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Details on Person UniProt:P04818 TYMS
| Class:Id | ReferenceGeneProduct:66647 |
|---|---|
| _chainChangeLog | initiator 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 |
| _displayName | UniProt:P04818 TYMS |
| _timestamp | 2026-02-20 22:05:25 |
| chain | initiator methionine:1 chain:2-313 |
| checksum | 148D377F19915B6A |
| comment | FUNCTION 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. |
| description | recommendedName: fullName evidence="12"Thymidylate synthase shortName: TS shortName: TSase ecNumber evidence="4"2.1.1.45 |
| geneName | TYMS TS OK/SW-cl.29 |
| identifier | P04818 |
| isSequenceChanged | FALSE |
| keyword | 3D-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 |
| name | TYMS |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8962048] ENSEMBL:ENSG00000176890 TYMS [Homo sapiens] |
| secondaryIdentifier | TYSY_HUMAN Q8WYK3 Q8WYK4 |
| sequenceLength | 313 |
| 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)
