3BHS5_RAT
ID 3BHS5_RAT Reviewed; 373 AA.
AC P27364; Q569C6;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=NADPH-dependent 3-keto-steroid reductase Hsd3b5 {ECO:0000305|PubMed:1537836};
DE AltName: Full=3 beta-hydroxysteroid dehydrogenase type 3;
DE AltName: Full=3 beta-hydroxysteroid dehydrogenase type III {ECO:0000305|PubMed:1537836};
DE Short=3 beta-HSD III;
DE EC=1.1.1.270 {ECO:0000269|PubMed:1537836};
DE AltName: Full=Dihydrotestosterone 3-ketoreductase {ECO:0000305|PubMed:1537836};
DE EC=1.1.1.210 {ECO:0000269|PubMed:1537836};
GN Name=Hsd3b5 {ECO:0000312|RGD:2838}; Synonyms=Hsd3b;
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], AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=2249649; DOI=10.1210/endo-127-6-3237;
RA Zhao H.-F., Rheaume E., Trudel C., Couet J., Labrie F., Simard J.;
RT "Structure and sexual dimorphic expression of a liver-specific rat 3 beta-
RT hydroxysteroid dehydrogenase/isomerase.";
RL Endocrinology 127:3237-3239(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
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 [3]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE
RP SPECIFICITY, AND PATHWAY.
RX PubMed=1537836; DOI=10.1016/s0021-9258(18)42863-3;
RA de Launoit Y., Zhao H.F., Belanger A., Labrie F., Simard J.;
RT "Expression of liver-specific member of the 3 beta-hydroxysteroid
RT dehydrogenase family, an isoform possessing an almost exclusive 3-
RT ketosteroid reductase activity.";
RL J. Biol. Chem. 267:4513-4517(1992).
CC -!- FUNCTION: Responsible for the reduction of the oxo group on the C-3 of
CC 5alpha-androstane steroids. Catalyzes the conversion of
CC dihydrotestosterone to its inactive form 5alpha-androstanediol, that
CC does not bind androgen receptor/AR. Also converts androstanedione, a
CC precursor of testosterone and estrone, to epiandrosterone. Does not
CC function as an isomerase. {ECO:0000269|PubMed:1537836}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3beta-hydroxysteroid + NADP(+) = a 3-oxosteroid + H(+) +
CC NADPH; Xref=Rhea:RHEA:34787, ChEBI:CHEBI:15378, ChEBI:CHEBI:36836,
CC ChEBI:CHEBI:47788, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC EC=1.1.1.270; Evidence={ECO:0000269|PubMed:1537836};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5alpha-androstane-3beta,17beta-diol + NADP(+) = 17beta-
CC hydroxy-5alpha-androstan-3-one + H(+) + NADPH; Xref=Rhea:RHEA:16297,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16330, ChEBI:CHEBI:18329,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.210;
CC Evidence={ECO:0000269|PubMed:1537836};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta-hydroxy-5alpha-androstan-17-one + NADP(+) = 5alpha-
CC androstan-3,17-dione + H(+) + NADPH; Xref=Rhea:RHEA:56916,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15994, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:541975;
CC Evidence={ECO:0000269|PubMed:1537836};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.12 uM for dihydrotestosterone (in the presence of NADPH)
CC {ECO:0000269|PubMed:1537836};
CC KM=6.16 uM for dihydrotestosterone (in the presence of NADH)
CC {ECO:0000269|PubMed:1537836};
CC Note=Catalytic efficiency for dihydrotestosterone reduction is 20-
CC fold better in the presence of NADPH than in the presence of NADH.
CC {ECO:0000269|PubMed:1537836};
CC -!- PATHWAY: Steroid metabolism. {ECO:0000269|PubMed:1537836}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass
CC membrane protein. Mitochondrion membrane; Single-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed predominantly in male liver.
CC {ECO:0000269|PubMed:2249649}.
