DHI2_MOUSE
ID DHI2_MOUSE Reviewed; 386 AA.
AC P51661; Q91WK3;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 30-APR-2003, sequence version 2.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=11-beta-hydroxysteroid dehydrogenase type 2;
DE Short=11-DH2;
DE Short=11-beta-HSD2;
DE EC=1.1.1.- {ECO:0000269|PubMed:30902677, ECO:0000305|PubMed:31600723};
DE AltName: Full=Corticosteroid 11-beta-dehydrogenase isozyme 2;
DE AltName: Full=NAD-dependent 11-beta-hydroxysteroid dehydrogenase;
GN Name=Hsd11b2; Synonyms=Hsd11k;
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 [GENOMIC DNA], TISSUE SPECIFICITY, AND FUNCTION.
RC STRAIN=129/Sv;
RX PubMed=7664690; DOI=10.1210/endo.136.10.7664690;
RA Cole T.J.;
RT "Cloning of the mouse 11 beta-hydroxysteroid dehydrogenase type 2 gene:
RT tissue specific expression and localization in distal convoluted tubules
RT and collecting ducts of the kidney.";
RL Endocrinology 136:4693-4696(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 CAUTION.
RX PubMed=1312193; DOI=10.1016/0024-3205(92)90204-3;
RA van Weerden W.M., Bierings H.G., van Steenbrugge G.J., de Jong F.H.,
RA Schroeder F.H.;
RT "Adrenal glands of mouse and rat do not synthesize androgens.";
RL Life Sci. 50:857-861(1992).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=22796344; DOI=10.1016/j.tox.2012.07.001;
RA Meyer A., Strajhar P., Murer C., Da Cunha T., Odermatt A.;
RT "Species-specific differences in the inhibition of human and zebrafish
RT 11beta-hydroxysteroid dehydrogenase 2 by thiram and organotins.";
RL Toxicology 301:72-78(2012).
RN [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=30902677; DOI=10.1016/j.jsbmb.2019.03.011;
RA Beck K.R., Kanagaratnam S., Kratschmar D.V., Birk J., Yamaguchi H.,
RA Sailer A.W., Seuwen K., Odermatt A.;
RT "Enzymatic interconversion of the oxysterols 7beta,25-dihydroxycholesterol
RT and 7-keto,25-hydroxycholesterol by 11beta-hydroxysteroid dehydrogenase
RT type 1 and 2.";
RL J. Steroid Biochem. Mol. Biol. 190:19-28(2019).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RX PubMed=31600723; DOI=10.1530/joe-19-0349;
RA Zheng H.T., Fu T., Zhang H.Y., Yang Z.S., Zheng Z.H., Yang Z.M.;
RT "Progesterone-regulated Hsd11b2 as a barrier to balance mouse uterine
RT corticosterone.";
RL J. Endocrinol. 244:177-187(2020).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
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: Catalyzes the conversion of biologically active 11beta-
CC hydroxyglucocorticoids (11beta-hydroxysteroid) such as corticosterone,
CC to inactive 11-ketoglucocorticoids (11-oxosteroid) such as 11-
CC dehydrocorticosterone, in the presence of NAD(+) (Probable)
CC (PubMed:30902677, PubMed:22796344). Functions as a dehydrogenase
CC (oxidase), thereby decreasing the concentration of active
CC glucocorticoids, thus protecting the nonselective mineralocorticoid
CC receptor from occupation by glucocorticoids (PubMed:7664690). Plays an
CC important role in maintaining glucocorticoids balance during
CC preimplantation and protects the fetus from excessive maternal
CC corticosterone exposure (PubMed:31600723). Catalyzes the oxidation of
CC 11beta-hydroxytestosterone (11beta,17beta-dihydroxyandrost-4-ene-3-one)
CC to 11-ketotestosterone (17beta-hydroxyandrost-4-ene-3,11-dione), a
CC major bioactive androgen (PubMed:22796344). Catalyzes the conversion of
CC 11beta-hydroxyandrostenedione (11beta-hydroxyandrost-4-ene-3,17-dione)
CC to 11-ketoandrostenedione (androst-4-ene-3,11,17-trione), which can be
CC further metabolized to 11-ketotestosterone (By similarity). Converts 7-
CC beta-25-dihydroxycholesterol to 7-oxo-25-hydroxycholesterol in vitro
CC (By similarity). 7-beta-25-dihydroxycholesterol (not 7-oxo-25-
CC hydroxycholesterol) acts as ligand for the G-protein-coupled receptor
CC (GPCR) Epstein-Barr virus-induced gene 2 (EBI2) and may thereby
CC regulate immune cell migration (By similarity).
