CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-004190
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial 
Protein Synonyms/Alias
 NAD-dependent methylenetetrahydrofolate dehydrogenase; Methenyltetrahydrofolate cyclohydrolase 
Gene Name
 MTHFD2 
Gene Synonyms/Alias
 NMDMC 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
50RKLAQQIKQEVRQEVacetylation[1]
50RKLAQQIKQEVRQEVubiquitination[2]
88SHSYVLNKTRAAAVVubiquitination[2]
104INSETIMKPASISEEubiquitination[3]
194TGIPTLGKNVVVAGRubiquitination[2, 3, 4]
237ISHRYTPKEQLKKHTubiquitination[4]
286VHDPVTAKPKLVGDVubiquitination[2, 3, 4]
288DPVTAKPKLVGDVDFubiquitination[2, 4]
301DFEGVRQKAGYITPVubiquitination[3]
341LEEREVLKSKELGVAubiquitination[5, 6]
343EREVLKSKELGVATNubiquitination[2, 3, 4]
Reference
 [1] 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]
 [2] 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]
 [3] 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]
 [4] 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]
 [5] 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]
 [6] 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
  
Sequence Annotation
 MOD_RES 50 50 N6-acetyllysine.  
Keyword
 3D-structure; Acetylation; Complete proteome; Hydrolase; Magnesium; Mitochondrion; Multifunctional enzyme; NAD; One-carbon metabolism; Oxidoreductase; Reference proteome; Transit peptide. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 350 AA 
Protein Sequence
MAATSLMSAL AARLLQPAHS CSLRLRPFHL AAVRNEAVVI SGRKLAQQIK QEVRQEVEEW 60
VASGNKRPHL SVILVGENPA SHSYVLNKTR AAAVVGINSE TIMKPASISE EELLNLINKL 120
NNDDNVDGLL VQLPLPEHID ERRICNAVSP DKDVDGFHVI NVGRMCLDQY SMLPATPWGV 180
WEIIKRTGIP TLGKNVVVAG RSKNVGMPIA MLLHTDGAHE RPGGDATVTI SHRYTPKEQL 240
KKHTILADIV ISAAGIPNLI TADMIKEGAA VIDVGINRVH DPVTAKPKLV GDVDFEGVRQ 300
KAGYITPVPG GVGPMTVAML MKNTIIAAKK VLRLEEREVL KSKELGVATN 350 
Gene Ontology
 GO:0005739; C:mitochondrion; ISS:UniProtKB.
 GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
 GO:0004477; F:methenyltetrahydrofolate cyclohydrolase activity; ISS:UniProtKB.
 GO:0004487; F:methylenetetrahydrofolate dehydrogenase (NAD+) activity; IDA:UniProtKB.
 GO:0004488; F:methylenetetrahydrofolate dehydrogenase (NADP+) activity; IDA:UniProtKB.
 GO:0042301; F:phosphate ion binding; IDA:UniProtKB.
 GO:0009396; P:folic acid-containing compound biosynthetic process; IEA:InterPro.
 GO:0006730; P:one-carbon metabolic process; IBA:RefGenome.
 GO:0009408; P:response to heat; IEA:Compara.
 GO:0046653; P:tetrahydrofolate metabolic process; IDA:UniProtKB. 
Interpro
 IPR016040; NAD(P)-bd_dom.
 IPR000672; THF_DH/CycHdrlase.
 IPR020630; THF_DH/CycHdrlase_cat_dom.
 IPR020867; THF_DH/CycHdrlase_CS.
 IPR020631; THF_DH/CycHdrlase_NAD-bd_dom. 
Pfam
 PF00763; THF_DHG_CYH
 PF02882; THF_DHG_CYH_C 
SMART
  
PROSITE
 PS00766; THF_DHG_CYH_1
 PS00767; THF_DHG_CYH_2 
PRINTS
 PR00085; THFDHDRGNASE.