3BHS2_HUMAN
ID 3BHS2_HUMAN Reviewed; 372 AA.
AC P26439; A2RRA5; Q16010; Q53GD4; Q6AI10; Q6LDB9; Q99890; Q9UD08;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 216.
DE RecName: Full=3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2 {ECO:0000305};
DE AltName: Full=3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type II;
DE Short=3-beta-HSD II;
DE AltName: Full=3-beta-HSD adrenal and gonadal type;
DE Includes:
DE RecName: Full=3-beta-hydroxy-Delta(5)-steroid dehydrogenase;
DE EC=1.1.1.145 {ECO:0000269|PubMed:25322271};
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 {ECO:0000305|PubMed:25322271};
DE AltName: Full=Delta-5-3-ketosteroid isomerase;
GN Name=HSD3B2 {ECO:0000312|HGNC:HGNC:5218}; Synonyms=HSDB3B;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1741954; DOI=10.1089/dna.1991.10.701;
RA Lachance Y., Luu-The V., Verreault H., Dumont M., Rheaume E., Leblanc G.,
RA Labrie F.;
RT "Structure of the human type II 3 beta-hydroxysteroid dehydrogenase/delta
RT 5-delta 4 isomerase (3 beta-HSD) gene: adrenal and gonadal specificity.";
RL DNA Cell Biol. 10:701-711(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Adrenal gland;
RX PubMed=1944309; DOI=10.1210/mend-5-8-1147;
RA Rheaume E., Lachance Y., Zhao H.-F., Breton N., Dumont M., de Launoit Y.,
RA Trudel C., Luu-The V., Simard J., Labrie F.;
RT "Structure and expression of a new complementary DNA encoding the almost
RT exclusive 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase in
RT human adrenals and gonads.";
RL Mol. Endocrinol. 5:1147-1157(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT GLN-94.
RC TISSUE=Adrenal gland;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Small intestine;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 49-102.
RX PubMed=7588414; DOI=10.3109/07435809509030466;
RA Russell A.J., McCartin S., Corcao G., Burridge S.M., McBride M.W.,
RA McNicol A.M., Hawes C.S., Mason J.I., Sutcliffe R.G.;
RT "Variation in the expression of human 3 beta-hydroxysteroid
RT dehydrogenase.";
RL Endocr. Res. 21:485-494(1995).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 167-205.
RX PubMed=1363812; DOI=10.1038/ng0792-239;
RA Rheaume E., Simard J., Morel Y., Mebarki F., Zachmann M., Forest M.G.,
RA New M.I., Labrie F.;
RT "Congenital adrenal hyperplasia due to point mutations in the type II 3
RT beta-hydroxysteroid dehydrogenase gene.";
RL Nat. Genet. 1:239-245(1992).
RN [10]
RP POSSIBLE INVOLVEMENT IN INSULIN-RESISTANT POLYCYSTIC OVARY SYNDROME.
RX PubMed=14764797; DOI=10.1210/jc.2003-030934;
RA Carbunaru G., Prasad P., Scoccia B., Shea P., Hopwood N., Ziai F.,
RA Chang Y.T., Myers S.E., Mason J.I., Pang S.;
RT "The hormonal phenotype of nonclassic 3 beta-hydroxysteroid dehydrogenase
RT (HSD3B) deficiency in hyperandrogenic females is associated with insulin-
RT resistant polycystic ovary syndrome and is not a variant of inherited
RT HSD3B2 deficiency.";
RL J. Clin. Endocrinol. Metab. 89:783-794(2004).
RN [11]
RP VARIANTS AH2 LYS-142; PRO-245 AND ASN-253.
RX PubMed=8316254; DOI=10.1210/mend.7.5.8316254;
RA Simard J., Rheaume E., Sanchez R., Laflamme N., de Launoit Y., Luu-The V.,
RA van Seters A.P., Gordon R.D., Bettendorf M., Heinrich U., Moshang T.,
RA New M.I., Labrie F.;
RT "Molecular basis of congenital adrenal hyperplasia due to 3 beta-
RT hydroxysteroid dehydrogenase deficiency.";
RL Mol. Endocrinol. 7:716-728(1993).
RN [12]
RP VARIANTS AH2 TRP-108 AND LEU-186.
