Tyms thymidylate synthase [Mus musculus (house mouse)] - Gene

Summary

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

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_000071.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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)

Endonuclease-mediated (1)
Targeted (2)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D5Mit176 (e-PCR), detects polymorphism
- UniSTS:130307

px-31f3 (e-PCR)
- UniSTS:257585

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables folic acid binding	IEA Inferred from Electronic Annotation more info
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	IEA Inferred from Electronic Annotation more info
enables mRNA regulatory element binding translation repressor activity	ISO Inferred from Sequence Orthology more info
enables protein homodimerization activity	IEA Inferred from Electronic Annotation more info
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables sequence-specific mRNA binding	IEA Inferred from Electronic Annotation 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

Process	Evidence Code	Pubs
involved_in cartilage development	IEA Inferred from Electronic Annotation more info
involved_in circadian rhythm	IEA Inferred from Electronic Annotation more info
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
involved_in dTTP biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in developmental growth	IEA Inferred from Electronic Annotation more info
involved_in intestinal epithelial cell maturation	IEA Inferred from Electronic Annotation more info
involved_in liver regeneration	IEA Inferred from Electronic Annotation more info
involved_in methylation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of translation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of translation	ISO Inferred from Sequence Orthology more info
involved_in regulation of translation	ISO Inferred from Sequence Orthology more info
involved_in response to cytokine	IEA Inferred from Electronic Annotation more info
involved_in response to ethanol	IEA Inferred from Electronic Annotation more info
involved_in response to folic acid	IEA Inferred from Electronic Annotation more info
involved_in response to glucocorticoid	IEA Inferred from Electronic Annotation more info
involved_in response to organophosphorus	IEA Inferred from Electronic Annotation more info
involved_in response to progesterone	IEA Inferred from Electronic Annotation more info
involved_in response to toxic substance	IEA Inferred from Electronic Annotation more info
involved_in response to vitamin A	IEA Inferred from Electronic Annotation more info
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation 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
involved_in uracil metabolic process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrial inner membrane	ISO Inferred from Sequence Orthology more info
located_in mitochondrial inner membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in mitochondrial matrix	ISO Inferred from Sequence Orthology more info
located_in mitochondrial matrix	ISS Inferred from Sequence or Structural Similarity 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
located_in mitochondrion	ISS Inferred from Sequence or Structural Similarity more info
is_active_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	ISO Inferred from Sequence Orthology more info
located_in nucleus	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: thymidylate synthase

Names: Tsase

NP_067263.1

EC 2.1.1.45

XP_011248064.1

EC 2.1.1.45

XP_017176290.1

EC 2.1.1.45

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_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

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

NC_000071.7 Reference GRCm39 C57BL/6J

Range

30243544..30279261 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017320801.2 → XP_017176290.1 thymidylate synthase isoform X1

Conserved Domains (1) summary

pfam00303
Location:5 → 165

Thymidylat_synt; Thymidylate synthase
XM_011249762.3 → XP_011248064.1 thymidylate synthase isoform X1

Conserved Domains (1) summary

pfam00303
Location:5 → 165

Thymidylat_synt; Thymidylate synthase