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Conserved domains on  [gi|66472348|ref|NP_001018534|]
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dihydropteridine reductase [Danio rerio]

Protein Classification

SDR family oxidoreductase( domain architecture ID 10143191)

classical SDR (short-chain dehydrogenase/reductase) family NAD(P)-dependent oxidoreductase similar to dihydropteridine reductase that converts dihydrobiopterin into tetrahydrobiopterin, a cofactor necessary in catecholamine synthesis; classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
DHPR_SDR_c_like cd05334
dihydropteridine reductase (DHPR), classical (c) SDRs; Dihydropteridine reductase is an ...
 6-228 2.17e-127

dihydropteridine reductase (DHPR), classical (c) SDRs; Dihydropteridine reductase is an NAD-binding protein related to the SDRs. It converts dihydrobiopterin into tetrahydrobiopterin, a cofactor necessary in catecholamines synthesis. Dihydropteridine reductase has the YXXXK of these tyrosine-dependent oxidoreductases, but lacks the typical upstream Asn and Ser catalytic residues. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes have a 3-glycine N-terminal NAD(P)(H)-binding pattern (typically, TGxxxGxG in classical SDRs and TGxxGxxG in extended SDRs), while substrate binding is in the C-terminal region. A critical catalytic Tyr residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering), is often found in a conserved YXXXK pattern. In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) or additional Ser, contributing to the active site. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving the conserved Tyr and Lys, as well as Asn (or Ser). Some SDR family members, including 17 beta-hydroxysteroid dehydrogenase contain an additional helix-turn-helix motif that is not generally found among SDRs.


:

Pssm-ID: 187595 [Multi-domain]  Cd Length: 221  Bit Score: 359.33  E-value: 2.17e-127
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348   6 AQKVIVYGGKGALGSACVQYFKAKHWWVASIDLSANEEANANVTVKMTESFTEQANQVTADVGDLlgEEKVDAIFCVAGG 85
Cdd:cd05334   1 ARVVLVYGGRGALGSAVVQAFKSRGWWVASIDLAENEEADASIIVLDSDSFTEQAKQVVASVARL--SGKVDALICVAGG 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348  86 WAGGSAKAKTLFKNADLMWKQSVWTSTICSHLATKHLREGGLLTLAGAKAALGPTAGCIGYGMAKASVHQLCQSLSAPNS 165
Cdd:cd05334  79 WAGGSAKSKSFVKNWDLMWKQNLWTSFIASHLATKHLLSGGLLVLTGAKAALEPTPGMIGYGAAKAAVHQLTQSLAAENS 158

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 66472348 166 GLPPGSAAVAILPVTLDTPMNRKFMPDADVSCWTPLEYITELFYKWTTGESRPPSGTLMQLVT 228
Cdd:cd05334 159 GLPAGSTANAILPVTLDTPANRKAMPDADFSSWTPLEFIAELILFWASGAARPKSGSLIPVVT 221
 
Name Accession Description Interval E-value
DHPR_SDR_c_like cd05334
dihydropteridine reductase (DHPR), classical (c) SDRs; Dihydropteridine reductase is an ...
 6-228 2.17e-127

dihydropteridine reductase (DHPR), classical (c) SDRs; Dihydropteridine reductase is an NAD-binding protein related to the SDRs. It converts dihydrobiopterin into tetrahydrobiopterin, a cofactor necessary in catecholamines synthesis. Dihydropteridine reductase has the YXXXK of these tyrosine-dependent oxidoreductases, but lacks the typical upstream Asn and Ser catalytic residues. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes have a 3-glycine N-terminal NAD(P)(H)-binding pattern (typically, TGxxxGxG in classical SDRs and TGxxGxxG in extended SDRs), while substrate binding is in the C-terminal region. A critical catalytic Tyr residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering), is often found in a conserved YXXXK pattern. In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) or additional Ser, contributing to the active site. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving the conserved Tyr and Lys, as well as Asn (or Ser). Some SDR family members, including 17 beta-hydroxysteroid dehydrogenase contain an additional helix-turn-helix motif that is not generally found among SDRs.


