LMTK3_HUMAN
ID LMTK3_HUMAN Reviewed; 1460 AA.
AC Q96Q04; Q4G0U1;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Serine/threonine-protein kinase LMTK3;
DE EC=2.7.11.1 {ECO:0000269|PubMed:21602804};
DE AltName: Full=Lemur tyrosine kinase 3;
DE Flags: Precursor;
GN Name=LMTK3; Synonyms=KIAA1883, TYKLM3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=11572484; DOI=10.1093/dnares/8.4.179;
RA Nagase T., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XXI. The
RT complete sequences of 60 new cDNA clones from brain which code for large
RT proteins.";
RL DNA Res. 8:179-187(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 774-1460.
RC 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 [4]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND INTERACTION WITH ESR1.
RX PubMed=21602804; DOI=10.1038/nm.2351;
RA Giamas G., Filipovic A., Jacob J., Messier W., Zhang H., Yang D., Zhang W.,
RA Shifa B.A., Photiou A., Tralau-Stewart C., Castellano L., Green A.R.,
RA Coombes R.C., Ellis I.O., Ali S., Lenz H.J., Stebbing J.;
RT "Kinome screening for regulators of the estrogen receptor identifies LMTK3
RT as a new therapeutic target in breast cancer.";
RL Nat. Med. 17:715-719(2011).
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 (PubMed:21602804). Involved in endocytic
CC trafficking of N-methyl-D-aspartate receptors (NMDAR) in neurons (By
CC similarity). {ECO:0000250|UniProtKB:Q5XJV6,
CC ECO:0000269|PubMed:21602804}.
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:0000269|PubMed:21602804};
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:0000269|PubMed:21602804};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:21602804};
CC -!- SUBUNIT: Interacts with ESR1 (PubMed:21602804). Interacts with AP-2
CC complex subunit alpha (By similarity). {ECO:0000250|UniProtKB:Q5XJV6,
CC ECO:0000269|PubMed:21602804}.
CC -!- INTERACTION:
CC Q96Q04; P03372: ESR1; NbExp=3; IntAct=EBI-720814, EBI-78473;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q5XJV6}; Single-
CC pass membrane protein {ECO:0000250|UniProtKB:Q5XJV6}. Cell projection,
CC axon {ECO:0000250|UniProtKB:Q5XJV6}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q5XJV6}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q5XJV6}. Note=Punctate pattern in cell
CC projections.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH36690.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAB67776.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB067470; BAB67776.1; ALT_INIT; mRNA.
DR EMBL; AC008403; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC036690; AAH36690.1; ALT_FRAME; mRNA.
DR CCDS; CCDS46136.1; -.
DR PDB; 6SEQ; X-ray; 2.10 A; A=1-1460.
DR PDBsum; 6SEQ; -.
DR AlphaFoldDB; Q96Q04; -.
DR SMR; Q96Q04; -.
DR BioGRID; 125345; 7.
DR IntAct; Q96Q04; 5.
DR STRING; 9606.ENSP00000270238; -.
DR BindingDB; Q96Q04; -.
DR ChEMBL; CHEMBL4523432; -.
DR GlyGen; Q96Q04; 3 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q96Q04; -.
DR PhosphoSitePlus; Q96Q04; -.
DR BioMuta; LMTK3; -.
DR DMDM; 117949603; -.
DR EPD; Q96Q04; -.
DR MassIVE; Q96Q04; -.
DR PaxDb; Q96Q04; -.
DR PeptideAtlas; Q96Q04; -.
DR PRIDE; Q96Q04; -.
DR ProteomicsDB; 77799; -.
DR Antibodypedia; 31727; 187 antibodies from 28 providers.
DR Ensembl; ENST00000600059.6; ENSP00000472020.1; ENSG00000142235.13.
DR Ensembl; ENST00000673139.1; ENSP00000500153.1; ENSG00000142235.13.
DR MANE-Select; ENST00000600059.6; ENSP00000472020.1; NM_001388485.1; NP_001375414.1.
DR UCSC; uc061aua.1; human.
DR GeneCards; LMTK3; -.
DR HGNC; HGNC:19295; LMTK3.
DR HPA; ENSG00000142235; Tissue enriched (brain).
