UniProt Accession

 C1TC_MOUSE; Q922D8; Q8R013 

Genbank Protein ID

 AF364579; AF364591; AF364580; AF364581; AF364582; AF364583; AF364584; AF364585; AF364586; AF364587; AF364588; AF364589; AF364590; AK088700; BC008523 

Genbank Nucleotide ID

 AAL99692.1; AAL99693.1; AAL99693.1; AAL99693.1; AAL99693.1; AAL99693.1; AAL99693.1; AAL99693.1; AAL99693.1; AAL99693.1; AAL99693.1; AAL99693.1; AAL99693.1; BAC40513.1; AAH08523.1 

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

  

Created Date

 July 27, 2013 

Organism

 Mus musculus (Mouse) 

NCBI Taxa ID

 10090 

Lysine Modification

Position	Peptide	Type	References
10	PAGILNGKLVSAQIR	ubiquitination	[1]
134	LTSVSAGKLARGDLN	ubiquitination	[1]
157	KGCLELIKEAGVQIA	ubiquitination	[1]
208	NLDKEVNKGDILVVA	ubiquitination	[1]
246	NYVPDDTKPNGRKVV	acetylation	[2]
251	DTKPNGRKVVGDVAY	ubiquitination	[1]
262	DVAYDEAKERASFIT	acetylation	[2, 3]
262	DVAYDEAKERASFIT	ubiquitination	[1]
297	SAQRFLQKFKPGKWT	acetylation	[2]
299	QRFLQKFKPGKWTIQ	acetylation	[4]
302	LQKFKPGKWTIQYNK	acetylation	[2, 4]
309	KWTIQYNKLNLKTPV	ubiquitination	[1]
313	QYNKLNLKTPVPSDI	ubiquitination	[1]
329	ISRSCKPKLIGNLAR	ubiquitination	[1]
352	VELYGETKAKVLLSA	ubiquitination	[1]
354	LYGETKAKVLLSALD	ubiquitination	[1]
364	LSALDRLKHQPDGKY	acetylation	[2]
370	LKHQPDGKYVVVTGI	ubiquitination	[1]
473	HELTQTDKALFNRLV	acetylation	[2, 3]
473	HELTQTDKALFNRLV	ubiquitination	[1]
488	PSVNGIRKFSDIQIR	acetylation	[5]
488	PSVNGIRKFSDIQIR	ubiquitination	[1]
504	LRRLGIEKTDPTTLT	ubiquitination	[1]
543	TNDRFLRKITIGQSP	ubiquitination	[1]
553	IGQSPTEKGHTRTAQ	acetylation	[6]
553	IGQSPTEKGHTRTAQ	ubiquitination	[1]
620	VLMKDAIKPNLMQTL	ubiquitination	[1]
721	TAGLPLPKAYTEEDL	ubiquitination	[1]
733	EDLDLVEKGFSNLRK	ubiquitination	[1]
784	HGAFDAVKCTHWAEG	ubiquitination	[1]
848	LLPEAQNKAEIYTKQ	ubiquitination	[1]
854	NKAEIYTKQGFGNLP	ubiquitination	[1]

Reference

 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023]
 [2] Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome.
 Hebert AS, Dittenhafer-Reed KE, Yu W, Bailey DJ, Selen ES, Boersma MD, Carson JJ, Tonelli M, Balloon AJ, Higbee AJ, Westphall MS, Pagliarini DJ, Prolla TA, Assadi-Porter F, Roy S, Denu JM, Coon JJ.
 Mol Cell. 2013 Jan 10;49(1):186-99. [PMID: 23201123]
 [3] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [4] Quantification of mitochondrial acetylation dynamics highlights prominent sites of metabolic regulation.
 Still AJ, Floyd BJ, Hebert AS, Bingman CA, Carson JJ, Gunderson DR, Dolan BK, Grimsrud PA, Dittenhafer-Reed KE, Stapleton DS, Keller MP, Westphall MS, Denu JM, Attie AD, Coon JJ, Pagliarini DJ.
 J Biol Chem. 2013 Jul 17;. [PMID: 23864654]
 [5] Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways.
 Chen Y, Zhao W, Yang JS, Cheng Z, Luo H, Lu Z, Tan M, Gu W, Zhao Y.
 Mol Cell Proteomics. 2012 Oct;11(10):1048-62. [PMID: 22826441]
 [6] SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways.
 Park J, Chen Y, Tishkoff DX, Peng C, Tan M, Dai L, Xie Z, Zhang Y, Zwaans BM, Skinner ME, Lombard DB, Zhao Y.
 Mol Cell. 2013 Jun 27;50(6):919-30. [PMID: 23806337] 

Functional Description

  

Sequence Annotation

 NP_BIND 172 174 NADP (By similarity).
 NP_BIND 380 387 ATP (By similarity).
 REGION 1 305 Methylenetetrahydrofolate dehydrogenase
 REGION 52 56 Substrate binding (By similarity).
 REGION 99 101 Substrate binding (By similarity).
 REGION 272 276 Substrate binding (By similarity).
 REGION 306 935 Formyltetrahydrofolate synthetase.
 BINDING 197 197 NADP (By similarity).
 MOD_RES 1 1 N-acetylmethionine (By similarity).
 MOD_RES 786 786 Phosphothreonine.  

Keyword

 Acetylation; Amino-acid biosynthesis; ATP-binding; Complete proteome; Cytoplasm; Direct protein sequencing; Histidine biosynthesis; Hydrolase; Ligase; Methionine biosynthesis; Multifunctional enzyme; NADP; Nucleotide-binding; One-carbon metabolism; Oxidoreductase; Phosphoprotein; Purine biosynthesis; Reference proteome. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 935 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; IBA:RefGenome.
 GO:0005739; C:mitochondrion; IDA:MGI.
 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: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.