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Conserved domains on  [gi|27808705|ref|NP_011390|]
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methylenetetrahydrofolate reductase (NAD(P)H) MET13 [Saccharomyces cerevisiae S288C]

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
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 ...
19-586 0e+00

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 PLN02540:

Pssm-ID: 444783  Cd Length: 565  Bit Score: 634.85  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705   19 YSFEYFVPKTTQGVQNLYDRMDRMYeASLPQFIDITWNAGGGRLShLSTDLVATAQSVLGLETCMHLTCTNMPISMIDDA 98
Cdd:PLN02540   1 FSFEFFPPKTEEGVDNLFERMDRMV-AHGPLFCDITWGAGGSTAD-LTLDIANRMQNMICVETMMHLTCTNMPVEKIDHA 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705   99 LENAYHSGCQNILALRGDPPRDAENWTPVEGGFQYAKDLIKYIKSKYGDHFAIGVAGYPECHP-------ELPNKDVKLD 171
Cdd:PLN02540  79 LETIKSNGIQNILALRGDPPHGQDKFVQVEGGFACALDLVKHIRSKYGDYFGITVAGYPEAHPdviggdgLATPEAYQKD 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705  172 LEYLKQKIDAGGDFIITQMFYDVDNFINWCSQVRAAGMDVPIIPGIMPITTYAAFLRRAQWGQISIPQHFSSRLDPIKDD 251
Cdd:PLN02540 159 LAYLKEKVDAGADLIITQLFYDTDIFLKFVNDCRQIGITCPIVPGIMPINNYKGFLRMTGFCKTKIPAEITAALEPIKDN 238
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705  252 DELVRDIGTNLIVEMCQKLLDSGyVSHLHIYTMNLEKAPLMILERLNiLPTESEFNahplAVLPWRKSLNPKRKNEEVRP 331
Cdd:PLN02540 239 DEAVKAYGIHLGTEMCKKILAHG-IKGLHLYTLNLEKSALAILMNLG-LIDESKVS----RPLPWRPPTNVFRTKEDVRP 312
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705  332 IFWKRRPYSYVARTSQWavDEFPNGRFGDSSSPAFGDLdlcgSD--LIRQSA--NKCLELW-STPTSINDVAFLVINYLN 406
Cdd:PLN02540 313 IFWANRPKSYISRTTGW--DQYPHGRWGDSRSPAYGAL----SDhqFMRPRArdKKLQAEWgVPLKSVEDVYEVFAKYCL 386
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705  407 GNLKCLPWSDIP-INDEINPIKAHLIELNQHSIITINSQPQVNGIRSNDKIHGWGPKDGYVYQKQYLEFMLPKTKLPKLI 485
Cdd:PLN02540 387 GKLKSSPWSELDgLQPETKIINEQLVKINRKGFLTINSQPAVNGEKSDSPSVGWGGPGGYVYQKAYLEFFCSPEKLDALV 466
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705  486 DTLKNNEFLTYFAIDSQGDLLSNHPDNSkSNAVTWGIFPGREILQPTIVEKISFLAWKEEFYHI-LNEWkLNMNKYDKPh 564
Cdd:PLN02540 467 EKCKAFPSLTYIAVNKAGEWISNVGPGD-VNAVTWGVFPAKEIIQPTVVDPASFMVWKDEAFELwSSEW-ANLYPEGDP- 543
                        570       580
                 ....*....|....*....|..
gi 27808705  565 SAQFIQSLIDDYCLVNIVDNDY 586
Cdd:PLN02540 544 SRKLLEEIKDSYYLVSLVDNDY 565
 
