Conserved Protein Domain Family
type2_17beta_HSD-like_SDR_c

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cd09805: type2_17beta_HSD-like_SDR_c 
human 17beta-hydroxysteroid dehydrogenase type 2 (type 2 17beta-HSD)-like, classical (c) SDRs
17beta-hydroxysteroid dehydrogenases are a group of isozymes that catalyze activation and inactivation of estrogen and androgens. This classical-SDR subgroup includes the human proteins: type 2 17beta-HSD, type 6 17beta-HSD, type 2 11beta-HSD, dehydrogenase/reductase SDR family member 9, short-chain dehydrogenase/reductase family 9C member 7, 3-hydroxybutyrate dehydrogenase type 1, and retinol dehydrogenase 5. 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.
Statistics
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PSSM-Id: 187665
View PSSM: cd09805
Aligned: 14 rows
Threshold Bit Score: 398.575
Threshold Setting Gi: 19922066
Created: 21-Jan-2011
Updated: 2-Oct-2020
Structure
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Aligned Rows:
 
Feature 1:active site [active site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                                                        
Q02338        56 KAVLVTGCDS----GFGFSLAKHLHSKGFLVFAGCLMkdkghdGVKELDSLnSDRLRTVQLNVCssEEVEKVVEIVrssl 131 human
P80365        83 RAVLITGCDS----GFGKETAKKLDSMGFTVLATVLEln--spGAIELRTCcSPRLRLLQMDLTkpGDISRVLEFTkaht 156 human
NP_002144     83 KAVLVTGGDC----GLGHALCKYLDELGFTVFAGVLNen--gpGAEELRRTcSPRLSVLQMDITkpVQIKDAYSKVaaml 156 human
AAH56045      30 KYILITGCDT----GFGNHAAKAFDKQGFRVLATCLTd----aGATGLREAtSERLKTIRLDVTnaDNVLSVAKWVkgev 101 African clawed ...
XP_414168    248 CPWILSGSDT----GIGHALAKYLDNLGFIVFAGVLNkd--gpGAEELRRTcSQRLSLLQLDITnpTQVKEAYLQVsekv 321 chicken
P51658        84 KAVLVTGADS----GFGHGLAKHLDKLGFTVFAGVLDke--gpGAEELRKHcSERLSVLQMDVTkpEQIKDAHSKVteki 157 house mouse
NP_001006547  48 SEVDQIGSRAvltlGLDLPWPKHLHTKGFIIYAGCLQknkgegGSKDLDNMnSDRMRTVQLNVCdsKEVDRAVEHVnssl 127 chicken
Q9BPW9        30 KYIFITGCDS----GFGNLAARTFDKKGFHVIAACLTe----sGSTALKAEtSERLRTVLLDVTdpENVKRTAQWVknqv 101 human
O14756        30 KYVFITGCDS----GFGNLLARQLDARGLRVLAACLTe----kGAEQLRGQtSDRLETVTLDVTkmESIAAATQWVkehv 101 human
Q92781        29 AFVFITGCDS----GFGRLLALQLDQRGFRVLASCLTp----sGAEDLQRVaSSRLHTTLLDITdpQSVQQAAKWVemhv 100 human
Feature 1                                             #                          #            #  
Q02338       132 kdpekGMWGLVNNAGISTFGEVEF-TSLETYKQVAEVNLWGTVRMTKSFLPLIRRAKGRVVNISSMLGRMANPaRSPYCI 210 human
P80365       157 --tstGLWGLVNNAGHNEVVADAElSPVATFRSCMEVNFFGALELTKGLLPLLRSSRGRIVTVGSPAGDMPYPcLGAYGT 234 human
NP_002144    157 --qdrGLWAVINNAGVLGFPTDGElLLMTDYKQCMAVNFFGTVEVTKTFLPLLRKSKGRLVNVSSMGGGAPMErLASYGS 234 human
AAH56045     102 --gnkGLWGLINNAGIMGTLAPFDwMTIDDIRKPIEVNLIGLIHVTLVLLPFIKKAKGRIVNVSSVGGRVAAS-GGAYFS 178 African clawed ...
