CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-011329
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Folylpolyglutamate synthase, mitochondrial 
Protein Synonyms/Alias
 Folylpoly-gamma-glutamate synthetase; FPGS; Tetrahydrofolylpolyglutamate synthase; Tetrahydrofolate synthase 
Gene Name
 FPGS 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
66AGYLEQVKRQRGDPQubiquitination[1, 2, 3, 4, 5]
105IIHVTGTKGKGSTCAubiquitination[3]
107HVTGTKGKGSTCAFTubiquitination[3]
124ILRSYGLKTGFFSSPubiquitination[2, 3]
154ISPELFTKYFWRLYHubiquitination[3, 6, 7, 8, 9, 10]
215DCTNIIRKPVVCGVSubiquitination[3]
238LLGDTVEKIAWQKGGubiquitination[3]
243VEKIAWQKGGIFKQGubiquitination[1, 2, 3, 5]
248WQKGGIFKQGVPAFTubiquitination[1, 2, 3, 4, 5, 7, 8]
329RHGAGEPKASRPGLLubiquitination[3]
Reference
 [1] 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]
 [2] 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]
 [3] 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]
 [4] 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]
 [5] 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]
 [6] 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]
 [7] 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]
 [8] 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]
 [9] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [10] 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] 
Functional Description
 Catalyzes conversion of folates to polyglutamate derivatives allowing concentration of folate compounds in the cell and the intracellular retention of these cofactors, which are important substrates for most of the folate-dependent enzymes that are involved in one-carbon transfer reactions involved in purine, pyrimidine and amino acid synthesis. Unsubstitued reduced folates are the preferred substrates. Metabolizes methotrexate (MTX) to polyglutamates. 
Sequence Annotation
 NP_BIND 103 109 ATP (Potential).  
Keyword
 Alternative initiation; Alternative splicing; ATP-binding; Complete proteome; Cytoplasm; Ligase; Membrane; Mitochondrion; Mitochondrion inner membrane; Nucleotide-binding; One-carbon metabolism; Polymorphism; Reference proteome; Transit peptide. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 587 AA 
Protein Sequence
MSRARSHLRA ALFLAAASAR GITTQVAARR GLSAWPVPQE PSMEYQDAVR MLNTLQTNAG 60
YLEQVKRQRG DPQTQLEAME LYLARSGLQV EDLDRLNIIH VTGTKGKGST CAFTECILRS 120
YGLKTGFFSS PHLVQVRERI RINGQPISPE LFTKYFWRLY HRLEETKDGS CVSMPPYFRF 180
LTLMAFHVFL QEKVDLAVVE VGIGGAYDCT NIIRKPVVCG VSSLGIDHTS LLGDTVEKIA 240
WQKGGIFKQG VPAFTVLQPE GPLAVLRDRA QQISCPLYLC PMLEALEEGG PPLTLGLEGE 300
HQRSNAALAL QLAHCWLQRQ DRHGAGEPKA SRPGLLWQLP LAPVFQPTSH MRLGLRNTEW 360
PGRTQVLRRG PLTWYLDGAH TASSAQACVR WFRQALQGRE RPSGGPEVRV LLFNATGDRD 420
PAALLKLLQP CQFDYAVFCP NLTEVSSTGN ADQQNFTVTL DQVLLRCLEH QQHWNHLDEE 480
QASPDLWSAP SPEPGGSASL LLAPHPPHTC SASSLVFSCI SHALQWISQG RDPIFQPPSP 540
PKGLLTHPVA HSGASILREA AAIHVLVTGS LHLVGGVLKL LEPALSQ 587 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
 GO:0005759; C:mitochondrial matrix; TAS:Reactome.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004326; F:tetrahydrofolylpolyglutamate synthase activity; TAS:ProtInc.
 GO:0007420; P:brain development; IEA:Compara.
 GO:0046655; P:folic acid metabolic process; TAS:Reactome.
 GO:0001889; P:liver development; IEA:Compara.
 GO:0006139; P:nucleobase-containing compound metabolic process; TAS:ProtInc.
 GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW.
 GO:0031100; P:organ regeneration; IEA:Compara.
 GO:0042221; P:response to chemical stimulus; IEA:Compara. 
Interpro
 IPR001645; Folylpolyglutamate_synth.
 IPR018109; Folylpolyglutamate_synth_CS.
 IPR023600; Folylpolyglutamate_synth_euk.
 IPR004101; Mur_ligase_C.
 IPR013221; Mur_ligase_cen. 
Pfam
  
SMART
  
PROSITE
 PS01011; FOLYLPOLYGLU_SYNT_1
 PS01012; FOLYLPOLYGLU_SYNT_2 
PRINTS