RX PubMed=7833923; DOI=10.1093/hmg/3.9.1639;
RA Sanchez R., Mebarki F., Rheaume E., Laflamme N., Forest M.G., Bey-Omar F.,
RA David M., Morel Y., Labrie F., Simard J.;
RT "Functional characterization of the novel L108W and P186L mutations
RT detected in the type II 3 beta-hydroxysteroid dehydrogenase gene of a male
RT pseudohermaphrodite with congenital adrenal hyperplasia.";
RL Hum. Mol. Genet. 3:1639-1645(1994).
RN [13]
RP VARIANT AH2 ASP-254.
RX PubMed=8126127; DOI=10.1210/jcem.78.3.8126127;
RA Sanchez R., Rheaume E., Laflamme N., Rosenfield R.L., Labrie F., Simard J.;
RT "Detection and functional characterization of the novel missense mutation
RT Y254D in type II 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) gene of a
RT female patient with nonsalt-losing 3 beta HSD deficiency.";
RL J. Clin. Endocrinol. Metab. 78:561-567(1994).
RN [14]
RP VARIANT AH2 ARG-129.
RX PubMed=7962268; DOI=10.1210/jcem.79.4.7962268;
RA Rheaume E., Sanchez R., Simard J., Chang Y.T., Wang J., Pang S., Labrie F.;
RT "Molecular basis of congenital adrenal hyperplasia in two siblings with
RT classical nonsalt-losing 3 beta-hydroxysteroid dehydrogenase deficiency.";
RL J. Clin. Endocrinol. Metab. 79:1012-1018(1994).
RN [15]
RP VARIANT AH2 THR-82.
RX PubMed=8185809; DOI=10.1677/jme.0.0120119;
RA Mendonca B.B., Russell A.J., Vasconcelos-Leite M., Arnhold I.J., Bloise W.,
RA Wajchenberg B.L., Nicolau W., Sutcliffe R.G., Wallace A.M.;
RT "Mutation in 3 beta-hydroxysteroid dehydrogenase type II associated with
RT pseudohermaphroditism in males and premature pubarche or cryptic expression
RT in females.";
RL J. Mol. Endocrinol. 12:119-122(1994).
RN [16]
RP VARIANT AH2 ARG-173.
RX PubMed=8060486; DOI=10.1677/jme.0.0120225;
RA Russell A.J., Wallace A.M., Forest M.G., Donaldson M.D., Edwards C.R.,
RA Sutcliffe R.G.;
RT "Mutation in the human gene for 3 beta-hydroxysteroid dehydrogenase type II
RT leading to male pseudohermaphroditism without salt loss.";
RL J. Mol. Endocrinol. 12:225-237(1994).
RN [17]
RP VARIANT AH2 ASP-15.
RX PubMed=7893703; DOI=10.1021/bi00009a020;
RA Rheaume E., Sanchez R., Mebarki F., Gagnon E., Carel J.-C.,
RA Chaussain J.-L., Morel Y., Labrie F., Simard J.;
RT "Identification and characterization of the G15D mutation found in a male
RT patient with 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency:
RT alteration of the putative NAD-binding domain of type II 3 beta-HSD.";
RL Biochemistry 34:2893-2900(1995).
RN [18]
RP VARIANT AH2 PRO-205.
RX PubMed=7633426; DOI=10.1093/hmg/4.4.745;
RA Katsumata N., Tanae A., Yasunaga T., Horikawa R., Tanaka T., Hibi I.;
RT "A novel missense mutation in the type II 3 beta-hydroxysteroid
RT dehydrogenase gene in a family with classical salt-wasting congenital
RT adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase
RT deficiency.";
RL Hum. Mol. Genet. 4:745-746(1995).
RN [19]
RP VARIANT AH2 ARG-259.
RX PubMed=7633460; DOI=10.1093/hmg/4.5.969;
RA Tajima T., Fujieda K., Nakae J., Shinohara N., Yoshimoto M., Baba T.,
RA Kinoshita E., Igarashi Y., Oomura T.;
RT "Molecular analysis of type II 3 beta-hydroxysteroid dehydrogenase gene in
RT Japanese patients with classical 3 beta-hydroxysteroid dehydrogenase
RT deficiency.";
RL Hum. Mol. Genet. 4:969-971(1995).
RN [20]
RP VARIANT AH2 SER-100.
