TTBK1_MOUSE
ID TTBK1_MOUSE Reviewed; 1308 AA.
AC Q6PCN3;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 3.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Tau-tubulin kinase 1;
DE EC=2.7.11.1;
GN Name=Ttbk1;
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 832-1308.
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 TISSUE SPECIFICITY.
RX PubMed=16923168; DOI=10.1111/j.1471-4159.2006.04059.x;
RA Sato S., Cerny R.L., Buescher J.L., Ikezu T.;
RT "Tau-tubulin kinase 1 (TTBK1), a neuron-specific tau kinase candidate, is
RT involved in tau phosphorylation and aggregation.";
RL J. Neurochem. 98:1573-1584(2006).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-441 AND SER-541, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [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).
CC -!- FUNCTION: Serine/threonine kinase which is able to phosphorylate TAU on
CC serine, threonine and tyrosine residues. Induces aggregation of TAU (By
CC similarity). {ECO:0000250}.
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 -!- 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;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC Note=Divalent metal cations. Mg(2+) or, to a lesser extent, Mn(2+), but
CC not Ca(2+) or Zn(2+). {ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in the brain. Strong expression in the
CC cortical layers, the CA1 layers of the hippocampus and the granular
CC layer of the cerebellum. Also expressed in the large cortical pyramidal
CC cells in the temporal cortex, the CA1 pyramidal neurons and the
CC cerebellum granular neurons. {ECO:0000269|PubMed:16923168}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CK1 Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; AC165445; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CAAA01116144; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC059249; AAH59249.3; -; mRNA.
DR CCDS; CCDS50125.1; -.
DR RefSeq; NP_001156336.1; NM_001162864.1.
DR AlphaFoldDB; Q6PCN3; -.
DR SMR; Q6PCN3; -.
DR BioGRID; 223124; 2.
DR STRING; 10090.ENSMUSP00000044580; -.
DR iPTMnet; Q6PCN3; -.
DR PhosphoSitePlus; Q6PCN3; -.
DR MaxQB; Q6PCN3; -.
DR PaxDb; Q6PCN3; -.
DR PeptideAtlas; Q6PCN3; -.
DR PRIDE; Q6PCN3; -.
DR ProteomicsDB; 297739; -.
DR Antibodypedia; 30359; 194 antibodies from 29 providers.
DR DNASU; 106763; -.
DR Ensembl; ENSMUST00000047034; ENSMUSP00000044580; ENSMUSG00000015599.
DR GeneID; 106763; -.
DR KEGG; mmu:106763; -.
DR UCSC; uc008csx.2; mouse.
DR CTD; 84630; -.
DR MGI; MGI:2147036; Ttbk1.
DR VEuPathDB; HostDB:ENSMUSG00000015599; -.
DR eggNOG; KOG1164; Eukaryota.
DR GeneTree; ENSGT00940000160981; -.
DR HOGENOM; CLU_003410_0_0_1; -.
DR InParanoid; Q6PCN3; -.
DR OMA; RRHAMPG; -.
DR OrthoDB; 75271at2759; -.
DR PhylomeDB; Q6PCN3; -.
DR TreeFam; TF351646; -.
DR BRENDA; 2.7.11.26; 3474.
DR BioGRID-ORCS; 106763; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Ttbk1; mouse.
DR PRO; PR:Q6PCN3; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q6PCN3; protein.
DR Bgee; ENSMUSG00000015599; Expressed in superior frontal gyrus and 113 other tissues.
DR ExpressionAtlas; Q6PCN3; baseline and differential.
DR Genevisible; Q6PCN3; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005875; C:microtubule associated complex; IC:ARUK-UCL.
DR GO; GO:0043025; C:neuronal cell body; IDA:ARUK-UCL.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:ARUK-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; ISO:MGI.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0004713; F:protein tyrosine kinase activity; ISO:MGI.
DR GO; GO:0048156; F:tau protein binding; ISO:MGI.
DR GO; GO:0050321; F:tau-protein kinase activity; ISO:MGI.
DR GO; GO:0007611; P:learning or memory; ISO:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0032091; P:negative regulation of protein binding; ISO:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:ARUK-UCL.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISS:ARUK-UCL.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:ARUK-UCL.
