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Identification
HMDB Protein ID HMDBP00923
Secondary Accession Numbers
  • 6211
  • HMDBP04205
Name C-1-tetrahydrofolate synthase, cytoplasmic
Synonyms
  1. C1-THF synthase
  2. Formyltetrahydrofolate synthetase
  3. Methenyltetrahydrofolate cyclohydrolase
  4. Methylenetetrahydrofolate dehydrogenase
Gene Name MTHFD1
Protein Type Enzyme
Biological Properties
General Function Involved in formate-tetrahydrofolate ligase activity
Specific Function Not Available
Pathways
  • Folate malabsorption, hereditary
  • Folate Metabolism
  • Methotrexate Pathway
  • Methylenetetrahydrofolate Reductase Deficiency (MTHFRD)
  • One carbon pool by folate
  • tetrahydrofolate interconversion
Reactions
5,10-Methylene-THF + NADP → 5,10-Methenyltetrahydrofolic acid + NADPH details
5,10-Methenyltetrahydrofolic acid + Water → 10-Formyltetrahydrofolate details
Adenosine triphosphate + Formic acid + Tetrahydrofolic acid → ADP + Phosphoric acid + 10-Formyltetrahydrofolate details
5,10-Methenyltetrahydrofolic acid + Water → 10-Formyltetrahydrofolate + Hydrogen Ion details
GO Classification
Biological Process
purine nucleotide biosynthetic process
methionine biosynthetic process
folic acid metabolic process
folic acid-containing compound biosynthetic process
histidine biosynthetic process
tetrahydrofolate interconversion
one-carbon metabolic process
Cellular Component
cytosol
mitochondrion
Function
binding
catalytic activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
ligase activity
formate-tetrahydrofolate ligase activity
ligase activity, forming carbon-nitrogen bonds
Molecular Function
ATP binding
formate-tetrahydrofolate ligase activity
methenyltetrahydrofolate cyclohydrolase activity
methylenetetrahydrofolate dehydrogenase (NADP+) activity
methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity
Process
metabolic process
cellular aromatic compound metabolic process
folic acid and derivative metabolic process
cellular metabolic process
folic acid and derivative biosynthetic process
Cellular Location
  1. Cytoplasm
Gene Properties
Chromosome Location 14
Locus 14q24
SNPs MTHFD1
Gene Sequence
>2808 bp
ATGGCGCCAGCAGAAATCCTGAACGGGAAGGAGATCTCCGCGCAAATAAGGGCGAGACTG
AAAAATCAAGTCACTCAGTTGAAGGAGCAAGTACCTGGTTTCACACCACGCCTGGCAATA
TTACAGGTTGGCAACAGAGATGATTCCAATCTTTATATAAATGTGAAGCTGAAGGCTGCT
GAAGAGATTGGGATCAAAGCCACTCACATTAAGTTACCAAGAACAACCACAGAATCTGAG
GTGATGAAGTACATTACATCTTTGAATGAAGACTCTACTGTACATGGGTTCTTAGTGCAG
CTACCTTTAGATTCAGAGAATTCCATTAACACTGAAGAAGTGATCAATGCTATTGCACCC
GAGAAGGATGTGGATGGATTGACTAGCATCAATGCTGGGAGACTTGCTAGAGGTGACCTC
