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    TTK TTK protein kinase [ Homo sapiens (human) ]

    Gene ID: 7272, updated on 3-Nov-2024

    Summary

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    Official Symbol
    TTKprovided by HGNC
    Official Full Name
    TTK protein kinaseprovided by HGNC
    Primary source
    HGNC:HGNC:12401
    See related
    Ensembl:ENSG00000112742 MIM:604092; AllianceGenome:HGNC:12401
    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
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    Genomic context

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    See TTK in Genome Data Viewer
    Location:
    6q14.1
    Exon count:
    23
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (80004649..80042527)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (81213044..81250924)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (80714366..80752244)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124901351 Neighboring gene glyceraldehyde 3 phosphate dehydrogenase pseudogene 63 Neighboring gene ribosomal protein L35a pseudogene 18 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:80702927-80703569 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:80713403-80714277 Neighboring gene Rho GTPase activating protein 21 pseudogene Neighboring gene adenylate kinase 4 pseudogene 5

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues 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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    Related articles in PubMed

    1. Universal quantitative kinase assay based on diagonal SCX chromatography and stable isotope dimethyl labeling provides high-definition kinase consensus motifs for PKA and human Mps1. Hennrich ML, et al. J Proteome Res, 2013 May 3. PMID 23510141
    2. Expression and function analysis of mitotic checkpoint genes identifies TTK as a potential therapeutic target for human hepatocellular carcinoma. Liang XD, et al. PLoS One, 2014. PMID 24905462, Free PMC Article
    3. Identification of prognostic biomarkers in hepatitis B virus-related hepatocellular carcinoma and stratification by integrative multi-omics analysis. Miao R, et al. J Hepatol, 2014 Oct. PMID 24859455
    4. 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. Chen K, et al. J Biomol Struct Dyn, 2019 Feb. PMID 29380674
    5. Selective inhibition of pancreatic ductal adenocarcinoma cell growth by the mitotic MPS1 kinase inhibitor NMS-P715. Slee RB, et al. Mol Cancer Ther, 2014 Feb. PMID 24282275, Free PMC Article

    See all (220) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. CWH43 Is a Novel Tumor Suppressor Gene with Negative Regulation of TTK in Colorectal Cancer.
      Title: CWH43 Is a Novel Tumor Suppressor Gene with Negative Regulation of TTK in Colorectal Cancer.
    2. TTK is a potential regulator of tumor progression correlated with dedifferentiation and immune cell infiltration in papillary thyroid cancer.
      Title: TTK is a potential regulator of tumor progression correlated with dedifferentiation and immune cell infiltration in papillary thyroid cancer.
    3. TTK Protein Kinase promotes temozolomide resistance through inducing autophagy in glioblastoma.
      Title: TTK Protein Kinase promotes temozolomide resistance through inducing autophagy in glioblastoma.
    4. TTK predicts triple positive breast cancer prognosis and regulates tumor proliferation and invasion.
      Title: TTK predicts triple positive breast cancer prognosis and regulates tumor proliferation and invasion.
    5. Hsp90 regulates the tumorigenic function of tyrosine protein kinase in osteosarcoma.
      Title: Hsp90 regulates the tumorigenic function of tyrosine protein kinase in osteosarcoma.
    6. Identification of hub genes associated with prognosis, diagnosis, immune infiltration and therapeutic drug in liver cancer by integrated analysis.
      Title: Identification of hub genes associated with prognosis, diagnosis, immune infiltration and therapeutic drug in liver cancer by integrated analysis.
    7. Frequent expression of a novel cancer testis antigen, protein kinase human monopolar spindle 1 (hMps1/TTK) in human urinary bladder transitional cell carcinoma.
      Title: Frequent expression of a novel cancer testis antigen, protein kinase human monopolar spindle 1 (hMps1/TTK) in human urinary bladder transitional cell carcinoma.
    8. Overexpressed MPS-1 contributes to endometrioma development through the NF-kappaB signaling pathway.
      Title: Overexpressed MPS-1 contributes to endometrioma development through the NF-κB signaling pathway.
    9. TTK (threonine tyrosine kinase) regulates the malignant behaviors of cancer cells and is regulated by microRNA-582-5p in ovarian cancer.
      Title: TTK (threonine tyrosine kinase) regulates the malignant behaviors of cancer cells and is regulated by microRNA-582-5p in ovarian cancer.
    10. CENPE, PRC1, TTK, and PLK4 May Play Crucial Roles in the Osteosarcoma Progression.
      Title: CENPE, PRC1, TTK, and PLK4 May Play Crucial Roles in the Osteosarcoma Progression.
    Submit: New GeneRIF Correction See all GeneRIFs (125)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See Variation Viewer (GRCh37.p13)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ38280

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables identical protein binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables kinetochore binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein serine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein serine/threonine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein serine/threonine/tyrosine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein tyrosine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in chromosome segregation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in female meiosis chromosome segregation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in meiotic spindle assembly checkpoint signaling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in mitotic spindle assembly checkpoint signaling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in mitotic spindle assembly checkpoint signaling IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in mitotic spindle organization TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in positive regulation of cell population proliferation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in protein localization to kinetochore IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein localization to meiotic spindle midzone IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein phosphorylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in repair of mitotic kinetochore microtubule attachment defect IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in spindle organization TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in kinetochore IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in membrane HDA PubMed 
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in spindle TAS
    Traceable Author Statement
    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
    NP_003309.2
    XP_011534401.1
    XP_011534402.1
    XP_016866731.1
    XP_054212283.1
    XP_054212284.1
    XP_054212285.1

    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)

    1. NM_001166691.2 → 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
      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

    2. 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
      A8K8U5, B2RDW2, E1P543, P33981, Q15272, Q5TCS0, Q9BW51, Q9NTM0
      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: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      80004649..80042527
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011536099.4 → XP_011534401.1  dual specificity protein kinase TTK isoform X1

      See identical proteins and their annotated locations for XP_011534401.1

      UniProtKB/Swiss-Prot
      A8K8U5, B2RDW2, E1P543, P33981, Q15272, Q5TCS0, Q9BW51, Q9NTM0
      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)

    2. XM_011536100.4 → 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

    3. XM_017011242.3 → XP_016866731.1  dual specificity protein kinase TTK isoform X3

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      81213044..81250924
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054356308.1 → XP_054212283.1  dual specificity protein kinase TTK isoform X1

      UniProtKB/Swiss-Prot
      A8K8U5, B2RDW2, E1P543, P33981, Q15272, Q5TCS0, Q9BW51, Q9NTM0

    2. XM_054356309.1 → XP_054212284.1  dual specificity protein kinase TTK isoform X2

    3. XM_054356310.1 → XP_054212285.1  dual specificity protein kinase TTK isoform X3

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P33981.2 GenPept UniProtKB/Swiss-Prot:P33981

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