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Protein

Thymidylate synthase

Gene

TYMS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.1 Publication

Catalytic activityi

5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP.

Pathwayi: dTTP biosynthesis

This protein is involved in the pathway dTTP biosynthesis, which is part of Pyrimidine metabolism.
View all proteins of this organism that are known to be involved in the pathway dTTP biosynthesis and in Pyrimidine metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei50dUMPBy similarity1
Active sitei195NucleophileBy similarity1
Binding sitei2185,10-methylenetetrahydrofolateBy similarity1
Binding sitei226dUMPBy similarity1
Binding sitei3125,10-methylenetetrahydrofolate; via carbonyl oxygenBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi175 – 176dUMP; shared with dimeric partnerBy similarity2
Nucleotide bindingi215 – 218dUMPBy similarity4
Nucleotide bindingi256 – 258dUMPBy similarity3

GO - Molecular functioni

  • cofactor binding Source: Ensembl
  • drug binding Source: Ensembl
  • folic acid binding Source: BHF-UCL
  • mRNA binding Source: Ensembl
  • nucleotide binding Source: Ensembl
  • thymidylate synthase activity Source: BHF-UCL

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Methyltransferase, Transferase

Keywords - Biological processi

Nucleotide biosynthesis

Enzyme and pathway databases

BioCyciMetaCyc:HS11096-MONOMER.
ZFISH:HS11096-MONOMER.
BRENDAi2.1.1.45. 2681.
ReactomeiR-HSA-113510. E2F mediated regulation of DNA replication.
R-HSA-500753. Pyrimidine biosynthesis.
R-HSA-69205. G1/S-Specific Transcription.
SABIO-RKP04818.
SIGNORiP04818.
UniPathwayiUPA00575.

Protein family/group databases

MoonProtiP04818.

Names & Taxonomyi

Protein namesi
Recommended name:
Thymidylate synthase (EC:2.1.1.45)
Short name:
TS
Short name:
TSase
Gene namesi
Name:TYMS
Synonyms:TS
ORF Names:OK/SW-cl.29
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 18

Organism-specific databases

HGNCiHGNC:12441. TYMS.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • mitochondrial inner membrane Source: UniProtKB
  • mitochondrial matrix Source: UniProtKB
  • mitochondrion Source: UniProtKB
  • nucleolus Source: Ensembl
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Mitochondrion, Mitochondrion inner membrane, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi7298.
MalaCardsiTYMS.
OpenTargetsiENSG00000176890.
Orphaneti240839. 5-fluorouracil toxicity.
PharmGKBiPA359.

Chemistry databases

ChEMBLiCHEMBL1952.
DrugBankiDB01101. Capecitabine.
DB00322. Floxuridine.
DB00544. Fluorouracil.
DB00441. Gemcitabine.
DB00650. Leucovorin.
DB00563. Methotrexate.
DB00642. Pemetrexed.
DB06813. Pralatrexate.
DB00293. Raltitrexed.
DB00432. Trifluridine.
DB00440. Trimethoprim.
GuidetoPHARMACOLOGYi2642.

Polymorphism and mutation databases

BioMutaiTYMS.
DMDMi136611.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved2 Publications
ChainiPRO_00001409012 – 313Thymidylate synthaseAdd BLAST312

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei114PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP04818.
PaxDbiP04818.
PeptideAtlasiP04818.
PRIDEiP04818.
TopDownProteomicsiP04818-1. [P04818-1]

PTM databases

iPTMnetiP04818.
PhosphoSitePlusiP04818.

Expressioni

Gene expression databases

BgeeiENSG00000176890.
CleanExiHS_TYMS.
ExpressionAtlasiP04818. baseline and differential.
GenevisibleiP04818. HS.

Organism-specific databases

HPAiCAB002784.

Interactioni

Subunit structurei

Homodimer.

