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Conserved domains on  [gi|2494091|sp|P78028|]
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RecName: Full=Dihydrofolate reductase

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
Gene Ontology:  GO:0004146|GO:0050661|GO:0005542
PubMed:  7004143

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 ...
2-156 9.76e-52

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: 161.92  E-value: 9.76e-52
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2494091    2 VKAIWAMDQNGLIGNGNSLPWRIKAELQHFRQTTLHQDVLMGSATYLSLPP-VFSERNVYILTRNLNFNPPDkGCltKVI 80
Cdd:cd00209   1 ISLIVAVDENGVIGKDNKLPWHLPEDLKHFKKTTTGNPVIMGRKTFESIPRrPLPGRTNIVLSRQLDYQDAE-GV--EVV 77
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2494091   81 HEYENFIQpYLHHPDKHLYICGGAQVYEQLIPRCDALIVSTIFGKYTGDKYLKV-DFSPFELTKEISFAEFKVAYYH 156
Cdd:cd00209  78 HSLEEALE-LAENTVEEIFVIGGAEIYKQALPYADRLYLTRIHAEFEGDTFFPEiDESEWELVSEEEVFEEDGYSYT 153
 
Name Accession Description Interval E-value
DHFR cd00209
Dihydrofolate reductase (DHFR). Reduces 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate with ...
2-156 9.76e-52

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: 161.92  E-value: 9.76e-52
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2494091    2 VKAIWAMDQNGLIGNGNSLPWRIKAELQHFRQTTLHQDVLMGSATYLSLPP-VFSERNVYILTRNLNFNPPDkGCltKVI 80
Cdd:cd00209   1 ISLIVAVDENGVIGKDNKLPWHLPEDLKHFKKTTTGNPVIMGRKTFESIPRrPLPGRTNIVLSRQLDYQDAE-GV--EVV 77
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2494091   81 HEYENFIQpYLHHPDKHLYICGGAQVYEQLIPRCDALIVSTIFGKYTGDKYLKV-DFSPFELTKEISFAEFKVAYYH 156
Cdd:cd00209  78 HSLEEALE-LAENTVEEIFVIGGAEIYKQALPYADRLYLTRIHAEFEGDTFFPEiDESEWELVSEEEVFEEDGYSYT 153
DHFR_1 pfam00186
Dihydrofolate reductase;
1-148 9.71e-41

Dihydrofolate reductase;


Pssm-ID: 425512 [Multi-domain]  Cd Length: 159  Bit Score: 134.21  E-value: 9.71e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2494091      1 MVKAIWAMDQNGLIGNGNSLPWRIKAELQHFRQTTLHQDVLMGSATYLSLPPVFSERNVYILTRNLNFNPPdkGCltKVI 80
Cdd:pfam00186   1 MISLIAAMDENGVIGKDNDLPWHLPADLKHFKKLTTGKPVIMGRKTFESIGRPLPGRKNIVLTRNPDYKVD--GV--EVV 76
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2494091     81 HEYENFIQPYLHHpdKHLYICGGAQVYEQLIPRCDALIVSTIFGKYTGDKYL-KVDFSPFELTKEISFA 148
Cdd:pfam00186  77 HSLEEALALAAEA--EEIFIIGGAEIYAQALPLADRLYITEIDAEFDGDTFFpEIDPSEWQLVSREEHE 143
scpA PRK00478
segregation and condensation protein ScpA;
1-157 5.07e-25

segregation and condensation protein ScpA;


Pssm-ID: 234776 [Multi-domain]  Cd Length: 505  Bit Score: 99.62  E-value: 5.07e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2494091     1 MVKAIWAMDQNGLIGNGNSLPWRIKAELQHFRQTTLHQDVLMGSATYLSLPPVFSERNVYILTRNLNFNPPDKGCLTKvi 80
Cdd:PRK00478   1 MIKLIWCEDLNFGIAKNNQIPWKIDEELNHFHQTTTNHTIVMGYNTFQAMNKILANQANIVISKKHQRELKNNNELFV-- 78
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2494091    81 heYENFIQPYLHHPDKHLYICGGAQVYEQLIPRCDALIVSTIFGKYTGDKYLKVDFSPFELTKEISFAEFKVAYYHK 157
Cdd:PRK00478  79 --FNDLKKLLIDFSNVDLFIIGGKKTIEQFIKYADQLIISKLNADYKCDLFVNLNYDDFSLVQTKEYDQFVVEYWEK 153
FolA COG0262
Dihydrofolate reductase [Coenzyme transport and metabolism]; Dihydrofolate reductase is part ...
1-155 1.80e-19

