Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

TYMS (P04818) - Overview - Molecular Target Synopsis

Protein


TYMS, Thymidylate synthase
Enzyme Classification 2.1.1.45
UniProt P04818

Also Known as TYSY_HUMAN, TYMS, TS

Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Homodimer.

6OJV
CRYSTAL STRUCTURE OF HUMAN THYMIDYLATE SYNTHASE DELTA(7-29) IN COMPLEX WITH DUMP AND 2-AMINO-4-OXO-4,7-DIHYDRO-PYRROLO[2,3-D]PYRIMIDINE- METHYL-PHENYL-L-GLUTAMIC ACID
RCSB/PDB
Inspect Structure
See all 3D Structures for TYMS

Isoforms / Transcripts (Protein Coding)


Drugs


TYMS is targeted by Approved Drugs Fluorouracil, Raltitrexed, Capecitabine, Pemetrexed, Flucytosine, Floxuridine. (see details)
Fluorouracil
Raltitrexed
Capecitabine
Pemetrexed
Flucytosine
Floxuridine

Sub-cellular localization


UniProt: TYMS is active in the following subcellular-locations: cytoplasm, mitochondrion, mitochondrion inner membrane, mitochondrion matrix, nucleus.
GO terms: TYMS is active in the following subcellular-locations: cytoplasm, cytosol, mitochondrial inner membrane, mitochondrial matrix, mitochondrion, nucleolus, nucleus.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project TYMS has gain in 9 cell-lines, loss in 8 cell-lines and no signal in 987 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: TK_10, HL_60, SK_OV_3

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: KYSE-70, LN-18, KYSE-510

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: HeLa-S3, A549, HSMM

(see details)

3D Structures


For TYMS there are:
56 structures (158 chains) solved
32 are solved in complex with at least one small molecule ligand
8 are solved with an approved drug

TYMS is solved in complex with the approved drug(s):

D16/RALTITREXED (1HVY_A, 1HVY_B, 1HVY_C, 1HVY_D, 1I00_A, 1I00_B, 5X5Q_A, 5X5Q_B, 5X5Q_C, 5X5Q_D, 5X5Q_E, 5X5Q_F),
MTX/METHOTREXATE (5X66_A, 5X66_B, 5X66_C, 5X66_D, 5X66_E, 5X66_F),
LYA/PEMETREXED (1JU6_A, 1JU6_B, 1JU6_C, 1JU6_D, 1JUJ_A, 1JUJ_B, 1JUJ_C, 1JUJ_D),
FFO/LEVOLEUCOVORIN (6QYQ_B, 6QYQ_D, 6R2E_A, 6R2E_B, 6R2E_C, 6R2E_D, 6R2E_E, 6R2E_F, 6R2E_G, 6R2E_H).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


TYMS has been screened with 954 compounds (1655 bioactivities), 232 compounds have bioactivities that show binding affinity of <= 500nM (379 bioactivities). (see details)