UniProt Accession

 TYSY_HUMAN; P04818 

Genbank Protein ID

 X02308; D00596; AB062290; BC002567; BC013919; BC083512; D00517 

Genbank Nucleotide ID

 CAA26178.1; BAA00472.1; BAB93473.1; AAH02567.1; AAH13919.1; AAH83512.1; BAA00404.1 

Protein Name

 Thymidylate synthase 

Protein Synonyms/Alias

 TS; TSase 

Gene Name

 TYMS 

Gene Synonyms/Alias

 TS; OK/SW-cl.29 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
77	EFPLLTTKRVFWKGV	ubiquitination	[1, 2, 3, 4, 5, 6, 7, 8]
93	EELLWFIKGSTNAKE	ubiquitination	[2]
99	IKGSTNAKELSSKGV	ubiquitination	[2, 5]
104	NAKELSSKGVKIWDA	ubiquitination	[1, 2, 5, 7]
107	ELSSKGVKIWDANGS	ubiquitination	[1, 2, 5, 6, 7, 8]
169	QRVIDTIKTNPDDRR	ubiquitination	[1, 2, 3, 4, 5, 6, 7, 8, 9]
278	REPRPFPKLRILRKV	ubiquitination	[5]
284	PKLRILRKVEKIDDF	ubiquitination	[4, 8]
292	VEKIDDFKAEDFQIE	ubiquitination	[2, 3, 4, 5, 6, 8, 9]
308	YNPHPTIKMEMAV**	ubiquitination	[2, 3, 4, 5, 6, 8]

Reference

 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [4] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [5] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [6] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [7] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [8] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [9] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572] 

Functional Description

 Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. 

Sequence Annotation

 ACT_SITE 195 195
 MOD_RES 114 114 Phosphoserine.  

Keyword

 3D-structure; Complete proteome; Cytoplasm; Direct protein sequencing; Membrane; Methyltransferase; Mitochondrion; Mitochondrion inner membrane; Nucleotide biosynthesis; Nucleus; Phosphoprotein; Reference proteome; Transferase. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 313 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
 GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
 GO:0005730; C:nucleolus; IEA:Compara.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0048037; F:cofactor binding; IEA:Compara.
 GO:0008144; F:drug binding; IEA:Compara.
 GO:0005542; F:folic acid binding; IEA:Compara.
 GO:0003729; F:mRNA binding; IEA:Compara.
 GO:0000166; F:nucleotide binding; IEA:Compara.
 GO:0004799; F:thymidylate synthase activity; TAS:Reactome.
 GO:0007568; P:aging; IEA:Compara.
 GO:0051216; P:cartilage development; IEA:Compara.
 GO:0007623; P:circadian rhythm; IEA:Compara.
 GO:0009157; P:deoxyribonucleoside monophosphate biosynthetic process; TAS:ProtInc.
 GO:0048589; P:developmental growth; IEA:Compara.
 GO:0006281; P:DNA repair; NAS:UniProtKB.
 GO:0006260; P:DNA replication; NAS:UniProtKB.
 GO:0006231; P:dTMP biosynthetic process; IEA:Compara.
 GO:0006235; P:dTTP biosynthetic process; IEA:UniProtKB-UniPathway.
 GO:0046078; P:dUMP metabolic process; IEA:Compara.
 GO:0019088; P:immortalization of host cell by virus; IEA:Compara.
 GO:0060574; P:intestinal epithelial cell maturation; IEA:Compara.
 GO:0031100; P:organ regeneration; IEA:Compara.
 GO:0048015; P:phosphatidylinositol-mediated signaling; NAS:UniProtKB.
 GO:0005976; P:polysaccharide metabolic process; IEA:Compara.
 GO:0006206; P:pyrimidine nucleobase metabolic process; TAS:Reactome.
 GO:0046134; P:pyrimidine nucleoside biosynthetic process; TAS:Reactome.
 GO:0000083; P:regulation of transcription involved in G1/S phase of mitotic cell cycle; TAS:Reactome.
 GO:0034097; P:response to cytokine stimulus; IEA:Compara.
 GO:0042493; P:response to drug; IEA:Compara.
 GO:0045471; P:response to ethanol; IEA:Compara.
 GO:0051593; P:response to folic acid; IEA:Compara.
 GO:0051384; P:response to glucocorticoid stimulus; IEA:Compara.
 GO:0046683; P:response to organophosphorus; IEP:UniProtKB.
 GO:0032570; P:response to progesterone stimulus; IEA:Compara.
 GO:0009636; P:response to toxic substance; IEA:Compara.
 GO:0033189; P:response to vitamin A; IEA:Compara.
 GO:0046653; P:tetrahydrofolate metabolic process; IEA:Compara.
 GO:0019860; P:uracil metabolic process; IEA:Compara. 

Interpro

 IPR023451; Thymidate_synth/dCMP_Mease.
 IPR000398; Thymidylate_synthase.
 IPR020940; Thymidylate_synthase_AS. 

Pfam

 PF00303; Thymidylat_synt 

SMART

  

PROSITE

 PS00091; THYMIDYLATE_SYNTHASE 

PRINTS

 PR00108; THYMDSNTHASE.