C-1-tetrahydrofolate synthase, cytoplasmic

Details

Name
C-1-tetrahydrofolate synthase, cytoplasmic
Synonyms
  • C1-THF synthase
  • MTHFC
  • MTHFD
Gene Name
MTHFD1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0016155|C-1-tetrahydrofolate synthase, cytoplasmic
MAPAEILNGKEISAQIRARLKNQVTQLKEQVPGFTPRLAILQVGNRDDSNLYINVKLKAA
EEIGIKATHIKLPRTTTESEVMKYITSLNEDSTVHGFLVQLPLDSENSINTEEVINAIAP
EKDVDGLTSINAGRLARGDLNDCFIPCTPKGCLELIKETGVPIAGRHAVVVGRSKIVGAP
MHDLLLWNNATVTTCHSKTAHLDEEVNKGDILVVATGQPEMVKGEWIKPGAIVIDCGINY
VPDDKKPNGRKVVGDVAYDEAKERASFITPVPGGVGPMTVAMLMQSTVESAKRFLEKFKP
GKWMIQYNNLNLKTPVPSDIDISRSCKPKPIGKLAREIGLLSEEVELYGETKAKVLLSAL
ERLKHRPDGKYVVVTGITPTPLGEGKSTTTIGLVQALGAHLYQNVFACVRQPSQGPTFGI
KGGAAGGGYSQVIPMEEFNLHLTGDIHAITAANNLVAAAIDARIFHELTQTDKALFNRLV
PSVNGVRRFSDIQIRRLKRLGIEKTDPTTLTDEEINRFARLDIDPETITWQRVLDTNDRF
LRKITIGQAPTEKGHTRTAQFDISVASEIMAVLALTTSLEDMRERLGKMVVASSKKGEPV
SAEDLGVSGALTVLMKDAIKPNLMQTLEGTPVFVHAGPFANIAHGNSSIIADRIALKLVG
PEGFVVTEAGFGADIGMEKFFNIKCRYSGLCPHVVVLVATVRALKMHGGGPTVTAGLPLP
KAYIQENLELVEKGFSNLKKQIENARMFGIPVVVAVNAFKTDTESELDLISRLSREHGAF
DAVKCTHWAEGGKGALALAQAVQRAAQAPSSFQLLYDLKLPVEDKIRIIAQKIYGADDIE
LLPEAQHKAEVYTKQGFGNLPICMAKTHLSLSHNPEQKGVPTGFILPIRDIRASVGAGFL
YPLVGTMSTMPGLPTRPCFYDIDLDPETEQVNGLF
Number of residues
935
Molecular Weight
101558.37
Theoretical pI
7.32
GO Classification
Functions
ATP binding / formate-tetrahydrofolate ligase activity / methenyltetrahydrofolate cyclohydrolase activity / methylenetetrahydrofolate dehydrogenase (NAD+) activity / methylenetetrahydrofolate dehydrogenase (NADP+) activity / methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity
Processes
10-formyltetrahydrofolate biosynthetic process / embryonic neurocranium morphogenesis / embryonic viscerocranium morphogenesis / folic acid metabolic process / heart development / histidine biosynthetic process / methionine biosynthetic process / methionine metabolic process / neural tube closure / neutrophil homeostasis / one-carbon metabolic process / purine nucleotide biosynthetic process / serine family amino acid biosynthetic process / serine family amino acid metabolic process / small molecule metabolic process / somite development / tetrahydrofolate interconversion / transsulfuration / vitamin metabolic process / water-soluble vitamin metabolic process
Components
cytosol / extracellular exosome / membrane / mitochondrion
General Function
Methylenetetrahydrofolate dehydrogenase [nad(p)+] activity
Specific Function
Not Available
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0016156|C-1-tetrahydrofolate synthase, cytoplasmic (MTHFD1)
ATGGCGCCAGCAGAAATCCTGAACGGGAAGGAGATCTCCGCGCAAATAAGGGCGAGACTG
AAAAATCAAGTCACTCAGTTGAAGGAGCAAGTACCTGGTTTCACACCACGCCTGGCAATA
TTACAGGTTGGCAACAGAGATGATTCCAATCTTTATATAAATGTGAAGCTGAAGGCTGCT
GAAGAGATTGGGATCAAAGCCACTCACATTAAGTTACCAAGAACAACCACAGAATCTGAG
GTGATGAAGTACATTACATCTTTGAATGAAGACTCTACTGTACATGGGTTCTTAGTGCAG
CTACCTTTAGATTCAGAGAATTCCATTAACACTGAAGAAGTGATCAATGCTATTGCACCC
GAGAAGGATGTGGATGGATTGACTAGCATCAATGCTGGGAAACTTGCTAGAGGTGACCTC