DR GO; GO:1904031; P:positive regulation of cyclin-dependent protein kinase activity; ISO:MGI.
DR GO; GO:2001056; P:positive regulation of cysteine-type endopeptidase activity; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:1903980; P:positive regulation of microglial cell activation; ISO:MGI.
DR GO; GO:0032273; P:positive regulation of protein polymerization; ISS:ARUK-UCL.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd14130; STKc_TTBK1; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR042714; TTBK1_STKc.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cytoplasm; Kinase; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..1308
FT /note="Tau-tubulin kinase 1"
FT /id="PRO_0000278542"
FT DOMAIN 34..297
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 364..397
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 418..448
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 474..671
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 720..899
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 985..1085
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1097..1308
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 372..391
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 484..499
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 533..556
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 569..593
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 617..635
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 734..771
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 780..801
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 806..825
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 862..887
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1024..1038
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1068..1085
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1098..1129
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1232..1255
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 154
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 40..48
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 63
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 441
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 541
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 1308 AA; 141613 MW; 8940FE7A58889736 CRC64;
MQCLAAALKD ETNMSGGGEQ ADILPANYVV KDRWKVLKKI GGGGFGEIYE AMDLLTRENV
ALKVESAQQP KQVLKMEVAV LKKLQGKDHV CRFIGCGRNE KFNYVVMQLQ GRNLADLRRS
QPRGTFTLST TLRLGKQILE SIEAIHSVGF LHRDIKPSNF AMGRLPSTYR KCYMLDFGLA
RQYTNTTGDV RPPRNVAGFR GTVRYASVNA HKNREMGRHD DLWSLFYMLV EFAVGQLPWR
KIKDKEQVGM IKEKYEHRML LKHMPSEFHL FLDHIASLDY FTKPDYQLIM SVFENSMKER
GIAENEAFDW EKAGTDALLS TSTSTPPQQN TRQTAAMFGV VNVTPVPGDL LRENTEDVLQ
GEHLSDQENA PPILPGRPPE GLGPGPHLVP HPGGPEAEVW EETDVNRNKL RINIGKTPCV
EEEQSRGVGV PSSPVRAPPD SPTTPVRSLC YRRVNSPESE RLSTAADGRV ELQERRSRMD
LPGSPSRQAC SSQPAQMLSV DTGHADRQAS GRMDVSASVE QEALSNAFRS VPLAEEEDFD
SKEWVIIDKE TELKDFPPGA EPSTSGTTDE EPEELRPLPE EGEERRRLGT EPTVRPRGRG
MHTLTEEDPR QMLPQPAPPQ LSQADGRSET SQPPTPGSPS HSPLHSGPRP RRRESDPTGP
QRQVFSVAPP FEVNGLPRAV PLALPYQDFK RDLSDYRERA RLLNRVRRVG FSHMLLTAPQ
VPLAPFQPQA NGKEGEEEEE EEEEEEEEEE EEEEEEEEEE EEEEEEEEAG ALGEVLGPRS
GSSSEGSERS TERSQEGAPS TLLADDQKEA RGRASMADGD LEPEEGSKTL VLVSPGDMKK
SPVTAELAPD PDLGTLAALT PQHERPQPTG SQLDVSEPGT LSSILKSEPK PSGPGAGGGV
GLVAPGAGVT AVTSPFTKVE RTFVHIAEKS HLNVMSSGGQ ASRPEELSTG GELGLEVLSE
GGIAEEGAPA PLENGMALAG LDGTEMESCA LSGPPGETPS EVVTDSLPNG PALADGPAPA
SQQEPVTKKG TTISPSRHAM PGSRPRSRIP VLLSEEDTGS EPSGSLSAKE RWSKRARPQQ
DLARLVMEKR QGRLLLRLAS GASSSSSEEQ RRASETLSGT GSEEDTPASE PTTALPRKAV
RAATTRSRIP RPISVSMPVE GQQLPGRPHG AASATDLAIT SRLQLQKPSG LAPAADLRPK
QSASRGPGPG RAQVSKPAAP RSPGLPASTA RHPSGSPRSQ SLSRKESSSP SHQARPGVPP
SRGVLQVRSQ PEASPVAPKK GPKGKQLQTQ RAATKGRAVV SEGRPGAR
