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Conserved domains on  [gi|594140703|ref|NP_001277283|]
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dihydrofolate reductase isoform 2 [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 ...
1-132 1.69e-41

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: 134.96  E-value: 1.69e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594140703   1 MGKKTWFSIPEknRPLKGRINLVLSRELKEPPQGAHFLSRSLDDALKLteqpeLANKVDMVWIVGGSSVYKEAMNHPGhl 80
Cdd:cd00209   41 MGRKTFESIPR--RPLPGRTNIVLSRQLDYQDAEGVEVVHSLEEALEL-----AENTVEEIFVIGGAEIYKQALPYAD-- 111
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 594140703  81 KLFVTRIMQDFESDTFFPEIDLEKYKLLPEypgvlSDVQEEKGIKYKFEVYE 132
Cdd:cd00209  112 RLYLTRIHAEFEGDTFFPEIDESEWELVSE-----EEVFEEDGYSYTFETYE 158
 
Name Accession Description Interval E-value
DHFR cd00209
Dihydrofolate reductase (DHFR). Reduces 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate with ...
1-132 1.69e-41

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: 134.96  E-value: 1.69e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594140703   1 MGKKTWFSIPEknRPLKGRINLVLSRELKEPPQGAHFLSRSLDDALKLteqpeLANKVDMVWIVGGSSVYKEAMNHPGhl 80
Cdd:cd00209   41 MGRKTFESIPR--RPLPGRTNIVLSRQLDYQDAEGVEVVHSLEEALEL-----AENTVEEIFVIGGAEIYKQALPYAD-- 111
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 594140703  81 KLFVTRIMQDFESDTFFPEIDLEKYKLLPEypgvlSDVQEEKGIKYKFEVYE 132
Cdd:cd00209  112 RLYLTRIHAEFEGDTFFPEIDESEWELVSE-----EEVFEEDGYSYTFETYE 158
PTZ00164 PTZ00164
bifunctional dihydrofolate reductase-thymidylate synthase; Provisional
1-135 1.22e-31

bifunctional dihydrofolate reductase-thymidylate synthase; Provisional


Pssm-ID: 240299 [Multi-domain]  Cd Length: 514  Bit Score: 117.08  E-value: 1.22e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594140703   1 MGKKTWFSIPEKNRPLKGRINLVLSRELKEPPQGAH-FLSRSLDDALKLTEQPelaNKVDMVWIVGGSSVYKEAMNHPGH 79
Cdd:PTZ00164  63 MGRKTWESIPKKFRPLKNRINVVLSRTLTEEEADPGvLVFGSLEDALRLLAED---LSIEKIFIIGGASVYREALSANLL 139
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 594140703  80 LKLFVTRIMQDFESDTFFPEIDLEKYKLlpeypGVLSDVQEEKGIKYKFEVYEKND 135
Cdd:PTZ00164 140 DKIYLTRVNSEYECDVFFPKIPESFFIV-----AIVSQTFSTNGTSYDFVIYEKKN 190
DHFR_1 pfam00186
Dihydrofolate reductase;
1-133 5.04e-27

Dihydrofolate reductase;


Pssm-ID: 425512 [Multi-domain]  Cd Length: 159  Bit Score: 98.00  E-value: 5.04e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594140703    1 MGKKTWFSIPeknRPLKGRINLVLSRELKEPPQGAHFLSrSLDDALklteqpELANKVDMVWIVGGSSVYKEAMNHPGhl 80
Cdd:pfam00186  42 MGRKTFESIG---RPLPGRKNIVLTRNPDYKVDGVEVVH-SLEEAL------ALAAEAEEIFIIGGAEIYAQALPLAD-- 109
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 594140703   81 KLFVTRIMQDFESDTFFPEIDLEKYKLLPEYPGvlsDVQEEKGIKYKFEVYEK 133
Cdd:pfam00186 110 RLYITEIDAEFDGDTFFPEIDPSEWQLVSREEH---EADEKNPYPYTFVTYER 159
FolA COG0262
Dihydrofolate reductase [Coenzyme transport and metabolism]; Dihydrofolate reductase is part ...
1-103 1.79e-15

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: 68.73  E-value: 1.79e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594140703   1 MGKKTWFSIPEK--NRPLKGRINLVLSRELKEPP-QGAHFLSRSLDDALKLTEQPELANkvdmVWIVGGSSVYKEAMNHp 77
Cdd:COG0262   47 MGRKTYESIAGYwpTRPLPGRPKIVLSRTLDEADwEGVTVVSGDLEEALAALKAAGGKD----IWVIGGGELYRQLLPA- 121
                         90       100
                 ....*....|....*....|....*...
gi 594140703  78 GHL-KLFVTRIMQDFES-DTFFPEIDLE 103
Cdd:COG0262  122 GLVdELYLTVVPVVLGEgDRLFPELDAP 149
dihyfolred_HdrA_Halo NF041386
dihydrofolate reductase HdrA;
6-110 9.17e-05

dihydrofolate reductase HdrA;


Pssm-ID: 469277 [Multi-domain]  Cd Length: 158  Bit Score: 39.94  E-value: 9.17e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594140703   6 WFSIPEKNRPLKGRIN---LVLSR----ELKEPPQGAH--FLSRS--------------LDDALKLTEQPElankVDMVW 62
Cdd:NF041386  23 WPSIPADKRQYRERVAddpVILGRrtfeSMRDDLPGSAqiVLSRSerefdvetahhaggVDEAIEIAESLG----AERAY 98
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 594140703  63 IVGGSSVYkeAMNHPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLLPE 110
Cdd:NF041386  99 VLGGAAIY--ELFQPHVDRMVLSRVPGEYEGDAYYPEWDEDEWELVEE 144
 