AATGACTGTTTCATTCCTTGTACGCCTAAGGGATGCTTGGAACTCATCAAAGAGACAGGG
GTGCCGATTGCCGGAAGGCATGCTGTGGTGGTTGGGCGCAGTAAAATAGTTGGGGCCCCG
ATGCATGACTTGCTTCTGTGGAACAATGCCACAGTGACCACCTGCCACTCCAAGACTGCC
CATCTGGATGAGGAGGTAAATAAAGGTGACATCCTGGTGGTTGCAACTGGTCAGCCTGAA
ATGGTTAAAGGGGAGTGGATCAAACCTGGGGCAATAGTCATCGACTGTGGAATCAATTAT
GTCCCAGATGATAAAAAACCAAATGGGAGAAAAGTTGTGGGTGATGTGGCATACGACGAG
GCCAAAGAGAGGGCGAGCTTCATCACTCCTGTTCCTGGCGGCGTAGGGCCCATGACAGTT
GCAATGCTCATGCAGAGCACAGTAGAGAGTGCCAAGCGTTTCCTGGAGAAATTTAAGCCA
GGAAAGTGGATGATTCAGTATAACAACCTTAACCTCAAGACACCTGTTCCAAGTGACATT
GATATATCACGATCTTGTAAACCGAAGCCCATTGGTAAGCTGGCTCGAGAAATTGGTCTG
CTGTCTGAAGAGGTAGAATTATATGGTGAAACAAAGGCCAAAGTTCTGCTGTCAGCACTA
GAACGCCTGAAGCACCGGCCTGATGGGAAATACGTGGTGGTGACTGGAATAACTCCAACA
CCCCTGGGAGAAGGGAAAAGCACAACTACAATCGGGCTAGTGCAAGCCCTTGGTGCCCAT
CTCTACCAGAATGTCTTTGCGTGTGTGCGACAGCCTTCTCAGGGCCCCACCTTTGGAATA
AAAGGTGGCGCTGCAGGAGGCGGCTACTCCCAGGTCATTCCTATGGAAGAGTTTAATCTC
CACCTCACAGGTGACATCCATGCCATCACTGCAGCTAATAACCTCGTTGCTGCGGCCATT
GATGCTCGGATATTTCATGAACTGACCCAGACAGACAAGGCTCTCTTTAATCGTTTGGTG
CCATCAGTAAATGGAGTGAGAAGGTTCTCTGACATCCAAATCCGAAGGTTAAAGAGACTA
GGCATTGAAAAGACTGACCCTACCACACTGACAGATGAAGAGATAAACAGATTTGCAAGA
TTGGACATTGATCCAGAAACCATAACTTGGCAAAGAGTGTTGGATACCAATGATAGATTC
CTGAGGAAGATCACGATTGGACAGGCTCCAACGGAGAAGGGTCACACACGGACGGCCCAG
TTTGATATCTCTGTGGCCAGTGAAATTATGGCTGTCCTGGCTCTCACCACTTCTCTAGAA
GACATGAGAGAGAGACTGGGCAAAATGGTGGTGGCATCCAGTAAGAAAGGAGAGCCCGTC
AGTGCCGAAGATCTGGGGGTGAGTGGTGCACTGACAGTGCTTATGAAGGACGCAATCAAG
CCCAATCTCATGCAGACACTGGAGGGCACTCCAGTGTTTGTCCATGCTGGCCCGTTTGCC
AACATCGCACATGGCAATTCCTCCATCATTGCAGACCGGATCGCACTCAAGCTTGTTGGC
CCAGAAGGGTTTGTAGTGACGGAAGCAGGATTTGGAGCAGACATTGGAATGGAAAAGTTT
TTTAACATCAAATGCCGGTATTCCGGCCTCTGCCCCCACGTGGTGGTGCTTGTTGCCACT
GTCAGGGCTCTCAAGATGCACGGGGGCGGCCCCACGGTCACTGCTGGACTGCCTCTTCCC
AAGGCTTACATACAGGAGAACCTGGAGCTGGTTGAAAAAGGCTTCAGTAACTTGAAGAAA
CAAATTGAAAATGCCAGAATGTTTGGAATTCCAGTAGTAGTGGCCGTGAATGCATTCAAG
ACGGATACAGAGTCTGAGCTGGACCTCATCAGCCGCCTTTCCAGAGAACATGGGGCTTTT
GATGCCGTGAAGTGCACTCACTGGGCAGAAGGGGGCAAGGGTGCCTTAGCCCTGGCTCAG
GCCGTCCAGAGAGCAGCACAAGCACCCAGCAGCTTCCAGCTCCTTTATGACCTCAAGCTC
CCAGTTGAGGATAAAATCAGGATCATTGCACAGAAGATCTATGGAGCAGATGACATTGAA
TTACTTCCCGAAGCTCAACACAAAGCTGAAGTCTACACGAAGCAGGGCTTTGGGAATCTC
CCCATCTGCATGGCTAAAACACACTTGTCTTTGTCTCACAACCCAGAGCAAAAAGGTGTC
CCTACAGGCTTCATTCTGCCCATTCGCGACATCCGCGCCAGCGTTGGGGCTGGTTTTCTG
TACCCCTTAGTAGGAACGATGAGCACAATGCCTGGACTCCCCACCCGGCCCTGTTTTTAT
GATATTGATTTGGACCCTGAAACAGAACAGGTGAATGGATTATTCTAA
Chromosome Location
14
Locus
14q24
External Identifiers
ResourceLink
UniProtKB IDP11586
UniProtKB Entry NameC1TC_HUMAN
GenBank Protein ID307178
GenBank Gene IDJ04031
GenAtlas IDMTHFD1
HGNC IDHGNC:7432
General References
  1. Hum DW, Bell AW, Rozen R, MacKenzie RE: Primary structure of a human trifunctional enzyme. Isolation of a cDNA encoding methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase. J Biol Chem. 1988 Nov 5;263(31):15946-50. [PubMed:3053686]
