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Conserved domains on  [gi|78057836|gb|ABB17330|]
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methylenetetrahydrofolate reductase, partial [Homo sapiens]

Protein Classification

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 ...
 3-39 3.16e-18

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: 73.61  E-value: 3.16e-18
                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 78057836     3 FLVTQLFFEADTFFRFVKACTDMGITCPIVPGIFPIQ 39
Cdd:TIGR00677 164 FIITQLFYDVDNFLKFVNDCRAIGIDCPIVPGIMPIN 200
 
Name Accession Description Interval E-value
fadh2_euk TIGR00677
methylenetetrahydrofolate reductase, eukaryotic type; The enzyme activities ...
 3-39 3.16e-18

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: 73.61  E-value: 3.16e-18
                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 78057836     3 FLVTQLFFEADTFFRFVKACTDMGITCPIVPGIFPIQ 39
Cdd:TIGR00677 164 FIITQLFYDVDNFLKFVNDCRAIGIDCPIVPGIMPIN 200
MTHFR pfam02219
Methylenetetrahydrofolate reductase; This family includes the 5,10-methylenetetrahydrofolate ...
 3-39 2.18e-16

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: 68.88  E-value: 2.18e-16
                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 78057836     3 FLVTQLFFEADTFFRFVKACTDMGITCPIVPGIFPIQ 39
Cdd:pfam02219 175 FIITQLFFDVDNFLRFVDRVRAAGIDIPIIPGIMPIT 211
MetF COG0685
5,10-methylenetetrahydrofolate reductase [Amino acid transport and metabolism];
3-38 2.36e-16

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


Pssm-ID: 440449  Cd Length: 284  Bit Score: 68.66  E-value: 2.36e-16
                        10        20        30
                ....*....|....*....|....*....|....*.
gi 78057836   3 FLVTQLFFEADTFFRFVKACTDMGITCPIVPGIFPI 38
Cdd:COG0685 171 FAITQLFFDNDAYFRFVDRARAAGIDVPIIPGIMPI 206
PLN02540 PLN02540
methylenetetrahydrofolate reductase
 3-39 1.01e-15

methylenetetrahydrofolate reductase


Pssm-ID: 215296  Cd Length: 565  Bit Score: 67.45  E-value: 1.01e-15
                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 78057836    3 FLVTQLFFEADTFFRFVKACTDMGITCPIVPGIFPIQ 39
Cdd:PLN02540 172 LIITQLFYDTDIFLKFVNDCRQIGITCPIVPGIMPIN 208
MTHFR cd00537
Methylenetetrahydrofolate reductase (MTHFR). 5,10-Methylenetetrahydrofolate is reduced to ...
 3-39 1.89e-15

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: 66.10  E-value: 1.89e-15
                        10        20        30
                ....*....|....*....|....*....|....*..
gi 78057836   3 FLVTQLFFEADTFFRFVKACTDMGITCPIVPGIFPIQ 39
Cdd:cd00537 163 FIITQLFFDNDAFLRFVDRCRAAGITVPIIPGIMPLT 199
 
Name Accession Description Interval E-value
fadh2_euk TIGR00677
methylenetetrahydrofolate reductase, eukaryotic type; The enzyme activities ...
 3-39 3.16e-18

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: 73.61  E-value: 3.16e-18
                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 78057836     3 FLVTQLFFEADTFFRFVKACTDMGITCPIVPGIFPIQ 39
Cdd:TIGR00677 164 FIITQLFYDVDNFLKFVNDCRAIGIDCPIVPGIMPIN 200
MTHFR pfam02219
Methylenetetrahydrofolate reductase; This family includes the 5,10-methylenetetrahydrofolate ...
 3-39 2.18e-16

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: 68.88  E-value: 2.18e-16
                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 78057836     3 FLVTQLFFEADTFFRFVKACTDMGITCPIVPGIFPIQ 39
Cdd:pfam02219 175 FIITQLFFDVDNFLRFVDRVRAAGIDIPIIPGIMPIT 211
MetF COG0685
5,10-methylenetetrahydrofolate reductase [Amino acid transport and metabolism];
3-38 2.36e-16

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


Pssm-ID: 440449  Cd Length: 284  Bit Score: 68.66  E-value: 2.36e-16
                        10        20        30
                ....*....|....*....|....*....|....*.
gi 78057836   3 FLVTQLFFEADTFFRFVKACTDMGITCPIVPGIFPI 38
Cdd:COG0685 171 FAITQLFFDNDAYFRFVDRARAAGIDVPIIPGIMPI 206
PLN02540 PLN02540
methylenetetrahydrofolate reductase
 3-39 1.01e-15

methylenetetrahydrofolate reductase


Pssm-ID: 215296  Cd Length: 565  Bit Score: 67.45  E-value: 1.01e-15
                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 78057836    3 FLVTQLFFEADTFFRFVKACTDMGITCPIVPGIFPIQ 39
Cdd:PLN02540 172 LIITQLFYDTDIFLKFVNDCRQIGITCPIVPGIMPIN 208
MTHFR cd00537
Methylenetetrahydrofolate reductase (MTHFR). 5,10-Methylenetetrahydrofolate is reduced to ...
 3-39 1.89e-15

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: 66.10  E-value: 1.89e-15
                        10        20        30
                ....*....|....*....|....*....|....*..
gi 78057836   3 FLVTQLFFEADTFFRFVKACTDMGITCPIVPGIFPIQ 39
Cdd:cd00537 163 FIITQLFFDNDAFLRFVDRCRAAGITVPIIPGIMPLT 199
fadh2 TIGR00676
5,10-methylenetetrahydrofolate reductase, prokaryotic form; The enzyme activities ...
 3-39 3.37e-14

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: 62.65  E-value: 3.37e-14
                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 78057836     3 FLVTQLFFEADTFFRFVKACTDMGITCPIVPGIFPIQ 39
Cdd:TIGR00676 160 YAITQLFFDNDDYYRFVDRCRAAGIDVPIIPGIMPIT 196
 
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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