3BHS6_MOUSE
ID 3BHS6_MOUSE Reviewed; 373 AA.
AC O35469; Q3UQN7;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 4.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 6;
DE EC=1.1.1.-;
DE AltName: Full=3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type VI;
DE Short=3-beta-HSD VI;
DE Includes:
DE RecName: Full=3-beta-hydroxy-Delta(5)-steroid dehydrogenase;
DE EC=1.1.1.145;
DE AltName: Full=3-beta-hydroxy-5-ene steroid dehydrogenase;
DE AltName: Full=Progesterone reductase;
DE Includes:
DE RecName: Full=Steroid Delta-isomerase;
DE EC=5.3.3.1;
DE AltName: Full=Delta-5-3-ketosteroid isomerase;
GN Name=Hsd3b6;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=9075693; DOI=10.1210/endo.138.4.5042;
RA Abbaszade I.G., Arensburg J., Park C.-H.J., Kasa-Vubu J.Z., Orly J.,
RA Payne A.H.;
RT "Isolation of a new mouse 3beta-hydroxysteroid dehydrogenase isoform,
RT 3beta-HSD VI, expressed during early pregnancy.";
RL Endocrinology 138:1392-1399(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Heart;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: 3-beta-HSD is a bifunctional enzyme, that catalyzes the
CC oxidative conversion of Delta(5)-ene-3-beta-hydroxy steroid, and the
CC oxidative conversion of ketosteroids. The 3-beta-HSD enzymatic system
CC plays a crucial role in the biosynthesis of all classes of hormonal
CC steroids. May be involved in local production of progesterone.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3beta-hydroxy-Delta(5)-steroid + NAD(+) = a 3-oxo-Delta(5)-
CC steroid + H(+) + NADH; Xref=Rhea:RHEA:24076, ChEBI:CHEBI:1722,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:47907, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.1.1.145;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3-oxo-Delta(5)-steroid = a 3-oxo-Delta(4)-steroid;
CC Xref=Rhea:RHEA:14709, ChEBI:CHEBI:47907, ChEBI:CHEBI:47909;
CC EC=5.3.3.1;
CC -!- PATHWAY: Lipid metabolism; steroid biosynthesis.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass
CC membrane protein. Mitochondrion membrane; Single-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed in skin and testis.
CC -!- DEVELOPMENTAL STAGE: Earliest isoform to be expressed during
CC embryogenesis in cells of embryonic origin at 7 and 9.5 dpc, and is the
CC major isoform expressed in uterine tissue at the time of implantation
CC (4.5 dpc) and continues to be expressed in uterine tissue at 6.5, 7.5
CC and 9.5 dpc. It is expressed in giant trophoblasts at 9.5 dpc and is
CC expressed in the placenta through 15.5 dpc.
CC -!- SIMILARITY: Belongs to the 3-beta-HSD family. {ECO:0000305}.
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DR EMBL; AF031170; AAB84299.1; -; mRNA.
DR EMBL; AK142267; BAE25002.1; -; mRNA.
DR EMBL; AL606755; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466620; EDL38971.1; -; Genomic_DNA.
DR CCDS; CCDS17669.1; -.
DR RefSeq; NP_038849.2; NM_013821.3.
DR AlphaFoldDB; O35469; -.
DR SMR; O35469; -.
DR STRING; 10090.ENSMUSP00000029463; -.
DR iPTMnet; O35469; -.
DR PhosphoSitePlus; O35469; -.
DR jPOST; O35469; -.
DR MaxQB; O35469; -.
DR PaxDb; O35469; -.
DR PeptideAtlas; O35469; -.
DR PRIDE; O35469; -.
DR ProteomicsDB; 285891; -.
DR DNASU; 15497; -.
DR Ensembl; ENSMUST00000029463; ENSMUSP00000029463; ENSMUSG00000027869.
DR Ensembl; ENSMUST00000170847; ENSMUSP00000129911; ENSMUSG00000027869.