RX PubMed=7608265; DOI=10.1210/jcem.80.7.7608265;
RA Mebarki F., Sanchez R., Rheaume E., Laflamme N., Simard J., Forest M.G.,
RA Bey-Omar F., David M., Labrie F., Morel Y.;
RT "Nonsalt-losing male pseudohermaphroditism due to the novel homozygous
RT N100S mutation in the type II 3 beta-hydroxysteroid dehydrogenase gene.";
RL J. Clin. Endocrinol. Metab. 80:2127-2134(1995).
RN [21]
RP VARIANT AH2 SER-236.
RX PubMed=9719627; DOI=10.1006/mgme.1998.2715;
RA Nayak S., Lee P.A., Witchel S.F.;
RT "Variants of the type II 3beta-hydroxysteroid dehydrogenase gene in
RT children with premature pubic hair and hyperandrogenic adolescents.";
RL Mol. Genet. Metab. 64:184-192(1998).
RN [22]
RP VARIANTS AH2 GLU-10; VAL-10; ASP-15; THR-82; SER-100; TRP-108; ARG-129;
RP LYS-142; LEU-155; VAL-167; ARG-173; LEU-186; PRO-205; GLY-213; GLU-216;
RP GLN-222; HIS-222; SER-236; PRO-245; ASN-253; ASP-254; ARG-259; MET-259 AND
RP VAL-294.
RX PubMed=10599696; DOI=10.1210/jcem.84.12.6288;
RA Moisan A.M., Ricketts M.L., Tardy V., Desrochers M., Mebarki F.,
RA Chaussain J.-L., Cabrol S., Raux-Demay M.C., Forest M.G., Sippell W.G.,
RA Peter M., Morel Y., Simard J.;
RT "New insight into the molecular basis of 3beta-hydroxysteroid dehydrogenase
RT deficiency: identification of eight mutations in the HSD3B2 gene in eleven
RT patients from seven new families and comparison of the functional
RT properties of twenty-five mutant enzymes.";
RL J. Clin. Endocrinol. Metab. 84:4410-4425(1999).
RN [23]
RP VARIANTS AH2 ARG-129; GLN-222 AND MET-259.
RX PubMed=10651755; DOI=10.1046/j.1365-2265.2000.00873.x;
RA Marui S., Castro M., Latronico A.C., Elias L.L., Arnhold I.J.,
RA Moreira A.C., Mendonca B.B.;
RT "Mutations in the type II 3beta-hydroxysteroid dehydrogenase (HSD3B2) gene
RT can cause premature pubarche in girls.";
RL Clin. Endocrinol. (Oxf.) 52:67-75(2000).
RN [24]
RP VARIANT AH2 GLU-10.
RX PubMed=10843183; DOI=10.1210/jcem.85.5.6581;
RA Alos N., Moisan A.M., Ward L., Desrochers M., Legault L., Leboeuf G.,
RA van Vliet G., Simard J.;
RT "A novel A10E homozygous mutation in the HSD3B2 gene causing severe salt-
RT wasting 3beta-hydroxysteroid dehydrogenase deficiency in 46,XX and 46,XY
RT French-Canadians: evaluation of gonadal function after puberty.";
RL J. Clin. Endocrinol. Metab. 85:1968-1974(2000).
RN [25]
RP VARIANTS AH2 LYS-142 AND THR-222.
RX PubMed=12050213; DOI=10.1210/jcem.87.6.8559;
RA Pang S., Wang W., Rich B., David R., Chang Y.T., Carbunaru G., Myers S.E.,
RA Howie A.F., Smillie K.J., Mason J.I.;
RT "A novel nonstop mutation in the stop codon and a novel missense mutation
RT in the type II 3-beta-hydroxysteroid dehydrogenase (3-beta-HSD) gene
RT causing, respectively, nonclassic and classic 3-beta-HSD deficiency
RT congenital adrenal hyperplasia.";
RL J. Clin. Endocrinol. Metab. 87:2556-2563(2002).
RN [26]
RP VARIANT AH2 LEU-341, AND CHARACTERIZATION OF VARIANT AH2 LEU-341.