Pssm-ID: 187595 [Multi-domain]  Cd Length: 221  Bit Score: 359.33  E-value: 2.17e-127
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348   6 AQKVIVYGGKGALGSACVQYFKAKHWWVASIDLSANEEANANVTVKMTESFTEQANQVTADVGDLlgEEKVDAIFCVAGG 85
Cdd:cd05334   1 ARVVLVYGGRGALGSAVVQAFKSRGWWVASIDLAENEEADASIIVLDSDSFTEQAKQVVASVARL--SGKVDALICVAGG 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348  86 WAGGSAKAKTLFKNADLMWKQSVWTSTICSHLATKHLREGGLLTLAGAKAALGPTAGCIGYGMAKASVHQLCQSLSAPNS 165
Cdd:cd05334  79 WAGGSAKSKSFVKNWDLMWKQNLWTSFIASHLATKHLLSGGLLVLTGAKAALEPTPGMIGYGAAKAAVHQLTQSLAAENS 158

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 66472348 166 GLPPGSAAVAILPVTLDTPMNRKFMPDADVSCWTPLEYITELFYKWTTGESRPPSGTLMQLVT 228
Cdd:cd05334 159 GLPAGSTANAILPVTLDTPANRKAMPDADFSSWTPLEFIAELILFWASGAARPKSGSLIPVVT 221
PRK12828 PRK12828
short chain dehydrogenase; Provisional
 5-224 4.48e-11

short chain dehydrogenase; Provisional


Pssm-ID: 237220 [Multi-domain]  Cd Length: 239  Bit Score: 60.58  E-value: 4.48e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348    5 DAQKVIVYGGKGALGSACVQYFKAKHWWVASIDLSANEEANANVTVKMTESFT--------EQANQVTADVGDLLGeeKV 76
Cdd:PRK12828   6 QGKVVAITGGFGGLGRATAAWLAARGARVALIGRGAAPLSQTLPGVPADALRIggidlvdpQAARRAVDEVNRQFG--RL 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348   77 DAIFCVAGGWAGGSAKAKTLfKNADLMWKQSVWTSTICSHLATKHLRE--GGLLTLAGAKAALGPTAGCIGYGMAKASVH 154
Cdd:PRK12828  84 DALVNIAGAFVWGTIADGDA-DTWDRMYGVNVKTTLNASKAALPALTAsgGGRIVNIGAGAALKAGPGMGAYAAAKAGVA 162

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348  155 QLCQSLSApnSGLPPGSAAVAILPVTLDTPMNRKFMPDADVSCWTPLEYITELFYKWTTGESRPPSGTLM 224
Cdd:PRK12828 163 RLTEALAA--ELLDRGITVNAVLPSIIDTPPNRADMPDADFSRWVTPEQIAAVIAFLLSDEAQAITGASI 230
FabG COG1028
NAD(P)-dependent dehydrogenase, short-chain alcohol dehydrogenase family [Lipid transport and ...
 1-195 7.46e-08

NAD(P)-dependent dehydrogenase, short-chain alcohol dehydrogenase family [Lipid transport and metabolism]; NAD(P)-dependent dehydrogenase, short-chain alcohol dehydrogenase family is part of the Pathway/BioSystem: Fatty acid biosynthesis


Pssm-ID: 440651 [Multi-domain]  Cd Length: 249  Bit Score: 51.71  E-value: 7.46e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348   1 MAATDAQKVIVYGGKGALGSACVQYFKAKHWWVASIDLSAnEEANAnvTVKMTESFTEQANQVTADVGDL-----LGEE- 74
Cdd:COG1028   1 MTRLKGKVALVTGGSSGIGRAIARALAAEGARVVITDRDA-EALEA--AAAELRAAGGRALAVAADVTDEaaveaLVAAa 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348  75 -----KVDAIFCVAGGWAGGSAKAKTLfKNADLMWKQSVWTSTICSHLATKHLRE--GGLLTLAGAKAALGPTAGCIGYG 147
Cdd:COG1028  78 vaafgRLDILVNNAGITPPGPLEELTE-EDWDRVLDVNLKGPFLLTRAALPHMRErgGGRIVNISSIAGLRGSPGQAAYA 156

