Thymidylate synthase - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot P04818 (TYSY_HUMAN)

Last modified June 16, 2009. Version 110. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Thymidylate synthase
      Short name=TSase
      Short name=TS
    EC=2.1.1.45

Gene names

Name:	TYMS
Synonyms:	TS
ORF Names:	OK/SW-cl.29

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	313 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Catalytic activity	5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP.
Pathway	Pyrimidine metabolism; dTTP biosynthesis.
Subunit structure	Homodimer.
Sequence similarities	Belongs to the thymidylate synthase family.

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Ontologies

Keywords
Biological process	Nucleotide biosynthesis
Molecular function	Methyltransferase Transferase
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	DNA repair Non-traceable author statement. Source: UniProtKB DNA replication Non-traceable author statement. Source: UniProtKB dTMP biosynthetic process Inferred from electronic annotation. Source: InterPro phosphoinositide-mediated signaling Non-traceable author statement. Source: UniProtKB response to organophosphorus Inferred from expression pattern. Source: UniProtKB
Cellular component	cytosol Ref.7 Inferred from Experiment. Source: Reactome
Molecular function	thymidylate synthase activity Ref.7 Inferred from Experiment. Source: Reactome
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

Removed Ref.6 Ref.7

Chain

2 – 313

312

Thymidylate synthase

PRO_0000140901

Sites

Active site

195

Secondary structure

313

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P04818-1 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 148D377F19915B6A
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FASTA

313

35,716

        10         20         30         40         50         60 
MPVAGSELPR RPLPPAAQER DAEPRPPHGE LQYLGQIQHI LRCGVRKDDR TGTGTLSVFG 

        70         80         90        100        110        120 
MQARYSLRDE FPLLTTKRVF WKGVLEELLW FIKGSTNAKE LSSKGVKIWD ANGSRDFLDS 

       130        140        150        160        170        180 
LGFSTREEGD LGPVYGFQWR HFGAEYRDME SDYSGQGVDQ LQRVIDTIKT NPDDRRIIMC 

       190        200        210        220        230        240 
AWNPRDLPLM ALPPCHALCQ FYVVNSELSC QLYQRSGDMG LGVPFNIASY ALLTYMIAHI 

       250        260        270        280        290        300 
TGLKPGDFIH TLGDAHIYLN HIEPLKIQLQ REPRPFPKLR ILRKVEKIDD FKAEDFQIEG 

       310 
YNPHPTIKME MAV

« Hide

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of a functional cDNA for human thymidylate synthase." Takeishi K., Kaneda S., Ayusawa D., Shimizu K., Gotoh O., Seno T. Nucleic Acids Res. 13:2035-2043(1985) [PubMed: 2987839] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Structural and functional analysis of the human thymidylate synthase gene." Kaneda S., Nalbantoglu J., Takeishi K., Shimizu K., Gotoh O., Seno T., Ayusawa D. J. Biol. Chem. 265:20277-20284(1990) [PubMed: 2243092] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Identification of immuno-peptidmics that are recognized by tumor-reactive CTL generated from TIL of colon cancer patients." Shichijo S., Itoh K. Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon adenocarcinoma.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Bone marrow, Placenta and Skin.
[5]	"Human thymidylate synthase gene: isolation of phage clones which cover a functionally active gene and structural analysis of the region upstream from the translation initiation codon." Takeishi K., Kaneda S., Ayusawa D., Shimizu K., Gotoh O., Seno T. J. Biochem. 106:575-583(1989) [PubMed: 2532645] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 1-68.
[6]	"Purification and NH2-terminal amino acid sequence of human thymidylate synthase in an overproducing transformant of mouse FM3A cells." Shimizu K., Ayusawa D., Takeishi K., Seno T. J. Biochem. 97:845-850(1985) [PubMed: 3839505] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-25.
[7]	"Expression of human thymidylate synthase in Escherichia coli." Davisson V.J., Sirawaraporn W., Santi D.V. J. Biol. Chem. 264:9145-9148(1989) [PubMed: 2656695] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-10.
[8]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[9]	"Crystal structure of human thymidylate synthase: a structural mechanism for guiding substrates into the active site." Schiffer C.A., Clifton I.J., Davisson V.J., Santi D.V., Stroud R.M. Biochemistry 34:16279-16287(1995) [PubMed: 8845352] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
[10]	"Human thymidylate synthase is in the closed conformation when complexed with dUMP and raltitrexed, an antifolate drug." Phan J., Koli S., Minor W., Dunlap R.B., Berger S.H., Lebioda L. Biochemistry 40:1897-1902(2001) [PubMed: 11329255] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
[11]	"Structure of human thymidylate synthase suggests advantages of chemotherapy with noncompetitive inhibitors." Phan J., Steadman D.J., Koli S., Ding W.C., Minor W., Dunlap R.B., Berger S.H., Lebioda L. J. Biol. Chem. 276:14170-14177(2001) [PubMed: 11278511] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
+	Additional computationally mapped references.