DR MIM; 619624; gene.
DR neXtProt; NX_Q96Q04; -.
DR OpenTargets; ENSG00000142235; -.
DR VEuPathDB; HostDB:ENSG00000142235; -.
DR eggNOG; ENOG502R1RA; Eukaryota.
DR GeneTree; ENSGT00940000154244; -.
DR HOGENOM; CLU_006998_0_0_1; -.
DR InParanoid; Q96Q04; -.
DR OMA; HNYVHRW; -.
DR PhylomeDB; Q96Q04; -.
DR TreeFam; TF332280; -.
DR PathwayCommons; Q96Q04; -.
DR SignaLink; Q96Q04; -.
DR ChiTaRS; LMTK3; human.
DR Pharos; Q96Q04; Tchem.
DR PRO; PR:Q96Q04; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q96Q04; protein.
DR Bgee; ENSG00000142235; Expressed in right frontal lobe and 102 other tissues.
DR ExpressionAtlas; Q96Q04; baseline and differential.
DR Genevisible; Q96Q04; HS.
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 3D-structure; ATP-binding; Cell projection; Glycoprotein; Golgi apparatus;
KW Kinase; Magnesium; Membrane; Metal-binding; Methylation;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Signal; Transferase; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..1460
FT /note="Serine/threonine-protein kinase LMTK3"
FT /id="PRO_0000259460"
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 75..95
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 413..456
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 486..513
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 544..578
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 591..669
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 686..855
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 872..1349
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1361..1460
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 414..443
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 744..773
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 823..848
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 911..927
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 947..982
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1141..1172
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1274..1292
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1331..1349
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1362..1379
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1380..1399
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:0000250|UniProtKB:Q5XJV6"
FT MOD_RES 490
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q5XJV6"
FT MOD_RES 531
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5XJV6"
FT MOD_RES 535
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5XJV6"
FT MOD_RES 981
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5XJV6"
FT CARBOHYD 1081
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1405
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 900
FT /note="V -> L (in dbSNP:rs1643478)"
FT /id="VAR_057116"
FT VARIANT 929
FT /note="L -> V (in dbSNP:rs1643478)"
FT /id="VAR_028943"
FT CONFLICT 774
FT /note="S -> A (in Ref. 3; AAH36690)"
FT /evidence="ECO:0000305"
FT CONFLICT 1398
FT /note="P -> R (in Ref. 3; AAH36690)"