Protein-protein interaction databases

BioGridi113149. 52 interactors.
IntActiP04818. 6 interactors.
MINTiMINT-2800458.
STRINGi9606.ENSP00000315644.

Chemistry databases

BindingDBiP04818.

Structurei

Secondary structure

1313
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi30 – 43Combined sources14
Beta strandi45 – 48Combined sources4
Beta strandi50 – 52Combined sources3
Beta strandi54 – 66Combined sources13
Beta strandi68 – 70Combined sources3
Turni75 – 78Combined sources4
Helixi81 – 92Combined sources12
Helixi98 – 101Combined sources4
Turni103 – 105Combined sources3
Turni108 – 110Combined sources3
Helixi111 – 113Combined sources3
Helixi117 – 120Combined sources4
Helixi123 – 127Combined sources5
Turni132 – 134Combined sources3
Helixi136 – 141Combined sources6
Beta strandi149 – 151Combined sources3
Beta strandi156 – 158Combined sources3
Helixi160 – 170Combined sources11
Beta strandi178 – 181Combined sources4
Helixi184 – 186Combined sources3
Turni187 – 189Combined sources3
Beta strandi190 – 192Combined sources3
Beta strandi196 – 204Combined sources9
Beta strandi207 – 218Combined sources12
Turni219 – 221Combined sources3
Helixi222 – 241Combined sources20
Beta strandi244 – 258Combined sources15
Helixi259 – 261Combined sources3
Helixi262 – 268Combined sources7
Beta strandi278 – 281Combined sources4
Helixi288 – 290Combined sources3
Helixi293 – 295Combined sources3
Beta strandi296 – 300Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1HVYX-ray1.90A/B/C/D26-313[»]
1HW3X-ray2.00A1-313[»]
1HW4X-ray2.06A1-313[»]
1HZWX-ray2.00A/B1-313[»]
1I00X-ray2.50A/B1-313[»]
1JU6X-ray2.89A/B/C/D1-313[»]
1JUJX-ray3.00A/B/C/D1-313[»]
1YPVX-ray1.80A1-313[»]
2ONBX-ray2.70A1-313[»]
2RD8X-ray2.50A/B1-313[»]
2RDAX-ray2.67A/B/C/D/E/F1-313[»]
3EAWX-ray1.86X1-313[»]
3EBUX-ray2.05A1-313[»]
3ED7X-ray1.56A26-313[»]
3EDWX-ray1.75X1-313[»]
3EF9X-ray3.20A1-313[»]
3EGYX-ray2.18X1-313[»]
3EHIX-ray2.00X1-313[»]
3EJLX-ray3.20A/B/C/D1-313[»]
3GG5X-ray2.77A/B/C/D1-313[»]
3GH0X-ray1.56A1-313[»]
3GH2X-ray1.75X1-313[»]
3H9KX-ray2.65A/B/C/D/E1-313[»]
3HB8X-ray2.74A/B/C/D/E1-313[»]
3N5EX-ray2.26A/B1-313[»]
3N5GX-ray2.27A1-313[»]
3OB7X-ray2.75A/B/C/D/E1-313[»]
4E28X-ray2.30A1-313[»]
4FGTX-ray2.00A1-311[»]
4G2OX-ray2.25X1-313[»]
4G6WX-ray2.30X1-313[»]
4GD7X-ray2.29A1-313[»]
4GYHX-ray3.00A1-313[»]
4H1IX-ray3.10A/B/C/D1-313[»]
4JEFX-ray2.31A26-311[»]
4KPWX-ray2.03A1-313[»]
4O1UX-ray2.26A/B1-313[»]
4O1XX-ray2.32A/B/C/D1-313[»]
4UP1X-ray2.99A/B/C/D1-313[»]
5HS3X-ray3.10A/B/C/D/E/F26-313[»]
DisProtiDP00073.
ProteinModelPortaliP04818.
SMRiP04818.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP04818.