RX PubMed=18252794; DOI=10.1210/jc.2007-1874;
RA Welzel M., Wustemann N., Simic-Schleicher G., Dorr H.G., Schulze E.,
RA Shaikh G., Clayton P., Grotzinger J., Holterhus P.M., Riepe F.G.;
RT "Carboxyl-terminal mutations in 3beta-hydroxysteroid dehydrogenase type II
RT cause severe salt-wasting congenital adrenal hyperplasia.";
RL J. Clin. Endocrinol. Metab. 93:1418-1425(2008).
RN [27]
RP VARIANT AH2 PRO-82.
RX PubMed=22579964; DOI=10.1016/j.gene.2012.04.080;
RA Rabbani B., Mahdieh N., Haghi Ashtiani M.T., Setoodeh A., Rabbani A.;
RT "In silico structural, functional and pathogenicity evaluation of a novel
RT mutation: an overview of HSD3B2 gene mutations.";
RL Gene 503:215-221(2012).
RN [28]
RP FUNCTION, SUBCELLULAR LOCATION, VARIANT AH2 VAL-250, CHARACTERIZATION OF
RP VARIANT AH2 VAL-250, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=25322271; DOI=10.1210/jc.2014-2676;
RA Baquedano M.S., Ciaccio M., Marino R., Perez Garrido N., Ramirez P.,
RA Maceiras M., Turjanski A., Defelipe L.A., Rivarola M.A., Belgorosky A.;
RT "A novel missense mutation in the HSD3B2 gene, underlying nonsalt-wasting
RT congenital adrenal hyperplasia. new insight into the structure-function
RT relationships of 3beta-hydroxysteroid dehidrogenase type II.";
RL J. Clin. Endocrinol. Metab. 100:E191-E196(2015).
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. {ECO:0000269|PubMed:1741954}.
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 Evidence={ECO:0000305|PubMed:25322271};
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; Evidence={ECO:0000305|PubMed:25322271};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+) + pregnenolone = H(+) + NADH + pregn-5-ene-3,20-dione;
CC Xref=Rhea:RHEA:43924, ChEBI:CHEBI:15378, ChEBI:CHEBI:16581,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:63837;
CC Evidence={ECO:0000269|PubMed:25322271};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43925;
CC Evidence={ECO:0000305|PubMed:25322271};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=pregn-5-ene-3,20-dione = progesterone; Xref=Rhea:RHEA:43928,
CC ChEBI:CHEBI:17026, ChEBI:CHEBI:63837;
CC Evidence={ECO:0000269|PubMed:25322271};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43929;
CC Evidence={ECO:0000305|PubMed:25322271};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta-hydroxyandrost-5-en-17-one + NAD(+) = androst-5-ene-
CC 3,17-dione + H(+) + NADH; Xref=Rhea:RHEA:43932, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:28689, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:83865; EC=1.1.1.145;
CC Evidence={ECO:0000269|PubMed:25322271};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43933;
CC Evidence={ECO:0000305|PubMed:25322271};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=androst-5-ene-3,17-dione = androst-4-ene-3,17-dione;
CC Xref=Rhea:RHEA:43936, ChEBI:CHEBI:16422, ChEBI:CHEBI:83865;
CC Evidence={ECO:0000269|PubMed:25322271};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43937;
CC Evidence={ECO:0000305|PubMed:25322271};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.84 uM for pregnenolone {ECO:0000269|PubMed:25322271};
CC Vmax=0.16 pmol/min/mg enzyme toward pregnenolone
CC {ECO:0000269|PubMed:25322271};
CC -!- PATHWAY: Lipid metabolism; steroid biosynthesis.
CC {ECO:0000269|PubMed:25322271}.
CC -!- INTERACTION:
CC P26439; Q53GS7: GLE1; NbExp=3; IntAct=EBI-21761225, EBI-1955541;
CC P26439; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-21761225, EBI-5235340;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:25322271}; Single-pass membrane protein
CC {ECO:0000255}. Mitochondrion membrane; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P26439-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P26439-2; Sequence=VSP_037399, VSP_037400;
CC -!- TISSUE SPECIFICITY: Expressed in adrenal gland, testis and ovary.
