TTK_MOUSE
ID TTK_MOUSE Reviewed; 856 AA.
AC P35761;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Dual specificity protein kinase TTK;
DE EC=2.7.12.1 {ECO:0000250|UniProtKB:P33981};
DE AltName: Full=ESK;
DE AltName: Full=PYT;
GN Name=Ttk; Synonyms=Esk;
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] (ISOFORMS 1 AND 2).
RX PubMed=1375325; DOI=10.1128/mcb.12.6.2681-2689.1992;
RA Douville E.M.J., Afar D.E.H., Howell B.W., Letwin K., Tannock L.,
RA Ben-David Y., Pawson T., Bell J.C.;
RT "Multiple cDNAs encoding the esk kinase predict transmembrane and
RT intracellular enzyme isoforms.";
RL Mol. Cell. Biol. 12:2681-2689(1992).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
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: Phosphorylates proteins on serine, threonine, and tyrosine
CC (By similarity). Probably associated with cell proliferation (By
CC similarity). Phosphorylates MAD1L1 to promote mitotic checkpoint
CC signaling (By similarity). Essential for chromosome alignment by
CC enhancing AURKB activity (via direct CDCA8 phosphorylation) at the
CC centromere, and for the mitotic checkpoint (By similarity).
CC {ECO:0000250|UniProtKB:P33981}.
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=2.7.12.1;
CC Evidence={ECO:0000250|UniProtKB:P33981};
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=2.7.12.1; Evidence={ECO:0000250|UniProtKB:P33981};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.12.1;
CC Evidence={ECO:0000250|UniProtKB:P33981};
CC -!- ACTIVITY REGULATION: Inhibited by the ATP-competitive kinase inhibitor,
CC SP600125. {ECO:0000250}.
CC -!- SUBUNIT: Interacts with TPR; the interactions occurs in a microtubule-
CC independent manner (By similarity). Interacts with MAD1L1 and MAD2L1
CC (By similarity). {ECO:0000250|UniProtKB:P33981}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P35761-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P35761-2; Sequence=VSP_004875;
CC -!- TISSUE SPECIFICITY: Present in rapidly proliferating cell lines; high
CC levels in testis, bone marrow, spleen and thymus. Low levels in brain,
CC heart, lung and kidney.
CC -!- PTM: Autophosphorylated.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; M86377; AAA37578.1; -; mRNA.
DR CCDS; CCDS52874.1; -. [P35761-2]
DR PIR; A44439; A44439.
DR PIR; B44439; B44439.
DR AlphaFoldDB; P35761; -.
DR SMR; P35761; -.
DR IntAct; P35761; 4.
DR STRING; 10090.ENSMUSP00000064839; -.
DR iPTMnet; P35761; -.
DR PhosphoSitePlus; P35761; -.
DR EPD; P35761; -.
DR MaxQB; P35761; -.
DR PaxDb; P35761; -.
DR PeptideAtlas; P35761; -.
DR PRIDE; P35761; -.
DR ProteomicsDB; 298012; -. [P35761-1]
DR ProteomicsDB; 298013; -. [P35761-2]
DR Antibodypedia; 4121; 485 antibodies from 34 providers.
DR Ensembl; ENSMUST00000070326; ENSMUSP00000064839; ENSMUSG00000038379. [P35761-2]
DR UCSC; uc009qwo.2; mouse. [P35761-2]
DR MGI; MGI:1194921; Ttk.
DR VEuPathDB; HostDB:ENSMUSG00000038379; -.
DR eggNOG; KOG0596; Eukaryota.
DR GeneTree; ENSGT00950000182984; -.
DR HOGENOM; CLU_010380_0_0_1; -.
DR InParanoid; P35761; -.
DR OMA; PISTPKW; -.
DR PhylomeDB; P35761; -.
DR TreeFam; TF105420; -.
DR BRENDA; 2.7.12.1; 3474.
DR ChiTaRS; Ttk; mouse.
DR PRO; PR:P35761; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; P35761; protein.
DR Bgee; ENSMUSG00000038379; Expressed in animal zygote and 151 other tissues.
