Human Gene MTHFD2 (ENST00000394053.7_4) from GENCODE V47lift37
  Description: methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase, transcript variant 1 (from RefSeq NM_006636.4)
Gencode Transcript: ENST00000394053.7_4
Gencode Gene: ENSG00000065911.13_12
Transcript (Including UTRs)
   Position: hg19 chr2:74,425,742-74,444,692 Size: 18,951 Total Exon Count: 8 Strand: +
Coding Region
   Position: hg19 chr2:74,425,769-74,441,369 Size: 15,601 Coding Exon Count: 8 

Page IndexSequence and LinksUniProtKB CommentsPrimersCTDGene Alleles
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr2:74,425,742-74,444,692)mRNA (may differ from genome)Protein (350 aa)
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-  Comments and Description Text from UniProtKB
  ID: MTDC_HUMAN
DESCRIPTION: RecName: Full=Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial; Includes: RecName: Full=NAD-dependent methylenetetrahydrofolate dehydrogenase; EC=1.5.1.15; Includes: RecName: Full=Methenyltetrahydrofolate cyclohydrolase; EC=3.5.4.9; Flags: Precursor;
CATALYTIC ACTIVITY: 5,10-methylenetetrahydrofolate + NAD(+) = 5,10-methenyltetrahydrofolate + NADH.
CATALYTIC ACTIVITY: 5,10-methenyltetrahydrofolate + H(2)O = 10- formyltetrahydrofolate.
COFACTOR: Magnesium.
SUBUNIT: Homodimer.
INTERACTION: Q9Y6F1:PARP3; NbExp=1; IntAct=EBI-1058895, EBI-1045281; Q9UNM6:PSMD13; NbExp=1; IntAct=EBI-1058895, EBI-356070;
SUBCELLULAR LOCATION: Mitochondrion.
DEVELOPMENTAL STAGE: Expressed only in developing normal tissues.
MISCELLANEOUS: This NAD-dependent bifunctional enzyme has very different kinetic properties than the larger NADP-dependent trifunctional enzyme and is unique in that it requires formation of an enzyme-magnesium complex to allow binding of NAD.
SIMILARITY: Belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family.
SEQUENCE CAUTION: Sequence=AAX93061.1; Type=Erroneous initiation; Sequence=BAD96546.1; Type=Erroneous initiation; Sequence=BAD96761.1; Type=Erroneous initiation; Sequence=CAA34431.1; Type=Erroneous initiation;

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 70.89 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 523.60 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -8.0027-0.296 Picture PostScript Text
3' UTR -924.303323-0.278 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
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 Domains:
PF00763 - Tetrahydrofolate dehydrogenase/cyclohydrolase, catalytic domain
PF02882 - Tetrahydrofolate dehydrogenase/cyclohydrolase, NAD(P)-binding domain

SCOP Domains:
51735 - NAD(P)-binding Rossmann-fold domains
53223 - Aminoacid dehydrogenase-like, N-terminal domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1ZN4 - Model


ModBase Predicted Comparative 3D Structure on P13995
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details Gene Details  
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-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000287 magnesium ion binding
GO:0003824 catalytic activity
GO:0004477 methenyltetrahydrofolate cyclohydrolase activity
GO:0004487 methylenetetrahydrofolate dehydrogenase (NAD+) activity
GO:0004488 methylenetetrahydrofolate dehydrogenase (NADP+) activity
GO:0016491 oxidoreductase activity
GO:0016787 hydrolase activity
GO:0042301 phosphate ion binding

Biological Process:
GO:0006730 one-carbon metabolic process
GO:0008152 metabolic process
GO:0046653 tetrahydrofolate metabolic process
GO:0046655 folic acid metabolic process
GO:0055114 oxidation-reduction process

Cellular Component:
GO:0005615 extracellular space
GO:0005739 mitochondrion
GO:0005759 mitochondrial matrix
GO:0005829 cytosol