FT /evidence="ECO:0000305"
FT STRAND 133..142
FT /evidence="ECO:0007829|PDB:6SEQ"
FT STRAND 145..152
FT /evidence="ECO:0007829|PDB:6SEQ"
FT STRAND 155..157
FT /evidence="ECO:0007829|PDB:6SEQ"
FT STRAND 159..165
FT /evidence="ECO:0007829|PDB:6SEQ"
FT HELIX 172..186
FT /evidence="ECO:0007829|PDB:6SEQ"
FT STRAND 196..200
FT /evidence="ECO:0007829|PDB:6SEQ"
FT STRAND 202..205
FT /evidence="ECO:0007829|PDB:6SEQ"
FT STRAND 207..211
FT /evidence="ECO:0007829|PDB:6SEQ"
FT HELIX 218..223
FT /evidence="ECO:0007829|PDB:6SEQ"
FT HELIX 239..259
FT /evidence="ECO:0007829|PDB:6SEQ"
FT HELIX 269..271
FT /evidence="ECO:0007829|PDB:6SEQ"
FT STRAND 272..274
FT /evidence="ECO:0007829|PDB:6SEQ"
FT STRAND 280..282
FT /evidence="ECO:0007829|PDB:6SEQ"
FT HELIX 288..291
FT /evidence="ECO:0007829|PDB:6SEQ"
FT HELIX 293..295
FT /evidence="ECO:0007829|PDB:6SEQ"
FT HELIX 307..309
FT /evidence="ECO:0007829|PDB:6SEQ"
FT HELIX 312..314
FT /evidence="ECO:0007829|PDB:6SEQ"
FT HELIX 329..344
FT /evidence="ECO:0007829|PDB:6SEQ"
FT TURN 350..353
FT /evidence="ECO:0007829|PDB:6SEQ"
FT HELIX 356..362
FT /evidence="ECO:0007829|PDB:6SEQ"
FT TURN 363..365
FT /evidence="ECO:0007829|PDB:6SEQ"
FT HELIX 381..390
FT /evidence="ECO:0007829|PDB:6SEQ"
FT HELIX 395..397
FT /evidence="ECO:0007829|PDB:6SEQ"
FT HELIX 401..412
FT /evidence="ECO:0007829|PDB:6SEQ"
SQ SEQUENCE 1460 AA; 153661 MW; FF99FBFD873C73D3 CRC64;
MPAPGALILL AAVSASGCLA SPAHPDGFAL GRAPLAPPYA VVLISCSGLL AFIFLLLTCL
CCKRGDVGFK EFENPEGEDC SGEYTPPAEE TSSSQSLPDV YILPLAEVSL PMPAPQPSHS
DMTTPLGLSR QHLSYLQEIG SGWFGKVILG EIFSDYTPAQ VVVKELRASA GPLEQRKFIS
EAQPYRSLQH PNVLQCLGLC VETLPFLLIM EFCQLGDLKR YLRAQRPPEG LSPELPPRDL
RTLQRMGLEI ARGLAHLHSH NYVHSDLALR NCLLTSDLTV RIGDYGLAHS NYKEDYYLTP
ERLWIPLRWA APELLGELHG TFMVVDQSRE SNIWSLGVTL WELFEFGAQP YRHLSDEEVL
AFVVRQQHVK LARPRLKLPY ADYWYDILQS CWRPPAQRPS ASDLQLQLTY LLSERPPRPP
PPPPPPRDGP FPWPWPPAHS APRPGTLSSP FPLLDGFPGA DPDDVLTVTE SSRGLNLECL
WEKARRGAGR GGGAPAWQPA SAPPAPHANP SNPFYEALST PSVLPVISAR SPSVSSEYYI
RLEEHGSPPE PLFPNDWDPL DPGVPAPQAP QAPSEVPQLV SETWASPLFP APRPFPAQSS
ASGSFLLSGW DPEGRGAGET LAGDPAEVLG ERGTAPWVEE EEEEEEGSSP GEDSSSLGGG
PSRRGPLPCP LCSREGACSC LPLERGDAVA GWGGHPALGC PHPPEDDSSL RAERGSLADL
PMAPPASAPP EFLDPLMGAA APQYPGRGPP PAPPPPPPPP RAPADPAASP DPPSAVASPG
SGLSSPGPKP GDSGYETETP FSPEGAFPGG GAAEEEGVPR PRAPPEPPDP GAPRPPPDPG
PLPLPGPREK PTFVVQVSTE QLLMSLREDV TRNLLGEKGA TARETGPRKA GRGPGNREKV
PGLNRDPTVL GNGKQAPSLS LPVNGVTVLE NGDQRAPGIE EKAAENGALG SPEREEKVLE
NGELTPPRRE EKALENGELR SPEAGEKVLV NGGLTPPKSE DKVSENGGLR FPRNTERPPE
TGPWRAPGPW EKTPESWGPA PTIGEPAPET SLERAPAPSA VVSSRNGGET APGPLGPAPK
NGTLEPGTER RAPETGGAPR APGAGRLDLG SGGRAPVGTG TAPGGGPGSG VDAKAGWVDN
TRPQPPPPPL PPPPEAQPRR LEPAPPRARP EVAPEGEPGA PDSRAGGDTA LSGDGDPPKP
ERKGPEMPRL FLDLGPPQGN SEQIKARLSR LSLALPPLTL TPFPGPGPRR PPWEGADAGA
AGGEAGGAGA PGPAEEDGED EDEDEEEDEE AAAPGAAAGP RGPGRARAAP VPVVVSSADA
DAARPLRGLL KSPRGADEPE DSELERKRKM VSFHGDVTVY LFDQETPTNE LSVQAPPEGD
TDPSTPPAPP TPPHPATPGD GFPSNDSGFG GSFEWAEDFP LLPPPGPPLC FSRFSVSPAL
ETPGPPARAP DARPAGPVEN
