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Conserved domains on  [gi|1065201870|gb|AOP17739|]
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methylenetetrahydrofolate reductase, partial [Homo sapiens]

Protein Classification

methylenetetrahydrofolate reductase( domain architecture ID 1049)

methylenetetrahydrofolate reductase catalyzes NADH-dependent reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate using FAD as a cofactor

CATH:  3.20.20.220
EC:  1.5.1.20
Gene Ontology:  GO:0004489|GO:0009396|GO:0006555|GO:0050660
SCOP:  4003348

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
MTHFR super family cl00246
Methylenetetrahydrofolate reductase (MTHFR). 5,10-Methylenetetrahydrofolate is reduced to ...
 1-64 1.63e-37

Methylenetetrahydrofolate reductase (MTHFR). 5,10-Methylenetetrahydrofolate is reduced to 5-methyltetrahydrofolate by methylenetetrahydrofolate reductase, a cytoplasmic, NAD(P)-dependent enzyme. 5-methyltetrahydrofolate is utilized by methionine synthase to convert homocysteine to methionine. The enzymatic mechanism is a ping-pong bi-bi mechanism, in which NAD(P)+ release precedes the binding of methylenetetrahydrofolate and the acceptor is free FAD. The family includes the 5,10-methylenetetrahydrofolate reductase EC:1.7.99.5 from prokaryotes and methylenetetrahydrofolate reductase EC: 1.5.1.20 from eukaryotes. 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.


The actual alignment was detected with superfamily member TIGR00677:

Pssm-ID: 444783  Cd Length: 281  Bit Score: 125.23  E-value: 1.63e-37
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1065201870   1 YPKGHPEAGSFEADLKHLKEKVSAGVDFIITQLFFEADTFFRFVKACTDMGITCPIVPGIFPIQ 64
Cdd:TIGR00677 137 YPEGHPEAESVELDLKYLKEKVDAGADFIITQLFYDVDNFLKFVNDCRAIGIDCPIVPGIMPIN 200
 
Name Accession Description Interval E-value
fadh2_euk TIGR00677
methylenetetrahydrofolate reductase, eukaryotic type; The enzyme activities ...
 1-64 1.63e-37

methylenetetrahydrofolate reductase, eukaryotic type; The enzyme activities methylenetetrahydrofolate reductase (EC 1.5.1.20) and 5,10-methylenetetrahydrofolate reductase (FADH) (EC 1.7.99.5) differ in that 1.5.1.20 (assigned in many eukaryotes) is defined to use NADP+ as an acceptor, while 1.7.99.5 (assigned in many bacteria) is flexible with respect to the acceptor; both convert 5-methyltetrahydrofolate to 5,10-methylenetetrahydrofolate. From a larger set of proteins assigned as 1.5.1.20 and 1.7.99.5, this model describes the subset of proteins found in eukaryotes and designated 1.5.1.20. This protein is an FAD-containing flavoprotein. [Biosynthesis of cofactors, prosthetic groups, and carriers, Folic acid]


Pssm-ID: 129760  Cd Length: 281  Bit Score: 125.23  E-value: 1.63e-37
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1065201870   1 YPKGHPEAGSFEADLKHLKEKVSAGVDFIITQLFFEADTFFRFVKACTDMGITCPIVPGIFPIQ 64
Cdd:TIGR00677 137 YPEGHPEAESVELDLKYLKEKVDAGADFIITQLFYDVDNFLKFVNDCRAIGIDCPIVPGIMPIN 200
MTHFR pfam02219
Methylenetetrahydrofolate reductase; This family includes the 5,10-methylenetetrahydrofolate ...
 1-64 1.41e-34

Methylenetetrahydrofolate reductase; This family includes the 5,10-methylenetetrahydrofolate reductase EC:1.7.99.5 from bacteria and methylenetetrahydrofolate reductase EC: 1.5.1.20 from eukaryotes. The structure for this domain is known to be a TIM barrel.


Pssm-ID: 396687  Cd Length: 287  Bit Score: 117.80  E-value: 1.41e-34
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1065201870   1 YPKGHPEAGSFEADLKHLKEKVSAGVDFIITQLFFEADTFFRFVKACTDMGITCPIVPGIFPIQ 64
Cdd:pfam02219 148 YPEGHPEAKSWQADLKYLKEKVDAGADFIITQLFFDVDNFLRFVDRVRAAGIDIPIIPGIMPIT 211
MetF COG0685
5,10-methylenetetrahydrofolate reductase [Amino acid transport and metabolism];
1-63 1.08e-33

5,10-methylenetetrahydrofolate reductase [Amino acid transport and metabolism];


Pssm-ID: 440449  Cd Length: 284  Bit Score: 115.65  E-value: 1.08e-33
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1065201870   1 YPKGHPEAGSFEADLKHLKEKVSAGVDFIITQLFFEADTFFRFVKACTDMGITCPIVPGIFPI 63
Cdd:COG0685   144 YPEKHPEAPSLEADLDRLKKKVDAGADFAITQLFFDNDAYFRFVDRARAAGIDVPIIPGIMPI 206
MTHFR cd00537
Methylenetetrahydrofolate reductase (MTHFR). 5,10-Methylenetetrahydrofolate is reduced to ...
 1-64 4.08e-32

