ID S5A2_RAT Reviewed; 254 AA. AC P31214; DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1993, sequence version 1. DT 27-MAR-2024, entry version 154. DE RecName: Full=3-oxo-5-alpha-steroid 4-dehydrogenase 2; DE EC=1.3.1.22 {ECO:0000269|PubMed:1527072}; DE AltName: Full=5 alpha-SR2; DE AltName: Full=SR type 2; DE AltName: Full=Steroid 5-alpha-reductase 2; DE Short=S5AR 2; GN Name=Srd5a2; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL RP PROPERTIES, AND TISSUE SPECIFICITY. RC TISSUE=Testis; RX PubMed=1527072; DOI=10.1016/s0021-9258(18)41809-1; RA Normington K., Russell D.W.; RT "Tissue distribution and kinetic characteristics of rat steroid 5 alpha- RT reductase isozymes. Evidence for distinct physiological functions."; RL J. Biol. Chem. 267:19548-19554(1992). CC -!- FUNCTION: Converts testosterone (T) into 5-alpha-dihydrotestosterone CC (DHT) and progesterone or corticosterone into their corresponding 5- CC alpha-3-oxosteroids (PubMed:1527072). It plays a central role in sexual CC differentiation and androgen physiology (By similarity). CC {ECO:0000250|UniProtKB:P31213, ECO:0000269|PubMed:1527072}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a 3-oxo-5alpha-steroid + NADP(+) = a 3-oxo-Delta(4)-steroid + CC H(+) + NADPH; Xref=Rhea:RHEA:54384, ChEBI:CHEBI:13601, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:47909, ChEBI:CHEBI:57783, CC ChEBI:CHEBI:58349; EC=1.3.1.22; CC Evidence={ECO:0000269|PubMed:1527072}; CC -!- CATALYTIC ACTIVITY: CC Reaction=17beta-hydroxy-5alpha-androstan-3-one + NADP(+) = H(+) + NADPH CC + testosterone; Xref=Rhea:RHEA:50820, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:16330, ChEBI:CHEBI:17347, ChEBI:CHEBI:57783, CC ChEBI:CHEBI:58349; EC=1.3.1.22; CC Evidence={ECO:0000269|PubMed:1527072}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:50822; CC Evidence={ECO:0000305|PubMed:1527072}; CC -!- CATALYTIC ACTIVITY: CC Reaction=5alpha-pregnane-3,20-dione + NADP(+) = H(+) + NADPH + CC progesterone; Xref=Rhea:RHEA:21952, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17026, ChEBI:CHEBI:28952, ChEBI:CHEBI:57783, CC ChEBI:CHEBI:58349; EC=1.3.1.22; CC Evidence={ECO:0000269|PubMed:1527072}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21954; CC Evidence={ECO:0000305|PubMed:1527072}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=74 nM for testosterone {ECO:0000269|PubMed:1527072}; CC KM=42 nM for progesterone {ECO:0000269|PubMed:1527072}; CC KM=170 nM for androstenedione {ECO:0000269|PubMed:1527072}; CC KM=376 nM for corticosterone {ECO:0000269|PubMed:1527072}; CC KM=11.2 uM for cortisol {ECO:0000269|PubMed:1527072}; CC Vmax=0.5 nmol/min/mg enzyme {ECO:0000269|PubMed:1527072}; CC pH dependence: CC Optimally active at acidic pHs. {ECO:0000269|PubMed:1527072}; CC -!- SUBCELLULAR LOCATION: Microsome membrane; Multi-pass membrane protein. CC Endoplasmic reticulum membrane {ECO:0000305}; Multi-pass membrane CC protein {ECO:0000305}. CC -!- TISSUE SPECIFICITY: Expressed in high levels in the prostate and many CC other androgen-sensitive tissues. {ECO:0000269|PubMed:1527072}. CC -!- SIMILARITY: Belongs to the steroid 5-alpha reductase family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M95058; AAA42182.1; -; mRNA. DR PIR; A44104; A44104. DR RefSeq; NP_073202.1; NM_022711.4. DR AlphaFoldDB; P31214; -. DR SMR; P31214; -. DR STRING; 10116.ENSRNOP00000009254; -. DR BindingDB; P31214; -. DR ChEMBL; CHEMBL5099; -. DR DrugCentral; P31214; -. DR PhosphoSitePlus; P31214; -. DR PaxDb; 10116-ENSRNOP00000009254; -. DR Ensembl; ENSRNOT00000008983.8; ENSRNOP00000009254.4; ENSRNOG00000027042.7. DR Ensembl; ENSRNOT00055035273; ENSRNOP00055028595; ENSRNOG00055020662. DR Ensembl; ENSRNOT00060021711; ENSRNOP00060017178; ENSRNOG00060012768. DR Ensembl; ENSRNOT00065035212; ENSRNOP00065028325; ENSRNOG00065020764. DR GeneID; 