CC -!- DISEASE: Adrenal hyperplasia 2 (AH2) [MIM:201810]: A form of congenital
CC adrenal hyperplasia, a common recessive disease due to defective
CC synthesis of cortisol. Congenital adrenal hyperplasia is characterized
CC by androgen excess leading to ambiguous genitalia in affected females,
CC rapid somatic growth during childhood in both sexes with premature
CC closure of the epiphyses and short adult stature. Four clinical types:
CC 'salt wasting' (SW, the most severe type), 'simple virilizing' (SV,
CC less severely affected patients), with normal aldosterone biosynthesis,
CC 'non-classic form' or late-onset (NC or LOAH) and 'cryptic'
CC (asymptomatic). In AH2, virilization is much less marked or does not
CC occur. AH2 is frequently lethal in early life.
CC {ECO:0000269|PubMed:10599696, ECO:0000269|PubMed:10651755,
CC ECO:0000269|PubMed:10843183, ECO:0000269|PubMed:12050213,
CC ECO:0000269|PubMed:18252794, ECO:0000269|PubMed:22579964,
CC ECO:0000269|PubMed:25322271, ECO:0000269|PubMed:7608265,
CC ECO:0000269|PubMed:7633426, ECO:0000269|PubMed:7633460,
CC ECO:0000269|PubMed:7833923, ECO:0000269|PubMed:7893703,
CC ECO:0000269|PubMed:7962268, ECO:0000269|PubMed:8060486,
CC ECO:0000269|PubMed:8126127, ECO:0000269|PubMed:8185809,
CC ECO:0000269|PubMed:8316254, ECO:0000269|PubMed:9719627}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Note=Mild HSD3B2 deficiency in hyperandrogenic females is
CC associated with characteristic traits of polycystic ovary syndrome,
CC such as insulin resistance and luteinizing hormone hypersecretion.
CC {ECO:0000269|PubMed:14764797}.
CC -!- SIMILARITY: Belongs to the 3-beta-HSD family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC60600.1; Type=Frameshift; Note=The frameshift is caused by a single nucleotide insertion which is found in AH2.; Evidence={ECO:0000305};
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DR EMBL; M77144; AAA36014.1; -; Genomic_DNA.
DR EMBL; M67466; AAA36016.1; -; mRNA.
DR EMBL; CR627415; CAH10504.1; -; mRNA.
DR EMBL; AK222997; BAD96717.1; -; mRNA.
DR EMBL; AL359553; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471122; EAW56700.1; -; Genomic_DNA.
DR EMBL; BC038419; AAH38419.1; -; mRNA.
DR EMBL; BC131488; AAI31489.1; -; mRNA.
DR EMBL; S80140; AAD14329.1; -; Genomic_DNA.
DR EMBL; S60309; AAC60599.1; -; Genomic_DNA.
DR EMBL; S60310; AAC60600.1; ALT_FRAME; Genomic_DNA.
DR CCDS; CCDS902.1; -. [P26439-1]
DR PIR; A39488; DEHUH2.
DR RefSeq; NP_000189.1; NM_000198.3. [P26439-1]
DR RefSeq; NP_001159592.1; NM_001166120.1. [P26439-1]
DR AlphaFoldDB; P26439; -.
DR SMR; P26439; -.
DR BioGRID; 109517; 21.
DR CORUM; P26439; -.
DR IntAct; P26439; 20.
DR STRING; 9606.ENSP00000445122; -.
DR BindingDB; P26439; -.
DR ChEMBL; CHEMBL3670; -.
DR DrugBank; DB01285; Corticotropin.
DR DrugBank; DB00603; Medroxyprogesterone acetate.
DR DrugBank; DB00157; NADH.
DR DrugBank; DB00717; Norethisterone.
DR DrugBank; DB09070; Tibolone.
DR DrugBank; DB01108; Trilostane.
DR DrugCentral; P26439; -.
DR SwissLipids; SLP:000001296; -.
DR iPTMnet; P26439; -.
DR PhosphoSitePlus; P26439; -.
DR BioMuta; HSD3B2; -.
DR DMDM; 112770; -.
DR MassIVE; P26439; -.
DR PaxDb; P26439; -.
DR PeptideAtlas; P26439; -.
DR PRIDE; P26439; -.
DR ProteomicsDB; 54346; -. [P26439-1]
DR ProteomicsDB; 54347; -. [P26439-2]
DR Antibodypedia; 33908; 180 antibodies from 26 providers.
DR DNASU; 3284; -.
DR Ensembl; ENST00000369416.4; ENSP00000358424.3; ENSG00000203859.10. [P26439-1]
DR Ensembl; ENST00000543831.5; ENSP00000445122.1; ENSG00000203859.10. [P26439-1]
DR GeneID; 3284; -.
