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Conserved domains on  [gi|767926003|ref|XP_011510839|]
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dihydrofolate reductase 2, mitochondrial isoform X1 [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
Gene Ontology:  GO:0004146|GO:0050661|GO:0005542
PubMed:  7004143
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 ...
5-182 4.28e-56

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: 174.25  E-value: 4.28e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767926003   5 LNCIVAVSQNMGIGKNGDLPRPpLRNEFRYFQRMTTTssvegkqNLVIMGRKTWFSIPEknRPLKDRINLVLSRELKEPP 84
Cdd:cd00209    1 ISLIVAVDENGVIGKDNKLPWH-LPEDLKHFKKTTTG-------NPVIMGRKTFESIPR--RPLPGRTNIVLSRQLDYQD 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767926003  85 QGAHFLARSLDDALKLterpeLANKVDMIWIVGGSSVYKEAMNHLGhlKLFVTRIMQDFESDTFFSEIDLEKYKLLPEyp 164
Cdd:cd00209   71 AEGVEVVHSLEEALEL-----AENTVEEIFVIGGAEIYKQALPYAD--RLYLTRIHAEFEGDTFFPEIDESEWELVSE-- 141
                        170
                 ....*....|....*...
gi 767926003 165 gvlSDVQEGKHIKYKFEV 182
Cdd:cd00209  142 ---EEVFEEDGYSYTFET 156
 
Name Accession Description Interval E-value
DHFR cd00209
Dihydrofolate reductase (DHFR). Reduces 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate with ...
5-182 4.28e-56

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: 174.25  E-value: 4.28e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767926003   5 LNCIVAVSQNMGIGKNGDLPRPpLRNEFRYFQRMTTTssvegkqNLVIMGRKTWFSIPEknRPLKDRINLVLSRELKEPP 84
Cdd:cd00209    1 ISLIVAVDENGVIGKDNKLPWH-LPEDLKHFKKTTTG-------NPVIMGRKTFESIPR--RPLPGRTNIVLSRQLDYQD 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767926003  85 QGAHFLARSLDDALKLterpeLANKVDMIWIVGGSSVYKEAMNHLGhlKLFVTRIMQDFESDTFFSEIDLEKYKLLPEyp 164
Cdd:cd00209   71 AEGVEVVHSLEEALEL-----AENTVEEIFVIGGAEIYKQALPYAD--RLYLTRIHAEFEGDTFFPEIDESEWELVSE-- 141
                        170
                 ....*....|....*...
gi 767926003 165 gvlSDVQEGKHIKYKFEV 182
Cdd:cd00209  142 ---EEVFEEDGYSYTFET 156
PTZ00164 PTZ00164
bifunctional dihydrofolate reductase-thymidylate synthase; Provisional
8-187 9.13e-41

bifunctional dihydrofolate reductase-thymidylate synthase; Provisional


Pssm-ID: 240299 [Multi-domain]  Cd Length: 514  Bit Score: 144.04  E-value: 9.13e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767926003   8 IVAVSQNMGIGKNGDLPRPpLRNEFRYFQRMTTT------SSVEGKQNLVIMGRKTWFSIPEKNRPLKDRINLVLSRELK 81
Cdd:PTZ00164  13 VVAVTLKRGIGIGNSLPWH-IPEDMKFFSKITTYvreekyEKSPKKQNAVIMGRKTWESIPKKFRPLKNRINVVLSRTLT 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767926003  82 EPPQGAH-FLARSLDDALKLTERPelaNKVDMIWIVGGSSVYKEAMNHLGHLKLFVTRIMQDFESDTFFSEIDLEKYKLl 160
Cdd:PTZ00164  92 EEEADPGvLVFGSLEDALRLLAED---LSIEKIFIIGGASVYREALSANLLDKIYLTRVNSEYECDVFFPKIPESFFIV- 167
                        170       180
                 ....*....|....*....|....*..
gi 767926003 161 peypGVLSDVQEGKHIKYKFEVCEKDD 187
Cdd:PTZ00164 168 ----AIVSQTFSTNGTSYDFVIYEKKN 190
DHFR_1 pfam00186
Dihydrofolate reductase;
8-159 1.48e-35

Dihydrofolate reductase;