Name Accession Description Interval E-value
PLN02540 PLN02540
methylenetetrahydrofolate reductase
19-586 0e+00

methylenetetrahydrofolate reductase


Pssm-ID: 215296  Cd Length: 565  Bit Score: 634.85  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705   19 YSFEYFVPKTTQGVQNLYDRMDRMYeASLPQFIDITWNAGGGRLShLSTDLVATAQSVLGLETCMHLTCTNMPISMIDDA 98
Cdd:PLN02540   1 FSFEFFPPKTEEGVDNLFERMDRMV-AHGPLFCDITWGAGGSTAD-LTLDIANRMQNMICVETMMHLTCTNMPVEKIDHA 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705   99 LENAYHSGCQNILALRGDPPRDAENWTPVEGGFQYAKDLIKYIKSKYGDHFAIGVAGYPECHP-------ELPNKDVKLD 171
Cdd:PLN02540  79 LETIKSNGIQNILALRGDPPHGQDKFVQVEGGFACALDLVKHIRSKYGDYFGITVAGYPEAHPdviggdgLATPEAYQKD 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705  172 LEYLKQKIDAGGDFIITQMFYDVDNFINWCSQVRAAGMDVPIIPGIMPITTYAAFLRRAQWGQISIPQHFSSRLDPIKDD 251
Cdd:PLN02540 159 LAYLKEKVDAGADLIITQLFYDTDIFLKFVNDCRQIGITCPIVPGIMPINNYKGFLRMTGFCKTKIPAEITAALEPIKDN 238
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705  252 DELVRDIGTNLIVEMCQKLLDSGyVSHLHIYTMNLEKAPLMILERLNiLPTESEFNahplAVLPWRKSLNPKRKNEEVRP 331
Cdd:PLN02540 239 DEAVKAYGIHLGTEMCKKILAHG-IKGLHLYTLNLEKSALAILMNLG-LIDESKVS----RPLPWRPPTNVFRTKEDVRP 312
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705  332 IFWKRRPYSYVARTSQWavDEFPNGRFGDSSSPAFGDLdlcgSD--LIRQSA--NKCLELW-STPTSINDVAFLVINYLN 406
Cdd:PLN02540 313 IFWANRPKSYISRTTGW--DQYPHGRWGDSRSPAYGAL----SDhqFMRPRArdKKLQAEWgVPLKSVEDVYEVFAKYCL 386
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705  407 GNLKCLPWSDIP-INDEINPIKAHLIELNQHSIITINSQPQVNGIRSNDKIHGWGPKDGYVYQKQYLEFMLPKTKLPKLI 485
Cdd:PLN02540 387 GKLKSSPWSELDgLQPETKIINEQLVKINRKGFLTINSQPAVNGEKSDSPSVGWGGPGGYVYQKAYLEFFCSPEKLDALV 466
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705  486 DTLKNNEFLTYFAIDSQGDLLSNHPDNSkSNAVTWGIFPGREILQPTIVEKISFLAWKEEFYHI-LNEWkLNMNKYDKPh 564
Cdd:PLN02540 467 EKCKAFPSLTYIAVNKAGEWISNVGPGD-VNAVTWGVFPAKEIIQPTVVDPASFMVWKDEAFELwSSEW-ANLYPEGDP- 543
                        570       580
                 ....*....|....*....|..
gi 27808705  565 SAQFIQSLIDDYCLVNIVDNDY 586
Cdd:PLN02540 544 SRKLLEEIKDSYYLVSLVDNDY 565
fadh2_euk TIGR00677
methylenetetrahydrofolate reductase, eukaryotic type; The enzyme activities ...
18-303 0e+00