DR ExpressionAtlas; P35761; baseline and differential.
DR Genevisible; P35761; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0000776; C:kinetochore; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0043515; F:kinetochore binding; IMP:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IDA:MGI.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0007059; P:chromosome segregation; IBA:GO_Central.
DR GO; GO:0051304; P:chromosome separation; IEA:InterPro.
DR GO; GO:0016321; P:female meiosis chromosome segregation; IMP:MGI.
DR GO; GO:0033316; P:meiotic spindle assembly checkpoint signaling; IMP:MGI.
DR GO; GO:0007094; P:mitotic spindle assembly checkpoint signaling; IMP:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:MGI.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:MGI.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MGI.
DR GO; GO:0034502; P:protein localization to chromosome; IMP:MGI.
DR GO; GO:0034501; P:protein localization to kinetochore; IMP:MGI.
DR GO; GO:1903096; P:protein localization to meiotic spindle midzone; IMP:MGI.
DR Gene3D; 1.25.40.10; -; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR027084; Prot_kin_Mps1_fam.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR PANTHER; PTHR22974:SF21; PTHR22974:SF21; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF48452; SSF48452; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; ATP-binding; Kinase; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase; Tyrosine-protein kinase.
FT CHAIN 1..856
FT /note="Dual specificity protein kinase TTK"
FT /id="PRO_0000086775"
FT DOMAIN 524..790
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 837..856
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 646
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 530..538
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 552
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P33981"
FT MOD_RES 32
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P33981"
FT MOD_RES 36
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P33981"
FT MOD_RES 277
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P33981"
FT MOD_RES 342
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P33981"
FT MOD_RES 435
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P33981"
FT MOD_RES 454
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P33981"
FT MOD_RES 820
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P33981"
FT VAR_SEQ 296..321
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:1375325"
FT /id="VSP_004875"
SQ SEQUENCE 856 AA; 96211 MW; 31F8C16C195E6E86 CRC64;
MEAEELIGSS VTIDSIMSKM RDIKNKINED CTDELSLSKI CADHTETVNQ IMRVGNTPEN
WLNFLLKLEK NSSPLNDDLL NKLIGRYSQA IEVLPPDKYG QNESFARIQV RLAELKAIQE
PDDARDYFQM ARENCKKFAF VHVSFAQFEL SQGNLKKSEQ LLHKAVETGA VPLQMLETAM
RNLHLQKKQL LPEEDKKSVS ASTVLSAQEP FSSSLGNVQN RSISCESRGQ AGAARVLYGE
NLPPQDAEVR HQNPFKQTHA AKRSCPFGRV PVNLLNSPDF YVKTDSSAVT QLTTRLALSS
VPLPYVTCLL HLQLLALAGL AKGSGPDRDA ILPGSRPRGS DSYELRGLKP IQTIYLKDSL
VSNEKSSELM SDLIALKSKT DSSLTKLEET KPEIAERRPM QWQSTRKPEC VFQNPAAFAP
LRHVPDVTPK ADKESPPISV PKWLDPKSAC ETPSSSSLDD YMKCFKTPVV KNDFPPACPS
STPYSQLARL QQQQQQGLST PLQSLQISGS SSINECISVN GRIYSILKQI GSGGSSKVFQ
VLNEKKQINA IKYVNLEDAD SQTIESYRNE IAFLNKLQQH SDKIIRLYDY EITEQYIYMV
MECGNIDLNS WLKKKKSINP WERKSYWKNM LEAVHIIHQH GIVHSDLKPA NFVIVDGMLK
LIDFGIANQM QPDTTSIVKD SQVGTVNYMA PEAIRDMSSS RENSKIRTKV SPRSDVWSLG
CILYYMTYGR TPFQHIINQV SKLHAIINPA HEIEFPEISE KDLRDVLKCC LVRNPKERIS
IPELLTHPYV QIQPHPGSQM ARGATDEMKY VLGQLVGLNS PNSILKTAKT LYERYNCGEG
QDSSSSKTFD KKRERK