Pssm-ID: 425512 [Multi-domain]  Cd Length: 159  Bit Score: 121.88  E-value: 1.48e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767926003    8 IVAVSQNMGIGKNGDLP-RppLRNEFRYFQRMTTtssveGKqnLVIMGRKTWFSIPeknRPLKDRINLVLSRELKEPPQG 86
Cdd:pfam00186   5 IAAMDENGVIGKDNDLPwH--LPADLKHFKKLTT-----GK--PVIMGRKTFESIG---RPLPGRKNIVLTRNPDYKVDG 72
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767926003   87 AHFLArSLDDALklterpELANKVDMIWIVGGSSVYKEAMNHLGhlKLFVTRIMQDFESDTFFSEIDLEKYKL 159
Cdd:pfam00186  73 VEVVH-SLEEAL------ALAAEAEEIFIIGGAEIYAQALPLAD--RLYITEIDAEFDGDTFFPEIDPSEWQL 136
FolA COG0262
Dihydrofolate reductase [Coenzyme transport and metabolism]; Dihydrofolate reductase is part ...
5-155 8.18e-21

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: 84.13  E-value: 8.18e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767926003   5 LNCIVAVSQNMGIG-KNGDLPR-PPLRNEFRYFQRMTTTSSVegkqnlVIMGRKTWFSIPEK--NRPLKDRINLVLSREL 80
Cdd:COG0262    3 LILIVAVSLDGVIGgPDGDLPWlFPDPEDLAHFKELTAGADA------VLMGRKTYESIAGYwpTRPLPGRPKIVLSRTL 76
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767926003  81 KEPP-QGAHFLARSLDDALKLTERPELANkvdmIWIVGGSSVYKEAMNHlGHL-KLFVTRIMQDFES-DTFFSEIDLE 155
Cdd:COG0262   77 DEADwEGVTVVSGDLEEALAALKAAGGKD----IWVIGGGELYRQLLPA-GLVdELYLTVVPVVLGEgDRLFPELDAP 149
dihyfolred_HdrA_Halo NF041386
dihydrofolate reductase HdrA;
10-162 1.34e-09

dihydrofolate reductase HdrA;


Pssm-ID: 469277 [Multi-domain]  Cd Length: 158  Bit Score: 54.19  E-value: 1.34e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767926003  10 AVSQNMGIGKNGDLPRPPLRNEFR-YFQRMTTTSsvegkqnlVIMGRKTWFSIPEKnrpLKDRINLVLSRELKEPPQGAH 88
Cdd:NF041386   8 AVAENGVIGRDGELPWPSIPADKRqYRERVADDP--------VILGRRTFESMRDD---LPGSAQIVLSRSEREFDVETA 76
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767926003  89 FLARSLDDALKLTERPElankVDMIWIVGGSSVYKEAMNHLGHLKLfvTRIMQDFESDTFFSEIDLEKYKLLPE 162
Cdd:NF041386  77 HHAGGVDEAIEIAESLG----AERAYVLGGAAIYELFQPHVDRMVL--SRVPGEYEGDAYYPEWDEDEWELVEE 144
 
Name Accession Description Interval E-value
DHFR cd00209
Dihydrofolate reductase (DHFR). Reduces 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate with ...
5-182 4.28e-56

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: 174.25  E-value: 4.28e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767926003   5 LNCIVAVSQNMGIGKNGDLPRPpLRNEFRYFQRMTTTssvegkqNLVIMGRKTWFSIPEknRPLKDRINLVLSRELKEPP 84
Cdd:cd00209    1 ISLIVAVDENGVIGKDNKLPWH-LPEDLKHFKKTTTG-------NPVIMGRKTFESIPR--RPLPGRTNIVLSRQLDYQD 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767926003  85 QGAHFLARSLDDALKLterpeLANKVDMIWIVGGSSVYKEAMNHLGhlKLFVTRIMQDFESDTFFSEIDLEKYKLLPEyp 164
Cdd:cd00209   71 AEGVEVVHSLEEALEL-----AENTVEEIFVIGGAEIYKQALPYAD--RLYLTRIHAEFEGDTFFPEIDESEWELVSE-- 141
                        170
                 ....*....|....*...
gi 767926003 165 gvlSDVQEGKHIKYKFEV 182
Cdd:cd00209  142 ---EEVFEEDGYSYTFET 156
PTZ00164 PTZ00164
bifunctional dihydrofolate reductase-thymidylate synthase; Provisional
8-187 9.13e-41

bifunctional dihydrofolate reductase-thymidylate synthase; Provisional


Pssm-ID: 240299 [Multi-domain]  Cd Length: 514  Bit Score: 144.04  E-value: 9.13e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767926003   8 IVAVSQNMGIGKNGDLPRPpLRNEFRYFQRMTTT------SSVEGKQNLVIMGRKTWFSIPEKNRPLKDRINLVLSRELK 81
Cdd:PTZ00164  13 VVAVTLKRGIGIGNSLPWH-IPEDMKFFSKITTYvreekyEKSPKKQNAVIMGRKTWESIPKKFRPLKNRINVVLSRTLT 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767926003  82 EPPQGAH-FLARSLDDALKLTERPelaNKVDMIWIVGGSSVYKEAMNHLGHLKLFVTRIMQDFESDTFFSEIDLEKYKLl 160
Cdd:PTZ00164  92 EEEADPGvLVFGSLEDALRLLAED---LSIEKIFIIGGASVYREALSANLLDKIYLTRVNSEYECDVFFPKIPESFFIV- 167
                        170       180
                 ....*....|....*....|....*..
gi 767926003 161 peypGVLSDVQEGKHIKYKFEVCEKDD 187
Cdd:PTZ00164 168 ----AIVSQTFSTNGTSYDFVIYEKKN 190
DHFR_1 pfam00186
Dihydrofolate reductase;
8-159 1.48e-35

