Short-chain dehydrogenase [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283   2 GTECHYFICDVGNREEVYQMAKAVREKVGDITILVNNAAVVHGKSLMDSDDDALLKSQHVNTLGQFWTTKAFLPRMLELQ 81
Cdd:COG0300    53 GARVEVVALDVTDPDAVAALAEAVLARFGPIDVLVNNAGVGGGGPFEELDLEDLRRVFEVNVFGPVRLTRALLPLMRARG 132

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283  82 NGHIVCLNSVLALSAIPGAIDYCTSKASAFAFMESLTLGLLDcPGVSATTVLPFHTSTEMFQGMRVRFPNlfPPLKPETV 161
Cdd:COG0300   133 RGRIVNVSSVAGLRGLPGMAAYAASKAALEGFSESLRAELAP-TGVRVTAVCPGPVDTPFTARAGAPAGR--PLLSPEEV 209

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1269612283 162 ARRTVDAVQQNQALLLLPWTMNILIILKSILPQA 195
Cdd:COG0300   210 ARAILRALERGRAEVYVGWDARLLARLLRLLPRL 243

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283   5 CHYFICDVGNREEVYQMAKAVREKVGDITILVNNAAVVHGKSLMDSDDDALLKSQHVNTLGQFWTTKAFLPRMLELQNGH 84
Cdd:PRK07825   52 VVGGPLDVTDPASFAAFLDAVEADLGPIDVLVNNAGVMPVGPFLDEPDAVTRRILDVNVYGVILGSKLAAPRMVPRGRGH 131

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283  85 IVCLNSVLALSAIPGAIDYCTSKASAFAFMESLTLGLLDcPGVSATTVLPFHTSTEMFQGmrVRFPNLFPPLKPETVARR 164
Cdd:PRK07825  132 VVNVASLAGKIPVPGMATYCASKHAVVGFTDAARLELRG-TGVHVSVVLPSFVNTELIAG--TGGAKGFKNVEPEDVAAA 208

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 1269612283 165 TVDAVQQNQALLLLPWTMNILIILKSILPQAALEEIHRFSGT 206
Cdd:PRK07825  209 IVGTVAKPRPEVRVPRALGPLAQAQRLLPRRVREALNRLLGG 250

This enzymatic domain is part of bacterial polyketide synthases; It catalyses the first step in the reductive modification of the beta-carbonyl centres in the growing polyketide chain. It uses NADPH to reduce the keto group to a hydroxy group.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283    1 MGTECHYFICDVGNREEVYQMAKAVREKVGDITILVNNAAVVhgkslmdsdDDALLKSQHVNTLGQFWTTK--------- 71
Cdd:smart00822  51 AGARVTVVACDVADRDALAAVLAAIPAVEGPLTGVIHAAGVL---------DDGVLASLTPERFAAVLAPKaagawnlhe 121

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1269612283   72 AFLPRMLElqngHIVCLNSVLALSAIPGAIDYctskASAFAFMESL 117
Cdd:smart00822 122 LTADLPLD----FFVLFSSIAGVLGSPGQANY----AAANAFLDAL 159

Short-chain dehydrogenase [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283   2 GTECHYFICDVGNREEVYQMAKAVREKVGDITILVNNAAVVHGKSLMDSDDDALLKSQHVNTLGQFWTTKAFLPRMLELQ 81
Cdd:COG0300    53 GARVEVVALDVTDPDAVAALAEAVLARFGPIDVLVNNAGVGGGGPFEELDLEDLRRVFEVNVFGPVRLTRALLPLMRARG 132

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283  82 NGHIVCLNSVLALSAIPGAIDYCTSKASAFAFMESLTLGLLDcPGVSATTVLPFHTSTEMFQGMRVRFPNlfPPLKPETV 161
Cdd:COG0300   133 RGRIVNVSSVAGLRGLPGMAAYAASKAALEGFSESLRAELAP-TGVRVTAVCPGPVDTPFTARAGAPAGR--PLLSPEEV 209

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1269612283 162 ARRTVDAVQQNQALLLLPWTMNILIILKSILPQA 195
Cdd:COG0300   210 ARAILRALERGRAEVYVGWDARLLARLLRLLPRL 243

NADP-dependent 3-hydroxy acid dehydrogenase YdfG [Energy production and conversion]; NADP-dependent 3-hydroxy acid dehydrogenase YdfG is part of the Pathway/BioSystem: Pyrimidine degradation

