Summary: Methylenetetrahydrofolate reductase
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Methylenetetrahydrofolate reductase Provide feedback
This family includes the 5,10-methylenetetrahydrofolate reductase EC:22.214.171.124 from bacteria and methylenetetrahydrofolate reductase EC: 126.96.36.199 from eukaryotes. The structure for this domain is known  to be a TIM barrel.
Guenther BD, Sheppard CA, Tran P, Rozen R, Matthews RG, Ludwig ML; , Nat Struct Biol 1999;6:359-365.: The structure and properties of methylenetetrahydrofolate reductase from Escherichia coli suggest how folate ameliorates human hyperhomocysteinemia [see comments] PUBMED:10201405 EPMC:10201405
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR003171This family includes the 5,10-methylenetetrahydrofolate reductase from bacteria and methylenetetrahydrofolate reductase from eukaryotes (EC). The bacterial enzyme is a homotetramer and NADH is the preferred reductant while the eukaryotic enzyme is a homodimer and NADPH is the preferred reductant. In humans, there are several clinically significant mutations in MTHFR that result in hyperhomocysteinemia, which is a risk factor for the development of cardiovascular disease [PUBMED:10201405].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||methylenetetrahydrofolate reductase (NAD(P)H) activity (GO:0004489)|
|Biological process||methionine metabolic process (GO:0006555)|
|oxidation-reduction process (GO:0055114)|
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The members of this clan adopt a TIM barrel fold, which is reminiscent of flavin mononucleotide binding proteins, rather than one similar to other flavin adenine dinucleotide binding domains. However, the way the FAD cofactor binds in quite different compared to the binding of FMN in the TIM-barrel structures .
The clan contains the following 2 members:MTHFR Pro_dh
We make a range of alignments for each Pfam-A family:
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Curation and family details
|Seed source:||Pfam-B_2407 (release 5.2)|
|Author:||Bateman A, Mian N|
|Number in seed:||12|
|Number in full:||5066|
|Average length of the domain:||273.40 aa|
|Average identity of full alignment:||28 %|
|Average coverage of the sequence by the domain:||70.04 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||16|
|Download:||download the raw HMM for this family|
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There is 1 interaction for this family. More...
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the MTHFR domain has been found. There are 40 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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