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: 517.75  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705    18 TYSFEYFVPKTTQGVQNLYDRMDRMyEASLPQFIDITWNAGGGRLSHLSTDLVaTAQSVLGLETCMHLTCTNMPISMIDD 97
Cdd:TIGR00677   1 TFSFEFFPPKTEEGVQNLYERMDRM-VASGPLFIDITWGAGGTTAELTLTIAS-RAQNVVGVETCMHLTCTNMPIEMIDD 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705    98 ALENAYHSGCQNILALRGDPPRDAENWTPVEGGFQYAKDLIKYIKSKYGDHFAIGVAGYPECHPELPNkdVKLDLEYLKQ 177
Cdd:TIGR00677  79 ALERAYSNGIQNILALRGDPPHIGDDWTEVEGGFQYAVDLVKYIRSKYGDYFCIGVAGYPEGHPEAES--VELDLKYLKE 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705   178 KIDAGGDFIITQMFYDVDNFINWCSQVRAAGMDVPIIPGIMPITTYAAFLRRAQWGQISIPQHFSSRLDPIKDDDELVRD 257
Cdd:TIGR00677 157 KVDAGADFIITQLFYDVDNFLKFVNDCRAIGIDCPIVPGIMPINNYASFLRRAKWSKTKIPQEIMSRLEPIKDDDEAVRD 236
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 27808705   258 IGTNLIVEMCQKLLDSGyVSHLHIYTMNLEKAPLMILERLNILPTE 303
Cdd:TIGR00677 237 YGIELIVEMCQKLLASG-IKGLHFYTLNLEKAALMILERLGLLDES 281
MTHFR pfam02219
Methylenetetrahydrofolate reductase; This family includes the 5,10-methylenetetrahydrofolate ...
6-298 8.54e-166

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: 473.73  E-value: 8.54e-166
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705     6 KLEQHRQTsGKPTYSFEYFVPKTTQGVQNLYDRMDRMYEASlPQFIDITWNAGGGRLsHLSTDLVATAQSVLGLETCMHL 85
Cdd:pfam02219   1 KIRQILAE-GKFFISFEFFPPKTENGERNLWERIDRMSAVG-PLFVSVTWGAGGSTR-DRTSSIASVIQQDTGLEACMHL 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705    86 TCTNMPISMIDDALENAYHSGCQNILALRGDPPRDAENWTPVEGGFQYAKDLIKYIKSKYGDHFAIGVAGYPECHPELpn 165
Cdd:pfam02219  78 TCTDMSKEELDDALEDAKALGIRNILALRGDPPKGTDDWERPEGGFKYALDLVRLIRQEYGDYFDIGVAAYPEGHPEA-- 155
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705   166 KDVKLDLEYLKQKIDAGGDFIITQMFYDVDNFINWCSQVRAAGMDVPIIPGIMPITTYAAFLRRAQWGQISIPQHFSSRL 245
Cdd:pfam02219 156 KSWQADLKYLKEKVDAGADFIITQLFFDVDNFLRFVDRVRAAGIDIPIIPGIMPITSYKSLKRIAKLSGVSIPQELIDRL 235
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 27808705   246 DPIKDDDELVRDIGTNLIVEMCQKLLDSGyVSHLHIYTMNLEKAPLMILERLN 298
Cdd:pfam02219 236 EPIKDDDEAVKSIGIELAVEMCKKLLAEG-VPGLHFYTLNREEATLEILENLG 287
MTHFR cd00537
Methylenetetrahydrofolate reductase (MTHFR). 5,10-Methylenetetrahydrofolate is reduced to ...
19-297 1.17e-120

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: 358.08  E-value: 1.17e-120
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705  19 YSFEYFVPKTTQGVQNLYDRMDRMYEASlPQFIDITWNAGGGRLsHLSTDLVATAQSVLGLETCMHLTCTNMPISMIDDA 98
Cdd:cd00537   1 ISFEFFPPKTADGEENLEAAADLLGALD-PDFVSVTDGAGGSTR-DMTLLAAARILQEGGIEPIPHLTCRDRNRIELQSI 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705  99 LENAYHSGCQNILALRGDPPRDAENWTPVEGGFQYAKDLIKYIKSKYGDHFAIGVAGYPECHPELPNKDVklDLEYLKQK 178
Cdd:cd00537  79 LLGAHALGIRNILALRGDPPKGGDQPGAKPVGFVYAVDLVELIRKENGGGFSIGVAAYPEGHPEAPSLEE--DIKRLKRK 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705 179 IDAGGDFIITQMFYDVDNFINWCSQVRAAGMDVPIIPGIMPITTYAAFLRRAQWGQISIPQHFSSRLDPIKDDDELVRDI 258
Cdd:cd00537 157 VDAGADFIITQLFFDNDAFLRFVDRCRAAGITVPIIPGIMPLTSYKQAKRFAKLCGVEIPDWLLERLEKLKDDAEAVRAE 236
                       250       260       270
                ....*....|....*....|....*....|....*....
gi 27808705 259 GTNLIVEMCQKLLDSGyVSHLHIYTMNLEKAPLMILERL 297
Cdd:cd00537 237 GIEIAAELCDELLEHG-VPGIHFYTLNREEATAEILENL 274
MetF COG0685
5,10-methylenetetrahydrofolate reductase [Amino acid transport and metabolism];
1-300 4.74e-97

