S5A1_RAT
ID S5A1_RAT Reviewed; 259 AA.
AC P24008; A0JPJ6;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=3-oxo-5-alpha-steroid 4-dehydrogenase 1 {ECO:0000305};
DE EC=1.3.1.22;
DE AltName: Full=SR type 1;
DE AltName: Full=Steroid 5-alpha-reductase 1;
DE Short=S5AR 1;
GN Name=Srd5a1 {ECO:0000312|RGD:3757};
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] (ISOFORM SHORT).
RX PubMed=2476440; DOI=10.1016/s0021-9258(18)71614-1;
RA Andersson S., Bishop R.W., Russell D.W.;
RT "Expression cloning and regulation of steroid 5 alpha-reductase, an enzyme
RT essential for male sexual differentiation.";
RL J. Biol. Chem. 264:16249-16255(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
RC TISSUE=Liver;
RX PubMed=8597599; DOI=10.1016/0167-4781(95)00198-0;
RA Lopez-Solache I., Luu-The V., Seralini G.E., Labrie F.;
RT "Heterogeneity of rat type I 5 alpha-reductase cDNA: cloning, expression
RT and regulation by pituitary implants and dihydrotestosterone.";
RL Biochim. Biophys. Acta 1305:139-144(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP CATALYTIC ACTIVITY, FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=2339109; DOI=10.1073/pnas.87.10.3640;
RA Andersson S., Russell D.W.;
RT "Structural and biochemical properties of cloned and expressed human and
RT rat steroid 5 alpha-reductases.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:3640-3644(1990).
CC -!- FUNCTION: Converts testosterone into 5-alpha-dihydrotestosterone and
CC progesterone or corticosterone into their corresponding 5-alpha-3-
CC oxosteroids. It plays a central role in sexual differentiation and
CC androgen physiology. {ECO:0000269|PubMed:2339109}.
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:0000305|PubMed:2476440};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:54386;
CC Evidence={ECO:0000305|PubMed:2476440};
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:2476440};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21954;
CC Evidence={ECO:0000305|PubMed:2476440};
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:2476440};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:50822;
CC Evidence={ECO:0000305|PubMed:2476440};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=androst-4-ene-3,17-dione + H(+) + NADPH = 5alpha-androstan-
CC 3,17-dione + NADP(+); Xref=Rhea:RHEA:50816, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15994, ChEBI:CHEBI:16422, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; Evidence={ECO:0000269|PubMed:2476440};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50817;
CC Evidence={ECO:0000305|PubMed:2476440};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.5 uM for testosterone {ECO:0000269|PubMed:2339109};
CC KM=2.8 uM for androstenedione {ECO:0000269|PubMed:2339109};
CC KM=0.5 uM for progesterone {ECO:0000269|PubMed:2339109};
CC Vmax=2.5 nmol/min/mg enzyme toward testosterone
CC {ECO:0000269|PubMed:2339109};
CC Vmax=2.2 nmol/min/mg enzyme toward androstenedione
CC {ECO:0000269|PubMed:2339109};
CC Vmax=1.8 nmol/min/mg enzyme toward progesterone
CC {ECO:0000269|PubMed:2339109};
CC pH dependence:
CC Optimally active at alkaline pHs.;
CC -!- SUBCELLULAR LOCATION: Microsome membrane; Multi-pass membrane protein.
CC Endoplasmic reticulum membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=Long;
CC IsoId=P24008-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P24008-2; Sequence=VSP_018884;
CC -!- TISSUE SPECIFICITY: Liver and prostate (at a low level).
CC -!- DEVELOPMENTAL STAGE: After the establishment of chromosomal sex at
CC fertilization.
CC -!- INDUCTION: Its expression is regulated by androgens such as
CC testosterone.
CC -!- SIMILARITY: Belongs to the steroid 5-alpha reductase family.
CC {ECO:0000305}.
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DR EMBL; J05035; AAA42102.1; -; mRNA.
DR EMBL; S81448; AAB36218.1; -; mRNA.
DR EMBL; BC127454; AAI27455.1; -; mRNA.
DR PIR; S65744; S65744.
DR RefSeq; NP_058766.2; NM_017070.3. [P24008-2]
DR AlphaFoldDB; P24008; -.
DR SMR; P24008; -.
DR STRING; 10116.ENSRNOP00000023659; -.
DR BindingDB; P24008; -.
DR ChEMBL; CHEMBL3422; -.
DR DrugCentral; P24008; -.
DR SwissLipids; SLP:000001641; -.
DR PaxDb; P24008; -.
DR Ensembl; ENSRNOT00000023659; ENSRNOP00000023659; ENSRNOG00000017601. [P24008-2]
DR GeneID; 24950; -.
DR KEGG; rno:24950; -.
DR UCSC; RGD:3757; rat. [P24008-1]
DR CTD; 6715; -.