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: 79.90  E-value: 1.80e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2494091    1 MVKAIWAMDQNGLIGN-GNSLPW--RIKAELQHFRQTTLHQD-VLMGSATYLSLPPV-----FSERNVYILTRNLNfNPP 71
Cdd:COG0262   2 KLILIVAVSLDGVIGGpDGDLPWlfPDPEDLAHFKELTAGADaVLMGRKTYESIAGYwptrpLPGRPKIVLSRTLD-EAD 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2494091   72 DKGCltKVIHEY-ENFIQPYLHHPDKHLYICGGAQVYEQLIP--RCDALIVSTI---FGKytGDKYLKVDFSP--FELTK 143
Cdd:COG0262  81 WEGV--TVVSGDlEEALAALKAAGGKDIWVIGGGELYRQLLPagLVDELYLTVVpvvLGE--GDRLFPELDAPsrLELVE 156
                       170
                ....*....|..
gi 2494091  144 EISFAEFKVAYY 155
Cdd:COG0262 157 SEADSGFVHLTY 168
dihyfolred_HdrA_Halo NF041386
dihydrofolate reductase HdrA;
7-150 9.98e-08

dihydrofolate reductase HdrA;


Pssm-ID: 469277 [Multi-domain]  Cd Length: 158  Bit Score: 48.41  E-value: 9.98e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2494091     7 AMDQNGLIGNGNSLPWR-IKAELQHFRQTTLHQDVLMGSATYLSL---PPvFSERNVyiltrnlnfnppdkgcLTKVIHE 82
Cdd:NF041386   8 AVAENGVIGRDGELPWPsIPADKRQYRERVADDPVILGRRTFESMrddLP-GSAQIV----------------LSRSERE 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2494091    83 YEnfiQPYLHHPD--------------KHLYICGGAQVYEQLIPRCDALIVSTIFGKYTGDKYLKV-DFSPFELTKEISF 147
Cdd:NF041386  71 FD---VETAHHAGgvdeaieiaeslgaERAYVLGGAAIYELFQPHVDRMVLSRVPGEYEGDAYYPEwDEDEWELVEETEY 147

                 ...
gi 2494091   148 AEF 150
Cdd:NF041386 148 DGF 150
trim_DfrL NF041668
trimethoprim-resistant dihydrofolate reductase DfrL;
5-158 3.54e-05

trimethoprim-resistant dihydrofolate reductase DfrL;


Pssm-ID: 469550 [Multi-domain]  Cd Length: 176  Bit Score: 41.95  E-value: 3.54e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2494091     5 IWAMDQNGLIGNGNSLPWRIKAELQHFRQTTLHQDVLMGSATYLSLPPVFSERNVYILTRNLNFNPPDKGCLTKVIHEYE 84
Cdd:NF041668   4 NIAEDCCGEIGKPGDLFVNAEDDMGHFGNSGDDDVNLMGDKKHEKIPTMDDKNRIGIKLTENIPVRADGAIICHSKEDNK 83
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2494091    85 NFIQPylHHPDKHLYICGGAQVYEQLIPRCDALIVSTIFGKYTGDKYLKVDFSPFELTKEIS--FAEFKVAYYHKI 158
Cdd:NF041668  84 NYLAD--GAIECHIHEDGGISAFEMFIDEPIHLHGGIIAEEFEGDEVMIEHDTIIDECFDGAdgMPDEDNKYFHCF 157
 
Name Accession Description Interval E-value
DHFR cd00209
Dihydrofolate reductase (DHFR). Reduces 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate with ...
2-156 9.76e-52