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


Pssm-ID: 440449  Cd Length: 284  Bit Score: 297.85  E-value: 4.74e-97
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705   1 MKITEKLEQhrqtsGKPTYSFEYFVPKTTQGVQNLYDRMDRMYEASlPQFIDITWNAGGGrlSHLST-DLVATAQSVLGL 79
Cdd:COG0685   1 MKLEELLKA-----GKPVVSFEFFPPKTAEGEEKLWETAEELAPLD-PDFVSVTYGAGGS--TRDRTlAIAARIQQETGL 72
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705  80 ETCMHLTCTNMPISMIDDALENAYHSGCQNILALRGDPPRDAenwtPVEGGFQYAKDLIKYIKSKYGDhFAIGVAGYPEC 159
Cdd:COG0685  73 EPVAHLTCVGRNREELESILLGLAALGIRNILALRGDPPKGD----GHPGGFLYASELVALIREMNGD-FCIGVAAYPEK 147
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705 160 HPELPNKDVklDLEYLKQKIDAGGDFIITQMFYDVDNFINWCSQVRAAGMDVPIIPGIMPITTYAAfLRR--AQWGqISI 237
Cdd:COG0685 148 HPEAPSLEA--DLDRLKKKVDAGADFAITQLFFDNDAYFRFVDRARAAGIDVPIIPGIMPITSFKQ-LARfaELCG-AEI 223
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 27808705 238 PQHFSSRLDPIKDDDElVRDIGTNLIVEMCQKLLDSGyVSHLHIYTMNLEKAPLMILERLNIL 300
Cdd:COG0685 224 PDWLLKRLEKAGDDEA-VRAVGIEIATEQCEELLAEG-VPGLHFYTLNRAEATLEILERLGLL 284
 
Name Accession Description Interval E-value
PLN02540 PLN02540
methylenetetrahydrofolate reductase
19-586 0e+00

