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Protein

Thymidylate synthase

Gene

TYMS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

GO - Biological processi

Keywordsi

Molecular functionMethyltransferase, Transferase
Biological processNucleotide biosynthesis

Enzyme and pathway databases

BioCyciMetaCyc:HS11096-MONOMER
BRENDAi2.1.1.45 2681
ReactomeiR-HSA-499943 Interconversion of nucleotide di- and triphosphates
R-HSA-539107 Activation of E2F1 target genes at G1/S
SABIO-RKiP04818
SIGNORiP04818
UniPathwayi
UPA00575

Protein family/group databases

MoonProtiP04818
UniLectiniP04818

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

EuPathDBiHostDB:ENSG00000176890.15
HGNCiHGNC:12441 TYMS
MIMi188350 gene
neXtProtiNX_P04818

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
DrugBankiDB03800 2'-deoxyuridylic acid
DB05308 ANX-510
DB01101 Capecitabine
DB00322 Floxuridine
DB00544 Fluorouracil
DB00441 Gemcitabine
DB00563 Methotrexate
DB08478 N-[2-chloro-5-(trifluoromethyl)phenyl]imidodicarbonimidic diamide
DB05116 NB1011
DB05457 OSI-7904L
DB00642 Pemetrexed
DB06813 Pralatrexate
DB00293 Raltitrexed
DB01643 Thymidine-5'-Phosphate
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
Cross-linki287Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki292Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki308Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP04818
PaxDbiP04818
PeptideAtlasiP04818
PRIDEiP04818
ProteomicsDBi51747
TopDownProteomicsiP04818-1 [P04818-1]

PTM databases

iPTMnetiP04818
PhosphoSitePlusiP04818

Expressioni

Gene expression databases

BgeeiENSG00000176890 Expressed in 204 organ(s), highest expression level in liver
CleanExiHS_TYMS
ExpressionAtlasiP04818 baseline and differential
GenevisibleiP04818 HS

Organism-specific databases

HPAiCAB002784

Interactioni

Subunit structurei

Homodimer.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113149, 56 interactors
IntActiP04818, 9 interactors
MINTiP04818
STRINGi9606.ENSP00000315644

Chemistry databases

BindingDBiP04818

Structurei

Secondary structure

1313
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
OMAiKQYLDLC
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
InterProiView protein in InterPro
IPR023451 Thymidate_synth/dCMP_Mease
IPR036926 Thymidate_synth/dCMP_Mease_sf
IPR000398 Thymidylate_synthase
IPR020940 Thymidylate_synthase_AS
PfamiView protein in Pfam
PF00303 Thymidylat_synt, 1 hit
PRINTSiPR00108 THYMDSNTHASE
SUPFAMiSSF55831 SSF55831, 1 hit
TIGRFAMsiTIGR03284 thym_sym, 1 hit
PROSITEiView protein in PROSITE
PS00091 THYMIDYLATE_SYNTHASE, 1 hit

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]
CCDS86658.1 [P04818-2]
CCDS86659.1 [P04818-3]
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

Similar proteinsi

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]
CCDS86658.1 [P04818-2]
CCDS86659.1 [P04818-3]
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[»]
5WRNX-ray2.39A/B/C/D/E/F26-313[»]
5X4WX-ray2.10A1-313[»]
5X4XX-ray2.31A1-313[»]
5X4YX-ray2.20A1-313[»]
5X5AX-ray2.39A/B/C/D/E/F26-313[»]
5X5DX-ray2.00A/B/C/D/E/F26-313[»]
5X5QX-ray2.79A/B/C/D/E/F26-313[»]
5X66X-ray1.99A/B/C/D/E/F26-313[»]
5X67X-ray2.13A/B26-313[»]
5X69X-ray2.69A/B/C/D/E/F26-313[»]
DisProtiDP00073
ProteinModelPortaliP04818
SMRiP04818
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113149, 56 interactors
IntActiP04818, 9 interactors
MINTiP04818
STRINGi9606.ENSP00000315644

Chemistry databases

BindingDBiP04818
ChEMBLiCHEMBL1952
DrugBankiDB03800 2'-deoxyuridylic acid
DB05308 ANX-510
DB01101 Capecitabine
DB00322 Floxuridine
DB00544 Fluorouracil
DB00441 Gemcitabine
DB00563 Methotrexate
DB08478 N-[2-chloro-5-(trifluoromethyl)phenyl]imidodicarbonimidic diamide
DB05116 NB1011
DB05457 OSI-7904L
DB00642 Pemetrexed
DB06813 Pralatrexate
DB00293 Raltitrexed
DB01643 Thymidine-5'-Phosphate
DB00432 Trifluridine
DB00440 Trimethoprim
GuidetoPHARMACOLOGYi2642

Protein family/group databases

MoonProtiP04818
UniLectiniP04818

PTM databases

iPTMnetiP04818
PhosphoSitePlusiP04818

Polymorphism and mutation databases

BioMutaiTYMS
DMDMi136611

Proteomic databases

EPDiP04818
PaxDbiP04818
PeptideAtlasiP04818
PRIDEiP04818
ProteomicsDBi51747
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
EuPathDBiHostDB:ENSG00000176890.15
GeneCardsiTYMS
H-InvDBiHIX0021150
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
OMAiKQYLDLC
OrthoDBiEOG091G0CV0
PhylomeDBiP04818
TreeFamiTF353027

Enzyme and pathway databases

UniPathwayi
UPA00575

BioCyciMetaCyc:HS11096-MONOMER
BRENDAi2.1.1.45 2681
ReactomeiR-HSA-499943 Interconversion of nucleotide di- and triphosphates
R-HSA-539107 Activation of E2F1 target genes at G1/S
SABIO-RKiP04818
SIGNORiP04818

Miscellaneous databases

ChiTaRSiTYMS human
EvolutionaryTraceiP04818
GeneWikiiThymidylate_synthase
GenomeRNAii7298
PROiPR:P04818
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000176890 Expressed in 204 organ(s), highest expression level in liver
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
InterProiView protein in InterPro
IPR023451 Thymidate_synth/dCMP_Mease
IPR036926 Thymidate_synth/dCMP_Mease_sf
IPR000398 Thymidylate_synthase
IPR020940 Thymidylate_synthase_AS
PfamiView protein in Pfam
PF00303 Thymidylat_synt, 1 hit
PRINTSiPR00108 THYMDSNTHASE
SUPFAMiSSF55831 SSF55831, 1 hit
TIGRFAMsiTIGR03284 thym_sym, 1 hit
PROSITEiView protein in PROSITE
PS00091 THYMIDYLATE_SYNTHASE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTYSY_HUMAN
AccessioniPrimary (citable) accession number: P04818
Secondary accession number(s): Q8WYK3, Q8WYK4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: January 23, 2007
Last modified: October 10, 2018
This is version 203 of the entry and version 3 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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