Family & Domainsi

Sequence similaritiesi

Belongs to the thymidylate synthase family.Curated

Phylogenomic databases

eggNOGiKOG0673. Eukaryota.
COG0207. LUCA.
GeneTreeiENSGT00390000014786.
HOGENOMiHOG000257899.
HOVERGENiHBG001934.
InParanoidiP04818.
KOiK00560.
OMAiIVYELLW.
OrthoDBiEOG091G0CV0.
PhylomeDBiP04818.
TreeFamiTF353027.

Family and domain databases

CDDicd00351. TS_Pyrimidine_HMase. 1 hit.
Gene3Di3.30.572.10. 1 hit.
HAMAPiMF_00008. Thymidy_synth_bact. 1 hit.
InterProiIPR023451. Thymidate_synth/dCMP_Mease.
IPR000398. Thymidylate_synthase.
IPR020940. Thymidylate_synthase_AS.
[Graphical view]
PfamiPF00303. Thymidylat_synt. 1 hit.
[Graphical view]
PRINTSiPR00108. THYMDSNTHASE.
SUPFAMiSSF55831. SSF55831. 1 hit.
TIGRFAMsiTIGR03284. thym_sym. 1 hit.
PROSITEiPS00091. THYMIDYLATE_SYNTHASE. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P04818-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPVAGSELPR RPLPPAAQER DAEPRPPHGE LQYLGQIQHI LRCGVRKDDR
60 70 80 90 100
TGTGTLSVFG MQARYSLRDE FPLLTTKRVF WKGVLEELLW FIKGSTNAKE
110 120 130 140 150
LSSKGVKIWD ANGSRDFLDS LGFSTREEGD LGPVYGFQWR HFGAEYRDME
160 170 180 190 200
SDYSGQGVDQ LQRVIDTIKT NPDDRRIIMC AWNPRDLPLM ALPPCHALCQ
210 220 230 240 250
FYVVNSELSC QLYQRSGDMG LGVPFNIASY ALLTYMIAHI TGLKPGDFIH
260 270 280 290 300
TLGDAHIYLN HIEPLKIQLQ REPRPFPKLR ILRKVEKIDD FKAEDFQIEG
310
YNPHPTIKME MAV
Length:313
Mass (Da):35,716
Last modified:January 23, 2007 - v3
Checksum:i148D377F19915B6A
GO
Isoform 2 (identifier: P04818-2) [UniParc]FASTAAdd to basket
Also known as: delta4

The sequence of this isoform differs from the canonical sequence as follows:
     152-185: Missing.

Note: Expressed both in normal and cancerous tissues.
Show »
Length:279
Mass (Da):31,759
Checksum:i10B3A53DE10AB763
GO
Isoform 3 (identifier: P04818-3) [UniParc]FASTAAdd to basket
Also known as: delta2+3

The sequence of this isoform differs from the canonical sequence as follows:
     69-151: Missing.

Note: Expressed only in cancerous tissues.
Show »
Length:230
Mass (Da):26,140
Checksum:iD09F8316A504A02A
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04774569 – 151Missing in isoform 3. 1 PublicationAdd BLAST83
Alternative sequenceiVSP_047746152 – 185Missing in isoform 2. 1 PublicationAdd BLAST34

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X02308 mRNA. Translation: CAA26178.1.
D00596 Genomic DNA. Translation: BAA00472.1.
AB077207 mRNA. Translation: BAB83676.1.
AB077208 mRNA. Translation: BAB83677.1.
AB062290 mRNA. Translation: BAB93473.1.
AP001178 Genomic DNA. No translation available.
CH471113 Genomic DNA. Translation: EAX01716.1.
CH471113 Genomic DNA. Translation: EAX01720.1.
BC002567 mRNA. Translation: AAH02567.1.
BC013919 mRNA. Translation: AAH13919.1.
BC083512 mRNA. Translation: AAH83512.1.
D00517 Genomic DNA. Translation: BAA00404.1.
CCDSiCCDS11821.1. [P04818-1]
PIRiA23047. YXHUT.
RefSeqiNP_001062.1. NM_001071.2. [P04818-1]
UniGeneiHs.369762.