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*...
gi 66472348 148 MAKASVHQLCQSLSApnSGLPPGSAAVAILPVTLDTPMNRKFMPDADV 195
Cdd:COG1028 157 ASKAAVVGLTRSLAL--ELAPRGIRVNAVAPGPIDTPMTRALLGAEEV 202
 
Name Accession Description Interval E-value
DHPR_SDR_c_like cd05334
dihydropteridine reductase (DHPR), classical (c) SDRs; Dihydropteridine reductase is an ...
 6-228 2.17e-127

dihydropteridine reductase (DHPR), classical (c) SDRs; Dihydropteridine reductase is an NAD-binding protein related to the SDRs. It converts dihydrobiopterin into tetrahydrobiopterin, a cofactor necessary in catecholamines synthesis. Dihydropteridine reductase has the YXXXK of these tyrosine-dependent oxidoreductases, but lacks the typical upstream Asn and Ser catalytic residues. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes have a 3-glycine N-terminal NAD(P)(H)-binding pattern (typically, TGxxxGxG in classical SDRs and TGxxGxxG in extended SDRs), while substrate binding is in the C-terminal region. A critical catalytic Tyr residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering), is often found in a conserved YXXXK pattern. In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) or additional Ser, contributing to the active site. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving the conserved Tyr and Lys, as well as Asn (or Ser). Some SDR family members, including 17 beta-hydroxysteroid dehydrogenase contain an additional helix-turn-helix motif that is not generally found among SDRs.


Pssm-ID: 187595 [Multi-domain]  Cd Length: 221  Bit Score: 359.33  E-value: 2.17e-127
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348   6 AQKVIVYGGKGALGSACVQYFKAKHWWVASIDLSANEEANANVTVKMTESFTEQANQVTADVGDLlgEEKVDAIFCVAGG 85
Cdd:cd05334   1 ARVVLVYGGRGALGSAVVQAFKSRGWWVASIDLAENEEADASIIVLDSDSFTEQAKQVVASVARL--SGKVDALICVAGG 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348  86 WAGGSAKAKTLFKNADLMWKQSVWTSTICSHLATKHLREGGLLTLAGAKAALGPTAGCIGYGMAKASVHQLCQSLSAPNS 165
Cdd:cd05334  79 WAGGSAKSKSFVKNWDLMWKQNLWTSFIASHLATKHLLSGGLLVLTGAKAALEPTPGMIGYGAAKAAVHQLTQSLAAENS 158

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 66472348 166 GLPPGSAAVAILPVTLDTPMNRKFMPDADVSCWTPLEYITELFYKWTTGESRPPSGTLMQLVT 228
Cdd:cd05334 159 GLPAGSTANAILPVTLDTPANRKAMPDADFSSWTPLEFIAELILFWASGAARPKSGSLIPVVT 221
SDR_c cd05233
classical (c) SDRs; SDRs are a functionally diverse family of oxidoreductases that have a ...
 9-194 9.21e-16

classical (c) SDRs; SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human prostaglandin dehydrogenase (PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, PGDH numbering) and/or an Asn (Asn-107, PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.