-  Descriptions from all associated GenBank mRNAs
  AK300035 - Homo sapiens cDNA FLJ52745 complete cds, highly similar to Bifunctional methylenetetrahydrofolatedehydrogenase/cyclohydrolase, mitochondrial precursor.
AK313138 - Homo sapiens cDNA, FLJ93628, Homo sapiens methylene tetrahydrofolate dehydrogenase (NAD+dependent), methenyltetrahydrofolate cyclohydrolase (MTHFD2),nuclear gene encoding mitochondrial protein, mRNA.
AK222826 - Homo sapiens mRNA for methylene tetrahydrofolate dehydrogenase 2 precursor variant, clone: HEP04310.
AK223041 - Homo sapiens mRNA for methylene tetrahydrofolate dehydrogenase 2 precursor variant, clone: JTH08505.
AK302245 - Homo sapiens cDNA FLJ55007 complete cds, highly similar to Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial precursor.
AK130664 - Homo sapiens cDNA FLJ27154 fis, clone SYN00680, highly similar to BIFUNCTIONAL METHYLENETETRAHYDROFOLATE DEHYDROGENASE/CYCLOHYDROLASE, MITOCHONDRIAL PRECURSOR.
BC015062 - Homo sapiens methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase, mRNA (cDNA clone MGC:13506 IMAGE:4285669), complete cds.
BC001548 - Homo sapiens methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase, mRNA (cDNA clone MGC:5008 IMAGE:3462450), complete cds.
BC017054 - Homo sapiens methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase, mRNA (cDNA clone MGC:9350 IMAGE:3846710), complete cds.
AB529041 - Synthetic construct DNA, clone: pF1KB3488, Homo sapiens MTHFD2 gene for methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase, without stop codon, in Flexi system.
X16396 - Human mRNA for NAD-dependent methylene tetrahydrofolate dehydrogenase cyclohydrolase (EC 1.5.1.15).
KJ902157 - Synthetic construct Homo sapiens clone ccsbBroadEn_11551 MTHFD2 gene, encodes complete protein.
DQ894679 - Synthetic construct Homo sapiens clone IMAGE:100009139; FLH263687.01L; RZPDo839H10123D methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase (MTHFD2) gene, encodes complete protein.
CU677205 - Synthetic construct Homo sapiens gateway clone IMAGE:100022126 5' read MTHFD2 mRNA.
KJ902158 - Synthetic construct Homo sapiens clone ccsbBroadEn_11552 MTHFD2 gene, encodes complete protein.
JD366809 - Sequence 347833 from Patent EP1572962.
JD052036 - Sequence 33060 from Patent EP1572962.
JD177371 - Sequence 158395 from Patent EP1572962.
JD287574 - Sequence 268598 from Patent EP1572962.
JD109426 - Sequence 90450 from Patent EP1572962.
JD460480 - Sequence 441504 from Patent EP1572962.
JD114177 - Sequence 95201 from Patent EP1572962.
JD511367 - Sequence 492391 from Patent EP1572962.
JD308570 - Sequence 289594 from Patent EP1572962.
JD303712 - Sequence 284736 from Patent EP1572962.
JD549460 - Sequence 530484 from Patent EP1572962.
JD345125 - Sequence 326149 from Patent EP1572962.
JD139652 - Sequence 120676 from Patent EP1572962.
JD492494 - Sequence 473518 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  BioCyc Knowledge Library
PWY-2201-1 - folate transformations I

Reactome (by CSHL, EBI, and GO)

Protein P13995 (Reactome details) participates in the following event(s):

R-HSA-6801462 MTHFD2, D2L oxidise 5,10-methenyl-THF to 10-formyl-THF
R-HSA-6801328 MTHFD2, D2L oxidise 5,10-methylene-THF to 5,10-methenyl-THF
R-HSA-196757 Metabolism of folate and pterines
R-HSA-196849 Metabolism of water-soluble vitamins and cofactors
R-HSA-196854 Metabolism of vitamins and cofactors
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000394053.1, ENST00000394053.2, ENST00000394053.3, ENST00000394053.4, ENST00000394053.5, ENST00000394053.6, MTDC_HUMAN, NMDMC, NM_006636, P13995, Q53G90, Q53GV5, Q53S36, Q7Z650, uc318wih.1, uc318wih.2
UCSC ID: ENST00000394053.7_4
RefSeq Accession: NM_006636.4
Protein: P13995 (aka MTDC_HUMAN)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.