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Conserved domains on  [gi|594140705|ref|NP_001277286|]
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dihydrofolate reductase isoform 3 [Homo sapiens]

Protein Classification

dihydrofolate reductase( domain architecture ID 10082841)

dihydrofolate reductase (DHFR) is involved in the biosynthesis of deoxythymidine phosphate; it reduces 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate with NADPH as a cofactor

CATH:  3.40.430.10
EC:  1.5.1.3
SCOP:  4000755

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
DHFR cd00209
Dihydrofolate reductase (DHFR). Reduces 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate with ...
5-128 9.46e-43

Dihydrofolate reductase (DHFR). Reduces 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate with NADPH as a cofactor. This is an essential step in the biosynthesis of deoxythymidine phosphate since 5,6,7,8-tetrahydrofolate is required to regenerate 5,10-methylenetetrahydrofolate which is then utilized by thymidylate synthase. Inhibition of DHFR interrupts thymidilate synthesis and DNA replication, inhibitors of DHFR (such as Methotrexate) are used in cancer chemotherapy. 5,6,7,8-tetrahydrofolate also is involved in glycine, serine, and threonine metabolism and aminoacyl-tRNA biosynthesis.


:

Pssm-ID: 238127 [Multi-domain]  Cd Length: 158  Bit Score: 138.04  E-value: 9.46e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594140705   5 LNCIVAVSQNMGIGKNGDLPWPpLRNEFRYFQRMTTTssvegkqNLVIMGKKTWFSIPEknRPLKGRINLVLSRELKEPP 84
Cdd:cd00209    1 ISLIVAVDENGVIGKDNKLPWH-LPEDLKHFKKTTTG-------NPVIMGRKTFESIPR--RPLPGRTNIVLSRQLDYQD 70
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 594140705  85 QGAHFLSRSLDDALKLteqpeLANKVDMVWIVGGSSVYK--IPRCS 128
Cdd:cd00209   71 AEGVEVVHSLEEALEL-----AENTVEEIFVIGGAEIYKqaLPYAD 111
 
Name Accession Description Interval E-value
DHFR cd00209
Dihydrofolate reductase (DHFR). Reduces 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate with ...
5-128 9.46e-43

Dihydrofolate reductase (DHFR). Reduces 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate with NADPH as a cofactor. This is an essential step in the biosynthesis of deoxythymidine phosphate since 5,6,7,8-tetrahydrofolate is required to regenerate 5,10-methylenetetrahydrofolate which is then utilized by thymidylate synthase. Inhibition of DHFR interrupts thymidilate synthesis and DNA replication, inhibitors of DHFR (such as Methotrexate) are used in cancer chemotherapy. 5,6,7,8-tetrahydrofolate also is involved in glycine, serine, and threonine metabolism and aminoacyl-tRNA biosynthesis.


Pssm-ID: 238127 [Multi-domain]  Cd Length: 158  Bit Score: 138.04  E-value: 9.46e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594140705   5 LNCIVAVSQNMGIGKNGDLPWPpLRNEFRYFQRMTTTssvegkqNLVIMGKKTWFSIPEknRPLKGRINLVLSRELKEPP 84
Cdd:cd00209    1 ISLIVAVDENGVIGKDNKLPWH-LPEDLKHFKKTTTG-------NPVIMGRKTFESIPR--RPLPGRTNIVLSRQLDYQD 70
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 594140705  85 QGAHFLSRSLDDALKLteqpeLANKVDMVWIVGGSSVYK--IPRCS 128
Cdd:cd00209   71 AEGVEVVHSLEEALEL-----AENTVEEIFVIGGAEIYKqaLPYAD 111
PTZ00164 PTZ00164
bifunctional dihydrofolate reductase-thymidylate synthase; Provisional
8-123 4.25e-33

bifunctional dihydrofolate reductase-thymidylate synthase; Provisional


Pssm-ID: 240299 [Multi-domain]  Cd Length: 514  Bit Score: 120.55  E-value: 4.25e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594140705   8 IVAVSQNMGIGKNGDLPWPpLRNEFRYFQRMTTT------SSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLSRELK 81
Cdd:PTZ00164  13 VVAVTLKRGIGIGNSLPWH-IPEDMKFFSKITTYvreekyEKSPKKQNAVIMGRKTWESIPKKFRPLKNRINVVLSRTLT 91
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 594140705  82 EPPQGAH-FLSRSLDDALKLTEQPelaNKVDMVWIVGGSSVYK 123
Cdd:PTZ00164  92 EEEADPGvLVFGSLEDALRLLAED---LSIEKIFIIGGASVYR 131
DHFR_1 pfam00186
Dihydrofolate reductase;
8-127 1.25e-27

Dihydrofolate reductase;