CC {ECO:0000250|UniProtKB:P80365, ECO:0000269|PubMed:22796344,
CC ECO:0000269|PubMed:30902677, ECO:0000303|PubMed:31600723,
CC ECO:0000303|PubMed:7664690, ECO:0000305|PubMed:31600723}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an 11beta-hydroxysteroid + NAD(+) = an 11-oxosteroid + H(+) +
CC NADH; Xref=Rhea:RHEA:53116, ChEBI:CHEBI:15378, ChEBI:CHEBI:35346,
CC ChEBI:CHEBI:47787, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000269|PubMed:22796344, ECO:0000269|PubMed:30902677,
CC ECO:0000305|PubMed:31600723};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53117;
CC Evidence={ECO:0000305|PubMed:22796344, ECO:0000305|PubMed:30902677,
CC ECO:0000305|PubMed:31600723};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=corticosterone + NAD(+) = 11-dehydrocorticosterone + H(+) +
CC NADH; Xref=Rhea:RHEA:42204, ChEBI:CHEBI:15378, ChEBI:CHEBI:16827,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78600;
CC Evidence={ECO:0000269|PubMed:22796344, ECO:0000269|PubMed:30902677,
CC ECO:0000305|PubMed:31600723};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42205;
CC Evidence={ECO:0000305|PubMed:22796344, ECO:0000305|PubMed:30902677,
CC ECO:0000305|PubMed:31600723};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=11beta,17beta-dihydroxyandrost-4-ene-3-one + NAD(+) = 17beta-
CC hydroxyandrost-4-ene-3,11-dione + H(+) + NADH; Xref=Rhea:RHEA:69368,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:34133, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:81481;
CC Evidence={ECO:0000269|PubMed:22796344};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69369;
CC Evidence={ECO:0000305|PubMed:22796344};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=11beta-hydroxyandrost-4-ene-3,17-dione + NAD(+) = androst-4-
CC ene-3,11,17-trione + H(+) + NADH; Xref=Rhea:RHEA:69408,
CC ChEBI:CHEBI:2495, ChEBI:CHEBI:15378, ChEBI:CHEBI:27967,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000250|UniProtKB:P80365};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69409;
CC Evidence={ECO:0000250|UniProtKB:P80365};
CC -!- ACTIVITY REGULATION: Inhibited by glycyrrhetinic acid (By similarity).
CC Induced by progesterone, through the Ihh signaling pathway
CC (PubMed:31600723). {ECO:0000250|UniProtKB:P80365,
CC ECO:0000269|PubMed:31600723}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=24 nM for corticosterone {ECO:0000269|PubMed:22796344};
CC KM=33 nM for 11beta,17beta-dihydroxyandrost-4-ene-3-one
CC {ECO:0000269|PubMed:22796344};
CC KM=44 nM for cortisol {ECO:0000269|PubMed:22796344};
CC -!- PATHWAY: Steroid metabolism. {ECO:0000305}.
CC -!- SUBUNIT: Interacts with ligand-free cytoplasmic NR3C2.
CC {ECO:0000250|UniProtKB:P80365}.
CC -!- SUBCELLULAR LOCATION: Microsome {ECO:0000250|UniProtKB:P80365}.
CC Endoplasmic reticulum {ECO:0000250|UniProtKB:P80365}.
CC -!- TISSUE SPECIFICITY: Highly expressed in kidney (PubMed:7664690). Also
CC found in colon and small intestine (PubMed:7664690). Not expressed in
CC the adrenal gland (PubMed:7664690). Expressed in uterus
CC (PubMed:31600723). {ECO:0000269|PubMed:31600723,
CC ECO:0000269|PubMed:7664690}.
CC -!- DEVELOPMENTAL STAGE: Expression (mRNA and protein) is highest in uteri
CC on days 3 and 4 during early pregnancy. {ECO:0000269|PubMed:31600723}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
CC -!- CAUTION: Rats and mice do not produce appreciable cortisol, because
CC they do not express the 17-alpha hydroxylase (Cyp17a1) enzyme in the
CC adrenals. {ECO:0000269|PubMed:1312193}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA62219.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; S79554; AAC60711.1; ALT_FRAME; Genomic_DNA.
DR EMBL; S79550; AAC60711.1; JOINED; Genomic_DNA.
DR EMBL; S79551; AAC60711.1; JOINED; Genomic_DNA.
DR EMBL; S79552; AAC60711.1; JOINED; Genomic_DNA.
DR EMBL; S79553; AAC60711.1; JOINED; Genomic_DNA.
DR EMBL; X90646; CAA62218.1; -; Genomic_DNA.
DR EMBL; X90647; CAA62219.1; ALT_FRAME; Genomic_DNA.
DR EMBL; BC014753; AAH14753.1; -; mRNA.
DR CCDS; CCDS40460.1; -.
DR PIR; S60188; S60188.
DR RefSeq; NP_032315.2; NM_008289.2.
DR AlphaFoldDB; P51661; -.
DR SMR; P51661; -.
DR BioGRID; 200431; 1.
DR STRING; 10090.ENSMUSP00000034363; -.
DR BindingDB; P51661; -.
