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Protein

Dual specificity protein kinase TTK

Gene

TTK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Phosphorylates proteins on serine, threonine, and tyrosine. Probably associated with cell proliferation. Essential for chromosome alignment by enhancing AURKB activity (via direct CDCA8 phosphorylation) at the centromere, and for the mitotic checkpoint.1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Activity regulationi

Inhibited by the ATP-competitive kinase inhibitor, SP600125.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei553ATPPROSITE-ProRule annotation1
Active sitei647Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi531 – 539ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.12.1 2681
SignaLinkiP33981
SIGNORiP33981

Names & Taxonomyi

Protein namesi
Recommended name:
Dual specificity protein kinase TTK (EC:2.7.12.1)
Alternative name(s):
Phosphotyrosine picked threonine-protein kinase
Short name:
PYT
Gene namesi
Name:TTK
Synonyms:MPS1, MPS1L1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000112742.9
HGNCiHGNC:12401 TTK
MIMi604092 gene
neXtProtiNX_P33981

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi664D → A: Loss of kinase activity. 2 Publications1
Mutagenesisi686T → A: Loss of kinase activity. 1 Publication1

Organism-specific databases

DisGeNETi7272
OpenTargetsiENSG00000112742
PharmGKBiPA37066

Chemistry databases

ChEMBLiCHEMBL3983
GuidetoPHARMACOLOGYi2264

Polymorphism and mutation databases

BioMutaiTTK
DMDMi160112977

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000867741 – 857Dual specificity protein kinase TTKAdd BLAST857

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei7PhosphoserineCombined sources1
Modified residuei33PhosphothreonineCombined sources1
Modified residuei37PhosphoserineCombined sources1
Modified residuei80PhosphoserineCombined sources1
Modified residuei281PhosphoserineCombined sources1
Modified residuei317PhosphoserineCombined sources1
Modified residuei321PhosphoserineCombined sources1
Modified residuei393PhosphoserineCombined sources1
Modified residuei436PhosphoserineCombined sources1
Modified residuei455PhosphoserineCombined sources1
Modified residuei821PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP33981
MaxQBiP33981
PaxDbiP33981
PeptideAtlasiP33981
PRIDEiP33981
ProteomicsDBi54932
54933 [P33981-2]

PTM databases

iPTMnetiP33981
PhosphoSitePlusiP33981

Expressioni

Tissue specificityi

Present in rapidly proliferating cell lines.

Gene expression databases

BgeeiENSG00000112742 Expressed in 125 organ(s), highest expression level in secondary oocyte
CleanExiHS_TTK
ExpressionAtlasiP33981 baseline and differential
GenevisibleiP33981 HS

Organism-specific databases

HPAiCAB010166
CAB013229

Interactioni

Subunit structurei

Interacts with TPR; the interactions occurs in a microtubule-independent manner.2 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113123, 82 interactors
DIPiDIP-40642N
IntActiP33981, 42 interactors
MINTiP33981
STRINGi9606.ENSP00000358813

Chemistry databases

BindingDBiP33981

Structurei

Secondary structure

1857
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP33981
SMRiP33981
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP33981

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini525 – 791Protein kinasePROSITE-ProRule annotationAdd BLAST267

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0596 Eukaryota
ENOG410XRRQ LUCA
GeneTreeiENSGT00790000123008
HOGENOMiHOG000013174
HOVERGENiHBG001029
InParanoidiP33981
KOiK08866
OMAiMSCFRTP
OrthoDBiEOG091G0GP7
PhylomeDBiP33981
TreeFamiTF105420