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: 161.92  E-value: 9.76e-52
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2494091    2 VKAIWAMDQNGLIGNGNSLPWRIKAELQHFRQTTLHQDVLMGSATYLSLPP-VFSERNVYILTRNLNFNPPDkGCltKVI 80
Cdd:cd00209   1 ISLIVAVDENGVIGKDNKLPWHLPEDLKHFKKTTTGNPVIMGRKTFESIPRrPLPGRTNIVLSRQLDYQDAE-GV--EVV 77
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2494091   81 HEYENFIQpYLHHPDKHLYICGGAQVYEQLIPRCDALIVSTIFGKYTGDKYLKV-DFSPFELTKEISFAEFKVAYYH 156
Cdd:cd00209  78 HSLEEALE-LAENTVEEIFVIGGAEIYKQALPYADRLYLTRIHAEFEGDTFFPEiDESEWELVSEEEVFEEDGYSYT 153
DHFR_1 pfam00186
Dihydrofolate reductase;
1-148 9.71e-41

Dihydrofolate reductase;


Pssm-ID: 425512 [Multi-domain]  Cd Length: 159  Bit Score: 134.21  E-value: 9.71e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2494091      1 MVKAIWAMDQNGLIGNGNSLPWRIKAELQHFRQTTLHQDVLMGSATYLSLPPVFSERNVYILTRNLNFNPPdkGCltKVI 80
Cdd:pfam00186   1 MISLIAAMDENGVIGKDNDLPWHLPADLKHFKKLTTGKPVIMGRKTFESIGRPLPGRKNIVLTRNPDYKVD--GV--EVV 76
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2494091     81 HEYENFIQPYLHHpdKHLYICGGAQVYEQLIPRCDALIVSTIFGKYTGDKYL-KVDFSPFELTKEISFA 148
Cdd:pfam00186  77 HSLEEALALAAEA--EEIFIIGGAEIYAQALPLADRLYITEIDAEFDGDTFFpEIDPSEWQLVSREEHE 143
scpA PRK00478
segregation and condensation protein ScpA;
1-157 5.07e-25

segregation and condensation protein ScpA;


Pssm-ID: 234776 [Multi-domain]  Cd Length: 505  Bit Score: 99.62  E-value: 5.07e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2494091     1 MVKAIWAMDQNGLIGNGNSLPWRIKAELQHFRQTTLHQDVLMGSATYLSLPPVFSERNVYILTRNLNFNPPDKGCLTKvi 80
Cdd:PRK00478   1 MIKLIWCEDLNFGIAKNNQIPWKIDEELNHFHQTTTNHTIVMGYNTFQAMNKILANQANIVISKKHQRELKNNNELFV-- 78
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2494091    81 heYENFIQPYLHHPDKHLYICGGAQVYEQLIPRCDALIVSTIFGKYTGDKYLKVDFSPFELTKEISFAEFKVAYYHK 157
Cdd:PRK00478  79 --FNDLKKLLIDFSNVDLFIIGGKKTIEQFIKYADQLIISKLNADYKCDLFVNLNYDDFSLVQTKEYDQFVVEYWEK 153
FolA COG0262
Dihydrofolate reductase [Coenzyme transport and metabolism]; Dihydrofolate reductase is part ...
1-155 1.80e-19

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: 79.90  E-value: 1.80e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2494091    1 MVKAIWAMDQNGLIGN-GNSLPW--RIKAELQHFRQTTLHQD-VLMGSATYLSLPPV-----FSERNVYILTRNLNfNPP 71
Cdd:COG0262   2 KLILIVAVSLDGVIGGpDGDLPWlfPDPEDLAHFKELTAGADaVLMGRKTYESIAGYwptrpLPGRPKIVLSRTLD-EAD 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2494091   72 DKGCltKVIHEY-ENFIQPYLHHPDKHLYICGGAQVYEQLIP--RCDALIVSTI---FGKytGDKYLKVDFSP--FELTK 143
Cdd:COG0262  81 WEGV--TVVSGDlEEALAALKAAGGKDIWVIGGGELYRQLLPagLVDELYLTVVpvvLGE--GDRLFPELDAPsrLELVE 156
                       170
                ....*....|..
gi 2494091  144 EISFAEFKVAYY 155
Cdd:COG0262 157 SEADSGFVHLTY 168
PTZ00164 PTZ00164
bifunctional dihydrofolate reductase-thymidylate synthase; Provisional
2-146 9.08e-17