Dihydrofolate reductase;


Pssm-ID: 425512 [Multi-domain]  Cd Length: 159  Bit Score: 121.88  E-value: 1.48e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767926003    8 IVAVSQNMGIGKNGDLP-RppLRNEFRYFQRMTTtssveGKqnLVIMGRKTWFSIPeknRPLKDRINLVLSRELKEPPQG 86
Cdd:pfam00186   5 IAAMDENGVIGKDNDLPwH--LPADLKHFKKLTT-----GK--PVIMGRKTFESIG---RPLPGRKNIVLTRNPDYKVDG 72
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767926003   87 AHFLArSLDDALklterpELANKVDMIWIVGGSSVYKEAMNHLGhlKLFVTRIMQDFESDTFFSEIDLEKYKL 159
Cdd:pfam00186  73 VEVVH-SLEEAL------ALAAEAEEIFIIGGAEIYAQALPLAD--RLYITEIDAEFDGDTFFPEIDPSEWQL 136
FolA COG0262
Dihydrofolate reductase [Coenzyme transport and metabolism]; Dihydrofolate reductase is part ...
5-155 8.18e-21

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: 84.13  E-value: 8.18e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767926003   5 LNCIVAVSQNMGIG-KNGDLPR-PPLRNEFRYFQRMTTTSSVegkqnlVIMGRKTWFSIPEK--NRPLKDRINLVLSREL 80
Cdd:COG0262    3 LILIVAVSLDGVIGgPDGDLPWlFPDPEDLAHFKELTAGADA------VLMGRKTYESIAGYwpTRPLPGRPKIVLSRTL 76
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767926003  81 KEPP-QGAHFLARSLDDALKLTERPELANkvdmIWIVGGSSVYKEAMNHlGHL-KLFVTRIMQDFES-DTFFSEIDLE 155
Cdd:COG0262   77 DEADwEGVTVVSGDLEEALAALKAAGGKD----IWVIGGGELYRQLLPA-GLVdELYLTVVPVVLGEgDRLFPELDAP 149
folA PRK10769
type 3 dihydrofolate reductase;
51-185 9.27e-11

type 3 dihydrofolate reductase;


Pssm-ID: 182714 [Multi-domain]  Cd Length: 159  Bit Score: 57.44  E-value: 9.27e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767926003  51 VIMGRKTWFSIpekNRPLKDRINLVLSRElkepPQGAHFL--ARSLDDALklterpELANKVDMIWIVGGSSVYKEAMNH 128
Cdd:PRK10769  40 VIMGRHTWESI---GRPLPGRKNIVISSQ----PGTDDRVtwVKSVDEAL------AAAGDVPEIMVIGGGRVYEQFLPK 106
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 767926003 129 LGhlKLFVTRIMQDFESDTFFSEIDLEkykllpEYPGVLS---DVQEGKHIKYKFEVCEK 185
Cdd:PRK10769 107 AQ--RLYLTHIDAEVEGDTHFPDYEPD------EWESVFSefhDADEQNSHSYCFEILER 158
dihyfolred_HdrA_Halo NF041386
dihydrofolate reductase HdrA;
10-162 1.34e-09

dihydrofolate reductase HdrA;


Pssm-ID: 469277 [Multi-domain]  Cd Length: 158  Bit Score: 54.19  E-value: 1.34e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767926003  10 AVSQNMGIGKNGDLPRPPLRNEFR-YFQRMTTTSsvegkqnlVIMGRKTWFSIPEKnrpLKDRINLVLSRELKEPPQGAH 88
Cdd:NF041386   8 AVAENGVIGRDGELPWPSIPADKRqYRERVADDP--------VILGRRTFESMRDD---LPGSAQIVLSRSEREFDVETA 76
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767926003  89 FLARSLDDALKLTERPElankVDMIWIVGGSSVYKEAMNHLGHLKLfvTRIMQDFESDTFFSEIDLEKYKLLPE 162
Cdd:NF041386  77 HHAGGVDEAIEIAESLG----AERAYVLGGAAIYELFQPHVDRMVL--SRVPGEYEGDAYYPEWDEDEWELVEE 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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