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283   2 GTECHYFICDVGNREEVYQMAKAVREKVGDITILVNNAAVVHGKSLMDSDDDALLKSQHVNTLGQFWTTKAFLPRMLELQ 81
Cdd:COG4221    50 GGRALAVPLDVTDEAAVEAAVAAAVAEFGRLDVLVNNAGVALLGPLEELDPEDWDRMIDVNVKGVLYVTRAALPAMRARG 129

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283  82 NGHIVCLNSVLALSAIPGAIDYCTSKASAFAFMESLTLGLLDCpGVSATTVLPFHTSTEMFQGMRVRFPN-------LFP 154
Cdd:COG4221   130 SGHIVNISSIAGLRPYPGGAVYAATKAAVRGLSESLRAELRPT-GIRVTVIEPGAVDTEFLDSVFDGDAEaaaavyeGLE 208

                         170
                  ....*....|....*..
gi 1269612283 155 PLKPETVARRTVDAVQQ 171
Cdd:COG4221   209 PLTPEDVAEAVLFALTQ 225

3-ketodihydrosphingosine reductase (KDSR) and related proteins, classical (c) SDR; These proteins include members identified as KDSR, ribitol type dehydrogenase, and others. The group shows strong conservation of the active site tetrad and glycine rich NAD-binding motif of the classical 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 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283   2 GTECHYFICDVGNREEVYQMAKAVREKVGDITILVNNAAVVHGKSLMDSDDDALLKSQHVNTLGQFWTTKAFLPRMLELQ 81
Cdd:cd08939    53 GQKVSYISADLSDYEEVEQAFAQAVEKGGPPDLVVNCAGISIPGLFEDLTAEEFERGMDVNYFGSLNVAHAVLPLMKEQR 132

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283  82 NGHIVCLNSVLALSAIPGAIDYCTSKASAFAFMESLTLGLLdCPGVSATTVLPFHTSTEMFQGMRVRFPNLF-------P 154
Cdd:cd08939   133 PGHIVFVSSQAALVGIYGYSAYCPSKFALRGLAESLRQELK-PYNIRVSVVYPPDTDTPGFEEENKTKPEETkaiegssG 211

                         170
                  ....*....|....
gi 1269612283 155 PLKPETVARRTVDA 168
Cdd:cd08939   212 PITPEEAARIIVKG 225

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1)-like, classical (c) SDRs; Human 11beta_HSD1 catalyzes the NADP(H)-dependent interconversion of cortisone and cortisol. This subgroup also includes human dehydrogenase/reductase SDR family member 7C (DHRS7C) and DHRS7B. These proteins have the GxxxGxG nucleotide binding motif and S-Y-K catalytic triad characteristic of the SDRs, but have an atypical C-terminal domain that contributes to homodimerization contacts. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283   2 GTECHYFICDVGNREEVYQMAKAVREKVGDITILVNNAAvVHGKSLMDSDD-DALLKSQHVNTLGQFWTTKAFLPRMLEL 80
Cdd:cd05332    52 APSPHVVPLDMSDLEDAEQVVEEALKLFGGLDILINNAG-ISMRSLFHDTSiDVDRKIMEVNYFGPVALTKAALPHLIER 130

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283  81 QNGHIVCLNSVLALSAIPGAIDYCTSKASAFAFMESLTLGlLDCPGVSATTVLP--------FHTSTEMFQGMRVRFPNL 152
Cdd:cd05332   131 SQGSIVVVSSIAGKIGVPFRTAYAASKHALQGFFDSLRAE-LSEPNISVTVVCPglidtniaMNALSGDGSMSAKMDDTT 209

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 1269612283 153 FPPLKPETVARRTVDAVQQNQALLLLPWTMNILII-LKSILPQ 194
Cdd:cd05332   210 ANGMSPEECALEILKAIALRKREVFYARQVPLLAVyLRQLFPG 252

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283  11 DVGNREEVYQMAkavrEKVGDITILVNNAAVVHGKSLMDSDDDALLKSQ-HVNTLGQFWTTKAFLPRMLELQNGHIVCLN 89
Cdd:PRK08264   57 DVTDPASVAAAA----EAASDVTILVNNAGIFRTGSLLLEGDEDALRAEmETNYFGPLAMARAFAPVLAANGGGAIVNVL 132