bifunctional dihydrofolate reductase-thymidylate synthase; Provisional


Pssm-ID: 240299 [Multi-domain]  Cd Length: 514  Bit Score: 76.25  E-value: 9.08e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2494091     2 VKAIWAMDQNGLIGNGNSLPWRIKAELQHFRQTTLHQD-------------VLMGSATYLSLPPVF---SERNVYILTRN 65
Cdd:PTZ00164  10 FSIVVAVTLKRGIGIGNSLPWHIPEDMKFFSKITTYVReekyekspkkqnaVIMGRKTWESIPKKFrplKNRINVVLSRT 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2494091    66 LNFNPPDKGCLtkVIHEYENFIQpYLHHPDKH--LYICGGAQVYEQLIPR--CDALIVSTIFGKYTGDKYLKVDFSPFEL 141
Cdd:PTZ00164  90 LTEEEADPGVL--VFGSLEDALR-LLAEDLSIekIFIIGGASVYREALSAnlLDKIYLTRVNSEYECDVFFPKIPESFFI 166

                 ....*
gi 2494091   142 TKEIS 146
Cdd:PTZ00164 167 VAIVS 171
folA PRK10769
type 3 dihydrofolate reductase;
1-150 5.23e-11

type 3 dihydrofolate reductase;


Pssm-ID: 182714 [Multi-domain]  Cd Length: 159  Bit Score: 57.44  E-value: 5.23e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2494091     1 MVKAIWAMDQNGLIGNGNSLPWRIKAELQHFRQTTLHQDVLMGSATYLSL-PPVFSERNVYILTRnlnfnppdKGCLTKV 79
Cdd:PRK10769   1 MISLIAALAVDRVIGMENAMPWNLPADLAWFKRNTLNKPVIMGRHTWESIgRPLPGRKNIVISSQ--------PGTDDRV 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2494091    80 IheyenfiqpYLHHPDKHLYIC---------GGAQVYEQLIPRCDALIVSTIFGKYTGDKYLKvDFSPFELtkEISFAEF 150
Cdd:PRK10769  73 T---------WVKSVDEALAAAgdvpeimviGGGRVYEQFLPKAQRLYLTHIDAEVEGDTHFP-DYEPDEW--ESVFSEF 140
dihyfolred_HdrA_Halo NF041386
dihydrofolate reductase HdrA;
7-150 9.98e-08

dihydrofolate reductase HdrA;


Pssm-ID: 469277 [Multi-domain]  Cd Length: 158  Bit Score: 48.41  E-value: 9.98e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2494091     7 AMDQNGLIGNGNSLPWR-IKAELQHFRQTTLHQDVLMGSATYLSL---PPvFSERNVyiltrnlnfnppdkgcLTKVIHE 82
Cdd:NF041386   8 AVAENGVIGRDGELPWPsIPADKRQYRERVADDPVILGRRTFESMrddLP-GSAQIV----------------LSRSERE 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2494091    83 YEnfiQPYLHHPD--------------KHLYICGGAQVYEQLIPRCDALIVSTIFGKYTGDKYLKV-DFSPFELTKEISF 147
Cdd:NF041386  71 FD---VETAHHAGgvdeaieiaeslgaERAYVLGGAAIYELFQPHVDRMVLSRVPGEYEGDAYYPEwDEDEWELVEETEY 147

                 ...
gi 2494091   148 AEF 150
Cdd:NF041386 148 DGF 150
trim_DfrL NF041668
trimethoprim-resistant dihydrofolate reductase DfrL;
5-158 3.54e-05

trimethoprim-resistant dihydrofolate reductase DfrL;


Pssm-ID: 469550 [Multi-domain]  Cd Length: 176  Bit Score: 41.95  E-value: 3.54e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2494091     5 IWAMDQNGLIGNGNSLPWRIKAELQHFRQTTLHQDVLMGSATYLSLPPVFSERNVYILTRNLNFNPPDKGCLTKVIHEYE 84
Cdd:NF041668   4 NIAEDCCGEIGKPGDLFVNAEDDMGHFGNSGDDDVNLMGDKKHEKIPTMDDKNRIGIKLTENIPVRADGAIICHSKEDNK 83
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2494091    85 NFIQPylHHPDKHLYICGGAQVYEQLIPRCDALIVSTIFGKYTGDKYLKVDFSPFELTKEIS--FAEFKVAYYHKI 158
Cdd:NF041668  84 NYLAD--GAIECHIHEDGGISAFEMFIDEPIHLHGGIIAEEFEGDEVMIEHDTIIDECFDGAdgMPDEDNKYFHCF 157
 
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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