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
AACATCGCACATGGCAATTCCTCCATCATTGCAGACCAGATCGCACTCAAGCTTGTTGGC
CCAGAAGGGTTTGTAGTGACGGAAGCAGGATTTGGAGCAGACATTGGAATGGAAAAGTTT
TTTAACATCAAATGCCGGTATTCCGGCCTCTGCCCCCACGTGGTGGTGCTTGTTGCCACT
GTCAGGGCTCTCAAGATGCACGGGGGCGGCCCCACGGTCACTGCTGGACTGCCTCTTCCC
AAGGCTTACATACAGGAGAACCTGGAGCTGGTTGAAAAAGGCTTCAGTAACTTGAAGAAA
CAAATTGAAAATGCCAGAATGTTTGGAATTCCAGTAGTAGTGGCCGTGAATGCATTCAAG
ACGGATACAGAGTCTGAGCTGGACCTCATCAGCCGCCTTTCCAGAGAACATGGGGCTTTT
GATGCCGTGAAGTGCACTCACTGGGCAGAAGGGGGCAAGGGTGCCTTAGCCCTGGCTCAG
GCCGTCCAGAGAGCAGCACAAGCACCCAGCAGCTTCCAGCTCCTTTATGACCTCAAGCTC
CCAGTTGAGGATAAAATCAGGATCATTGCACAGAAGATCTATGGAGCAGATGACATTGAA
TTACTTCCCGAAGCTCAACACAAAGCTGAAGTCTACACGAAGCAGGGCTTTGGGAATCTC
CCCATCTGCATGGCTAAAACACACTTGTCTTTGTCTCACAACCCAGAGCAAAAAGGTGTC
CCTACAGGCTTCATTCTGCCCATTCGCGACATCCGCGCCAGCGTTGGGGCTGGTTTTCTG
TACCCCTTAGTAGGAACGATGAGCACAATGCCTGGACTCCCCACCCGGCCCTGTTTTTAT
GATATTGATTTGGACCCTGAAACAGAACAGGTGAATGGATTATTCTAA
Protein Properties
Number of Residues 935
Molecular Weight 101530.36
Theoretical pI 7.296
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>C-1-tetrahydrofolate synthase, cytoplasmic
MAPAEILNGKEISAQIRARLKNQVTQLKEQVPGFTPRLAILQVGNRDDSNLYINVKLKAA
EEIGIKATHIKLPRTTTESEVMKYITSLNEDSTVHGFLVQLPLDSENSINTEEVINAIAP
EKDVDGLTSINAGRLARGDLNDCFIPCTPKGCLELIKETGVPIAGRHAVVVGRSKIVGAP
MHDLLLWNNATVTTCHSKTAHLDEEVNKGDILVVATGQPEMVKGEWIKPGAIVIDCGINY
VPDDKKPNGRKVVGDVAYDEAKERASFITPVPGGVGPMTVAMLMQSTVESAKRFLEKFKP
GKWMIQYNNLNLKTPVPSDIDISRSCKPKPIGKLAREIGLLSEEVELYGETKAKVLLSAL
ERLKHRPDGKYVVVTGITPTPLGEGKSTTTIGLVQALGAHLYQNVFACVRQPSQGPTFGI
KGGAAGGGYSQVIPMEEFNLHLTGDIHAITAANNLVAAAIDARIFHELTQTDKALFNRLV
PSVNGVRRFSDIQIRRLKRLGIEKTDPTTLTDEEINRFARLDIDPETITWQRVLDTNDRF
LRKITIGQAPTEKGHTRTAQFDISVASEIMAVLALTTSLEDMRERLGKMVVASSKKGEPV
SAEDLGVSGALTVLMKDAIKPNLMQTLEGTPVFVHAGPFANIAHGNSSIIADRIALKLVG
PEGFVVTEAGFGADIGMEKFFNIKCRYSGLCPHVVVLVATVRALKMHGGGPTVTAGLPLP
KAYIQENLELVEKGFSNLKKQIENARMFGIPVVVAVNAFKTDTESELDLISRLSREHGAF
DAVKCTHWAEGGKGALALAQAVQRAAQAPSSFQLLYDLKLPVEDKIRIIAQKIYGADDIE
LLPEAQHKAEVYTKQGFGNLPICMAKTHLSLSHNPEQKGVPTGFILPIRDIRASVGAGFL
YPLVGTMSTMPGLPTRPCFYDIDLDPETEQVNGLF
GenBank ID Protein 189065440
UniProtKB/Swiss-Prot ID P11586
UniProtKB/Swiss-Prot Entry Name C1TC_HUMAN
PDB IDs
GenBank Gene ID AK312361
GeneCard ID MTHFD1
GenAtlas ID MTHFD1
HGNC ID HGNC:7432
References
General References
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  3. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
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  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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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