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283  90 SVLALSAIPGAIDYCTSKASAFafmeSLTLGL---LDCPGVSATTVLPFHTSTEMFQGMRVrfpnlfPPLKPETVARRTV 166
Cdd:PRK08264  133 SVLSWVNFPNLGTYSASKAAAW----SLTQALraeLAPQGTRVLGVHPGPIDTDMAAGLDA------PKASPADVARQIL 202

                         170
                  ....*....|.
gi 1269612283 167 DAVQQNQALLL 177
Cdd:PRK08264  203 DALEAGDEEVL 213

classical (c) SDR, subgroup 3; These proteins are members of the classical SDR family, with a canonical active site triad (and also active site Asn) and a typical Gly-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 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283   2 GTECHYFICDVGNREEVYQMAKAVREKVGDITILVNNAAV-VHGKsLMDSDDDALLKSQHVNTLGQFWTTKAFLPRMLEL 80
Cdd:cd05360    48 GGEAIAVVADVADAAQVERAADTAVERFGRIDTWVNNAGVaVFGR-FEDVTPEEFRRVFDVNYLGHVYGTLAALPHLRRR 126

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283  81 QNGHIVCLNSVLALSAIPGAIDYCTSKASAFAFMESLTLGL-LDCPGVSATTVLPFHTSTEMFQGMRVRF---PNLFPPL 156
Cdd:cd05360   127 GGGALINVGSLLGYRSAPLQAAYSASKHAVRGFTESLRAELaHDGAPISVTLVQPTAMNTPFFGHARSYMgkkPKPPPPI 206

                         170
                  ....*....|....*
gi 1269612283 157 -KPETVARRTVDAVQ 170
Cdd:cd05360   207 yQPERVAEAIVRAAE 221

beta-Keto acyl carrier protein reductase (BKR), involved in Type II FAS, classical (c) SDRs; This subgroup includes the Escherichai coli K12 BKR, FabG. BKR catalyzes the NADPH-dependent reduction of ACP in the first reductive step of de novo fatty acid synthesis (FAS). FAS consists of four elongation steps, which are repeated to extend the fatty acid chain through the addition of two-carbo units from malonyl acyl-carrier protein (ACP): condensation, reduction, dehydration, and a final reduction. Type II FAS, typical of plants and many bacteria, maintains these activities on discrete polypeptides, while type I FAS utilizes one or two multifunctional polypeptides. BKR resembles enoyl reductase, which catalyzes the second reduction step in FAS. SDRs are a functionally diverse family of oxidoreductases that have a single domain with structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet) 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: TGxxxGxG in classical SDRs. 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 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. 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-151 and Lys-155, and well as Asn-111 (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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283   2 GTECHYFICDVGNREEVYQMAKAVREKVGDITILVNNAAVVHGKSLM---DSDDDALLKsqhVNTLGQFWTTKAFLPRML 78
Cdd:cd05333    48 GGNAAALEADVSDREAVEALVEKVEAEFGPVDILVNNAGITRDNLLMrmsEEDWDAVIN---VNLTGVFNVTQAVIRAMI 124

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1269612283  79 ELQNGHIVCLNSVLALSAIPGAIDYCTSKASAFAFMESLTLGLLDcPGVSATTVLPFHTSTEM 141
Cdd:cd05333   125 KRRSGRIINISSVVGLIGNPGQANYAASKAGVIGFTKSLAKELAS-RGITVNAVAPGFIDTDM 186

HetN oxidoreductase-like, classical (c) SDR; This subgroup includes Anabaena sp. strain PCC 7120 HetN, a putative oxidoreductase involved in heterocyst differentiation, and related proteins. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283  10 CDVGNREEVYQMAKAVREKVGDITILVNNAAVVHGKSLMDSDDDALLKSQHVNTLGQFWTTKAFLPRMLELQNGHIVCLN 89
Cdd:cd08932    52 YDARDPEDARALVDALRDRFGRIDVLVHNAGIGRPTTLREGSDAELEAHFSINVIAPAELTRALLPALREAGSGRVVFLN 131

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1269612283  90 SVLALSAIPGAIDYCTSKASAFAFMESLTLGLLDcPGVSATTVLPFHTSTEMFQGMRVRfpNLFPPL---KPETVAR 163
Cdd:cd08932   132 SLSGKRVLAGNAGYSASKFALRALAHALRQEGWD-HGVRVSAVCPGFVDTPMAQGLTLV--GAFPPEemiQPKDIAN 205

