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 27-MAR-2024, entry version 178. 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 a 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}; 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; 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; 10090-ENSMUSP00000034363; -. DR PeptideAtlas; P51661; -. DR ProteomicsDB; 277335; -. DR Antibodypedia; 29548; 398 antibodies from 32 providers. DR DNASU; 15484; -. DR Ensembl; ENSMUST00000034363.7; ENSMUSP00000034363.6; ENSMUSG00000031891.7. DR GeneID; 15484; -. DR KEGG; mmu:15484; -. DR UCSC; uc009nde.1; mouse. DR AGR; MGI:104720; -. 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; SHVLEFT; -. DR OrthoDB; 5403248at2759; -. 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 Reactome; R-MMU-9757110; Prednisone ADME. DR BioGRID-ORCS; 15484; 0 hits in 79 CRISPR screens. DR PRO; PR:P51661; -. DR Proteomes; UP000000589; Chromosome 8. DR RNAct; P51661; Protein. DR Bgee; ENSMUSG00000031891; Expressed in left colon and 126 other cell types or tissues. DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; 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:0005496; F:steroid binding; ISO:MGI. 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 CDD; cd09805; type2_17beta_HSD-like_SDR_c; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. DR InterPro; IPR020904; Sc_DH/Rdtase_CS. DR InterPro; IPR002347; SDR_fam. DR PANTHER; PTHR43313:SF2; 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 2; 1. DR PANTHER; PTHR43313; SHORT-CHAIN DEHYDROGENASE/REDUCTASE FAMILY 9C; 1. DR Pfam; PF00106; adh_short; 1. DR PRINTS; PR00081; GDHRDH. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. DR PROSITE; PS00061; ADH_SHORT; 1. DR Genevisible; P51661; MM. 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 //