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    Tyms thymidylate synthase [ Mus musculus (house mouse) ]

    Gene ID: 22171, updated on 5-Mar-2024

    Summary

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    Official Symbol
    Tymsprovided by MGI
    Official Full Name
    thymidylate synthaseprovided by MGI
    Primary source
    MGI:MGI:98878
    See related
    Ensembl:ENSMUSG00000025747 AllianceGenome:MGI:98878
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Also known as
    Ts
    Summary
    This gene encodes an enzyme that catalyzes the methylation of deoxyuridylate to deoxythymidylate using 5,10-methylenetetrahydrofolate as a cofactor. This function maintains the thymidine-5-prime monophosphate concentration critical for DNA replication and repair. The encoded enzyme is a target for cancer chemotherapeutic agents. The majority of transcripts for this gene lack a 3' UTR (PMID: 3022294, 3444407). The stop codon in these transcripts is UAA, compared to the UAG found in the genome and longer transcripts, as the polyA site is located within the stop codon (PMID: 3444407, 2157203). A related pseudogene has been identified on chromosome 10. [provided by RefSeq, Mar 2010]
    Expression
    Broad expression in liver E14 (RPKM 10.5), liver E14.5 (RPKM 8.8) and 23 other tissues See more
    Orthologs
    human all
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    Genomic context

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    Location:
    5 B1; 5 15.81 cM
    Exon count:
    9
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 5 NC_000071.7 (30243544..30279261, complement)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 5 NC_000071.6 (30038546..30073645, complement)

    Chromosome 5 - NC_000071.7Genomic Context describing neighboring genes Neighboring gene STARR-positive B cell enhancer ABC_E11285 Neighboring gene vacuole membrane protein 1 pseudogene Neighboring gene STARR-positive B cell enhancer ABC_E9637 Neighboring gene STARR-seq mESC enhancer starr_12744 Neighboring gene STARR-positive B cell enhancer mm9_chr5:30299320-30299620 Neighboring gene RIKEN cDNA A230098N10 gene Neighboring gene STARR-seq mESC enhancer starr_12745 Neighboring gene STARR-seq mESC enhancer starr_12746 Neighboring gene interleukin 6 Neighboring gene CapStarr-seq enhancer MGSCv37_chr5:30400119-30400228 Neighboring gene STARR-seq mESC enhancer starr_12748 Neighboring gene STARR-seq mESC enhancer starr_12749 Neighboring gene RIKEN cDNA 3110082J24 gene Neighboring gene kinesin family member 2C pseudogene Neighboring gene kinesin superfamily protein 2C pseudogene Neighboring gene GRB2 associated regulator of MAPK1 subtype 2

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Mouse ENCODE transcriptome data
    • Description: RNA profiling data sets generated by the Mouse ENCODE project.
    • BioProject: PRJNA66167
    • Publication: PMID 25409824
    • Analysis date: n/a

    Bibliography

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    Related articles in PubMed

    1. Advanced Spectroscopy and APBS Modeling for Determination of the Role of His190 and Trp103 in Mouse Thymidylate Synthase Interaction with Selected dUMP Analogues. Prokopowicz M, et al. Int J Mol Sci, 2021 Mar 6. PMID 33800923, Free PMC Article
    2. 5-Fluorouracil targets thymidylate synthase in the selective suppression of TH17 cell differentiation. Wang J, et al. Oncotarget, 2016 Apr 12. PMID 27027355, Free PMC Article
    3. Crystal structure of mouse thymidylate synthase in tertiary complex with dUMP and raltitrexed reveals N-terminus architecture and two different active site conformations. Dowierciał A, et al. Biomed Res Int, 2014. PMID 24995339, Free PMC Article
    4. Altered mouse leukemia L1210 thymidylate synthase, associated with cell resistance to 5-fluoro-dUrd, is not mutated but rather reflects posttranslational modification. Cieśla J, et al. Acta Biochim Pol, 2006. PMID 16505899
    5. Regulation of mouse thymidylate synthase gene expression in growth-stimulated cells: upstream S phase control elements are indistinguishable from the essential promoter elements. Ash J, et al. Nucleic Acids Res, 1995 Nov 25. PMID 8524656, Free PMC Article