17beta hydroxysteroid dehydrogenase-like, classical (c) SDRs; 17beta-hydroxysteroid dehydrogenases are a group of isozymes that catalyze activation and inactivation of estrogen and androgens. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283   6 HYFICDVGNREEVYQMAKAVREKVGDITILVNNAAVVHGKSLMDSDDDALLKSQHVNTLGQFWTTKAFLPRMLELQNGHI 85
Cdd:cd05374    49 EVLELDVTDEESIKAAVKEVIERFGRIDVLVNNAGYGLFGPLEETSIEEVRELFEVNVFGPLRVTRAFLPLMRKQGSGRI 128

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283  86 VCLNSVLALSAIPGAIDYCTSKasaFAfMESLTLGL---LDCPGVSATTVLPFHTSTEMFQGMRVRFP------------ 150
Cdd:cd05374   129 VNVSSVAGLVPTPFLGPYCASK---AA-LEALSESLrleLAPFGIKVTIIEPGPVRTGFADNAAGSALedpeispyaper 204

                         170       180
                  ....*....|....*....|....*...
gi 1269612283 151 ---------NLFPPLKPETVARRTVDAV 169
Cdd:cd05374   205 keikenaagVGSNPGDPEKVADVIVKAL 232

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283   2 GTECHYFICDVGNREEVYQMAKAVREKVGDITILVNNAAVVHGKSLMDSDDDALLKSQHVNTLGQFWTTKAFLPRMLELQ 81
Cdd:PRK12825   55 GRRAQAVQADVTDKAALEAAVAAAVERFGRIDILVNNAGIFEDKPLADMSDDEWDEVIDVNLSGVFHLLRAVVPPMRKQR 134

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1269612283  82 NGHIVCLNSVLALSAIPGAIDYCTSKASAFAFMESL 117
Cdd:PRK12825  135 GGRIVNISSVAGLPGWPGRSNYAAAKAGLVGLTKAL 170

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283   2 GTECHYFICDVGNREEVYQMAKAVREKVGDITILVNNAAVVHGKSLMDSDDDALLKSQHVNTLGQFWTTKAFLPRMLELQ 81
Cdd:cd05338    63 GGQALPIVVDVRDEDQVRALVEATVDQFGRLDILVNNAGAIWLSLVEDTPAKRFDLMQRVNLRGTYLLSQAALPHMVKAG 142

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283  82 NGHIVCLNSVLALSAIPGAIDYCTSKASafafMESLTLGL---LDCPGVSATTVLPfHTSTEMFQGMRVrFPNLFPPL-- 156
Cdd:cd05338   143 QGHILNISPPLSLRPARGDVAYAAGKAG----MSRLTLGLaaeLRRHGIAVNSLWP-STAIETPAATEL-SGGSDPARar 216

                  ....*..
gi 1269612283 157 KPETVAR 163
Cdd:cd05338   217 SPEILSD 223

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283  11 DVGNREEVYQMAKAVREKVGDITILVNNAAVVHGKSLMDSDDDALLKSQHVNTLGQFWTTKAFLPRMLELQNGHIVCLNS 90
Cdd:PRK07666   64 DVSDYEEVTAAIEQLKNELGSIDILINNAGISKFGKFLELDPAEWEKIIQVNLMGVYYATRAVLPSMIERQSGDIINISS 143

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283  91 VLALSAIPGAIDYCTSKASAFAFMESLTLGLLDcPGVSATTVLPFHTSTEMFQGMRVRFPNLFPPLKPETVARRTVDAVQ 170
Cdd:PRK07666  144 TAGQKGAAVTSAYSASKFGVLGLTESLMQEVRK-HNIRVTALTPSTVATDMAVDLGLTDGNPDKVMQPEDLAEFIVAQLK 222

