UniProt Accession

 MTDC_HUMAN; P13995; Q53G90; Q53GV5; Q53S36 

Genbank Protein ID

 X16396; AK222826; AK223041; AC073263; BC001548; BC017054 

Genbank Nucleotide ID

 CAA34431.1; BAD96546.1; BAD96761.1; AAX93061.1; AAH01548.2; AAH17054.2 

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
50	RKLAQQIKQEVRQEV	acetylation	[1]
50	RKLAQQIKQEVRQEV	ubiquitination	[2]
88	SHSYVLNKTRAAAVV	ubiquitination	[2]
104	INSETIMKPASISEE	ubiquitination	[3]
194	TGIPTLGKNVVVAGR	ubiquitination	[2, 3, 4]
237	ISHRYTPKEQLKKHT	ubiquitination	[4]
286	VHDPVTAKPKLVGDV	ubiquitination	[2, 3, 4]
288	DPVTAKPKLVGDVDF	ubiquitination	[2, 4]
301	DFEGVRQKAGYITPV	ubiquitination	[3]
341	LEEREVLKSKELGVA	ubiquitination	[5, 6]
343	EREVLKSKELGVATN	ubiquitination	[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

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.