    See all (46) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. TYMS promotes genomic instability and tumor progression in Ink4a/Arf null background.
      Title: TYMS promotes genomic instability and tumor progression in Ink4a/Arf null background.
    2. Advanced Spectroscopy and APBS Modeling for Determination of the Role of His190 and Trp103 in Mouse Thymidylate Synthase Interaction with Selected dUMP Analogues.
      Title: Advanced Spectroscopy and APBS Modeling for Determination of the Role of His190 and Trp103 in Mouse Thymidylate Synthase Interaction with Selected dUMP Analogues.
    3. Thymidylate synthase drives the phenotypes of epithelial-to-mesenchymal transition in non-small cell lung cancer.
      Title: Thymidylate synthase drives the phenotypes of epithelial-to-mesenchymal transition in non-small cell lung cancer.
    4. Data show that knockdown of thymidylate synthase (TS) significantly impairs TH17 and TH1 cell differentiation.
      Title: 5-Fluorouracil targets thymidylate synthase in the selective suppression of TH17 cell differentiation.
    5. Possible interaction routes between hydrophobic residues of the mouse thymidylate synthase protein N-terminal segment and the active site are also discussed
      Title: Crystal structure of mouse thymidylate synthase in tertiary complex with dUMP and raltitrexed reveals N-terminus architecture and two different active site conformations.
    6. SHMT1 and TYMS localization to the nucleus is essential to prevent uracil accumulation in DNA
      Title: Nuclear localization of de novo thymidylate biosynthesis pathway is required to prevent uracil accumulation in DNA.
    7. Synergistic activation of the TATA-less thymidylate synthase promoter by the Ets transcription factor GABP and Sp1.
      Title: Synergistic activation of the TATA-less mouse thymidylate synthase promoter by the Ets transcription factor GABP and Sp1.
    8. posttranslationally-modified thymidylate synthase is associated with cell resistance to 5-fluoro-dUrd
      Title: Altered mouse leukemia L1210 thymidylate synthase, associated with cell resistance to 5-fluoro-dUrd, is not mutated but rather reflects posttranslational modification.
    9. downregulation of expression results in block of cell cycle expression when influenced by Fe65
      Title: Fe65, a ligand of the Alzheimer's beta-amyloid precursor protein, blocks cell cycle progression by down-regulating thymidylate synthase expression.
    Submit: New GeneRIF Correction

    Variation

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    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)
    • Targeted (2) 
    • Endonuclease-mediated (1) 

    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

    Gene Ontology Provided by MGI

    Function Evidence Code Pubs
    enables folic acid binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables heterocyclic compound binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables mRNA binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables mRNA regulatory element binding translation repressor activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables methyltransferase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein homodimerization activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables sequence-specific mRNA binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables thymidylate synthase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables thymidylate synthase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables thymidylate synthase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables transferase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables transferase activity, transferring one-carbon groups IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in dTMP biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in dTMP biosynthetic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in dTMP biosynthetic process ISO
    Inferred from Sequence Orthology
    more info
    		  
    acts_upstream_of_or_within methylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of translation ISO
    Inferred from Sequence Orthology
    more info
    		  
    acts_upstream_of_or_within nucleotide biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of translation ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in tetrahydrofolate interconversion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in tetrahydrofolate interconversion ISO
    Inferred from Sequence Orthology
    more info
    		  
    Component Evidence Code Pubs
    located_in cytoplasm ISO
    Inferred from Sequence Orthology
    more info
    		  
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in mitochondrial inner membrane ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in mitochondrial matrix ISO
    Inferred from Sequence Orthology
    more info
    		  
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrion ISO
    Inferred from Sequence Orthology
    more info
    		  
    is_active_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus ISO
    Inferred from Sequence Orthology
    more info
    		  

    General protein information

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    Preferred Names
    thymidylate synthase
    Names
    Tsase
    NP_067263.1
    XP_011248064.1
    XP_017176290.1

    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_021288.4 → NP_067263.1  thymidylate synthase

      See identical proteins and their annotated locations for NP_067263.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the shorter transcript and encodes the functional protein.
      Source sequence(s)
      AC112933, AK035663
      Consensus CDS
      CCDS19154.1
      UniProtKB/Swiss-Prot
      P07607
      UniProtKB/TrEMBL
      Q544L2, Q8VDV6, Q9D0H1
      Related
      ENSMUSP00000026846.7, ENSMUST00000026846.11
      Conserved Domains (1) summary
      PTZ00164
      Location:22 → 307
      PTZ00164; bifunctional dihydrofolate reductase-thymidylate synthase; Provisional

    RNA

    1. NR_033402.1 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate splice site in an internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AC112933
      Related
      ENSMUST00000141630.8

    RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000071.7 Reference GRCm39 C57BL/6J

      Range
      30243544..30279261 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017320801.2 → XP_017176290.1  thymidylate synthase isoform X1

      Conserved Domains (1) summary
      pfam00303
      Location:5 → 165
      Thymidylat_synt; Thymidylate synthase

    2. XM_011249762.3 → XP_011248064.1  thymidylate synthase isoform X1

      Conserved Domains (1) summary
      pfam00303
      Location:5 → 165
      Thymidylat_synt; Thymidylate synthase

    RNA

    1. XR_003955620.2 RNA Sequence

    2. XR_003955621.2 RNA Sequence

    3. XR_001784663.2 RNA Sequence

    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P07607.1 GenPept UniProtKB/Swiss-Prot:P07607

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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