Genome annotation databases

EnsembliENST00000323224; ENSP00000314727; ENSG00000176890. [P04818-2]
ENST00000323250; ENSP00000314902; ENSG00000176890. [P04818-3]
ENST00000323274; ENSP00000315644; ENSG00000176890. [P04818-1]
GeneIDi7298.
KEGGihsa:7298.
UCSCiuc010dkb.2. human. [P04818-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

SHMPD

The Singapore human mutation and polymorphism database

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X02308 mRNA. Translation: CAA26178.1.
D00596 Genomic DNA. Translation: BAA00472.1.
AB077207 mRNA. Translation: BAB83676.1.
AB077208 mRNA. Translation: BAB83677.1.
AB062290 mRNA. Translation: BAB93473.1.
AP001178 Genomic DNA. No translation available.
CH471113 Genomic DNA. Translation: EAX01716.1.
CH471113 Genomic DNA. Translation: EAX01720.1.
BC002567 mRNA. Translation: AAH02567.1.
BC013919 mRNA. Translation: AAH13919.1.
BC083512 mRNA. Translation: AAH83512.1.
D00517 Genomic DNA. Translation: BAA00404.1.
CCDSiCCDS11821.1. [P04818-1]
PIRiA23047. YXHUT.
RefSeqiNP_001062.1. NM_001071.2. [P04818-1]
UniGeneiHs.369762.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1HVYX-ray1.90A/B/C/D26-313[»]
1HW3X-ray2.00A1-313[»]
1HW4X-ray2.06A1-313[»]
1HZWX-ray2.00A/B1-313[»]
1I00X-ray2.50A/B1-313[»]
1JU6X-ray2.89A/B/C/D1-313[»]
1JUJX-ray3.00A/B/C/D1-313[»]
1YPVX-ray1.80A1-313[»]
2ONBX-ray2.70A1-313[»]
2RD8X-ray2.50A/B1-313[»]
2RDAX-ray2.67A/B/C/D/E/F1-313[»]
3EAWX-ray1.86X1-313[»]
3EBUX-ray2.05A1-313[»]
3ED7X-ray1.56A26-313[»]
3EDWX-ray1.75X1-313[»]
3EF9X-ray3.20A1-313[»]
3EGYX-ray2.18X1-313[»]
3EHIX-ray2.00X1-313[»]
3EJLX-ray3.20A/B/C/D1-313[»]
3GG5X-ray2.77A/B/C/D1-313[»]
3GH0X-ray1.56A1-313[»]
3GH2X-ray1.75X1-313[»]
3H9KX-ray2.65A/B/C/D/E1-313[»]
3HB8X-ray2.74A/B/C/D/E1-313[»]
3N5EX-ray2.26A/B1-313[»]
3N5GX-ray2.27A1-313[»]
3OB7X-ray2.75A/B/C/D/E1-313[»]
4E28X-ray2.30A1-313[»]
4FGTX-ray2.00A1-311[»]
4G2OX-ray2.25X1-313[»]
4G6WX-ray2.30X1-313[»]
4GD7X-ray2.29A1-313[»]
4GYHX-ray3.00A1-313[»]
4H1IX-ray3.10A/B/C/D1-313[»]
4JEFX-ray2.31A26-311[»]
4KPWX-ray2.03A1-313[»]
4O1UX-ray2.26A/B1-313[»]
4O1XX-ray2.32A/B/C/D1-313[»]
4UP1X-ray2.99A/B/C/D1-313[»]
5HS3X-ray3.10A/B/C/D/E/F26-313[»]
DisProtiDP00073.
ProteinModelPortaliP04818.
SMRiP04818.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113149. 52 interactors.
IntActiP04818. 6 interactors.
MINTiMINT-2800458.
STRINGi9606.ENSP00000315644.