Pssm-ID: 212491 [Multi-domain]  Cd Length: 234  Bit Score: 73.86  E-value: 9.21e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348   9 VIVYGGKGALGSACVQYFKAKHWWVASIDLSA---------NEEANANVTVKMTESFTEQANQVTADVGDLLGeeKVDAI 79
Cdd:cd05233   1 ALVTGASSGIGRAIARRLAREGAKVVLADRNEealaelaaiEALGGNAVAVQADVSDEEDVEALVEEALEEFG--RLDIL 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348  80 FCVAGGWAGGSAkAKTLFKNADLMWKQSVWTSTICSHLATKHLRE--GGLLTLAGAKAALGPTAGCIGYGMAKASVHQLC 157
Cdd:cd05233  79 VNNAGIARPGPL-EELTDEDWDRVLDVNLTGVFLLTRAALPHMKKqgGGRIVNISSVAGLRPLPGQAAYAASKAALEGLT 157

                       170       180       190
                ....*....|....*....|....*....|....*..
gi 66472348 158 QSLSApnSGLPPGSAAVAILPVTLDTPMNRKFMPDAD 194
Cdd:cd05233 158 RSLAL--ELAPYGIRVNAVAPGLVDTPMLAKLGPEEA 192
PRK12828 PRK12828
short chain dehydrogenase; Provisional
 5-224 4.48e-11

short chain dehydrogenase; Provisional


Pssm-ID: 237220 [Multi-domain]  Cd Length: 239  Bit Score: 60.58  E-value: 4.48e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348    5 DAQKVIVYGGKGALGSACVQYFKAKHWWVASIDLSANEEANANVTVKMTESFT--------EQANQVTADVGDLLGeeKV 76
Cdd:PRK12828   6 QGKVVAITGGFGGLGRATAAWLAARGARVALIGRGAAPLSQTLPGVPADALRIggidlvdpQAARRAVDEVNRQFG--RL 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348   77 DAIFCVAGGWAGGSAKAKTLfKNADLMWKQSVWTSTICSHLATKHLRE--GGLLTLAGAKAALGPTAGCIGYGMAKASVH 154
Cdd:PRK12828  84 DALVNIAGAFVWGTIADGDA-DTWDRMYGVNVKTTLNASKAALPALTAsgGGRIVNIGAGAALKAGPGMGAYAAAKAGVA 162

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348  155 QLCQSLSApnSGLPPGSAAVAILPVTLDTPMNRKFMPDADVSCWTPLEYITELFYKWTTGESRPPSGTLM 224
Cdd:PRK12828 163 RLTEALAA--ELLDRGITVNAVLPSIIDTPPNRADMPDADFSRWVTPEQIAAVIAFLLSDEAQAITGASI 230
FabG COG1028
NAD(P)-dependent dehydrogenase, short-chain alcohol dehydrogenase family [Lipid transport and ...
 1-195 7.46e-08

NAD(P)-dependent dehydrogenase, short-chain alcohol dehydrogenase family [Lipid transport and metabolism]; NAD(P)-dependent dehydrogenase, short-chain alcohol dehydrogenase family is part of the Pathway/BioSystem: Fatty acid biosynthesis


Pssm-ID: 440651 [Multi-domain]  Cd Length: 249  Bit Score: 51.71  E-value: 7.46e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348   1 MAATDAQKVIVYGGKGALGSACVQYFKAKHWWVASIDLSAnEEANAnvTVKMTESFTEQANQVTADVGDL-----LGEE- 74
Cdd:COG1028   1 MTRLKGKVALVTGGSSGIGRAIARALAAEGARVVITDRDA-EALEA--AAAELRAAGGRALAVAADVTDEaaveaLVAAa 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348  75 -----KVDAIFCVAGGWAGGSAKAKTLfKNADLMWKQSVWTSTICSHLATKHLRE--GGLLTLAGAKAALGPTAGCIGYG 147
Cdd:COG1028  78 vaafgRLDILVNNAGITPPGPLEELTE-EDWDRVLDVNLKGPFLLTRAALPHMRErgGGRIVNISSIAGLRGSPGQAAYA 156

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*...
gi 66472348 148 MAKASVHQLCQSLSApnSGLPPGSAAVAILPVTLDTPMNRKFMPDADV 195
Cdd:COG1028 157 ASKAAVVGLTRSLAL--ELAPRGIRVNAVAPGPIDTPMTRALLGAEEV 202
SDR_c12 cd08944
classical (c) SDR, subgroup 12; These are classical SDRs, with the canonical active site ...
 9-194 2.05e-05

classical (c) SDR, subgroup 12; These are classical SDRs, with the canonical active site tetrad and glycine-rich NAD-binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.