methylenetetrahydrofolate reductase


Pssm-ID: 215296  Cd Length: 565  Bit Score: 634.85  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705   19 YSFEYFVPKTTQGVQNLYDRMDRMYeASLPQFIDITWNAGGGRLShLSTDLVATAQSVLGLETCMHLTCTNMPISMIDDA 98
Cdd:PLN02540   1 FSFEFFPPKTEEGVDNLFERMDRMV-AHGPLFCDITWGAGGSTAD-LTLDIANRMQNMICVETMMHLTCTNMPVEKIDHA 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705   99 LENAYHSGCQNILALRGDPPRDAENWTPVEGGFQYAKDLIKYIKSKYGDHFAIGVAGYPECHP-------ELPNKDVKLD 171
Cdd:PLN02540  79 LETIKSNGIQNILALRGDPPHGQDKFVQVEGGFACALDLVKHIRSKYGDYFGITVAGYPEAHPdviggdgLATPEAYQKD 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705  172 LEYLKQKIDAGGDFIITQMFYDVDNFINWCSQVRAAGMDVPIIPGIMPITTYAAFLRRAQWGQISIPQHFSSRLDPIKDD 251
Cdd:PLN02540 159 LAYLKEKVDAGADLIITQLFYDTDIFLKFVNDCRQIGITCPIVPGIMPINNYKGFLRMTGFCKTKIPAEITAALEPIKDN 238
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705  252 DELVRDIGTNLIVEMCQKLLDSGyVSHLHIYTMNLEKAPLMILERLNiLPTESEFNahplAVLPWRKSLNPKRKNEEVRP 331
Cdd:PLN02540 239 DEAVKAYGIHLGTEMCKKILAHG-IKGLHLYTLNLEKSALAILMNLG-LIDESKVS----RPLPWRPPTNVFRTKEDVRP 312
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705  332 IFWKRRPYSYVARTSQWavDEFPNGRFGDSSSPAFGDLdlcgSD--LIRQSA--NKCLELW-STPTSINDVAFLVINYLN 406
Cdd:PLN02540 313 IFWANRPKSYISRTTGW--DQYPHGRWGDSRSPAYGAL----SDhqFMRPRArdKKLQAEWgVPLKSVEDVYEVFAKYCL 386
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705  407 GNLKCLPWSDIP-INDEINPIKAHLIELNQHSIITINSQPQVNGIRSNDKIHGWGPKDGYVYQKQYLEFMLPKTKLPKLI 485
Cdd:PLN02540 387 GKLKSSPWSELDgLQPETKIINEQLVKINRKGFLTINSQPAVNGEKSDSPSVGWGGPGGYVYQKAYLEFFCSPEKLDALV 466
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705  486 DTLKNNEFLTYFAIDSQGDLLSNHPDNSkSNAVTWGIFPGREILQPTIVEKISFLAWKEEFYHI-LNEWkLNMNKYDKPh 564
Cdd:PLN02540 467 EKCKAFPSLTYIAVNKAGEWISNVGPGD-VNAVTWGVFPAKEIIQPTVVDPASFMVWKDEAFELwSSEW-ANLYPEGDP- 543
                        570       580
                 ....*....|....*....|..
gi 27808705  565 SAQFIQSLIDDYCLVNIVDNDY 586
Cdd:PLN02540 544 SRKLLEEIKDSYYLVSLVDNDY 565
fadh2_euk TIGR00677
methylenetetrahydrofolate reductase, eukaryotic type; The enzyme activities ...
18-303 0e+00

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: 517.75  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705    18 TYSFEYFVPKTTQGVQNLYDRMDRMyEASLPQFIDITWNAGGGRLSHLSTDLVaTAQSVLGLETCMHLTCTNMPISMIDD 97
Cdd:TIGR00677   1 TFSFEFFPPKTEEGVQNLYERMDRM-VASGPLFIDITWGAGGTTAELTLTIAS-RAQNVVGVETCMHLTCTNMPIEMIDD 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705    98 ALENAYHSGCQNILALRGDPPRDAENWTPVEGGFQYAKDLIKYIKSKYGDHFAIGVAGYPECHPELPNkdVKLDLEYLKQ 177
Cdd:TIGR00677  79 ALERAYSNGIQNILALRGDPPHIGDDWTEVEGGFQYAVDLVKYIRSKYGDYFCIGVAGYPEGHPEAES--VELDLKYLKE 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705   178 KIDAGGDFIITQMFYDVDNFINWCSQVRAAGMDVPIIPGIMPITTYAAFLRRAQWGQISIPQHFSSRLDPIKDDDELVRD 257
Cdd:TIGR00677 157 KVDAGADFIITQLFYDVDNFLKFVNDCRAIGIDCPIVPGIMPINNYASFLRRAKWSKTKIPQEIMSRLEPIKDDDEAVRD 236
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 27808705   258 IGTNLIVEMCQKLLDSGyVSHLHIYTMNLEKAPLMILERLNILPTE 303
Cdd:TIGR00677 237 YGIELIVEMCQKLLASG-IKGLHFYTLNLEKAALMILERLGLLDES 281
MTHFR pfam02219
Methylenetetrahydrofolate reductase; This family includes the 5,10-methylenetetrahydrofolate ...
6-298 8.54e-166

