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0C1TC_HUMAN*   SwissProt (?) | Description Local Annotation Link Reference
General Information
NameMTHFD1
DescriptionC-1-tetrahydrofolate synthase, cytoplasmic (c1-thf synthase) .
SpeciesHomo sapiens (NCBI taxonomy ID: 9606)
GO0005739 mitochondrion (TAS)
0004329 formate-tetrahydrofolate ligase activity (TAS)
0004477 methenyltetrahydrofolate cyclohydrolase act... (TAS)
0004486 methylenetetrahydrofolate dehydrogenase act... (TAS)

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schematic display of those terms with internal associations, click the node and browse the corresponding GO term
Domain Architecture (Details)
InterPro domains unassigned to SynO:
Formate--tetrahydrofolate ligase () (formyltetrahydrofolate synthetase) (FTHFS) is one of the enzymesparticipating in the transfer of one-carbon units.n essential element of various biosynthetic pathways. In many ofthese processes the transfers of one-carbon units are mediated by the coenzyme tetrahydrofolate (THF). In eukaryotesthe FTHFS activity is expressed by a multifunctional enzyme.-1-tetrahydrofolate synthase (C1-THF synthase).hichalso catalyzes the dehydrogenase and cyclohydrolase activities. Two forms of C1-THF synthases are known .ne is located in the mitochondrial matrix.hile the second one is cytoplasmic. In both forms the FTHFS domainconsists of about 600 amino acid residues and is located in the C-terminal section of C1-THF synthase. In prokaryotesFTHFS activity is expressed by a monofunctional homotetrameric enzyme of about 560 amino acid residues .The crystal structure of N(10)-formyltetrahydrofolate synthetase from Moorella thermoacetica shows that the subunit is composed of three domains organized around three mixed beta-sheets. There are two cavities between adjacent domains. One of them was identified as the nucleotide binding site by homology modeling. The large domain contains a seven-stranded beta-sheet surrounded by helices on both sides. The second domain contains a five-stranded beta-sheet with two alpha-helices packed on one side while the other two are a wall of the active site cavity. The third domain contains a four-stranded beta-sheet forming a half-barrel. The concave side is covered by two helices while the convex side is another wall of the large cavity. Arg 97 is likely involved in formyl phosphate binding. The tetrameric molecule is relatively flat with the shape of the letter X.nd the active sites are located at the end of the subunits far from the subunit interface .
  IPR000559:Formate-tetrahydrofolate ligase, FTHFS
Enzymes that participate in the transfer of one-carbon units require the coenzyme tetrahydrofolate (THF).Various reactions generate one-carbon derivatives of THF.hich can be interconverted between differentoxidation states by methylene-THF dehydrogenase ().ethenyl-THF cyclohydrolase ()and formyl-THF synthetase () . The dehydrogenase and cyclohydrolaseactivities are expressed by a variety of multifunctional enzymes.ncluding the tri-functional eukaryoticC1-tetrahydrofolate synthase ; a bifunctional eukaryotic mitochondrial protein; and thebifunctional Escherichia coli folD protein . Methylene-tetrahydrofolate dehydrogenase andmethenyltetrahydrofolate cyclo-hydrolase share an overlapping active site .nd as such areusually located together in proteins.cting in tandem on the carbon-nitrogen bonds of substrates otherthan peptide bonds.
  IPR000672:Tetrahydrofolate dehydrogenase/cyclohydrolase
IPR000559:FTHFS 
Evalue:-1e+125 
Location:315-934IPR000672:THF_DHG_CYH_C 
Evalue:-105.638275146484 
Location:127-294IPR000672:THF_DHG_CYH 
Evalue:-65.3979415893555 
Location:4-124
SequencesProtein: C1TC_HUMAN (934 aa)
mRNA: NM_005956
Local Annotation
Synapse Ontology
Microglias, one kind of glias in CNS, are responsible for removing most of the waste and cellular debris from the CNS
sdb:0267 removing metabolic mass  (Evidence:keywords)
KO assignmentK00288
  Level 3 annotation:
    methylenetetrahydrofolate dehydrogenase (NADP+)
  Level 2 annotation:
    Glyoxylate and dicarboxylate metabolism
    One carbon pool by folate
K00295
  Level 3 annotation:
    methylenetetrahydrofolate dehydrogenase (NAD+)
  Level 2 annotation:
    One carbon pool by folate
K01491
  Level 3 annotation:
    methenyltetrahydrofolate cyclohydrolase
  Level 2 annotation:
    Glyoxylate and dicarboxylate metabolism
    One carbon pool by folate
K01938
  Level 3 annotation:
    formate--tetrahydrofolate ligase
  Level 2 annotation:
    Glyoxylate and dicarboxylate metabolism
    One carbon pool by folate
Loci Structure (Details)Loci index, Chromosomal location, Length, Possible relational loci clusterExon1: 32 residues, 63924845-63924939Exon2: 30 residues, 63937263-63937348Exon3: 22 residues, 63947560-63947620Exon4: 20 residues, 63948942-63948996Exon5: 47 residues, 63951828-63951965Exon6: 35 residues, 63952109-63952210Exon7: 47 residues, 63954358-63954495Exon8: 39 residues, 63956284-63956396Exon9: 44 residues, 63961274-63961402Exon10: 34 residues, 63962200-63962298Exon11: 60 residues, 63962489-63962663Exon12: 47 residues, 63963807-63963944Exon13: 17 residues, 63966654-63966701Exon14: 38 residues, 63968002-63968110Exon15: 27 residues, 63968257-63968332Exon16: 36 residues, 63972039-63972142Exon17: 27 residues, 63975566-63975643Exon18: 49 residues, 63976596-63976737Exon19: 25 residues, 63977855-63977924Exon20: 39 residues, 63978524-63978636Exon21: 48 residues, 63978733-63978873Exon22: 16 residues, 63981163-63981205Exon23: 35 residues, 63984687-63984788Exon24: 61 residues, 63985915-63986093Exon25: 38 residues, 63990224-63990332Exon26: 53 residues, 63991193-63991346Exon27: 33 residues, 63994684-63994778Exon28: 83 residues, 63996229-63996474Exon29: 2 residues, -Jump to C1TC_HUMAN  
Tune and view alternative isoforms
Loci Cluster (Details)Loci: 2847 64003577-64006172 ~-3K 11293(AKAP5)(+)Loci: 2846 63924845-63996474 ~-72K 11292(MTHFD1)(+)Link out to UCSC