64677; -. DR KEGG; rno:64677; -. DR UCSC; RGD:621480; rat. DR AGR; RGD:621480; -. DR CTD; 6716; -. DR RGD; 621480; Srd5a2. DR eggNOG; KOG1638; Eukaryota. DR GeneTree; ENSGT00950000182886; -. DR HOGENOM; CLU_065395_1_1_1; -. DR InParanoid; P31214; -. DR OMA; SYGKHTE; -. DR OrthoDB; 152402at2759; -. DR PhylomeDB; P31214; -. DR TreeFam; TF314668; -. DR BRENDA; 1.3.1.22; 5301. DR Reactome; R-RNO-193048; Androgen biosynthesis. DR SABIO-RK; P31214; -. DR PRO; PR:P31214; -. DR Proteomes; UP000002494; Chromosome 6. DR Bgee; ENSRNOG00000027042; Expressed in duodenum and 4 other cell types or tissues. DR GO; GO:0070852; C:cell body fiber; IDA:RGD. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0043025; C:neuronal cell body; IDA:RGD. DR GO; GO:0003865; F:3-oxo-5-alpha-steroid 4-dehydrogenase activity; IDA:RGD. DR GO; GO:0047751; F:3-oxo-5alpha-steroid 4-dehydrogenase (NADP+); IEA:UniProtKB-EC. DR GO; GO:0033218; F:amide binding; IPI:RGD. DR GO; GO:0009917; F:sterol 5-alpha reductase activity; ISO:RGD. DR GO; GO:0030283; F:testosterone dehydrogenase [NAD(P)] activity; ISS:UniProtKB. DR GO; GO:0006702; P:androgen biosynthetic process; IDA:RGD. DR GO; GO:0008209; P:androgen metabolic process; IDA:RGD. DR GO; GO:0018879; P:biphenyl metabolic process; IEP:RGD. DR GO; GO:0060348; P:bone development; IEP:RGD. DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW. DR GO; GO:0018894; P:dibenzo-p-dioxin metabolic process; IEP:RGD. DR GO; GO:0030540; P:female genitalia development; IEP:RGD. DR GO; GO:0021766; P:hippocampus development; IEP:RGD. DR GO; GO:0021854; P:hypothalamus development; IEP:RGD. DR GO; GO:0030539; P:male genitalia development; IEP:RGD. DR GO; GO:0008584; P:male gonad development; IEP:RGD. DR GO; GO:0018963; P:phthalate metabolic process; IEP:RGD. DR GO; GO:0032354; P:response to follicle-stimulating hormone; IEP:RGD. DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD. DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD. DR GO; GO:0010033; P:response to organic substance; IDA:RGD. DR GO; GO:0043434; P:response to peptide hormone; IDA:RGD. DR GO; GO:0048545; P:response to steroid hormone; IEP:RGD. DR GO; GO:0033574; P:response to testosterone; IEP:RGD. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD. DR GO; GO:0007548; P:sex differentiation; TAS:RGD. DR GO; GO:0006694; P:steroid biosynthetic process; IDA:RGD. DR GO; GO:0006706; P:steroid catabolic process; IDA:RGD. DR GO; GO:0061370; P:testosterone biosynthetic process; ISS:UniProtKB. DR Gene3D; 1.20.120.1630; -; 1. DR InterPro; IPR016636; 3-oxo-5-alpha-steroid_4-DH. DR InterPro; IPR001104; 3-oxo-5_a-steroid_4-DH_C. DR InterPro; IPR039357; SRD5A/TECR. DR PANTHER; PTHR10556; 3-OXO-5-ALPHA-STEROID 4-DEHYDROGENASE; 1. DR PANTHER; PTHR10556:SF43; 3-OXO-5-ALPHA-STEROID 4-DEHYDROGENASE 2; 1. DR Pfam; PF02544; Steroid_dh; 1. DR PIRSF; PIRSF015596; 5_alpha-SR2; 1. DR PROSITE; PS50244; S5A_REDUCTASE; 1. DR Genevisible; P31214; RN. PE 1: Evidence at protein level; KW Differentiation; Endoplasmic reticulum; Lipid metabolism; Membrane; KW Microsome; NADP; Oxidoreductase; Reference proteome; KW Sexual differentiation; Transmembrane; Transmembrane helix. FT CHAIN 1..254 FT /note="3-oxo-5-alpha-steroid 4-dehydrogenase 2" FT /id="PRO_0000213680" FT TRANSMEM 8..28 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 72..92 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 146..166 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 206..226 FT /note="Helical" FT /evidence="ECO:0000255" SQ SEQUENCE 254 AA; 28772 MW; 8874C533DF3BD123 CRC64; MQIVCHQVPV LAGSATLATM GTLILCLGKP ASYGKHTESV SSGVPFLPAR IAWFLQELPS FVVSVGMLAW QPRSLFGPPG NVLLALFSAH YFHRTFIYSL LTRGRPFPAV LFLRATAFCI GNGLLQAYYL VYCAEYPEEW YTDVRFSFGV FLFILGMGIN IHSDYTLRQL RKPGEVIYRI PRGGLFTYVS GANFLGEIIE WIGYALATWS VPAFAFAFFT LCFLGMQAFY HHRFYLKMFK DYPKSRKALI PFIF //