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   04-NOV-2026, entry version 182.
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: Involved in mitotic spindle assembly checkpoint signaling, a
CC       process that delays anaphase until chromosomes are bioriented on the
CC       spindle, and in the repair of incorrect mitotic kinetochore-spindle
CC       microtubule attachments. Phosphorylates MAD1L1 to promote the mitotic
CC       spindle assembly checkpoint. Phosphorylates CDCA8/Borealin leading to
CC       enhanced AURKB activity at the kinetochore. Phosphorylates SKA3 at
CC       'Ser-34' leading to dissociation of the SKA complex from microtubules
CC       and destabilization of microtubule-kinetochore attachments.
CC       Phosphorylates KNL1, KNTC1 and autophosphorylates. Phosphorylates MCRS1
CC       which enhances recruitment of KIF2A to the minus end of spindle
CC       microtubules and promotes chromosome alignment.
CC       {ECO:0000250|UniProtKB:P33981}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP +
CC         H(+); 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=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] +
CC         ADP + H(+); Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-
CC         COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.12.1;
CC         Evidence={ECO:0000250|UniProtKB:P33981};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] +
CC         ADP + H(+); Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC         COMP:20101, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC         ChEBI:CHEBI:61978, 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   RefSeq; NP_033471.2; NM_009445.3. [P35761-2]
DR   AlphaFoldDB; P35761; -.
DR   SMR; P35761; -.
DR   FunCoup; P35761; 1557.
DR   IntAct; P35761; 4.
DR   STRING; 10090.ENSMUSP00000064839; -.
DR   iPTMnet; P35761; -.
DR   PhosphoSitePlus; P35761; -.
DR   SwissPalm; P35761; -.
DR   jPOST; P35761; -.
DR   PaxDb; 10090-ENSMUSP00000064839; -.
DR   PeptideAtlas; P35761; -.
DR   ProteomicsDB; 298012; -. [P35761-1]
DR   ProteomicsDB; 298013; -. [P35761-2]
DR   Pumba; P35761; -.
DR   Antibodypedia; 4121; 530 antibodies from 37 providers.
DR   Ensembl; ENSMPUT00000018247; ENSMPUP00000017984; ENSMPUG00000018096.
DR   Ensembl; ENSMUST00000070326.14; ENSMUSP00000064839.8; ENSMUSG00000038379.16. [P35761-2]
DR   UCSC; uc009qwo.2; mouse. [P35761-2]
DR   AGR; MGI:1194921; -.
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; AACFQTP; -.
DR   PhylomeDB; P35761; -.
DR   BRENDA; 2.7.12.1; 3474.
DR   CD-CODE; 01CA17F3; Centrosome.
DR   PRO; PR:P35761; -.
DR   Proteomes; UP000000589; Chromosome 9.
DR   RNAct; P35761; protein.
DR   Bgee; ENSMUSG00000038379; Expressed in animal zygote and 155 other cell types or tissues.
DR   ExpressionAtlas; P35761; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISO:GO_Central.
DR   GO; GO:0000776; C:kinetochore; IDA:MGI.
DR   GO; GO:0016020; C:membrane; ISM:MGI.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IEA:InterPro.
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; ISS:UniProtKB.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:GO_Central.
DR   GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IDA:MGI.
DR   GO; GO:0004713; F:protein tyrosine kinase activity; ISS:UniProtKB.
DR   GO; GO:0007059; P:chromosome segregation; IBA:GO_Central.
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   GO; GO:0140273; P:repair of mitotic kinetochore microtubule attachment defect; ISO:GO_Central.
DR   CDD; cd14131; PKc_Mps1; 1.
DR   FunFam; 1.10.510.10:FF:000308; Dual specificity protein kinase TTK; 1.
DR   FunFam; 1.25.40.10:FF:000101; Dual specificity protein kinase TTK; 1.
DR   FunFam; 3.30.200.20:FF:000131; Dual specificity protein kinase TTK; 1.
DR   Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 1.
DR   Gene3D; 1.25.40.10; Tetratricopeptide repeat domain; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR027084; Mps1_cat.
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; DUAL SPECIFICITY PROTEIN KINASE TTK; 1.
DR   PANTHER; PTHR22974; MIXED LINEAGE PROTEIN KINASE; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   SUPFAM; SSF48452; TPR-like; 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         380
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P33981"
FT   MOD_RES         383
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
//