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Details on Person UniProt:P04818 TYMS

Class:IdReferenceGeneProduct:66647
_chainChangeLoginitiator methionine:1 added on Sat February 7 2015;chain:2-313 added on Sat February 7 2015;initiator methionine:1 for 66647 removed on Fri Nov 03 2023;initiator methionine: for 66647 added on Fri Nov 03 2023;initiator methionine: for 66647 removed on Fri Aug 15 2025;initiator methionine:1 for 66647 added on Fri Aug 15 2025
_displayNameUniProt:P04818 TYMS
_timestamp2026-02-20 22:05:25
chaininitiator methionine:1
chain:2-313
checksum148D377F19915B6A
commentFUNCTION Catalyzes the reductive methylation of 2'-deoxyuridine 5'-monophosphate (dUMP) to thymidine 5'-monophosphate (dTMP), using the cosubstrate, 5,10- methylenetetrahydrofolate (CH2H4folate) as a 1-carbon donor and reductant and contributes to the mitochondrial and nuclear de novo thymidylate biosynthesis pathway.CATALYTIC ACTIVITY dUMP + (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate = 7,8-dihydrofolate + dTMPPATHWAY Pyrimidine metabolism; dTTP biosynthesis.SUBUNIT Homodimer. Part of the de novo thymidylate synthesis complex composed at least by SHMT1, DHFR and TYMS (PubMed:22235121). Interacts with SHMT1; this interaction is DNA-dependent and mediates TYMS co-localization with LMNB1 (PubMed:22235121).SUBCELLULAR LOCATION Localized to the nucleus during S and G2/M phases of the cell cycle. As a component of the de novo thymidylate synthesis complex, localizes specifically to replication forks during DNA synthesis (PubMed:22235121).ALTERNATIVE PRODUCTS Sumoylated by UBE2I/UBC9.DISEASE The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. TYMS germline variants in the presence of a common ENOSF1 haplotype (defined by rs699517, rs2790 and rs1512643) result in severe thymidylate synthase deficiency and disease. The pathogenic mechanism involves increased expression of ENOSF1 relative to TYMS, and post-transcriptional inhibition of TYMS translation through ENOSF1-TYMS RNA-RNA interactions.MISCELLANEOUS Expressed both in normal and cancerous tissues.MISCELLANEOUS Expressed only in cancerous tissues.SIMILARITY Belongs to the thymidylate synthase family.
descriptionrecommendedName: fullName evidence="12"Thymidylate synthase shortName: TS shortName: TSase ecNumber evidence="4"2.1.1.45
geneNameTYMS
TS
OK/SW-cl.29
identifierP04818
isSequenceChangedFALSE
keyword3D-structure
Alternative splicing
Cytoplasm
Direct protein sequencing
Disease variant
Dyskeratosis congenita
Isopeptide bond
Membrane
Methyltransferase
Mitochondrion
Mitochondrion inner membrane
Nucleotide biosynthesis
Nucleus
Phosphoprotein
Proteomics identification
Reference proteome
Transferase
Ubl conjugation
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
[InstanceEdit:9963647] Weiser, Joel, 2025-08-15
[InstanceEdit:9983091] Weiser, Joel, 2026-02-20
nameTYMS
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8962048] ENSEMBL:ENSG00000176890 TYMS [Homo sapiens]
secondaryIdentifierTYSY_HUMAN
Q8WYK3
Q8WYK4
sequenceLength313
species[Species:48887] Homo sapiens
(isoformParent)[ReferenceIsoform:8973118] UniProt:P04818-1 TYMS [Homo sapiens]
[ReferenceIsoform:8973119] UniProt:P04818-2 TYMS [Homo sapiens]
[ReferenceIsoform:8973120] UniProt:P04818-3 TYMS [Homo sapiens]
(referenceEntity)[EntityWithAccessionedSequence:73518] TYMS [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:613424] TYMS [nucleoplasm] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:P04818 TYMS (66647)