CC -!- SIMILARITY: Belongs to the 3-beta-HSD family. {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; M67465; AAA41352.1; -; mRNA.
DR EMBL; BC092571; AAH92571.1; -; mRNA.
DR PIR; A37404; A37404.
DR RefSeq; NP_036716.1; NM_012584.1.
DR AlphaFoldDB; P27364; -.
DR STRING; 10116.ENSRNOP00000026290; -.
DR CarbonylDB; P27364; -.
DR iPTMnet; P27364; -.
DR PhosphoSitePlus; P27364; -.
DR PaxDb; P27364; -.
DR PRIDE; P27364; -.
DR GeneID; 24470; -.
DR KEGG; rno:24470; -.
DR UCSC; RGD:2838; rat.
DR CTD; 15496; -.
DR RGD; 2838; Hsd3b5.
DR eggNOG; KOG1430; Eukaryota.
DR InParanoid; P27364; -.
DR OrthoDB; 930591at2759; -.
DR PhylomeDB; P27364; -.
DR TreeFam; TF343138; -.
DR PRO; PR:P27364; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
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:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003854; F:3-beta-hydroxy-delta5-steroid dehydrogenase activity; IDA:RGD.
DR GO; GO:0000253; F:3-keto sterol reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0047024; F:5alpha-androstane-3beta,17beta-diol dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0102176; F:cycloeucalenone reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IBA:GO_Central.
DR GO; GO:0005496; F:steroid binding; IDA:RGD.
DR GO; GO:0016229; F:steroid dehydrogenase activity; TAS:RGD.
DR GO; GO:0008207; P:C21-steroid hormone metabolic process; IBA:GO_Central.
DR GO; GO:0021766; P:hippocampus development; IBA:GO_Central.
DR GO; GO:0042448; P:progesterone metabolic process; IDA:RGD.
DR GO; GO:0050810; P:regulation of steroid biosynthetic process; IDA:RGD.
DR GO; GO:0051412; P:response to corticosterone; IBA:GO_Central.
DR GO; GO:0006694; P:steroid biosynthetic process; IDA:RGD.
DR InterPro; IPR002225; 3Beta_OHSteriod_DH/Estase.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF01073; 3Beta_HSD; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW Acetylation; Endoplasmic reticulum; Lipid metabolism; Membrane;
KW Mitochondrion; NADP; Oxidoreductase; Reference proteome;
KW Steroid metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..373
FT /note="NADPH-dependent 3-keto-steroid reductase Hsd3b5"
FT /id="PRO_0000087789"
FT TRANSMEM 288..308
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 159
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q12068"
FT BINDING 10..15
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q12068"
FT BINDING 155
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q12068"
FT BINDING 159
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q12068"
FT MOD_RES 350
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q61694"
FT CONFLICT 180
FT /note="F -> L (in Ref. 2; AAH92571)"
FT /evidence="ECO:0000305"
FT CONFLICT 204
FT /note="R -> T (in Ref. 2; AAH92571)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 373 AA; 42206 MW; B96538F2EF056935 CRC64;
MPGWSCLVTG AGGFLGQRIV QMLVQEKELQ EVRVLYRTFS PKHKEELSKL QTKAKVTVLR
GDIVDAQFLR RACQGMSVII HTAAALDIAG FLPRQTILDV NVKGTQLLLD ACVEASVPAF
IYSSSTGVAG PNSYKETILN DREEEHREST WSNPYPYSKR MAEKAVLAAN GSILKNGGTF
HTCALRLPFI YGEESQIIST MVNRALKNNS IIKRHATFSI ANPVYVGNAA WAHILAARGL
RDPEKSQSIQ GQFYYISDDT PHQSYDDLNY TLSKEWGFCL DSSWSLPLPL LYWLAFLLET
VSFLLRPFYN YRPPFNRFMV TILNSVFTIS YKKAQRDLGY EPLVSWEEAK QKTSEWIGTL
VEQHRETLDT KSQ
