TTK TTK protein kinase [Homo sapiens (human)] - Gene

Summary

Official Symbol: TTKprovided by HGNC
Official Full Name: TTK protein kinaseprovided by HGNC
Primary source: HGNC:HGNC:12401
See related: Ensembl:ENSG00000112742 MIM:604092
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ESK; PYT; CT96; MPH1; MPS1; MPS1L1
Summary: This gene encodes a dual specificity protein kinase with the ability to phosphorylate tyrosine, serine and threonine. Associated with cell proliferation, this protein is essential for chromosome alignment at the centromere during mitosis and is required for centrosome duplication. It has been found to be a critical mitotic checkpoint protein for accurate segregation of chromosomes during mitosis. Tumorigenesis may occur when this protein fails to degrade and produces excess centrosomes resulting in aberrant mitotic spindles. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2009]
Expression: Biased expression in testis (RPKM 13.6), bone marrow (RPKM 6.1) and 10 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 6q14.1

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
109.20190905	current	GRCh38.p13 (GCF_000001405.39)	6	NC_000006.12 (80004147..80042651)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (80714322..80752244)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Authors show that Mps1 regulates chromosome alignment through MCRS1, a spindle assembly factor that controls the dynamics of the minus end of kinetochore microtubules. Mps1 binds and phosphorylates MCRS1.
Title: Mps1 regulates spindle morphology through MCRS1 to promote chromosome alignment.
molecular dynamics simulations of protein MPS1 itself as well as protein bound systems with the inhibitor and natural substrate based on crystal structures, were performed.
Title: Identification of the hot spot residues for pyridine derivative inhibitor CCT251455 and ATP substrate binding on monopolar spindle 1 (MPS1) kinase by molecular dynamic simulation.
The USP9X-TTK axis may play a critical role in NSCLC, and could be considered as a potential therapeutic target.
Title: A novel USP9X substrate TTK contributes to tumorigenesis in non-small-cell lung cancer.
Diverses studies provide evidence that Mps1, an evolutionary conserved kinase, is indispensable for error correction and the chief conductor of the spindle assembly checkpoint. [review]
Title: Leader of the SAC: molecular mechanisms of Mps1/TTK regulation in mitosis.
Treatment of a xenograft model of a CTNNB1-mutant cell line with the TTK inhibitor NTRC 0066-0 resulted in complete inhibition of tumor growth. Mutations in CTNNB1 occur at relatively high frequency in endometrial cancer and hepatocellular carcinoma, which are known to express high TTK levels. We propose mutant CTNNB1 as a prognostic drug response biomarker, enabling the selection of patients most likely to respond to TTK
Title: TTK Inhibitors as a Targeted Therapy for <i>CTNNB1</i> (<b>β</b>-catenin) Mutant Cancers.
Following lentiviral shRNA knockdown in several human liver cancer cell lines, we demonstrated that TTK boosts cell growth and promotes cell spreading; as well as protects against senescence and decreases autophagy. In an experimental animal model, we show that in vitro knockdown of TTK effectively blocks intrahepatic growth of human HCC xenografts.
Title: Utility of the dual-specificity protein kinase TTK as a therapeutic target for intrahepatic spread of liver cancer.
The expression of TTK in gallbladder cancer (GBC) is lower than that in normal tissues. Higher levels of TTK expression in GBC are concomitant with longer overall survival.
Title: Threonine and tyrosine kinase may serve as a prognostic biomarker for gallbladder cancer.
TTK is a favorable prognostic biomarker associated with triple-negative breast cancer survival.
Title: TTK is a favorable prognostic biomarker for triple-negative breast cancer survival.
Therefore, Mps1 promotes checkpoint activation through sequentially phosphorylating Knl1, Bub1, and Mad1. This sequential multi-target phosphorylation cascade makes the checkpoint highly responsive to Mps1 and to kinetochore-microtubule attachment.
Title: A sequential multi-target Mps1 phosphorylation cascade promotes spindle checkpoint signaling.
Both monopolar spindle 1 (MPS1) and miR-21 depletion suppressed glioblastoma (GBM) cell proliferation, whereas, ectopic expression of miR-21 rescued GBM cell growth from MPS1 inhibition.
Title: Modulation of miR-21 signaling by MPS1 in human glioblastoma.

Submit: New GeneRIF Correction See all GeneRIFs (101)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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Cell cycle, organism-specific biosystem (from KEGG)
Cell cycle, organism-specific biosystemMitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cycli...
Cell cycle, conserved biosystem (from KEGG)
Cell cycle, conserved biosystemMitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cycli...
Retinoblastoma (RB) in Cancer, organism-specific biosystem (from WikiPathways)
Retinoblastoma (RB) in Cancer, organism-specific biosystemDescribes the role of retinoblastoma (RB) gene in cancer.