DR ChEMBL; CHEMBL3490; -.
DR DrugCentral; P51661; -.
DR iPTMnet; P51661; -.
DR PhosphoSitePlus; P51661; -.
DR jPOST; P51661; -.
DR MaxQB; P51661; -.
DR PaxDb; P51661; -.
DR PeptideAtlas; P51661; -.
DR PRIDE; P51661; -.
DR ProteomicsDB; 277335; -.
DR Antibodypedia; 29548; 323 antibodies from 32 providers.
DR DNASU; 15484; -.
DR Ensembl; ENSMUST00000034363; ENSMUSP00000034363; ENSMUSG00000031891.
DR GeneID; 15484; -.
DR KEGG; mmu:15484; -.
DR UCSC; uc009nde.1; mouse.
DR CTD; 3291; -.
DR MGI; MGI:104720; Hsd11b2.
DR VEuPathDB; HostDB:ENSMUSG00000031891; -.
DR eggNOG; KOG1610; Eukaryota.
DR GeneTree; ENSGT00940000159716; -.
DR HOGENOM; CLU_010194_2_0_1; -.
DR InParanoid; P51661; -.
DR OMA; ATFRNCM; -.
DR OrthoDB; 1313182at2759; -.
DR PhylomeDB; P51661; -.
DR TreeFam; TF325617; -.
DR BRENDA; 1.1.1.146; 3474.
DR BRENDA; 1.1.1.B40; 3474.
DR Reactome; R-MMU-194002; Glucocorticoid biosynthesis.
DR BioGRID-ORCS; 15484; 0 hits in 74 CRISPR screens.
DR PRO; PR:P51661; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; P51661; protein.
DR Bgee; ENSMUSG00000031891; Expressed in left colon and 124 other tissues.
DR Genevisible; P51661; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005811; C:lipid droplet; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0070523; F:11-beta-hydroxysteroid dehydrogenase (NAD+) activity; ISO:MGI.
DR GO; GO:0051287; F:NAD binding; ISO:MGI.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0005496; F:steroid binding; ISO:MGI.
DR GO; GO:0016229; F:steroid dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0034650; P:cortisol metabolic process; ISO:MGI.
DR GO; GO:0007565; P:female pregnancy; IMP:MGI.
DR GO; GO:0008211; P:glucocorticoid metabolic process; ISO:MGI.
DR GO; GO:0002017; P:regulation of blood volume by renal aldosterone; ISO:MGI.
DR GO; GO:0032094; P:response to food; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0032868; P:response to insulin; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0008202; P:steroid metabolic process; IBA:GO_Central.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Lipid metabolism; Microsome; NAD; Oxidoreductase;
KW Reference proteome; Steroid metabolism.
FT CHAIN 1..386
FT /note="11-beta-hydroxysteroid dehydrogenase type 2"
FT /id="PRO_0000054628"
FT ACT_SITE 232
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 82..111
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 219
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT CONFLICT 49
FT /note="Q -> L (in Ref. 1; AAC60711/CAA62218)"
FT /evidence="ECO:0000305"
FT CONFLICT 52
FT /note="L -> M (in Ref. 1; AAC60711/CAA62218)"
FT /evidence="ECO:0000305"
FT CONFLICT 178
FT /note="E -> G (in Ref. 1; AAC60711/CAA62218)"
FT /evidence="ECO:0000305"
FT CONFLICT 216
FT /note="T -> P (in Ref. 1; AAC60711/CAA62218)"
FT /evidence="ECO:0000305"
FT CONFLICT 265
FT /note="F -> S (in Ref. 1; AAC60711/CAA62218)"
FT /evidence="ECO:0000305"
FT CONFLICT 268
FT /note="D -> A (in Ref. 1; AAC60711/CAA62218)"
FT /evidence="ECO:0000305"
FT CONFLICT 297
FT /note="E -> A (in Ref. 1; AAC60711/CAA62218)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 386 AA; 42187 MW; 687FD253568487AB CRC64;
MERWPWPSGG AWLLVAARAL LQLLRSDLRL GRPLLAALAL LAALDWLCQR LLPPPAALVV
LAGAGWIALS RLARPPRLPV ATRAVLITGC DTGFGKETAK KLDAMGFTVL ATVLDLNSPG
ALELRDLCSP RLKLLQMDLT KAEDISRVLE ITKAHTASTG LWGLVNNAGL NIVVADVELS
PVATFRKCME VNFFGALELT KGLLPLLRHS RGRIVTVGSP AGDMPYPCLA AYGTSKAAIA
LLMDTFGCEL LPWGIKVSII KPGCFKTDAV TNVNLWEKRK QLLLANIPRE LLQAYGEDYI
EHVHGQFLNS LRMALPDLSP VVDAIIDALL AAQPRSRYYP GRGLGLMYFI HHYLPEGLRR
CFLQNFFINH LLPRALRPGQ HGPAPA