Pssm-ID: 187648 [Multi-domain]  Cd Length: 246  Bit Score: 44.40  E-value: 2.05e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348   9 VIVYGGKGALGSACVQYFKAK--HWWVASIDLSANEEAnanvtvkmTESFTEQANQVTADVGDllgEEKVDAIFCVAGGW 86
Cdd:cd08944   6 AIVTGAGAGIGAACAARLAREgaRVVVADIDGGAAQAV--------VAQIAGGALALRVDVTD---EQQVAALFERAVEE 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348  87 AGGSAKaktLFKNADLMWKQS--------VWTSTICSHL-----ATKHL------REGGLLTLAGAKAALGPTAGCIGYG 147
Cdd:cd08944  75 FGGLDL---LVNNAGAMHLTPaiidtdlaVWDQTMAINLrgtflCCRHAaprmiaRGGGSIVNLSSIAGQSGDPGYGAYG 151

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 66472348 148 MAKASVHQLCQSLSAPNSGlpPGSAAVAILPVTLDTPMNRKFMPDAD 194
Cdd:cd08944 152 ASKAAIRNLTRTLAAELRH--AGIRCNALAPGLIDTPLLLAKLAGFE 196
PRK12827 PRK12827
short chain dehydrogenase; Provisional
 1-192 2.34e-05

short chain dehydrogenase; Provisional


Pssm-ID: 237219 [Multi-domain]  Cd Length: 249  Bit Score: 44.33  E-value: 2.34e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348    1 MAATDAQKVIVYGGKGALGSACVQYFKAKHWWVASIDLSANE-EANANVTVKMTESFTEQANQVTADVGDL--------- 70
Cdd:PRK12827   1 MASLDSRRVLITGGSGGLGRAIAVRLAADGADVIVLDIHPMRgRAEADAVAAGIEAAGGKALGLAFDVRDFaatraalda 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348   71 LGEE--KVDAIFCVAGGWAGGSAKAKTLFKNADLMWKQSVWTSTICsHLATKHL---REGGLLTLAGAKAALGPTAGCIG 145
Cdd:PRK12827  81 GVEEfgRLDILVNNAGIATDAAFAELSIEEWDDVIDVNLDGFFNVT-QAALPPMiraRRGGRIVNIASVAGVRGNRGQVN 159

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 66472348  146 YGMAKASVHQLCQSLSapNSGLPPGSAAVAILPVTLDTPMNRKFMPD 192
Cdd:PRK12827 160 YAASKAGLIGLTKTLA--NELAPRGITVNAVAPGAINTPMADNAAPT 204
DHRS1_HSDL2-like_SDR_c cd05338
human dehydrogenase/reductase (SDR family) member 1 (DHRS1) and human hydroxysteroid ...
 101-206 1.72e-04

human dehydrogenase/reductase (SDR family) member 1 (DHRS1) and human hydroxysteroid dehydrogenase-like protein 2 (HSDL2), classical (c) SDRs; This subgroup includes human DHRS1 and human HSDL2 and related proteins. These are members of the classical SDR family, with a canonical Gly-rich NAD-binding motif and the typical YXXXK active site motif. However, the rest of the catalytic tetrad is not strongly conserved. DHRS1 mRNA has been detected in many tissues, liver, heart, skeletal muscle, kidney and pancreas; a longer transcript is predominantly expressed in the liver , a shorter one in the heart. HSDL2 may play a part in fatty acid metabolism, as it is found in peroxisomes. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes have a 3-glycine N-terminal NAD(P)(H)-binding pattern (typically, TGxxxGxG in classical SDRs and TGxxGxxG in extended SDRs), while substrate binding is in the C-terminal region. A critical catalytic Tyr residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering), is often found in a conserved YXXXK pattern. In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) or additional Ser, contributing to the active site. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving the conserved Tyr and Lys, as well as Asn (or Ser). Some SDR family members, including 17 beta-hydroxysteroid dehydrogenase contain an additional helix-turn-helix motif that is not generally found among SDRs.