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: 473.73  E-value: 8.54e-166
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705     6 KLEQHRQTsGKPTYSFEYFVPKTTQGVQNLYDRMDRMYEASlPQFIDITWNAGGGRLsHLSTDLVATAQSVLGLETCMHL 85
Cdd:pfam02219   1 KIRQILAE-GKFFISFEFFPPKTENGERNLWERIDRMSAVG-PLFVSVTWGAGGSTR-DRTSSIASVIQQDTGLEACMHL 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705    86 TCTNMPISMIDDALENAYHSGCQNILALRGDPPRDAENWTPVEGGFQYAKDLIKYIKSKYGDHFAIGVAGYPECHPELpn 165
Cdd:pfam02219  78 TCTDMSKEELDDALEDAKALGIRNILALRGDPPKGTDDWERPEGGFKYALDLVRLIRQEYGDYFDIGVAAYPEGHPEA-- 155
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705   166 KDVKLDLEYLKQKIDAGGDFIITQMFYDVDNFINWCSQVRAAGMDVPIIPGIMPITTYAAFLRRAQWGQISIPQHFSSRL 245
Cdd:pfam02219 156 KSWQADLKYLKEKVDAGADFIITQLFFDVDNFLRFVDRVRAAGIDIPIIPGIMPITSYKSLKRIAKLSGVSIPQELIDRL 235
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 27808705   246 DPIKDDDELVRDIGTNLIVEMCQKLLDSGyVSHLHIYTMNLEKAPLMILERLN 298
Cdd:pfam02219 236 EPIKDDDEAVKSIGIELAVEMCKKLLAEG-VPGLHFYTLNREEATLEILENLG 287
MTHFR cd00537
Methylenetetrahydrofolate reductase (MTHFR). 5,10-Methylenetetrahydrofolate is reduced to ...
19-297 1.17e-120

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: 358.08  E-value: 1.17e-120
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705  19 YSFEYFVPKTTQGVQNLYDRMDRMYEASlPQFIDITWNAGGGRLsHLSTDLVATAQSVLGLETCMHLTCTNMPISMIDDA 98
Cdd:cd00537   1 ISFEFFPPKTADGEENLEAAADLLGALD-PDFVSVTDGAGGSTR-DMTLLAAARILQEGGIEPIPHLTCRDRNRIELQSI 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705  99 LENAYHSGCQNILALRGDPPRDAENWTPVEGGFQYAKDLIKYIKSKYGDHFAIGVAGYPECHPELPNKDVklDLEYLKQK 178
Cdd:cd00537  79 LLGAHALGIRNILALRGDPPKGGDQPGAKPVGFVYAVDLVELIRKENGGGFSIGVAAYPEGHPEAPSLEE--DIKRLKRK 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705 179 IDAGGDFIITQMFYDVDNFINWCSQVRAAGMDVPIIPGIMPITTYAAFLRRAQWGQISIPQHFSSRLDPIKDDDELVRDI 258
Cdd:cd00537 157 VDAGADFIITQLFFDNDAFLRFVDRCRAAGITVPIIPGIMPLTSYKQAKRFAKLCGVEIPDWLLERLEKLKDDAEAVRAE 236
                       250       260       270
                ....*....|....*....|....*....|....*....
gi 27808705 259 GTNLIVEMCQKLLDSGyVSHLHIYTMNLEKAPLMILERL 297
Cdd:cd00537 237 GIEIAAELCDELLEHG-VPGIHFYTLNREEATAEILENL 274
MetF COG0685
5,10-methylenetetrahydrofolate reductase [Amino acid transport and metabolism];
1-300 4.74e-97

