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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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