Pssm-ID: 425512 [Multi-domain]  Cd Length: 159  Bit Score: 99.54  E-value: 1.25e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594140705    8 IVAVSQNMGIGKNGDLPWpPLRNEFRYFQRMTTtssveGKqnLVIMGKKTWFSIPeknRPLKGRINLVLSRELKEPPQGA 87
Cdd:pfam00186   5 IAAMDENGVIGKDNDLPW-HLPADLKHFKKLTT-----GK--PVIMGRKTFESIG---RPLPGRKNIVLTRNPDYKVDGV 73
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 594140705   88 HFLSrSLDDALklteqpELANKVDMVWIVGGSSVYK--IPRC 127
Cdd:pfam00186  74 EVVH-SLEEAL------ALAAEAEEIFIIGGAEIYAqaLPLA 108
FolA COG0262
Dihydrofolate reductase [Coenzyme transport and metabolism]; Dihydrofolate reductase is part ...
5-123 9.25e-20

Dihydrofolate reductase [Coenzyme transport and metabolism]; Dihydrofolate reductase is part of the Pathway/BioSystem: Folate biosynthesis


Pssm-ID: 440032 [Multi-domain]  Cd Length: 168  Bit Score: 79.51  E-value: 9.25e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594140705   5 LNCIVAVSQNMGIG-KNGDLPW-PPLRNEFRYFQRMTTTSSVegkqnlVIMGKKTWFSIPEK--NRPLKGRINLVLSREL 80
Cdd:COG0262    3 LILIVAVSLDGVIGgPDGDLPWlFPDPEDLAHFKELTAGADA------VLMGRKTYESIAGYwpTRPLPGRPKIVLSRTL 76
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 594140705  81 KEPP-QGAHFLSRSLDDALKLTEQPELANkvdmVWIVGGSSVYK 123
Cdd:COG0262   77 DEADwEGVTVVSGDLEEALAALKAAGGKD----IWVIGGGELYR 116
dihyfolred_HdrA_Halo NF041386
dihydrofolate reductase HdrA;
10-122 1.46e-08

dihydrofolate reductase HdrA;


Pssm-ID: 469277 [Multi-domain]  Cd Length: 158  Bit Score: 49.95  E-value: 1.46e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594140705  10 AVSQNMGIGKNGDLPWPPLRNEFR-YFQRMTTTSsvegkqnlVIMGKKTWFSIPEKnrpLKGRINLVLSRELKEPPQGAH 88
Cdd:NF041386   8 AVAENGVIGRDGELPWPSIPADKRqYRERVADDP--------VILGRRTFESMRDD---LPGSAQIVLSRSEREFDVETA 76
                         90       100       110
                 ....*....|....*....|....*....|....
gi 594140705  89 FLSRSLDDALKLTEQPElankVDMVWIVGGSSVY 122
Cdd:NF041386  77 HHAGGVDEAIEIAESLG----AERAYVLGGAAIY 106
 
Name Accession Description Interval E-value
DHFR cd00209
Dihydrofolate reductase (DHFR). Reduces 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate with ...
5-128 9.46e-43

Dihydrofolate reductase (DHFR). Reduces 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate with NADPH as a cofactor. This is an essential step in the biosynthesis of deoxythymidine phosphate since 5,6,7,8-tetrahydrofolate is required to regenerate 5,10-methylenetetrahydrofolate which is then utilized by thymidylate synthase. Inhibition of DHFR interrupts thymidilate synthesis and DNA replication, inhibitors of DHFR (such as Methotrexate) are used in cancer chemotherapy. 5,6,7,8-tetrahydrofolate also is involved in glycine, serine, and threonine metabolism and aminoacyl-tRNA biosynthesis.


Pssm-ID: 238127 [Multi-domain]  Cd Length: 158  Bit Score: 138.04  E-value: 9.46e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594140705   5 LNCIVAVSQNMGIGKNGDLPWPpLRNEFRYFQRMTTTssvegkqNLVIMGKKTWFSIPEknRPLKGRINLVLSRELKEPP 84
Cdd:cd00209    1 ISLIVAVDENGVIGKDNKLPWH-LPEDLKHFKKTTTG-------NPVIMGRKTFESIPR--RPLPGRTNIVLSRQLDYQD 70
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 594140705  85 QGAHFLSRSLDDALKLteqpeLANKVDMVWIVGGSSVYK--IPRCS 128
Cdd:cd00209   71 AEGVEVVHSLEEALEL-----AENTVEEIFVIGGAEIYKqaLPYAD 111
PTZ00164 PTZ00164
bifunctional dihydrofolate reductase-thymidylate synthase; Provisional
8-123 4.25e-33