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


Pssm-ID: 440449  Cd Length: 284  Bit Score: 297.85  E-value: 4.74e-97
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705   1 MKITEKLEQhrqtsGKPTYSFEYFVPKTTQGVQNLYDRMDRMYEASlPQFIDITWNAGGGrlSHLST-DLVATAQSVLGL 79
Cdd:COG0685   1 MKLEELLKA-----GKPVVSFEFFPPKTAEGEEKLWETAEELAPLD-PDFVSVTYGAGGS--TRDRTlAIAARIQQETGL 72
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705  80 ETCMHLTCTNMPISMIDDALENAYHSGCQNILALRGDPPRDAenwtPVEGGFQYAKDLIKYIKSKYGDhFAIGVAGYPEC 159
Cdd:COG0685  73 EPVAHLTCVGRNREELESILLGLAALGIRNILALRGDPPKGD----GHPGGFLYASELVALIREMNGD-FCIGVAAYPEK 147
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705 160 HPELPNKDVklDLEYLKQKIDAGGDFIITQMFYDVDNFINWCSQVRAAGMDVPIIPGIMPITTYAAfLRR--AQWGqISI 237
Cdd:COG0685 148 HPEAPSLEA--DLDRLKKKVDAGADFAITQLFFDNDAYFRFVDRARAAGIDVPIIPGIMPITSFKQ-LARfaELCG-AEI 223
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 27808705 238 PQHFSSRLDPIKDDDElVRDIGTNLIVEMCQKLLDSGyVSHLHIYTMNLEKAPLMILERLNIL 300
Cdd:COG0685 224 PDWLLKRLEKAGDDEA-VRAVGIEIATEQCEELLAEG-VPGLHFYTLNRAEATLEILERLGLL 284
fadh2 TIGR00676
5,10-methylenetetrahydrofolate reductase, prokaryotic form; The enzyme activities ...
19-297 1.75e-86

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: 270.27  E-value: 1.75e-86
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705    19 YSFEYFVPKTTQGVQNLYDRMDRMYEASlPQFIDITWNAGGgrlSHLST--DLVATAQSVLGLETCMHLTCTNMPISMID 96
Cdd:TIGR00676   1 FSFEFFPPKTDEGEENLWETVDRLSPLD-PDFVSVTYGAGG---STRDRtvRIVRRIKKETGIPTVPHLTCIGATREEIR 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705    97 DALENAYHSGCQNILALRGDPPRDaeNWTPVEGGFQYAKDLIKYIKSKYGDhFAIGVAGYPECHPELPNKDVklDLEYLK 176
Cdd:TIGR00676  77 EILREYRELGIRHILALRGDPPKG--EGTPTPGGFNYASELVEFIRNEFGD-FDIGVAAYPEKHPEAPNLEE--DIENLK 151
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705   177 QKIDAGGDFIITQMFYDVDNFINWCSQVRAAGMDVPIIPGIMPITTYAAFLRRAQWGQISIPQHFSSRLDPIKDDDELVR 256
Cdd:TIGR00676 152 RKVDAGADYAITQLFFDNDDYYRFVDRCRAAGIDVPIIPGIMPITNFKQLLRFAERCGAEIPAWLVKRLEKYDDDPEEVR 231
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|.
gi 27808705   257 DIGTNLIVEMCQKLLDSGyVSHLHIYTMNLEKAPLMILERL 297
Cdd:TIGR00676 232 AVGIEYATDQCEDLIAEG-VPGIHFYTLNRADATLEICENL 271
metF PRK09432
methylenetetrahydrofolate reductase;
5-285 9.25e-48

methylenetetrahydrofolate reductase;