Methylenetetrahydrofolate reductase (MTHFR). 5,10-Methylenetetrahydrofolate is reduced to 5-methyltetrahydrofolate by methylenetetrahydrofolate reductase, a cytoplasmic, NAD(P)-dependent enzyme. 5-methyltetrahydrofolate is utilized by methionine synthase to convert homocysteine to methionine. The enzymatic mechanism is a ping-pong bi-bi mechanism, in which NAD(P)+ release precedes the binding of methylenetetrahydrofolate and the acceptor is free FAD. The family includes the 5,10-methylenetetrahydrofolate reductase EC:1.7.99.5 from prokaryotes and methylenetetrahydrofolate reductase EC: 1.5.1.20 from eukaryotes. 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.


Pssm-ID: 238299  Cd Length: 274  Bit Score: 111.17  E-value: 4.08e-32
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1065201870   1 YPKGHPEAGSFEADLKHLKEKVSAGVDFIITQLFFEADTFFRFVKACTDMGITCPIVPGIFPIQ 64
Cdd:cd00537   136 YPEGHPEAPSLEEDIKRLKRKVDAGADFIITQLFFDNDAFLRFVDRCRAAGITVPIIPGIMPLT 199
PLN02540 PLN02540
methylenetetrahydrofolate reductase
 1-64 1.01e-27

methylenetetrahydrofolate reductase


Pssm-ID: 215296  Cd Length: 565  Bit Score: 102.89  E-value: 1.01e-27
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1065201870   1 YPKGHPEA---------GSFEADLKHLKEKVSAGVDFIITQLFFEADTFFRFVKACTDMGITCPIVPGIFPIQ 64
Cdd:PLN02540  136 YPEAHPDViggdglatpEAYQKDLAYLKEKVDAGADLIITQLFYDTDIFLKFVNDCRQIGITCPIVPGIMPIN 208
 
Name Accession Description Interval E-value
fadh2_euk TIGR00677
methylenetetrahydrofolate reductase, eukaryotic type; The enzyme activities ...
 1-64 1.63e-37

methylenetetrahydrofolate reductase, eukaryotic type; The enzyme activities methylenetetrahydrofolate reductase (EC 1.5.1.20) and 5,10-methylenetetrahydrofolate reductase (FADH) (EC 1.7.99.5) differ in that 1.5.1.20 (assigned in many eukaryotes) is defined to use NADP+ as an acceptor, while 1.7.99.5 (assigned in many bacteria) is flexible with respect to the acceptor; both convert 5-methyltetrahydrofolate to 5,10-methylenetetrahydrofolate. From a larger set of proteins assigned as 1.5.1.20 and 1.7.99.5, this model describes the subset of proteins found in eukaryotes and designated 1.5.1.20. This protein is an FAD-containing flavoprotein. [Biosynthesis of cofactors, prosthetic groups, and carriers, Folic acid]


Pssm-ID: 129760  Cd Length: 281  Bit Score: 125.23  E-value: 1.63e-37
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1065201870   1 YPKGHPEAGSFEADLKHLKEKVSAGVDFIITQLFFEADTFFRFVKACTDMGITCPIVPGIFPIQ 64
Cdd:TIGR00677 137 YPEGHPEAESVELDLKYLKEKVDAGADFIITQLFYDVDNFLKFVNDCRAIGIDCPIVPGIMPIN 200
MTHFR pfam02219
Methylenetetrahydrofolate reductase; This family includes the 5,10-methylenetetrahydrofolate ...
 1-64 1.41e-34

Methylenetetrahydrofolate reductase; This family includes the 5,10-methylenetetrahydrofolate reductase EC:1.7.99.5 from bacteria and methylenetetrahydrofolate reductase EC: 1.5.1.20 from eukaryotes. The structure for this domain is known to be a TIM barrel.


Pssm-ID: 396687  Cd Length: 287  Bit Score: 117.80  E-value: 1.41e-34
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1065201870   1 YPKGHPEAGSFEADLKHLKEKVSAGVDFIITQLFFEADTFFRFVKACTDMGITCPIVPGIFPIQ 64
Cdd:pfam02219 148 YPEGHPEAKSWQADLKYLKEKVDAGADFIITQLFFDVDNFLRFVDRVRAAGIDIPIIPGIMPIT 211
MetF COG0685
5,10-methylenetetrahydrofolate reductase [Amino acid transport and metabolism];
1-63 1.08e-33

5,10-methylenetetrahydrofolate reductase [Amino acid transport and metabolism];