Pssm-ID: 187597 [Multi-domain]  Cd Length: 246  Bit Score: 41.61  E-value: 1.72e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348 101 DLMWKQSVWTSTICSHLATKHL--REGGLLTLAGAKAALGPTAGCIGYGMAKASVHQLCQSLSAPNSGlpPGSAAVAILP 178
Cdd:cd05338 117 DLMQRVNLRGTYLLSQAALPHMvkAGQGHILNISPPLSLRPARGDVAYAAGKAGMSRLTLGLAAELRR--HGIAVNSLWP 194

                        90       100
                ....*....|....*....|....*....
gi 66472348 179 VTL-DTPMNRKFMPDADVSCWTPLEYITE 206
Cdd:cd05338 195 STAiETPAATELSGGSDPARARSPEILSD 223
YqjQ COG0300
Short-chain dehydrogenase [General function prediction only];
1-200 3.01e-04

Short-chain dehydrogenase [General function prediction only];


Pssm-ID: 440069 [Multi-domain]  Cd Length: 252  Bit Score: 41.01  E-value: 3.01e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348   1 MAATDaQKVIVYGGKGALGSACVQYFKAKHW--WVASIDLSANEEANANVTVKMTESFT--------EQANQVTADVGDL 70
Cdd:COG0300   1 MSLTG-KTVLITGASSGIGRALARALAARGArvVLVARDAERLEALAAELRAAGARVEVvaldvtdpDAVAALAEAVLAR 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348  71 LGeeKVDAIFCVAGGWAGGSAKAKTLfKNADLMWKQSVWTSTICSHLATKHLRE---GGLLTLAGAkAALGPTAGCIGYG 147
Cdd:COG0300  80 FG--PIDVLVNNAGVGGGGPFEELDL-EDLRRVFEVNVFGPVRLTRALLPLMRArgrGRIVNVSSV-AGLRGLPGMAAYA 155

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 66472348 148 MAKASVHQLCQSLSA--PNSGLppgsAAVAILPVTLDTPMNRKFMPDADVSCWTP 200
Cdd:COG0300 156 ASKAALEGFSESLRAelAPTGV----RVTAVCPGPVDTPFTARAGAPAGRPLLSP 206
fabG PRK06077
3-ketoacyl-(acyl-carrier-protein) reductase; Provisional
 8-161 3.02e-04

3-ketoacyl-(acyl-carrier-protein) reductase; Provisional


Pssm-ID: 235693 [Multi-domain]  Cd Length: 252  Bit Score: 40.86  E-value: 3.02e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348    8 KVIVYGGKG-ALGSACVQYFKAKHWWVASIDLSANEEANAnvTVKMTESFTEQANQVTADVGDLLG-EEKVDAIFCVAGG 85
Cdd:PRK06077   7 KVVVVTGSGrGIGRAIAVRLAKEGSLVVVNAKKRAEEMNE--TLKMVKENGGEGIGVLADVSTREGcETLAKATIDRYGV 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348   86 W------AG-GSAkakTLFKNAD--LMWKQ--SVWTSTI-CSHLATKHLREGGLLTLAGAKAALGPTAGCIGYGMAKASV 153
Cdd:PRK06077  85 AdilvnnAGlGLF---SPFLNVDdkLIDKHisTDFKSVIyCSQELAKEMREGGAIVNIASVAGIRPAYGLSIYGAMKAAV 161