DR GeneID; 15497; -.
DR KEGG; mmu:15497; -.
DR UCSC; uc012cuq.1; mouse.
DR CTD; 15497; -.
DR MGI; MGI:109598; Hsd3b6.
DR VEuPathDB; HostDB:ENSMUSG00000027869; -.
DR eggNOG; KOG1430; Eukaryota.
DR GeneTree; ENSGT00940000155444; -.
DR HOGENOM; CLU_007383_6_3_1; -.
DR InParanoid; O35469; -.
DR OMA; IIGVTHR; -.
DR OrthoDB; 930591at2759; -.
DR PhylomeDB; O35469; -.
DR TreeFam; TF343138; -.
DR BRENDA; 1.1.1.145; 3474.
DR Reactome; R-MMU-193048; Androgen biosynthesis.
DR Reactome; R-MMU-193993; Mineralocorticoid biosynthesis.
DR Reactome; R-MMU-194002; Glucocorticoid biosynthesis.
DR UniPathway; UPA00062; -.
DR BioGRID-ORCS; 15497; 2 hits in 73 CRISPR screens.
DR PRO; PR:O35469; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; O35469; protein.
DR Bgee; ENSMUSG00000027869; Expressed in adrenal gland and 63 other tissues.
DR Genevisible; O35469; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
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:0045171; C:intercellular bridge; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISO:MGI.
DR GO; GO:0005758; C:mitochondrial intermembrane space; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0003854; F:3-beta-hydroxy-delta5-steroid dehydrogenase activity; ISO:MGI.
DR GO; GO:0102294; F:cholesterol dehydrogenase 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:0004769; F:steroid delta-isomerase activity; ISO:MGI.
DR GO; GO:0006702; P:androgen biosynthetic process; ISO:MGI.
DR GO; GO:0006700; P:C21-steroid hormone biosynthetic process; ISO:MGI.
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:0034757; P:negative regulation of iron ion transport; ISO:MGI.
DR GO; GO:0051412; P:response to corticosterone; IBA:GO_Central.
DR GO; GO:0006694; P:steroid biosynthetic process; IBA:GO_Central.
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 Endoplasmic reticulum; Isomerase; Membrane; Mitochondrion;
KW Multifunctional enzyme; NAD; Oxidoreductase; Reference proteome;
KW Steroidogenesis; Transmembrane; Transmembrane helix.
FT CHAIN 1..373
FT /note="3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-
FT isomerase type 6"
FT /id="PRO_0000087785"
FT TRANSMEM 288..308
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 155
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 159
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT CONFLICT 189
FT /note="Y -> F (in Ref. 1; AAB84299)"
FT /evidence="ECO:0000305"
FT CONFLICT 366
FT /note="E -> A (in Ref. 1; AAB84299)"
FT /evidence="ECO:0000305"
FT CONFLICT 371
FT /note="K -> T (in Ref. 1; AAB84299)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 373 AA; 41977 MW; 10FE9278C5BDC534 CRC64;
MPGWSCLVTG AGGFLGQRIV QLLMQEKDLE EIRVLDKFFR PETREQFFNL DTNIKVTVLE
GDILDTQYLR KACQGISVVI HTAAVIDVTG VIPRQTILDV NLKGTQNLLE ACIQASVPAF
IFSSSVDVAG PNSYKEIILN GNEEEHHESI WSDPYPYSKK MAEKAVLAAN GSMLKIGGTL
HTCALRPMYI YGERSPFISN TIITALKNKN ILGCTGKFST ANPVYVGNVA WAHILAARGL
RDPKKSPNIQ GEFYYISDDT PHQSYDDLNY TLSKEWGFCP DSSWSLPVPL LYWLAFMLET
VSFLLSPIYR FIPPFNRHLV TLTGSTFTFS YKKAQRDLGY EPLVSWEEAK QKTSEWIGTL
VEQHRETLDT KSQ
