CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-003948
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 C-1-tetrahydrofolate synthase, cytoplasmic 
Protein Synonyms/Alias
 C1-THF synthase; Methylenetetrahydrofolate dehydrogenase; Methenyltetrahydrofolate cyclohydrolase; Formyltetrahydrofolate synthetase; C-1-tetrahydrofolate synthase, cytoplasmic, N-terminally processed 
Gene Name
 MTHFD1 
Gene Synonyms/Alias
 MTHFC; MTHFD 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
28KNQVTQLKEQVPGFTubiquitination[1]
56SNLYINVKLKAAEEIacetylation[2]
262DVAYDEAKERASFITacetylation[3]
262DVAYDEAKERASFITubiquitination[1]
313QYNNLNLKTPVPSDIubiquitination[1]
352VELYGETKAKVLLSAubiquitination[1]
354LYGETKAKVLLSALEubiquitination[4, 5]
370LKHRPDGKYVVVTGIubiquitination[4, 5]
473HELTQTDKALFNRLVubiquitination[1, 4, 5]
504LKRLGIEKTDPTTLTubiquitination[1]
543TNDRFLRKITIGQAPubiquitination[6]
553IGQAPTEKGHTRTAQacetylation[2]
588DMRERLGKMVVASSKubiquitination[4, 5, 6]
784HGAFDAVKCTHWAEGubiquitination[4, 5, 6]
819FQLLYDLKLPVEDKIubiquitination[1]
832KIRIIAQKIYGADDIubiquitination[1]
848LLPEAQHKAEVYTKQubiquitination[1]
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] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [3] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [4] 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]
 [5] 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]
 [6] 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] 
Functional Description
  
Sequence Annotation
 NP_BIND 172 174 NADP.
 NP_BIND 380 387 ATP (By similarity).
 REGION 2 305 Methylenetetrahydrofolate dehydrogenase
 REGION 52 56 Substrate binding.
 REGION 99 101 Substrate binding.
 REGION 272 276 Substrate binding.
 REGION 306 935 Formyltetrahydrofolate synthetase.
 BINDING 197 197 NADP.
 MOD_RES 1 1 N-acetylmethionine.
 MOD_RES 786 786 Phosphothreonine (By similarity).  
Keyword
 3D-structure; Acetylation; Amino-acid biosynthesis; ATP-binding; Complete proteome; Cytoplasm; Direct protein sequencing; Disease mutation; Histidine biosynthesis; Hydrolase; Ligase; Methionine biosynthesis; Multifunctional enzyme; NADP; Nucleotide-binding; One-carbon metabolism; Oxidoreductase; Phosphoprotein; Polymorphism; Purine biosynthesis; Reference proteome. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 935 AA 
Protein Sequence
MAPAEILNGK EISAQIRARL KNQVTQLKEQ VPGFTPRLAI LQVGNRDDSN LYINVKLKAA 60
EEIGIKATHI KLPRTTTESE VMKYITSLNE DSTVHGFLVQ LPLDSENSIN TEEVINAIAP 120
EKDVDGLTSI NAGRLARGDL NDCFIPCTPK GCLELIKETG VPIAGRHAVV VGRSKIVGAP 180
MHDLLLWNNA TVTTCHSKTA HLDEEVNKGD ILVVATGQPE MVKGEWIKPG AIVIDCGINY 240
VPDDKKPNGR KVVGDVAYDE AKERASFITP VPGGVGPMTV AMLMQSTVES AKRFLEKFKP 300
GKWMIQYNNL NLKTPVPSDI DISRSCKPKP IGKLAREIGL LSEEVELYGE TKAKVLLSAL 360
ERLKHRPDGK YVVVTGITPT PLGEGKSTTT IGLVQALGAH LYQNVFACVR QPSQGPTFGI 420
KGGAAGGGYS QVIPMEEFNL HLTGDIHAIT AANNLVAAAI DARIFHELTQ TDKALFNRLV 480
PSVNGVRRFS DIQIRRLKRL GIEKTDPTTL TDEEINRFAR LDIDPETITW QRVLDTNDRF 540
LRKITIGQAP TEKGHTRTAQ FDISVASEIM AVLALTTSLE DMRERLGKMV VASSKKGEPV 600
SAEDLGVSGA LTVLMKDAIK PNLMQTLEGT PVFVHAGPFA NIAHGNSSII ADRIALKLVG 660
PEGFVVTEAG FGADIGMEKF FNIKCRYSGL CPHVVVLVAT VRALKMHGGG PTVTAGLPLP 720
KAYIQENLEL VEKGFSNLKK QIENARMFGI PVVVAVNAFK TDTESELDLI SRLSREHGAF 780
DAVKCTHWAE GGKGALALAQ AVQRAAQAPS SFQLLYDLKL PVEDKIRIIA QKIYGADDIE 840
LLPEAQHKAE VYTKQGFGNL PICMAKTHLS LSHNPEQKGV PTGFILPIRD IRASVGAGFL 900
YPLVGTMSTM PGLPTRPCFY DIDLDPETEQ VNGLF 935 
Gene Ontology
 GO:0005829; C:cytosol; IBA:RefGenome.
 GO:0005739; C:mitochondrion; TAS:ProtInc.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004329; F:formate-tetrahydrofolate ligase activity; IBA:RefGenome.
 GO:0004477; F:methenyltetrahydrofolate cyclohydrolase activity; IBA:RefGenome.
 GO:0004488; F:methylenetetrahydrofolate dehydrogenase (NADP+) activity; IBA:RefGenome.
 GO:0004486; F:methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity; TAS:Reactome.
 GO:0046655; P:folic acid metabolic process; TAS:Reactome.
 GO:0009396; P:folic acid-containing compound biosynthetic process; IEA:InterPro.
 GO:0000105; P:histidine biosynthetic process; IEA:UniProtKB-KW.
 GO:0009086; P:methionine biosynthetic process; IEA:UniProtKB-KW.
 GO:0006730; P:one-carbon metabolic process; IBA:RefGenome.
 GO:0006164; P:purine nucleotide biosynthetic process; IEA:UniProtKB-KW.
 GO:0035999; P:tetrahydrofolate interconversion; IEA:UniProtKB-UniPathway. 
Interpro
 IPR000559; Formate_THF_ligase.
 IPR020628; Formate_THF_ligase_CS.
 IPR016040; NAD(P)-bd_dom.
 IPR027417; P-loop_NTPase.
 IPR000672; THF_DH/CycHdrlase.
 IPR020630; THF_DH/CycHdrlase_cat_dom.
 IPR020867; THF_DH/CycHdrlase_CS.
 IPR020631; THF_DH/CycHdrlase_NAD-bd_dom. 
Pfam
 PF01268; FTHFS
 PF00763; THF_DHG_CYH
 PF02882; THF_DHG_CYH_C 
SMART
  
PROSITE
 PS00721; FTHFS_1
 PS00722; FTHFS_2
 PS00766; THF_DHG_CYH_1
 PS00767; THF_DHG_CYH_2 
PRINTS
 PR00085; THFDHDRGNASE.