                 ....*...
gi 66472348  154 HQLCQSLS 161
Cdd:PRK06077 162 INLTKYLA 169
PRK06484 PRK06484
short chain dehydrogenase; Validated
 3-162 3.89e-04

short chain dehydrogenase; Validated


Pssm-ID: 168574 [Multi-domain]  Cd Length: 520  Bit Score: 40.99  E-value: 3.89e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348    3 ATDAQKVIVYGGKGALGSACVQYFKAKHWWVASIDLSANEeananvTVKMTESFTEQANQVTADVGDllgEEKVDAIFCV 82
Cdd:PRK06484 266 AESPRVVAITGGARGIGRAVADRFAAAGDRLLIIDRDAEG------AKKLAEALGDEHLSVQADITD---EAAVESAFAQ 336

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348   83 AGGWAG-------GSAKAKTLFKNADlmwkQSV--WTSTI---------CSHLATKHLREGGLLTLAGAKAALGPTAGCI 144
Cdd:PRK06484 337 IQARWGrldvlvnNAGIAEVFKPSLE----QSAedFTRVYdvnlsgafaCARAAARLMSQGGVIVNLGSIASLLALPPRN 412

                        170
                 ....*....|....*...
gi 66472348  145 GYGMAKASVHQLCQSLSA 162
Cdd:PRK06484 413 AYCASKAAVTMLSRSLAC 430
PRK08324 PRK08324
bifunctional aldolase/short-chain dehydrogenase;
9-162 6.54e-04

bifunctional aldolase/short-chain dehydrogenase;


Pssm-ID: 236241 [Multi-domain]  Cd Length: 681  Bit Score: 40.60  E-value: 6.54e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348    9 VIVYGGKGALGSACVQYFKAK--HWWVASIDLSANEEANANVTVKmtesftEQANQVTADVGDllgEEKVDAIF---CVA 83
Cdd:PRK08324 425 ALVTGAAGGIGKATAKRLAAEgaCVVLADLDEEAAEAAAAELGGP------DRALGVACDVTD---EAAVQAAFeeaALA 495

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348   84 -GGW-----AGGSAKAKTLFKNADLMWKQS----VWTSTICSHLATKHLRE---GGLLTLAGAKAALGPTAGCIGYGMAK 150
Cdd:PRK08324 496 fGGVdivvsNAGIAISGPIEETSDEDWRRSfdvnATGHFLVAREAVRIMKAqglGGSIVFIASKNAVNPGPNFGAYGAAK 575

                        170
                 ....*....|..
gi 66472348  151 ASVHQLCQSLSA 162
Cdd:PRK08324 576 AAELHLVRQLAL 587
PRK12829 PRK12829
short chain dehydrogenase; Provisional
 1-192 9.52e-04

short chain dehydrogenase; Provisional


Pssm-ID: 183778 [Multi-domain]  Cd Length: 264  Bit Score: 39.27  E-value: 9.52e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348    1 MAATDAQKVIVYGGKGALGSACVQYFKAKHWWVASIDLSaneEANANVTVKMTESFTEQAnqVTADVGDllgEEKVDAIF 80
Cdd:PRK12829   6 LKPLDGLRVLVTGGASGIGRAIAEAFAEAGARVHVCDVS---EAALAATAARLPGAKVTA--TVADVAD---PAQVERVF 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348   81 CVA----GGW------AGGSAKAKTLFKNADLMWKQSV---WTSTI-CSHLATKHLREGGLltlAGAKAALGPTAGCIGY 146
Cdd:PRK12829  78 DTAverfGGLdvlvnnAGIAGPTGGIDEITPEQWEQTLavnLNGQFyFARAAVPLLKASGH---GGVIIALSSVAGRLGY 154