Family and domain databases

Gene3Di1.25.40.10, 1 hit
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR027084 Prot_kin_Mps1_fam
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
IPR011990 TPR-like_helical_dom_sf
PANTHERiPTHR22974:SF21 PTHR22974:SF21, 1 hit
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF48452 SSF48452, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P33981-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MESEDLSGRE LTIDSIMNKV RDIKNKFKNE DLTDELSLNK ISADTTDNSG
60 70 80 90 100
TVNQIMMMAN NPEDWLSLLL KLEKNSVPLS DALLNKLIGR YSQAIEALPP
110 120 130 140 150
DKYGQNESFA RIQVRFAELK AIQEPDDARD YFQMARANCK KFAFVHISFA
160 170 180 190 200
QFELSQGNVK KSKQLLQKAV ERGAVPLEML EIALRNLNLQ KKQLLSEEEK
210 220 230 240 250
KNLSASTVLT AQESFSGSLG HLQNRNNSCD SRGQTTKARF LYGENMPPQD
260 270 280 290 300
AEIGYRNSLR QTNKTKQSCP FGRVPVNLLN SPDCDVKTDD SVVPCFMKRQ
310 320 330 340 350
TSRSECRDLV VPGSKPSGND SCELRNLKSV QNSHFKEPLV SDEKSSELII
360 370 380 390 400
TDSITLKNKT ESSLLAKLEE TKEYQEPEVP ESNQKQWQSK RKSECINQNP
410 420 430 440 450
AASSNHWQIP ELARKVNTEQ KHTTFEQPVF SVSKQSPPIS TSKWFDPKSI
460 470 480 490 500
CKTPSSNTLD DYMSCFRTPV VKNDFPPACQ LSTPYGQPAC FQQQQHQILA
510 520 530 540 550
TPLQNLQVLA SSSANECISV KGRIYSILKQ IGSGGSSKVF QVLNEKKQIY
560 570 580 590 600
AIKYVNLEEA DNQTLDSYRN EIAYLNKLQQ HSDKIIRLYD YEITDQYIYM
610 620 630 640 650
VMECGNIDLN SWLKKKKSID PWERKSYWKN MLEAVHTIHQ HGIVHSDLKP
660 670 680 690 700
ANFLIVDGML KLIDFGIANQ MQPDTTSVVK DSQVGTVNYM PPEAIKDMSS
710 720 730 740 750
SRENGKSKSK ISPKSDVWSL GCILYYMTYG KTPFQQIINQ ISKLHAIIDP
760 770 780 790 800
NHEIEFPDIP EKDLQDVLKC CLKRDPKQRI SIPELLAHPY VQIQTHPVNQ
810 820 830 840 850
MAKGTTEEMK YVLGQLVGLN SPNSILKAAK TLYEHYSGGE SHNSSSSKTF

EKKRGKK
Length:857
Mass (Da):97,072
Last modified:November 13, 2007 - v2
Checksum:i51F40A3CD1677AC5
GO
Isoform 2 (identifier: P33981-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     420-420: Missing.

Note: No experimental confirmation available.
Show »
Length:856
Mass (Da):96,944
Checksum:i13FDD345AE1B52DA
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6REX1D6REX1_HUMAN
Dual-specificity protein kinase TTK
TTK
150Annotation score:
D6RF82D6RF82_HUMAN
Dual-specificity protein kinase TTK
TTK
139Annotation score:
D6RIC6D6RIC6_HUMAN
Dual-specificity protein kinase TTK
TTK
175Annotation score:
D6RFY1D6RFY1_HUMAN
Dual-specificity protein kinase TTK
TTK
79Annotation score:

Sequence cautioni

The sequence AAA61239 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti389S → A in AAA61239 (PubMed:1639825).Curated1
Sequence conflicti768L → V in CAA49912 (PubMed:7678926).Curated1
Sequence conflicti768L → V (PubMed:1956325).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03714197A → V. Corresponds to variant dbSNP:rs2230513Ensembl.1
Natural variantiVAR_037142758D → N. Corresponds to variant dbSNP:rs2230512Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_043072420Missing in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M86699 mRNA Translation: AAA61239.1 Different initiation.
AK292460 mRNA Translation: BAF85149.1
AK315696 mRNA Translation: BAG38059.1
AL133475 Genomic DNA No translation available.
CH471051 Genomic DNA Translation: EAW48699.1
CH471051 Genomic DNA Translation: EAW48700.1
BC000633 mRNA Translation: AAH00633.1
BC032858 mRNA Translation: AAH32858.1
X70500 mRNA Translation: CAA49912.1
CCDSiCCDS4993.1 [P33981-1]
CCDS55040.1 [P33981-2]
PIRiA42861
RefSeqiNP_001160163.1, NM_001166691.1 [P33981-2]
NP_003309.2, NM_003318.4 [P33981-1]
XP_011534401.1, XM_011536099.2 [P33981-1]
XP_011534402.1, XM_011536100.2 [P33981-2]
UniGeneiHs.169840