bifunctional dihydrofolate reductase-thymidylate synthase; Provisional


Pssm-ID: 240299 [Multi-domain]  Cd Length: 514  Bit Score: 120.55  E-value: 4.25e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594140705   8 IVAVSQNMGIGKNGDLPWPpLRNEFRYFQRMTTT------SSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLSRELK 81
Cdd:PTZ00164  13 VVAVTLKRGIGIGNSLPWH-IPEDMKFFSKITTYvreekyEKSPKKQNAVIMGRKTWESIPKKFRPLKNRINVVLSRTLT 91
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 594140705  82 EPPQGAH-FLSRSLDDALKLTEQPelaNKVDMVWIVGGSSVYK 123
Cdd:PTZ00164  92 EEEADPGvLVFGSLEDALRLLAED---LSIEKIFIIGGASVYR 131
DHFR_1 pfam00186
Dihydrofolate reductase;
8-127 1.25e-27

Dihydrofolate reductase;


Pssm-ID: 425512 [Multi-domain]  Cd Length: 159  Bit Score: 99.54  E-value: 1.25e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594140705    8 IVAVSQNMGIGKNGDLPWpPLRNEFRYFQRMTTtssveGKqnLVIMGKKTWFSIPeknRPLKGRINLVLSRELKEPPQGA 87
Cdd:pfam00186   5 IAAMDENGVIGKDNDLPW-HLPADLKHFKKLTT-----GK--PVIMGRKTFESIG---RPLPGRKNIVLTRNPDYKVDGV 73
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 594140705   88 HFLSrSLDDALklteqpELANKVDMVWIVGGSSVYK--IPRC 127
Cdd:pfam00186  74 EVVH-SLEEAL------ALAAEAEEIFIIGGAEIYAqaLPLA 108
FolA COG0262
Dihydrofolate reductase [Coenzyme transport and metabolism]; Dihydrofolate reductase is part ...
5-123 9.25e-20

Dihydrofolate reductase [Coenzyme transport and metabolism]; Dihydrofolate reductase is part of the Pathway/BioSystem: Folate biosynthesis


Pssm-ID: 440032 [Multi-domain]  Cd Length: 168  Bit Score: 79.51  E-value: 9.25e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594140705   5 LNCIVAVSQNMGIG-KNGDLPW-PPLRNEFRYFQRMTTTSSVegkqnlVIMGKKTWFSIPEK--NRPLKGRINLVLSREL 80
Cdd:COG0262    3 LILIVAVSLDGVIGgPDGDLPWlFPDPEDLAHFKELTAGADA------VLMGRKTYESIAGYwpTRPLPGRPKIVLSRTL 76
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 594140705  81 KEPP-QGAHFLSRSLDDALKLTEQPELANkvdmVWIVGGSSVYK 123
Cdd:COG0262   77 DEADwEGVTVVSGDLEEALAALKAAGGKD----IWVIGGGELYR 116
folA PRK10769
type 3 dihydrofolate reductase;
8-128 8.13e-11

type 3 dihydrofolate reductase;


Pssm-ID: 182714 [Multi-domain]  Cd Length: 159  Bit Score: 55.90  E-value: 8.13e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594140705   8 IVAVSQNMGIGKNGDLPWPpLRNEFRYFQRMTTTSSVegkqnlvIMGKKTWFSIpekNRPLKGRINLVLSRElkepPQGA 87
Cdd:PRK10769   5 IAALAVDRVIGMENAMPWN-LPADLAWFKRNTLNKPV-------IMGRHTWESI---GRPLPGRKNIVISSQ----PGTD 69
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 594140705  88 HFLS--RSLDDALklteqpELANKVDMVWIVGGSSVYK--IPRCS 128
Cdd:PRK10769  70 DRVTwvKSVDEAL------AAAGDVPEIMVIGGGRVYEqfLPKAQ 108
dihyfolred_HdrA_Halo NF041386
dihydrofolate reductase HdrA;
10-122 1.46e-08

dihydrofolate reductase HdrA;


Pssm-ID: 469277 [Multi-domain]  Cd Length: 158  Bit Score: 49.95  E-value: 1.46e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594140705  10 AVSQNMGIGKNGDLPWPPLRNEFR-YFQRMTTTSsvegkqnlVIMGKKTWFSIPEKnrpLKGRINLVLSRELKEPPQGAH 88
Cdd:NF041386   8 AVAENGVIGRDGELPWPSIPADKRqYRERVADDP--------VILGRRTFESMRDD---LPGSAQIVLSRSEREFDVETA 76
                         90       100       110
                 ....*....|....*....|....*....|....
gi 594140705  89 FLSRSLDDALKLTEQPElankVDMVWIVGGSSVY 122
Cdd:NF041386  77 HHAGGVDEAIEIAESLG----AERAYVLGGAAIY 106
 
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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