Chemistry databases

BindingDBiP04818.
ChEMBLiCHEMBL1952.
DrugBankiDB01101. Capecitabine.
DB00322. Floxuridine.
DB00544. Fluorouracil.
DB00441. Gemcitabine.
DB00650. Leucovorin.
DB00563. Methotrexate.
DB00642. Pemetrexed.
DB06813. Pralatrexate.
DB00293. Raltitrexed.
DB00432. Trifluridine.
DB00440. Trimethoprim.
GuidetoPHARMACOLOGYi2642.

Protein family/group databases

MoonProtiP04818.

PTM databases

iPTMnetiP04818.
PhosphoSitePlusiP04818.

Polymorphism and mutation databases

BioMutaiTYMS.
DMDMi136611.

Proteomic databases

EPDiP04818.
PaxDbiP04818.
PeptideAtlasiP04818.
PRIDEiP04818.
TopDownProteomicsiP04818-1. [P04818-1]

Protocols and materials databases

DNASUi7298.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000323224; ENSP00000314727; ENSG00000176890. [P04818-2]
ENST00000323250; ENSP00000314902; ENSG00000176890. [P04818-3]
ENST00000323274; ENSP00000315644; ENSG00000176890. [P04818-1]
GeneIDi7298.
KEGGihsa:7298.
UCSCiuc010dkb.2. human. [P04818-1]

Organism-specific databases

CTDi7298.
DisGeNETi7298.
GeneCardsiTYMS.
HGNCiHGNC:12441. TYMS.
HPAiCAB002784.
MalaCardsiTYMS.
MIMi188350. gene.
neXtProtiNX_P04818.
OpenTargetsiENSG00000176890.
Orphaneti240839. 5-fluorouracil toxicity.
PharmGKBiPA359.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0673. Eukaryota.
COG0207. LUCA.
GeneTreeiENSGT00390000014786.
HOGENOMiHOG000257899.
HOVERGENiHBG001934.
InParanoidiP04818.
KOiK00560.
OMAiIVYELLW.
OrthoDBiEOG091G0CV0.
PhylomeDBiP04818.
TreeFamiTF353027.

Enzyme and pathway databases

UniPathwayiUPA00575.
BioCyciMetaCyc:HS11096-MONOMER.
ZFISH:HS11096-MONOMER.
BRENDAi2.1.1.45. 2681.
ReactomeiR-HSA-113510. E2F mediated regulation of DNA replication.
R-HSA-500753. Pyrimidine biosynthesis.
R-HSA-69205. G1/S-Specific Transcription.
SABIO-RKP04818.
SIGNORiP04818.

Miscellaneous databases

ChiTaRSiTYMS. human.
EvolutionaryTraceiP04818.
GeneWikiiThymidylate_synthase.
GenomeRNAii7298.
PROiP04818.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000176890.
CleanExiHS_TYMS.
ExpressionAtlasiP04818. baseline and differential.
GenevisibleiP04818. HS.

Family and domain databases

CDDicd00351. TS_Pyrimidine_HMase. 1 hit.
Gene3Di3.30.572.10. 1 hit.
HAMAPiMF_00008. Thymidy_synth_bact. 1 hit.
InterProiIPR023451. Thymidate_synth/dCMP_Mease.
IPR000398. Thymidylate_synthase.
IPR020940. Thymidylate_synthase_AS.
[Graphical view]
PfamiPF00303. Thymidylat_synt. 1 hit.
[Graphical view]
PRINTSiPR00108. THYMDSNTHASE.
SUPFAMiSSF55831. SSF55831. 1 hit.
TIGRFAMsiTIGR03284. thym_sym. 1 hit.
PROSITEiPS00091. THYMIDYLATE_SYNTHASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTYSY_HUMAN
AccessioniPrimary (citable) accession number: P04818
Secondary accession number(s): Q8WYK3, Q8WYK4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 187 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.