Genome annotation databases

EnsembliENST00000230510; ENSP00000230510; ENSG00000112742 [P33981-2]
ENST00000369798; ENSP00000358813; ENSG00000112742 [P33981-1]
ENST00000509894; ENSP00000422936; ENSG00000112742 [P33981-2]
GeneIDi7272
KEGGihsa:7272
UCSCiuc003pjb.5 human [P33981-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M86699 mRNA Translation: AAA61239.1 Different initiation.
AK292460 mRNA Translation: BAF85149.1
AK315696 mRNA Translation: BAG38059.1
AL133475 Genomic DNA No translation available.
CH471051 Genomic DNA Translation: EAW48699.1
CH471051 Genomic DNA Translation: EAW48700.1
BC000633 mRNA Translation: AAH00633.1
BC032858 mRNA Translation: AAH32858.1
X70500 mRNA Translation: CAA49912.1
CCDSiCCDS4993.1 [P33981-1]
CCDS55040.1 [P33981-2]
PIRiA42861
RefSeqiNP_001160163.1, NM_001166691.1 [P33981-2]
NP_003309.2, NM_003318.4 [P33981-1]
XP_011534401.1, XM_011536099.2 [P33981-1]
XP_011534402.1, XM_011536100.2 [P33981-2]
UniGeneiHs.169840

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2X9EX-ray3.10A514-828[»]
2ZMCX-ray3.14A510-857[»]
2ZMDX-ray2.88A510-857[»]
3CEKX-ray2.30A519-808[»]
3DBQX-ray2.70A515-857[»]
3GFWX-ray2.74A519-808[»]
3H9FX-ray2.60A519-808[»]
3HMNX-ray2.70A510-809[»]
3HMOX-ray2.40A510-809[»]
3HMPX-ray2.30A510-809[»]
3VQUX-ray2.40A516-820[»]
3W1FX-ray2.70A516-820[»]
3WYXX-ray2.90A516-820[»]
3WYYX-ray3.05A516-820[»]
3WZJX-ray2.75A516-820[»]
3WZKX-ray2.30A516-820[»]
4B94X-ray2.20A/B/C/D62-239[»]
4BHZX-ray2.85A519-808[»]
4BI0X-ray2.84A519-808[»]
4BI1X-ray2.70A519-808[»]
4BI2X-ray3.11A519-808[»]
4C4EX-ray2.60A519-808[»]
4C4FX-ray2.36A519-808[»]
4C4GX-ray2.65A519-808[»]
4C4HX-ray2.80A519-808[»]
4C4IX-ray2.65A519-808[»]
4C4JX-ray2.50A519-808[»]
4CV8X-ray3.00A519-808[»]
4CV9X-ray2.50A519-808[»]
4CVAX-ray2.50A519-808[»]
4D2SX-ray2.50A514-795[»]
4H7XX-ray2.60A/B55-210[»]
4H7YX-ray1.80A/B/C/D55-210[»]
4JS8X-ray1.94A515-795[»]
4JT3X-ray2.20A515-795[»]
4O6LX-ray2.38A/B515-795[»]
4ZEGX-ray2.33A515-795[»]
5AP0X-ray2.15A519-808[»]
5AP1X-ray2.05A519-808[»]
5AP2X-ray2.80A519-808[»]
5AP3X-ray2.70A519-808[»]
5AP4X-ray2.85A519-808[»]
5AP5X-ray2.80A519-808[»]
5AP6X-ray2.10A519-808[»]
5AP7X-ray2.45A519-808[»]
5EH0X-ray2.18A519-794[»]
5EHLX-ray2.66A519-808[»]
5EHOX-ray2.18A519-808[»]
5EHYX-ray2.26A519-808[»]
5EI2X-ray2.67A519-808[»]
5EI6X-ray2.01A519-808[»]
5EI8X-ray2.17A519-753[»]
5LJJX-ray3.00A519-808[»]
5MRBX-ray2.20A519-808[»]
5N7VX-ray2.52A519-808[»]
5N84X-ray2.30A519-808[»]
5N87X-ray2.29A519-808[»]
5N93X-ray2.10A519-808[»]
5N9SX-ray2.30A519-808[»]
5NA0X-ray2.90A519-808[»]
5NADX-ray2.80A519-808[»]
5NTTX-ray2.75A519-797[»]
5O91X-ray3.20A519-808[»]
6B4WX-ray2.90A515-795[»]
6H3KX-ray2.48A519-794[»]
ProteinModelPortaliP33981
SMRiP33981
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113123, 82 interactors
DIPiDIP-40642N
IntActiP33981, 42 interactors
MINTiP33981
STRINGi9606.ENSP00000358813