XP_414168    322 --qktGLWGVVNNAGILGFPADGElLPMSMYRQCMEVNFFGAVHVSKTFLPLLRKSRGRLVNMSSMTGGIPLPrYAAYGA 399 chicken
P51658       158 --qdkGLWAVVNNAGVFHLPIDGElIPMSIYRKCMAVNFFGTVEVTKAFLPLLRKSKGRLVNVSSMGGTVPLQmTSAYAA 235 house mouse
NP_001006547 128 edpekGLWGLVNNAGISTFGEVEF-TSMDTYMEVAEVNLWGTVRTTKAFLPLIRRSKGRVVNISSMMGRMGSPaRSPYCI 206 chicken
Q9BPW9       102 --gekGLWGLINNAGVPGVLAPTDwLTLEDYREPIEVNLFGLISVTLNMLPLVKKAQGRVINVSSVGGRLAIV-GGGYTP 178 human
O14756       102 --gdrGLWGLVNNAGILTPITLCEwLNTEDSMNMLKVNLIGVIQVTLSMLPLVRRARGRIVNVSSILGRVAFF-VGGYCV 178 human
Q92781       101 --keaGLFGLVNNAGVAGIIGPTPwLTRDDFQRVLNVNTMGPIGVTLALLPLLQQARGRVINITSVLGRLAAN-GGGYCV 177 human
Feature 1         #                                                                              
Q02338       211 TKFGVEAFSDCLRYEMYPLGVKVSVVEPGNFIAATSLYSPesiqaiakkMWEELPevvrkdYGk----kYFDEKIAKMet 286 human
P80365       235 SKAAVALLMDTFSCELLPWGVKVSIIQPGCFKTESVRNVGqwek-rkqlLLANLPqellqaYGk----dYIEHLHGQFlh 309 human
NP_002144    235 SKAAVTMFSSVMRLELSKWGIKVASIQPGGFLTNIAGTSDkwek-lekdILDHLPaevqedYGq----dYILAQRNFLll 309 human
AAH56045     179 SKFGVEGFNDSLRRDMKAFGVKVSCIEPGLFKTPLSDPAKviqq--rtdIWKRLPveikkeYGd----nYIQIDASKKqk 252 African clawed ...
XP_414168    400 SKAALSMFSGVMRQELSKWGIKVAAIHPSGFRTGIQGTPElwvk-qekeLVEHLSvdvqqdYGr----dYLLGLKSYLlr 474 chicken
P51658       236 TKAALTMFSTIIRQELDKWGVKVVTIKPGGFKTNITGSQDiwdk-mekeILDHFSkdiqenYGq----dYVHTQKLIIpt 310 house mouse
NP_001006547 207 TKFGVEAFSDCLRYEMQPQGVMVSIVEPGNFIAVTNLYSPerikaiadkMWDELPeivrkdYGr----kYFDEQVSKMet 282 chicken
Q9BPW9       179 SKYAVEGFNDSLRRDMKAFGVHVSCIEPGLFKTNLADPVKviek--klaIWEQLSpdikqqYGe----gYIEKSLDKLkg 252 human
O14756       179 SKYGVEAFSDILRREIQHFGVKISIVEPGYFRTGMTNMTQsler--mkqSWKEAPkhiketYGq----qYFDALYNIMke 252 human
Q92781       178 SKFGLEAFSDSLRRDVAHFGIRVSIVEPGFFRTPVTNLESlekt--lqaCWARLPpatqahYGgafltkYLKMQQRIMnl 255 human
Feature 1                                                                
Q02338       287 ycs-sgstDTSPVIDAVTHALTAttPYTRYHPMDYYWWLrmqimtHLPGAISDMIY 341 human
P80365       310 slr-lamsDLTPVVDAITDALLAarPRRRYYPGQGLGLMyfi-hyYLPEGLRRRFL 363 human
NP_002144    310 ins-laskDFSPVLRDIQHAILAksPFAYYTPGKGAYLWicl-ahYLPIGIYDYFA 363 human
AAH56045     253 lnqrilnsDLSLVVQCMEHALTSrhPRTRYSAGFDAAFLwip-lsYMPTFIQDFVI 307 African clawed frog
XP_414168    475 ips-ccdaDLTPVLSSILHALLSkrPHGLYTPGKGAYMMlci-fcYFPLWFYDFLV 528 chicken
P51658       311 lke-rsnpDITPVLRDIQHAISArnPSSFYYPGRMAYLWvcl-aaYCPTSLLDYVI 364 house mouse
NP_001006547 283 ycn-sgstDTSPVIESVAHALTStaPYTRYHPMDYYWWLrmqimtHMPAAISDRLY 337 chicken
Q9BPW9       253 nks-yvnmDLSPVVECMDHALTSlfPKTHYAAGKDAKIFwip-lsHMPAALQDFLL 306 human
O14756       253 gll-ncstNLNLVTDCMEHALTSvhPRTRYSAGWDAKFFfip-lsYLPTSLADYIL 306 human
Q92781       256 i----cdpDLTKVSRCLEHALTArhPRTRYSPGWDAKLLwlp-asYLPASLVDAVL 306 human

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