Name Accession Description Interval E-value
DHFR cd00209
Dihydrofolate reductase (DHFR). Reduces 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate with ...
1-132 1.69e-41

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: 134.96  E-value: 1.69e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594140703   1 MGKKTWFSIPEknRPLKGRINLVLSRELKEPPQGAHFLSRSLDDALKLteqpeLANKVDMVWIVGGSSVYKEAMNHPGhl 80
Cdd:cd00209   41 MGRKTFESIPR--RPLPGRTNIVLSRQLDYQDAEGVEVVHSLEEALEL-----AENTVEEIFVIGGAEIYKQALPYAD-- 111
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 594140703  81 KLFVTRIMQDFESDTFFPEIDLEKYKLLPEypgvlSDVQEEKGIKYKFEVYE 132
Cdd:cd00209  112 RLYLTRIHAEFEGDTFFPEIDESEWELVSE-----EEVFEEDGYSYTFETYE 158
PTZ00164 PTZ00164
bifunctional dihydrofolate reductase-thymidylate synthase; Provisional
1-135 1.22e-31

bifunctional dihydrofolate reductase-thymidylate synthase; Provisional


Pssm-ID: 240299 [Multi-domain]  Cd Length: 514  Bit Score: 117.08  E-value: 1.22e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594140703   1 MGKKTWFSIPEKNRPLKGRINLVLSRELKEPPQGAH-FLSRSLDDALKLTEQPelaNKVDMVWIVGGSSVYKEAMNHPGH 79
Cdd:PTZ00164  63 MGRKTWESIPKKFRPLKNRINVVLSRTLTEEEADPGvLVFGSLEDALRLLAED---LSIEKIFIIGGASVYREALSANLL 139
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 594140703  80 LKLFVTRIMQDFESDTFFPEIDLEKYKLlpeypGVLSDVQEEKGIKYKFEVYEKND 135
Cdd:PTZ00164 140 DKIYLTRVNSEYECDVFFPKIPESFFIV-----AIVSQTFSTNGTSYDFVIYEKKN 190
DHFR_1 pfam00186
Dihydrofolate reductase;
1-133 5.04e-27

Dihydrofolate reductase;


Pssm-ID: 425512 [Multi-domain]  Cd Length: 159  Bit Score: 98.00  E-value: 5.04e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594140703    1 MGKKTWFSIPeknRPLKGRINLVLSRELKEPPQGAHFLSrSLDDALklteqpELANKVDMVWIVGGSSVYKEAMNHPGhl 80
Cdd:pfam00186  42 MGRKTFESIG---RPLPGRKNIVLTRNPDYKVDGVEVVH-SLEEAL------ALAAEAEEIFIIGGAEIYAQALPLAD-- 109
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 594140703   81 KLFVTRIMQDFESDTFFPEIDLEKYKLLPEYPGvlsDVQEEKGIKYKFEVYEK 133
Cdd:pfam00186 110 RLYITEIDAEFDGDTFFPEIDPSEWQLVSREEH---EADEKNPYPYTFVTYER 159
FolA COG0262
Dihydrofolate reductase [Coenzyme transport and metabolism]; Dihydrofolate reductase is part ...
1-103 1.79e-15

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: 68.73  E-value: 1.79e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594140703   1 MGKKTWFSIPEK--NRPLKGRINLVLSRELKEPP-QGAHFLSRSLDDALKLTEQPELANkvdmVWIVGGSSVYKEAMNHp 77
Cdd:COG0262   47 MGRKTYESIAGYwpTRPLPGRPKIVLSRTLDEADwEGVTVVSGDLEEALAALKAAGGKD----IWVIGGGELYRQLLPA- 121
                         90       100
                 ....*....|....*....|....*...
gi 594140703  78 GHL-KLFVTRIMQDFES-DTFFPEIDLE 103
Cdd:COG0262  122 GLVdELYLTVVPVVLGEgDRLFPELDAP 149
folA PRK10769
type 3 dihydrofolate reductase;
1-133 6.73e-12

type 3 dihydrofolate reductase;


Pssm-ID: 182714 [Multi-domain]  Cd Length: 159  Bit Score: 58.98  E-value: 6.73e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594140703   1 MGKKTWFSIpekNRPLKGRINLVLSRElkepPQGAHFLS--RSLDDALklteqpELANKVDMVWIVGGSSVYKEAMnhPG 78
Cdd:PRK10769  42 MGRHTWESI---GRPLPGRKNIVISSQ----PGTDDRVTwvKSVDEAL------AAAGDVPEIMVIGGGRVYEQFL--PK 106
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 594140703  79 HLKLFVTRIMQDFESDTFFPEIDLEkykllpEYPGVLS---DVQEEKGIKYKFEVYEK 133
Cdd:PRK10769 107 AQRLYLTHIDAEVEGDTHFPDYEPD------EWESVFSefhDADEQNSHSYCFEILER 158
dihyfolred_HdrA_Halo NF041386
dihydrofolate reductase HdrA;
6-110 9.17e-05

dihydrofolate reductase HdrA;


Pssm-ID: 469277 [Multi-domain]  Cd Length: 158  Bit Score: 39.94  E-value: 9.17e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594140703   6 WFSIPEKNRPLKGRIN---LVLSR----ELKEPPQGAH--FLSRS--------------LDDALKLTEQPElankVDMVW 62
Cdd:NF041386  23 WPSIPADKRQYRERVAddpVILGRrtfeSMRDDLPGSAqiVLSRSerefdvetahhaggVDEAIEIAESLG----AERAY 98
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 594140703  63 IVGGSSVYkeAMNHPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLLPE 110
Cdd:NF041386  99 VLGGAAIY--ELFQPHVDRMVLSRVPGEYEGDAYYPEWDEDEWELVEE 144
 
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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