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH1535 (e-PCR)
- UniSTS:88910

D6S2407 (e-PCR)
- UniSTS:29430

Homology

Homologs of the TTK gene: The TTK gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 280 organisms have orthologs with human gene TTK
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
kinetochore binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein homodimerization activity	IEA Inferred from Electronic Annotation more info
protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein serine/threonine/tyrosine kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein tyrosine kinase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
chromosome segregation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
chromosome separation	IEA Inferred from Electronic Annotation more info
female meiosis chromosome segregation	IEA Inferred from Electronic Annotation more info
meiotic spindle assembly checkpoint	IBA Inferred from Biological aspect of Ancestor more info	PubMed
mitotic spindle assembly checkpoint	IBA Inferred from Biological aspect of Ancestor more info	PubMed
mitotic spindle organization	TAS Traceable Author Statement more info	PubMed
peptidyl-serine phosphorylation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
peptidyl-threonine phosphorylation	IEA Inferred from Electronic Annotation more info
peptidyl-tyrosine phosphorylation	IEA Inferred from Electronic Annotation more info
positive regulation of cell proliferation	TAS Traceable Author Statement more info	PubMed
positive regulation of pathway-restricted SMAD protein phosphorylation	TAS Traceable Author Statement more info	PubMed
protein autophosphorylation	IEA Inferred from Electronic Annotation more info
protein localization to kinetochore	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein localization to meiotic spindle midzone	IEA Inferred from Electronic Annotation more info
spindle organization	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
kinetochore	IBA Inferred from Biological aspect of Ancestor more info	PubMed
membrane	HDA more info	PubMed
nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
spindle	IBA Inferred from Biological aspect of Ancestor more info	PubMed

General protein information

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Preferred Names: dual specificity protein kinase TTK

Names: cancer/testis antigen 96; monopolar spindle 1 kinase; monopolar spindle 1-like 1; phosphotyrosine picked threonine kinase; phosphotyrosine picked threonine-protein kinase

NP_001160163.1

EC 2.7.12.1

NP_003309.2

EC 2.7.12.1

XP_011534401.1

EC 2.7.12.1

XP_011534402.1

EC 2.7.12.1

XP_016866731.1

EC 2.7.12.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001166691.1 → NP_001160163.1 dual specificity protein kinase TTK isoform 2

See identical proteins and their annotated locations for NP_001160163.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses alternate in-frame splice sites in the 5' UTR and in the central coding region, compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1.

Source sequence(s)

AK292460, AL133475, AU154042, DA853919

Consensus CDS

CCDS55040.1

UniProtKB/Swiss-Prot

P33981

Related

ENSP00000230510.3, ENST00000230510.7

Conserved Domains (2) summary

cd14131
Location:522 → 790

PKc_Mps1; Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle 1 (also called TTK)

pfam00069
Location:524 → 790

Pkinase; Protein kinase domain
NM_003318.5 → NP_003309.2 dual specificity protein kinase TTK isoform 1

See identical proteins and their annotated locations for NP_003309.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the shorter transcript and encodes the longer isoform (1).

Source sequence(s)

AK315696, AU154042, DA853919

Consensus CDS

CCDS4993.1

UniProtKB/Swiss-Prot

P33981

Related

ENSP00000358813.2, ENST00000369798.7

Conserved Domains (1) summary

cd14131
Location:523 → 791

PKc_Mps1; Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle 1 (also called TTK)

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p13 Primary Assembly

Range

80004147..80042651

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011536099.3 → XP_011534401.1 dual specificity protein kinase TTK isoform X1

See identical proteins and their annotated locations for XP_011534401.1

UniProtKB/Swiss-Prot

P33981

Conserved Domains (1) summary

cd14131
Location:523 → 791

PKc_Mps1; Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle 1 (also called TTK)
XM_017011242.2 → XP_016866731.1 dual specificity protein kinase TTK isoform X3
XM_011536100.3 → XP_011534402.1 dual specificity protein kinase TTK isoform X2

See identical proteins and their annotated locations for XP_011534402.1

UniProtKB/Swiss-Prot

P33981

Related

ENSP00000422936.1, ENST00000509894.5

Conserved Domains (2) summary

cd14131
Location:522 → 790

PKc_Mps1; Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle 1 (also called TTK)

pfam00069
Location:524 → 790

Pkinase; Protein kinase domain