Chemistry databases

BindingDBiP33981
ChEMBLiCHEMBL3983
GuidetoPHARMACOLOGYi2264

PTM databases

iPTMnetiP33981
PhosphoSitePlusiP33981

Polymorphism and mutation databases

BioMutaiTTK
DMDMi160112977

Proteomic databases

EPDiP33981
MaxQBiP33981
PaxDbiP33981
PeptideAtlasiP33981
PRIDEiP33981
ProteomicsDBi54932
54933 [P33981-2]

Protocols and materials databases

DNASUi7272
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000230510; ENSP00000230510; ENSG00000112742 [P33981-2]
ENST00000369798; ENSP00000358813; ENSG00000112742 [P33981-1]
ENST00000509894; ENSP00000422936; ENSG00000112742 [P33981-2]
GeneIDi7272
KEGGihsa:7272
UCSCiuc003pjb.5 human [P33981-1]

Organism-specific databases

CTDi7272
DisGeNETi7272
EuPathDBiHostDB:ENSG00000112742.9
GeneCardsiTTK
HGNCiHGNC:12401 TTK
HPAiCAB010166
CAB013229
MIMi604092 gene
neXtProtiNX_P33981
OpenTargetsiENSG00000112742
PharmGKBiPA37066
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0596 Eukaryota
ENOG410XRRQ LUCA
GeneTreeiENSGT00790000123008
HOGENOMiHOG000013174
HOVERGENiHBG001029
InParanoidiP33981
KOiK08866
OMAiMSCFRTP
OrthoDBiEOG091G0GP7
PhylomeDBiP33981
TreeFamiTF105420

Enzyme and pathway databases

BRENDAi2.7.12.1 2681
SignaLinkiP33981
SIGNORiP33981

Miscellaneous databases

EvolutionaryTraceiP33981
GeneWikiiTTK_(gene)
GenomeRNAii7272
PROiPR:P33981
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000112742 Expressed in 125 organ(s), highest expression level in secondary oocyte
CleanExiHS_TTK
ExpressionAtlasiP33981 baseline and differential
GenevisibleiP33981 HS

Family and domain databases

Gene3Di1.25.40.10, 1 hit
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR027084 Prot_kin_Mps1_fam
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
IPR011990 TPR-like_helical_dom_sf
PANTHERiPTHR22974:SF21 PTHR22974:SF21, 1 hit
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF48452 SSF48452, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTTK_HUMAN
AccessioniPrimary (citable) accession number: P33981
Secondary accession number(s): A8K8U5
, B2RDW2, E1P543, Q15272, Q5TCS0, Q9BW51, Q9NTM0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: November 13, 2007
Last modified: November 7, 2018
This is version 195 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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