Pssm-ID: 440449  Cd Length: 284  Bit Score: 115.65  E-value: 1.08e-33
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1065201870   1 YPKGHPEAGSFEADLKHLKEKVSAGVDFIITQLFFEADTFFRFVKACTDMGITCPIVPGIFPI 63
Cdd:COG0685   144 YPEKHPEAPSLEADLDRLKKKVDAGADFAITQLFFDNDAYFRFVDRARAAGIDVPIIPGIMPI 206
MTHFR cd00537
Methylenetetrahydrofolate reductase (MTHFR). 5,10-Methylenetetrahydrofolate is reduced to ...
 1-64 4.08e-32

Methylenetetrahydrofolate reductase (MTHFR). 5,10-Methylenetetrahydrofolate is reduced to 5-methyltetrahydrofolate by methylenetetrahydrofolate reductase, a cytoplasmic, NAD(P)-dependent enzyme. 5-methyltetrahydrofolate is utilized by methionine synthase to convert homocysteine to methionine. The enzymatic mechanism is a ping-pong bi-bi mechanism, in which NAD(P)+ release precedes the binding of methylenetetrahydrofolate and the acceptor is free FAD. The family includes the 5,10-methylenetetrahydrofolate reductase EC:1.7.99.5 from prokaryotes and methylenetetrahydrofolate reductase EC: 1.5.1.20 from eukaryotes. 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.


Pssm-ID: 238299  Cd Length: 274  Bit Score: 111.17  E-value: 4.08e-32
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1065201870   1 YPKGHPEAGSFEADLKHLKEKVSAGVDFIITQLFFEADTFFRFVKACTDMGITCPIVPGIFPIQ 64
Cdd:cd00537   136 YPEGHPEAPSLEEDIKRLKRKVDAGADFIITQLFFDNDAFLRFVDRCRAAGITVPIIPGIMPLT 199
fadh2 TIGR00676
5,10-methylenetetrahydrofolate reductase, prokaryotic form; The enzyme activities ...
 1-64 3.59e-30

5,10-methylenetetrahydrofolate reductase, prokaryotic form; The enzyme activities methylenetetrahydrofolate reductase (EC 1.5.1.20) and 5,10-methylenetetrahydrofolate reductase (FADH) (EC 1.7.99.5) differ in that 1.5.1.20 (assigned in many eukaryotes) is defined to use NADP+ as an acceptor, while 1.7.99.5 (assigned in many bacteria) is flexible with respect to the acceptor; both convert 5-methyltetrahydrofolate to 5,10-methylenetetrahydrofolate. From a larger set of proteins assigned as 1.5.1.20 and 1.7.99.5, this model describes the subset of proteins found in bacteria, and currently designated 1.7.99.5. This protein is an FAD-containing flavoprotein. [Amino acid biosynthesis, Aspartate family]


Pssm-ID: 273212  Cd Length: 272  Bit Score: 106.18  E-value: 3.59e-30
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1065201870   1 YPKGHPEAGSFEADLKHLKEKVSAGVDFIITQLFFEADTFFRFVKACTDMGITCPIVPGIFPIQ 64
Cdd:TIGR00676 133 YPEKHPEAPNLEEDIENLKRKVDAGADYAITQLFFDNDDYYRFVDRCRAAGIDVPIIPGIMPIT 196
PLN02540 PLN02540
methylenetetrahydrofolate reductase
 1-64 1.01e-27

methylenetetrahydrofolate reductase


Pssm-ID: 215296  Cd Length: 565  Bit Score: 102.89  E-value: 1.01e-27
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1065201870   1 YPKGHPEA---------GSFEADLKHLKEKVSAGVDFIITQLFFEADTFFRFVKACTDMGITCPIVPGIFPIQ 64
Cdd:PLN02540  136 YPEAHPDViggdglatpEAYQKDLAYLKEKVDAGADLIITQLFYDTDIFLKFVNDCRQIGITCPIVPGIMPIN 208
metF PRK09432
methylenetetrahydrofolate reductase;
1-63 2.44e-20

methylenetetrahydrofolate reductase;


Pssm-ID: 181852  Cd Length: 296  Bit Score: 80.84  E-value: 2.44e-20
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1065201870   1 YPKGHPEAGSFEADLKHLKEKVSAGVDFIITQLFFEADTFFRFVKACTDMGITCPIVPGIFPI 63
Cdd:PRK09432  152 YPEVHPEAKSAQADLINLKRKVDAGANRAITQFFFDVESYLRFRDRCVSAGIDVEIVPGILPV 214
PRK08645 PRK08645
bifunctional homocysteine S-methyltransferase/5,10-methylenetetrahydrofolate reductase protein; ...
 11-64 5.47e-08

bifunctional homocysteine S-methyltransferase/5,10-methylenetetrahydrofolate reductase protein; Reviewed


Pssm-ID: 236321 [Multi-domain]  Cd Length: 612  Bit Score: 47.15  E-value: 5.47e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1065201870  11 FEADLKHLKEKVSAGVDFIITQLFFEADTFFRFVKACTDMGItcPIVPGIFPIQ 64
Cdd:PRK08645  477 LDKEVKRLEKKIEAGADYFITQPVYDEELIEELLEATKHLGV--PIFIGIMPLV 528
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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