DR KEGG; hsa:3284; -.
DR MANE-Select; ENST00000369416.4; ENSP00000358424.3; NM_000198.4; NP_000189.1.
DR UCSC; uc001eht.4; human. [P26439-1]
DR CTD; 3284; -.
DR DisGeNET; 3284; -.
DR GeneCards; HSD3B2; -.
DR HGNC; HGNC:5218; HSD3B2.
DR HPA; ENSG00000203859; Tissue enriched (adrenal).
DR MalaCards; HSD3B2; -.
DR MIM; 201810; phenotype.
DR MIM; 613890; gene.
DR neXtProt; NX_P26439; -.
DR OpenTargets; ENSG00000203859; -.
DR Orphanet; 90791; Congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency.
DR PharmGKB; PA29487; -.
DR VEuPathDB; HostDB:ENSG00000203859; -.
DR eggNOG; KOG1430; Eukaryota.
DR GeneTree; ENSGT00940000161374; -.
DR HOGENOM; CLU_007383_6_3_1; -.
DR OMA; SLEDCRG; -.
DR PhylomeDB; P26439; -.
DR TreeFam; TF343138; -.
DR BioCyc; MetaCyc:HS10943-MON; -.
DR BRENDA; 1.1.1.145; 2681.
DR BRENDA; 5.3.3.1; 2681.
DR PathwayCommons; P26439; -.
DR Reactome; R-HSA-193048; Androgen biosynthesis.
DR Reactome; R-HSA-193993; Mineralocorticoid biosynthesis.
DR Reactome; R-HSA-194002; Glucocorticoid biosynthesis.
DR SignaLink; P26439; -.
DR SIGNOR; P26439; -.
DR UniPathway; UPA00062; -.
DR BioGRID-ORCS; 3284; 8 hits in 1031 CRISPR screens.
DR ChiTaRS; HSD3B2; human.
DR GeneWiki; HSD3B2; -.
DR GenomeRNAi; 3284; -.
DR Pharos; P26439; Tclin.
DR PRO; PR:P26439; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P26439; protein.
DR Bgee; ENSG00000203859; Expressed in right adrenal gland and 94 other tissues.
DR ExpressionAtlas; P26439; baseline and differential.
DR Genevisible; P26439; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0045171; C:intercellular bridge; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005758; C:mitochondrial intermembrane space; ISS:UniProtKB.
DR GO; GO:0031966; C:mitochondrial membrane; NAS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0030868; C:smooth endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0003854; F:3-beta-hydroxy-delta5-steroid dehydrogenase activity; IDA:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0006702; P:androgen biosynthetic process; IMP:UniProtKB.
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:0051412; P:response to corticosterone; IBA:GO_Central.
DR GO; GO:0006694; P:steroid biosynthetic process; IDA:UniProtKB.
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 Alternative splicing; Congenital adrenal hyperplasia; Disease variant;
KW Endoplasmic reticulum; Isomerase; Lipid metabolism; Membrane;
KW Mitochondrion; Multifunctional enzyme; NAD; Oxidoreductase;
KW Reference proteome; Steroidogenesis; Transmembrane; Transmembrane helix.