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  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  5. Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J: Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9. Epub 2003 Mar 31. [PubMed:12665801]
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  12. Allaire M, Li Y, MacKenzie RE, Cygler M: The 3-D structure of a folate-dependent dehydrogenase/cyclohydrolase bifunctional enzyme at 1.5 A resolution. Structure. 1998 Feb 15;6(2):173-82. [PubMed:9519408]
  13. Schmidt A, Wu H, MacKenzie RE, Chen VJ, Bewly JR, Ray JE, Toth JE, Cygler M: Structures of three inhibitor complexes provide insight into the reaction mechanism of the human methylenetetrahydrofolate dehydrogenase/cyclohydrolase. Biochemistry. 2000 May 30;39(21):6325-35. [PubMed:10828945]
  14. Hol FA, van der Put NM, Geurds MP, Heil SG, Trijbels FJ, Hamel BC, Mariman EC, Blom HJ: Molecular genetic analysis of the gene encoding the trifunctional enzyme MTHFD (methylenetetrahydrofolate-dehydrogenase, methenyltetrahydrofolate-cyclohydrolase, formyltetrahydrofolate synthetase) in patients with neural tube defects. Clin Genet. 1998 Feb;53(2):119-25. [PubMed:9611072]
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  16. Parle-McDermott A, Kirke PN, Mills JL, Molloy AM, Cox C, O'Leary VB, Pangilinan F, Conley M, Cleary L, Brody LC, Scott JM: Confirmation of the R653Q polymorphism of the trifunctional C1-synthase enzyme as a maternal risk for neural tube defects in the Irish population. Eur J Hum Genet. 2006 Jun;14(6):768-72. [PubMed:16552426]
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  18. Christensen KE, Rohlicek CV, Andelfinger GU, Michaud J, Bigras JL, Richter A, Mackenzie RE, Rozen R: The MTHFD1 p.Arg653Gln variant alters enzyme function and increases risk for congenital heart defects. Hum Mutat. 2009 Feb;30(2):212-20. doi: 10.1002/humu.20830. [PubMed:18767138]
  19. Watkins D, Schwartzentruber JA, Ganesh J, Orange JS, Kaplan BS, Nunez LD, Majewski J, Rosenblatt DS: Novel inborn error of folate metabolism: identification by exome capture and sequencing of mutations in the MTHFD1 gene in a single proband. J Med Genet. 2011 Sep;48(9):590-2. doi: 10.1136/jmedgenet-2011-100286. Epub 2011 Aug 3. [PubMed:21813566]
  20. Burda P, Kuster A, Hjalmarson O, Suormala T, Burer C, Lutz S, Roussey G, Christa L, Asin-Cayuela J, Kollberg G, Andersson BA, Watkins D, Rosenblatt DS, Fowler B, Holme E, Froese DS, Baumgartner MR: Characterization and review of MTHFD1 deficiency: four new patients, cellular delineation and response to folic and folinic acid treatment. J Inherit Metab Dis. 2015 Sep;38(5):863-72. doi: 10.1007/s10545-015-9810-3. Epub 2015 Jan 30. [PubMed:25633902]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00116Tetrahydrofolic acidnutraceuticalunknowncofactorDetails
DB00157NADHapproved, nutraceuticalunknownDetails
DB02358LY374571experimentalunknownDetails
DB03461Nicotinamide adenine dinucleotide phosphateexperimentalunknownDetails
DB04322LY249543experimentalunknownDetails