TYMS

Protein identityUniProt · HPA

UniProt accession

P04818

Gene

TYMS

Ensembl

ENSG00000176890

Chromosome

18

Canonical length

313 aa

Protein class

Cancer-related genes, Enzymes, FDA approved drug targets, Metabolic proteins, Plasma proteins, Predicted intracellular proteins

Quaternary structure

Homodimer

OverviewNCBI Gene

Thymidylate synthase catalyzes the methylation of deoxyuridylate to deoxythymidylate using, 10-methylenetetrahydrofolate (methylene-THF) as a cofactor. This function maintains the dTMP (thymidine-5-prime monophosphate) pool critical for DNA replication and repair. The enzyme has been of interest as a target for cancer chemotherapeutic agents. It is considered to be the primary site of action for 5-fluorouracil, 5-fluoro-2-prime-deoxyuridine, and some folate analogs. Expression of this gene and that of a naturally occurring antisense transcript, mitochondrial enolase superfamily member 1 (GeneID:55556), vary inversely when cell-growth progresses from late-log to plateau phase. Polymorphisms in this gene may be associated with etiology of neoplasia, including breast cancer, and response to chemotherapy. [provided by RefSeq, Aug 2017]

Canonical amino-acid sequenceUniProt

313 residues, UniProt reviewed canonical sequence.

>P04818|TYMS
     1  MPVAGSELPR RPLPPAAQER DAEPRPPHGE LQYLGQIQHI LRCGVRKDDR TGTGTLSVFG
    61  MQARYSLRDE FPLLTTKRVF WKGVLEELLW FIKGSTNAKE LSSKGVKIWD ANGSRDFLDS
   121  LGFSTREEGD LGPVYGFQWR HFGAEYRDME SDYSGQGVDQ LQRVIDTIKT NPDDRRIIMC
   181  AWNPRDLPLM ALPPCHALCQ FYVVNSELSC QLYQRSGDMG LGVPFNIASY ALLTYMIAHI
   241  TGLKPGDFIH TLGDAHIYLN HIEPLKIQLQ REPRPFPKLR ILRKVEKIDD FKAEDFQIEG
   301  YNPHPTIKME MAV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TYMS can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.28

Highest tissue expression

106 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TYMS.

Disease | AllUniProt

Conditions TYMS is implicated in, by any mechanism.

• Dyskeratosis congenita, digenic (DKCD) MIM:620040

Disease | GeneticClinVar

5 pathogenic / likely-pathogenic of 37 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Dyskeratosis congenita
• Dyskeratosis congenita, digenic

Disease | ImmuneIEDB

Conditions an epitope on TYMS was assayed in.

• cancer T cell

ReferencesPubMed · IEDB

Publications for TYMS from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.45

gnomAD pLI

0.72

gnomAD missense Z

2.58

DepMap mean gene effect

-0.7

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• DNA biosynthetic process
• dTMP biosynthetic process
• dTTP biosynthetic process
• methylation
• negative regulation of translation
• tetrahydrofolate interconversion

Molecular functions

• folic acid binding
• mRNA regulatory element binding translation repressor activity
• sequence-specific mRNA binding
• thymidylate synthase activity

Cellular components

• cytoplasm
• cytosol
• mitochondrial inner membrane
• mitochondrial matrix
• mitochondrion
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Thymidylate synthase
• Thymidylate synthase, active site
• Thymidylate synthase/dCMP hydroxymethylase domain
• Thymidylate synthase/dCMP hydroxymethylase superfamily
• Thymidylate synthase/dCMP hydroxymethylase
• Thymidylate synthase

KeywordsUniProt

• Cytoplasm
• Dyskeratosis congenita
• Isopeptide bond
• Membrane
• Methyltransferase
• Mitochondrion
• Mitochondrion inner membrane
• Nucleotide biosynthesis
• Nucleus
• Phosphoprotein
• Transferase
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of TYMS in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SHMT1