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 66472348  147 GM------AKASVHQLCQSLSAPNSglPPGSAAVAILPVTLDTPMNRKFMPD 192
Cdd:PRK12829 155 PGrtpyaaSKWAVVGLVKSLAIELG--PLGIRVNAILPGIVRGPRMRRVIEA 204
ADH_SDR_c_like cd05323
insect type alcohol dehydrogenase (ADH)-like, classical (c) SDRs; This subgroup contains ...
 9-196 3.49e-03

insect type alcohol dehydrogenase (ADH)-like, classical (c) SDRs; This subgroup contains insect type ADH, and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) type I; these proteins are classical SDRs. ADH catalyzes the NAD+-dependent oxidation of alcohols to aldehydes/ketones. This subgroup is distinct from the zinc-dependent alcohol dehydrogenases of the medium chain dehydrogenase/reductase family, and evolved in fruit flies to allow the digestion of fermenting fruit. 15-PGDH catalyzes the NAD-dependent interconversion of (5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-13-enoate and (5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-13-enoate, and has a typical SDR glycine-rich NAD-binding motif, which is not fully present in ADH. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.


Pssm-ID: 187584 [Multi-domain]  Cd Length: 244  Bit Score: 37.67  E-value: 3.49e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348   9 VIVYGGKGALGSACVQYFKAKHWWVASIDLsaNEEANANVTVKMTESFTeQANQVTADVGDLLGEEK-----------VD 77
Cdd:cd05323   3 AIITGGASGIGLATAKLLLKKGAKVAILDR--NENPGAAAELQAINPKV-KATFVQCDVTSWEQLAAafkkaiekfgrVD 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348  78 AIFCVAGGwaggsAKAKTLFKNADLmwkQSVWTSTI---------CSHLATKHLR-----EGGLLTLAGAKAALGPTAGC 143
Cdd:cd05323  80 ILINNAGI-----LDEKSYLFAGKL---PPPWEKTIdvnltgvinTTYLALHYMDknkggKGGVIVNIGSVAGLYPAPQF 151

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348 144 IGYGMAKASVHQLCQSLsAPNSGLPPGSAAVAILPVTLDTPM-------NRKFMPDADVS 196
Cdd:cd05323 152 PVYSASKHGVVGFTRSL-ADLLEYKTGVRVNAICPGFTNTPLlpdlvakEAEMLPSAPTQ 210
Tthb094_like_SDR_c cd11730
Tthb094 and related proteins, classical (c) SDRs; Tthb094 from Thermus Thermophilus is a ...
 9-185 5.81e-03

Tthb094 and related proteins, classical (c) SDRs; Tthb094 from Thermus Thermophilus is a classical SDR which binds NADP. Members of this subgroup contain the YXXXK active site characteristic of SDRs. Also, an upstream Asn residue of the canonical catalytic tetrad is partially conserved in this subgroup of proteins of undetermined function. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human prostaglandin dehydrogenase (PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, PGDH numbering) and/or an Asn (Asn-107, PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.


Pssm-ID: 212496 [Multi-domain]  Cd Length: 206  Bit Score: 36.73  E-value: 5.81e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348   9 VIVYGGKGALGSACVQYFKAKHWWVASIdlSANEEANANVTVKMTESfteqanqvtADVGDLLGEEKVDAIFCVAGG--- 85
Cdd:cd11730   1 ALILGATGGIGRALARALAGRGWRLLLS--GRDAGALAGLAAEVGAL---------ARPADVAAELEVWALAQELGPldl 69

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66472348  86 --WAGGSAKAKTLFKNADLMWKQSVWTSTICSHLATKH----LREGGLLTLAGAKAALGPTAGCIGYGMAKASVHQLCQS 159
Cdd:cd11730  70 lvYAAGAILGKPLARTKPAAWRRILDANLTGAALVLKHalalLAAGARLVFLGAYPELVMLPGLSAYAAAKAALEAYVEV 149

                       170       180
                ....*....|....*....|....*.
gi 66472348 160 LSAPNSGLppgsAAVAILPVTLDTPM 185
Cdd:cd11730 150 ARKEVRGL----RLTLVRPPAVDTGL 171
 
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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