETETPFSP EGAFPGGGAA KEEGVPRPRA PPEPPDPGAP RPPPDPGPLP
LPGSQEKPTF VVQVSTEQLL MSLREDVTKN LLGDKGSTPG ETGPRKAGRS PANREKGPGP
NRDLTSLVSR KKVPSRSLPV NGVTVLENGK PGVPDMKEKV AENGLESPEK EERALVNGEP
MSPEAGEKVL ANGVLMSPKS EEKVAENGVL RLPRNTERPP EIGPRRVPGP WEKTPETGGL
APETLLDRAP APCEAALPQN GLEMAPGQLG PAPKSGNPDP GTEWRVHESG GAPRAPGAGK
LDLGSGGRAL GGVGTAPAGG PASAVDAKAG WVDNSRPLPP PPQPLGAQQR RPEPVPLKAR
PEVAQEEEPG VPDNRLGGDM APSVDEDPLK PERKGPEMPR LFLDLGPPQG NSEQIKAKLS
RLSLALPPLT LTPFPGPGPR RPPWEGADAG AAGGEAGGAG APGPAEEDGE DEDEDEEDEE
AAGSRDPGRT REAPVPVVVS SADGDTVRPL RGLLKSPRAA DEPEDSELER KRKMVSFHGD
VTVYLFDQET PTNELSVQGT PEGDTEPSTP PAPPTPPHPT TPGDGFPNSD SGFGGSFEWA
EDFPLLPPPG PPLCFSRFSV SPALETPGPP ARAPDARPAG PVEN