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Web resources

SHMPD

The Singapore human mutation and polymorphism database

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Cross-references

Sequence databases

X02308 mRNA. Translation: CAA26178.1.
D00596 Genomic DNA. Translation: BAA00472.1.
AB062290 mRNA. Translation: BAB93473.1.
BC002567 mRNA. Translation: AAH02567.1.
BC013919 mRNA. Translation: AAH13919.1.
BC083512 mRNA. Translation: AAH83512.1.
D00517 Genomic DNA. Translation: BAA00404.1.

IPI

IPI00221108.

PIR

YXHUT. A23047.

RefSeq

NP_001062.1.

UniGene

Hs.592338

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HVY	X-ray	1.90	A/B/C/D	26-313	[»]
1HW3	X-ray	2.00	A	1-313	[»]
1HW4	X-ray	2.06	A	1-313	[»]
1HZW	X-ray	2.00	A/B	30-313	[»]
1I00	X-ray	2.50	A/B	30-313	[»]
1JU6	X-ray	2.89	A/B/C/D	1-313	[»]
1JUJ	X-ray	3.00	A/B/C/D	1-313	[»]
1YPV	X-ray	1.80	A	1-313	[»]
2ONB	X-ray	2.70	A	1-313	[»]
2RD8	X-ray	2.50	A	1-313	[»]
			B	1-313	[»]
2RDA	X-ray	2.67	A/B/C/D/E/F	1-313	[»]

DisProt

DP00073.

ModBase

Search...

PTM databases

PhosphoSite

P04818.

Proteomic databases

PRIDE

P04818.

Genome annotation databases

Ensembl

ENSG00000176890. Homo sapiens. [Contig view]

GeneID

7298.

KEGG

hsa:7298.

Organism-specific databases

GeneCards

GC18P000647.

H-InvDB

HIX0014293.
HIX0017793.

HGNC

HGNC:12441. TYMS.

HPA

CAB002784.

MIM

188350. gene.

PharmGKB

PA359.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P04818.

HOVERGEN

P04818.

OMA

P04818. QYLGQIE.

Enzyme and pathway databases

BRENDA

2.1.1.45. 247.

Reactome

REACT_152. Cell Cycle, Mitotic.
REACT_1698. Nucleotide metabolism.

Gene expression databases

ArrayExpress

P04818.

Bgee

P04818.

CleanEx

HS_TYMS.

GermOnline

ENSG00000176890. Homo sapiens.

Family and domain databases

InterPro

IPR000398. Thymidylat_synth_C.
[Graphical view]

Gene3D

G3DSA:3.30.572.10. Thymidylat_synth_C. 1 hit.

PANTHER

PTHR11549:SF2. Thymidylat_synth_C. 1 hit.

Pfam

PF00303. Thymidylat_synt. 1 hit.
[Graphical view]

PRINTS

PR00108. THYMDSNTHASE.

ProDom

PD001180. Thymidylat_synth. 1 hit.
[Graphical view] [Entries sharing at least one domain]

TIGRFAMs

TIGR03284. thym_sym. 1 hit.

PROSITE

PS00091. THYMIDYLATE_SYNTHASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

BindingDB

P04818.

DrugBank

DB01101. Capecitabine.
DB00322. Floxuridine.
DB00544. Fluorouracil.
DB00441. Gemcitabine.
DB00650. Leucovorin.
DB00642. Pemetrexed.
DB00293. Raltitrexed.
DB00432. Trifluridine.

NextBio

28543.

SOURCE

Search...

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Entry information

Entry name

TYSY_HUMAN

Accession

Primary (citable) accession number: P04818

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 110 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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