FT CHAIN 1..372
FT /note="3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-
FT isomerase type 2"
FT /id="PRO_0000087775"
FT TRANSMEM 287..307
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 154
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 158
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT VAR_SEQ 103..222
FT /note="GTQLLLEACVQASVPVFIYTSSIEVAGPNSYKEIIQNGHEEEPLENTWPTPY
FT PYSKKLAEKAVLAANGWNLKNGDTLYTCALRPTYIYGEGGPFLSASINEALNNNGILSS
FT VGKFSTVNP -> ELQNKIKLTVLEGDILDEPFLKRACQDVSVVIHTACIIDVFGVTHR
FT QSIMNVNVKGRVAWGGDKARWGNEDQKEGQEGKRSLSIEHLLCSGPSDFADHYQLGELK
FT AAIFSFIDEKTRTEQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_037399"
FT VAR_SEQ 223..372
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_037400"
FT VARIANT 10
FT /note="A -> E (in AH2; activity abolished;
FT dbSNP:rs28934880)"
FT /evidence="ECO:0000269|PubMed:10599696,
FT ECO:0000269|PubMed:10843183"
FT /id="VAR_010517"
FT VARIANT 10
FT /note="A -> V (in AH2; nonsalt-wasting form;
FT dbSNP:rs28934880)"
FT /evidence="ECO:0000269|PubMed:10599696"
FT /id="VAR_010518"
FT VARIANT 15
FT /note="G -> D (in AH2; activity abolished)"
FT /evidence="ECO:0000269|PubMed:10599696,
FT ECO:0000269|PubMed:7893703"
FT /id="VAR_010519"
FT VARIANT 74
FT /note="D -> N (in dbSNP:rs4986954)"
FT /id="VAR_048099"
FT VARIANT 82
FT /note="A -> P (in AH2)"
FT /evidence="ECO:0000269|PubMed:22579964"
FT /id="VAR_070028"
FT VARIANT 82
FT /note="A -> T (in AH2; dbSNP:rs757033996)"
FT /evidence="ECO:0000269|PubMed:10599696,
FT ECO:0000269|PubMed:8185809"
FT /id="VAR_010520"
FT VARIANT 94
FT /note="E -> Q (in dbSNP:rs6211)"
FT /evidence="ECO:0000269|PubMed:17974005"
FT /id="VAR_014818"
FT VARIANT 100
FT /note="N -> S (in AH2; nonsalt-wasting form;
FT dbSNP:rs1388517943)"
FT /evidence="ECO:0000269|PubMed:10599696,
FT ECO:0000269|PubMed:7608265"
FT /id="VAR_010521"
FT VARIANT 108
FT /note="L -> W (in AH2; activity abolished)"
FT /evidence="ECO:0000269|PubMed:10599696,
FT ECO:0000269|PubMed:7833923"
FT /id="VAR_010522"
FT VARIANT 129
FT /note="G -> R (in AH2; nonsalt-wasting form;
FT dbSNP:rs587628683)"
FT /evidence="ECO:0000269|PubMed:10599696,
FT ECO:0000269|PubMed:10651755, ECO:0000269|PubMed:7962268"
FT /id="VAR_010523"
FT VARIANT 142
FT /note="E -> K (in AH2; activity abolished;
FT dbSNP:rs80358219)"
FT /evidence="ECO:0000269|PubMed:10599696,
FT ECO:0000269|PubMed:12050213, ECO:0000269|PubMed:8316254"
FT /id="VAR_000006"
FT VARIANT 155
FT /note="P -> L (in AH2; nonsalt-wasting form;
FT dbSNP:rs779418168)"
FT /evidence="ECO:0000269|PubMed:10599696"
FT /id="VAR_010524"
FT VARIANT 167
FT /note="A -> V (in AH2; late onset; almost normal activity;
FT dbSNP:rs35486059)"
FT /evidence="ECO:0000269|PubMed:10599696"
FT /id="VAR_010525"
FT VARIANT 173
FT /note="L -> R (in AH2; nonsalt-wasting form;
FT dbSNP:rs762479018)"
FT /evidence="ECO:0000269|PubMed:10599696,
FT ECO:0000269|PubMed:8060486"
FT /id="VAR_010526"
FT VARIANT 186
FT /note="P -> L (in AH2; activity abolished)"
FT /evidence="ECO:0000269|PubMed:10599696,
FT ECO:0000269|PubMed:7833923"
FT /id="VAR_010527"
FT VARIANT 205
FT /note="L -> P (in AH2)"
FT /evidence="ECO:0000269|PubMed:10599696,
FT ECO:0000269|PubMed:7633426"
FT /id="VAR_000007"
FT VARIANT 213