Pssm-ID: 181852  Cd Length: 296  Bit Score: 169.05  E-value: 9.25e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705    5 EKLEQH-RQTSGKPTYSFEYFVPKTTQGVQNLYDRMDRMyeASL-PQFIDITWNAGGGRLSHlSTDLVATAQSVLGLETC 82
Cdd:PRK09432  10 DALNQSlAELQGQINVSFEFFPPRTSEMEQTLWNSIDRL--SSLkPKFVSVTYGANSGERDR-THSIIKGIKKRTGLEAA 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705   83 MHLTCTNMPISMIDDALENAYHSGCQNILALRGDPPrdaenwtpvEGGFQ---YAKDLIKYIKSkYGDhFAIGVAGYPEC 159
Cdd:PRK09432  87 PHLTCIDATPDELRTIAKDYWNNGIRHIVALRGDLP---------PGSGKpemYASDLVTLLKS-VAD-FDISVAAYPEV 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705  160 HPElpNKDVKLDLEYLKQKIDAGGDFIITQMFYDVDNFINWCSQVRAAGMDVPIIPGIMPITTYAAFLRRAQWGQISIPQ 239
Cdd:PRK09432 156 HPE--AKSAQADLINLKRKVDAGANRAITQFFFDVESYLRFRDRCVSAGIDVEIVPGILPVSNFKQLKKFADMTNVRIPA 233
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*.
gi 27808705  240 HFSSRLDPIKDDDELVRDIGTNLIVEMCQKLLDSGyVSHLHIYTMN 285
Cdd:PRK09432 234 WMAKMFDGLDDDAETRKLVGASIAMDMVKILSREG-VKDFHFYTLN 278
PRK08645 PRK08645
bifunctional homocysteine S-methyltransferase/5,10-methylenetetrahydrofolate reductase protein; ...
74-283 2.07e-17

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


Pssm-ID: 236321 [Multi-domain]  Cd Length: 612  Bit Score: 85.67  E-value: 2.07e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705   74 QSVLGLETCMHLTC--TNMpISMIDDaLENAYHSGCQNILALRGDPPR--DAENWTPVeggfqY---AKDLIKYIKS--- 143
Cdd:PRK08645 377 KRELGIEPLVHITCrdRNL-IGLQSH-LLGLHALGIRNVLAITGDPAKvgDFPGATSV-----YdlnSFGLIKLIKQlne 449
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705  144 ---------KYGDHFAIGVAgypeCHPELPNKDVKLDLeyLKQKIDAGGDFIITQMFYDVDNFINWCSQVRaaGMDVPII 214
Cdd:PRK08645 450 gisysgkplGKKTNFSIGGA----FNPNVRNLDKEVKR--LEKKIEAGADYFITQPVYDEELIEELLEATK--HLGVPIF 521
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 27808705  215 PGIMPITTY--AAFLRRAQWGqISIPQHFSSRLDPIKDDDElvrdiGTNLIVEMCQKLLD--SGYVSHLHIYT 283
Cdd:PRK08645 522 IGIMPLVSYrnAEFLHNEVPG-ITLPEEIRERMRAVEDKEE-----AREEGVAIARELIDaaREYFNGIYLIT 588
Eda COG0800
2-keto-3-deoxy-6-phosphogluconate aldolase [Carbohydrate transport and metabolism]; ...
113-218 9.91e-03

2-keto-3-deoxy-6-phosphogluconate aldolase [Carbohydrate transport and metabolism]; 2-keto-3-deoxy-6-phosphogluconate aldolase is part of the Pathway/BioSystem: Entner-Doudoroff pathway


Pssm-ID: 440563  Cd Length: 213  Bit Score: 37.76  E-value: 9.91e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27808705 113 LRGDPPRDAEnwtPV-----EGGFQ---------YAKDLIKYIKSKYGDHFAIGvAGypechpelpnkDVkLDLEYLKQK 178
Cdd:COG0800  18 LRGDDPEDAV---PLaealvAGGIRaievtlrtpAALEAIRALAKEVGPDALVG-AG-----------TV-LTPEQARAA 81
                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 27808705 179 IDAGGDFIITQmfydvdnfiNWCSQV--RAAGMDVPIIPGIM 218
Cdd:COG0800  82 IAAGARFIVSP---------GLDPEVikAANRAGLPVLPGVA 114
 
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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