DR RGD; 3757; Srd5a1.
DR VEuPathDB; HostDB:ENSRNOG00000017601; -.
DR eggNOG; KOG1638; Eukaryota.
DR GeneTree; ENSGT00950000182886; -.
DR InParanoid; P24008; -.
DR OMA; WLEWLGF; -.
DR OrthoDB; 1574389at2759; -.
DR PhylomeDB; P24008; -.
DR BRENDA; 1.3.1.22; 5301.
DR Reactome; R-RNO-193048; Androgen biosynthesis.
DR SABIO-RK; P24008; -.
DR PRO; PR:P24008; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000017601; Expressed in liver and 20 other tissues.
DR GO; GO:0070852; C:cell body fiber; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
DR GO; GO:0043209; C:myelin sheath; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0003865; F:3-oxo-5-alpha-steroid 4-dehydrogenase activity; IDA:RGD.
DR GO; GO:0033218; F:amide binding; IDA:RGD.
DR GO; GO:0047751; F:cholestenone 5-alpha-reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0070402; F:NADPH binding; IDA:RGD.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0050213; F:progesterone 5-alpha-reductase activity; IEA:RHEA.
DR GO; GO:0006702; P:androgen biosynthetic process; IDA:RGD.
DR GO; GO:0006710; P:androgen catabolic process; IDA:RGD.
DR GO; GO:0008209; P:androgen metabolic process; IDA:RGD.
DR GO; GO:0060348; P:bone development; IEP:RGD.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0071320; P:cellular response to cAMP; IEP:RGD.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEP:RGD.
DR GO; GO:0071872; P:cellular response to epinephrine stimulus; IEP:RGD.
DR GO; GO:0071392; P:cellular response to estradiol stimulus; IEP:RGD.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IEP:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEP:RGD.
DR GO; GO:0009267; P:cellular response to starvation; IEP:RGD.
DR GO; GO:0071394; P:cellular response to testosterone stimulus; IEP:RGD.
DR GO; GO:0021987; P:cerebral cortex development; IEP:RGD.
DR GO; GO:0042747; P:circadian sleep/wake cycle, REM sleep; IEP:RGD.
DR GO; GO:0016101; P:diterpenoid 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:0001889; P:liver 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:0046661; P:male sex differentiation; TAS:RGD.
DR GO; GO:0021983; P:pituitary gland development; IEP:RGD.
DR GO; GO:0042448; P:progesterone metabolic process; IDA:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0043627; P:response to estrogen; IEP:RGD.
DR GO; GO:0032354; P:response to follicle-stimulating hormone; IEP:RGD.
DR GO; GO:0060992; P:response to fungicide; IEP:RGD.
DR GO; GO:0060416; P:response to growth hormone; IEP:RGD.
DR GO; GO:0014850; P:response to muscle activity; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0033574; P:response to testosterone; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:RGD.
DR GO; GO:0042428; P:serotonin metabolic process; IEP:RGD.
DR GO; GO:0021510; P:spinal cord development; IEP:RGD.
DR GO; GO:0006694; P:steroid biosynthetic process; IDA:RGD.
DR GO; GO:0021794; P:thalamus development; IEP:RGD.
DR GO; GO:0001655; P:urogenital system development; IEP:RGD.
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; PTHR10556; 1.
DR Pfam; PF02544; Steroid_dh; 1.
DR PIRSF; PIRSF015596; 5_alpha-SR2; 1.
DR PROSITE; PS50244; S5A_REDUCTASE; 1.
PE 1: Evidence at protein level;
KW Alternative initiation; Differentiation; Endoplasmic reticulum;
KW Lipid metabolism; Membrane; Microsome; NADP; Oxidoreductase;
KW Reference proteome; Sexual differentiation; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..259
FT /note="3-oxo-5-alpha-steroid 4-dehydrogenase 1"
FT /id="PRO_0000031565"
FT TRANSMEM 10..30
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 86..106
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 111..131
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"
FT VAR_SEQ 1..4
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:2476440"
FT /id="VSP_018884"
SQ SEQUENCE 259 AA; 29780 MW; FE6705AC1D7CAE11 CRC64;
MVPLMELDEL CLLDMLVYLE GFMAFVSIVG LRSVGSPYGR YSPQWPGIRV PARPAWFIQE
LPSMAWPLYE YIRPAAARLG NLPNRVLLAM FLIHYVQRTL VFPVLIRGGK PTLLVTFVLA
FLFCTFNGYV QSRYLSQFAV YAEDWVTHPC FLTGFALWLV GMVINIHSDH ILRNLRKPGE
TGYKIPRGGL FEYVSAANYF GELVEWCGFA LASWSLQGVV FALFTLSTLL TRAKQHHQWY
HEKFEDYPKS RKILIPFVL