FT /note="S -> G (in AH2; late onset; partial loss of
FT activity; dbSNP:rs759422374)"
FT /evidence="ECO:0000269|PubMed:10599696"
FT /id="VAR_010528"
FT VARIANT 216
FT /note="K -> E (in AH2; late onset; partial loss of
FT activity)"
FT /evidence="ECO:0000269|PubMed:10599696"
FT /id="VAR_010529"
FT VARIANT 222
FT /note="P -> H (in AH2; nonsalt-wasting form; activity
FT abolished)"
FT /evidence="ECO:0000269|PubMed:10599696"
FT /id="VAR_010530"
FT VARIANT 222
FT /note="P -> Q (in AH2; activity abolished;
FT dbSNP:rs765547422)"
FT /evidence="ECO:0000269|PubMed:10599696,
FT ECO:0000269|PubMed:10651755"
FT /id="VAR_010531"
FT VARIANT 222
FT /note="P -> T (in AH2; dbSNP:rs80358220)"
FT /evidence="ECO:0000269|PubMed:12050213"
FT /id="VAR_015411"
FT VARIANT 231..238
FT /note="Missing (in AH2; activity abolished)"
FT /id="VAR_010532"
FT VARIANT 236
FT /note="L -> S (in AH2; mild; 100% of activity;
FT dbSNP:rs35887327)"
FT /evidence="ECO:0000269|PubMed:10599696,
FT ECO:0000269|PubMed:9719627"
FT /id="VAR_010533"
FT VARIANT 245
FT /note="A -> P (in AH2; loss of 88% of activity)"
FT /evidence="ECO:0000269|PubMed:10599696,
FT ECO:0000269|PubMed:8316254"
FT /id="VAR_000008"
FT VARIANT 250
FT /note="G -> V (in AH2; nonsalt-wasting form; loss of 75% of
FT enzymatic activity for the conversion of pregnenolone to
FT progesterone and dehydroepiandrosterone to androstenedione;
FT no effect on endoplasmic reticulum location)"
FT /evidence="ECO:0000269|PubMed:25322271"
FT /id="VAR_083841"
FT VARIANT 253
FT /note="Y -> N (in AH2; activity abolished;
FT dbSNP:rs1399005702)"
FT /evidence="ECO:0000269|PubMed:10599696,
FT ECO:0000269|PubMed:8316254"
FT /id="VAR_000009"
FT VARIANT 254
FT /note="Y -> D (in AH2; activity abolished;
FT dbSNP:rs1411029929)"
FT /evidence="ECO:0000269|PubMed:10599696,
FT ECO:0000269|PubMed:8126127"
FT /id="VAR_000010"
FT VARIANT 259
FT /note="T -> M (in AH2; activity abolished;
FT dbSNP:rs80358221)"
FT /evidence="ECO:0000269|PubMed:10599696,
FT ECO:0000269|PubMed:10651755"
FT /id="VAR_010534"
FT VARIANT 259
FT /note="T -> R (in AH2; activity abolished)"
FT /evidence="ECO:0000269|PubMed:10599696,
FT ECO:0000269|PubMed:7633460"
FT /id="VAR_000011"
FT VARIANT 294
FT /note="G -> V (in AH2; nonsalt-wasting form; activity
FT abolished)"
FT /evidence="ECO:0000269|PubMed:10599696"
FT /id="VAR_010535"
FT VARIANT 341
FT /note="P -> L (in AH2; strongly reduced activity;
FT dbSNP:rs121964897)"
FT /evidence="ECO:0000269|PubMed:18252794"
FT /id="VAR_065665"
FT CONFLICT 52..53
FT /note="RT -> KI (in Ref. 8; AAD14329)"
FT /evidence="ECO:0000305"
FT CONFLICT 92..94
FT /note="HRE -> RRQ (in Ref. 8; AAD14329)"
FT /evidence="ECO:0000305"
FT CONFLICT 232
FT /note="H -> L (in Ref. 4; BAD96717)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 372 AA; 42052 MW; 8E0D933488988451 CRC64;
MGWSCLVTGA GGLLGQRIVR LLVEEKELKE IRALDKAFRP ELREEFSKLQ NRTKLTVLEG
DILDEPFLKR ACQDVSVVIH TACIIDVFGV THRESIMNVN VKGTQLLLEA CVQASVPVFI
YTSSIEVAGP NSYKEIIQNG HEEEPLENTW PTPYPYSKKL AEKAVLAANG WNLKNGDTLY
TCALRPTYIY GEGGPFLSAS INEALNNNGI LSSVGKFSTV NPVYVGNVAW AHILALRALR
DPKKAPSVRG QFYYISDDTP HQSYDNLNYI LSKEFGLRLD SRWSLPLTLM YWIGFLLEVV
SFLLSPIYSY QPPFNRHTVT LSNSVFTFSY KKAQRDLAYK PLYSWEEAKQ KTVEWVGSLV
DRHKETLKSK TQ