                         170
                  ....*....|....*.
gi 1269612283 171 QNQALLL---LPWTMN 183
Cdd:PRK07666  223 LNKRTFIksaGLWSTN 238

human DHRS6-like, classical (c) SDRs; Human DHRS6, and similar proteins. These proteins are classical SDRs, with a canonical active site tetrad and a close match to the typical Gly-rich NAD-binding motif. Human DHRS6 is a cytosolic type 2 (R)-hydroxybutyrate dehydrogenase, which catalyses the conversion of (R)-hydroxybutyrate to acetoacetate. Also included in this subgroup is Escherichia coli UcpA (upstream cys P). 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. Note: removed : needed to make this chiodl smaller when drew final trees: rmeoved text form description: Other proteins in this subgroup include Thermoplasma acidophilum aldohexose dehydrogenase, which has high dehydrogenase activity against D-mannose, Bacillus subtilis BacC involved in the biosynthesis of the dipeptide bacilysin and its antibiotic moiety anticapsin, Sphingomonas paucimobilis strain B90 LinC, involved in the degradation of hexachlorocyclohexane isomers...... P).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283  11 DVGNREEVYQMAKavreKVGDITILVNNAAVVHGKSLMDSDDDALLKSQHVNTLGQFWTTKAFLPRMLELQNGHIVCLNS 90
Cdd:cd05368    54 DVTDKEQVAALAK----EEGRIDVLFNCAGFVHHGSILDCEDDDWDFAMNLNVRSMYLMIKAVLPKMLARKDGSIINMSS 129

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1269612283  91 VLA-LSAIPGAIDYCTSKASAFAFMESLTLGLLD--------CPGVSATTVL 133
Cdd:cd05368   130 VASsIKGVPNRFVYSTTKAAVIGLTKSVAADFAQqgircnaiCPGTVDTPSL 181

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283   1 MGTECHYFICDVGNREEVYQMAKAVREKVGDITILVNNAAVVHGKSLMDSDD-DALLKSQHVNTLGQFWTTKAFLPRMLE 79
Cdd:PRK07024   48 KAARVSVYAADVRDADALAAAAADFIAAHGLPDVVIANAGISVGTLTEEREDlAVFREVMDTNYFGMVATFQPFIAPMRA 127

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283  80 LQNGHIVCLNSVLALSAIPGAIDYCTSKASAFAFMESLTLGLLDcPGVSATTVLPFHTSTEMFQGMRVRFPNLFPplkPE 159
Cdd:PRK07024  128 ARRGTLVGIASVAGVRGLPGAGAYSASKAAAIKYLESLRVELRP-AGVRVVTIAPGYIRTPMTAHNPYPMPFLMD---AD 203

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 1269612283 160 TVARRTVDAVQQNQALLLLPWTMNILIILKSILPQA 195
Cdd:PRK07024  204 RFAARAARAIARGRRFRVIPWQMGVVAKLLRVLPRW 239

classical (c) SDR, subgroup 6; These proteins are members of the classical SDR family, with a canonical active site tetrad and a fairly well conserved typical Gly-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 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283   8 FICDVGNREEVYQMAKAVREKVGDITILVNNAAVVHGKSLMDSDDDALLKSQHVNTLGQFWTTKAFLPRMLELQNGHIVC 87
Cdd:cd05350    52 EILDVTDEERNQLVIAELEAELGGLDLVIINAGVGKGTSLGDLSFKAFRETIDTNLLGAAAILEAALPQFRAKGRGHLVL 131

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283  88 LNSVLALSAIPGAIDYCTSKASAFAFMESLTlGLLDCPGVSATTVLPFHTSTEMFQGMrvrFPnLFPPLKPETVARRTVD 167
Cdd:cd05350   132 ISSVAALRGLPGAAAYSASKAALSSLAESLR-YDVKKRGIRVTVINPGFIDTPLTANM---FT-MPFLMSVEQAAKRIYK 206

                         170       180
                  ....*....|....*....|....*..
gi 1269612283 168 AVQQNQALLLLPWTMNILIILKSILPQ 194
Cdd:cd05350   207 AIKKGAAEPTFPWRLAVPLRLLKLLPE 233

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1269612283   2 GTECHYFICDVGNREEVYQMAKAVREKVGDITILVNNAAVVHG-KSLMDSDDDALLKSQHVNTLGQFWTTKAFLPRMLEL 80
Cdd:PRK07231   52 GGRAIAVAADVSDEADVEAAVAAALERFGSVDILVNNAGTTHRnGPLLDVDEAEFDRIFAVNVKSPYLWTQAAVPAMRGE 131

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1269612283  81 QNGHIVCLNSVLALSAIPGAIDYCTSKASAFAFMESLTLGLLD--------CPGVSATTVL 133
Cdd:PRK07231  132 GGGAIVNVASTAGLRPRPGLGWYNASKGAVITLTKALAAELGPdkirvnavAPVVVETGLL 192