DHI1_RAT
ID DHI1_RAT Reviewed; 288 AA.
AC P16232; O09170; Q6LDH6;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 10-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=11-beta-hydroxysteroid dehydrogenase 1 {ECO:0000303|PubMed:12460758, ECO:0000303|PubMed:14973125};
DE Short=11-DH {ECO:0000303|PubMed:2808402};
DE Short=11-beta-HSD1 {ECO:0000303|PubMed:12460758, ECO:0000303|PubMed:14973125};
DE EC=1.1.1.146 {ECO:0000269|PubMed:12460758, ECO:0000269|PubMed:14973125, ECO:0000269|PubMed:2808402, ECO:0000269|PubMed:8613810};
DE AltName: Full=7-oxosteroid reductase;
DE EC=1.1.1.201 {ECO:0000269|PubMed:14973125};
DE AltName: Full=Corticosteroid 11-beta-dehydrogenase isozyme 1 {ECO:0000305};
GN Name=Hsd11b1 {ECO:0000312|RGD:2834}; Synonyms=Hsd11;
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] (ISOFORM 11-HSD1A), CATALYTIC ACTIVITY, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=2808402; DOI=10.1016/s0021-9258(19)47248-7;
RA Agarwal A.K., Monder C., Eckstein B., White P.C.;
RT "Cloning and expression of rat cDNA encoding corticosteroid 11 beta-
RT dehydrogenase.";
RL J. Biol. Chem. 264:18939-18943(1989).
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 NUCLEOTIDE SEQUENCE OF 1-69 (ISOFORMS 11-HSD1A AND 11-HSD1B), AND
RP ALTERNATIVE PROMOTER USAGE.
RX PubMed=1508221; DOI=10.1210/mend.6.7.1508221;
RA Moisan M.P., Edwards C.R., Seckl J.R.;
RT "Differential promoter usage by the rat 11 beta-hydroxysteroid
RT dehydrogenase gene.";
RL Mol. Endocrinol. 6:1082-1087(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-69 (ISOFORM 11-HSD1A).
RC STRAIN=Sprague-Dawley;
RX PubMed=10906322; DOI=10.1074/jbc.m001286200;
RA Williams L.J.S., Lyons V., MacLeod I., Rajan V., Darlington G.J., Poli V.,
RA Seckl J.R., Chapman K.E.;
RT "C/EBP regulates hepatic transcription of 11beta-hydroxysteroid
RT dehydrogenase type 1. A novel mechanism for cross-talk between the C/EBP
RT and glucocorticoid signaling pathways.";
RL J. Biol. Chem. 275:30232-30239(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE OF 21-273, FUNCTION, CATALYTIC ACTIVITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=12460758; DOI=10.1016/s1046-5928(02)00547-8;
RA Nobel C.S.I., Dunas F., Abrahmsen L.B.;
RT "Purification of full-length recombinant human and rat type 1 11beta-
RT hydroxysteroid dehydrogenases with retained oxidoreductase activities.";
RL Protein Expr. Purif. 26:349-356(2002).
RN [6]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 11-HSD1A AND 11-HSD1B), AND
RP ALTERNATIVE PROMOTER USAGE.
RC STRAIN=Sprague-Dawley; TISSUE=Kidney;
RX PubMed=1733955; DOI=10.1016/s0021-9258(18)45918-2;
RA Krozowski Z., Obeyesekere V., Smith R., Mercer W.;
RT "Tissue-specific expression of an 11 beta-hydroxysteroid dehydrogenase with
RT a truncated N-terminal domain. A potential mechanism for differential
RT intracellular localization within mineralocorticoid target cells.";
RL J. Biol. Chem. 267:2569-2574(1992).
RN [7]
RP PROTEIN SEQUENCE OF 1-40.
RX PubMed=3460996; DOI=10.1210/jcem-63-3-550;
RA Monder C., Shackleton C.H.L., Bradlow H.L., New M.I., Stoner E., Iohan F.,
RA Lakshmi V.;
RT "The syndrome of apparent mineralocorticoid excess: its association with 11
RT beta-dehydrogenase and 5 beta-reductase deficiency and some consequences
RT for corticosteroid metabolism.";
RL J. Clin. Endocrinol. Metab. 63:550-557(1986).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=2387261; DOI=10.1210/endo-127-3-1450;
RA Moisan M.P., Seckl J.R., Edwards C.R.;
RT "11 beta-hydroxysteroid dehydrogenase bioactivity and messenger RNA
RT expression in rat forebrain: localization in hypothalamus, hippocampus, and
RT cortex.";
RL Endocrinology 127:1450-1455(1990).
RN [9]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=8613810; DOI=10.1523/jneurosci.16-01-00065.1996;
RA Rajan V., Edwards C.R., Seckl J.R.;
RT "11 beta-Hydroxysteroid dehydrogenase in cultured hippocampal cells
RT reactivates inert 11-dehydrocorticosterone, potentiating neurotoxicity.";
RL J. Neurosci. 16:65-70(1996).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=14973125; DOI=10.1074/jbc.m313615200;
RA Schweizer R.A.S., Zuercher M., Balazs Z., Dick B., Odermatt A.;
RT "Rapid hepatic metabolism of 7-ketocholesterol by 11beta-hydroxysteroid
RT dehydrogenase type 1: species-specific differences between the rat, human,
RT and hamster enzyme.";
RL J. Biol. Chem. 279:18415-18424(2004).
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=21453287; DOI=10.1042/bj20110022;
RA Odermatt A., Da Cunha T., Penno C.A., Chandsawangbhuwana C., Reichert C.,
RA Wolf A., Dong M., Baker M.E.;
RT "Hepatic reduction of the secondary bile acid 7-oxolithocholic acid is
RT mediated by 11beta-hydroxysteroid dehydrogenase 1.";
RL Biochem. J. 436:621-629(2011).
RN [12]
RP MUTAGENESIS OF TYR-179 AND LYS-183.
RX PubMed=1417845; DOI=10.1016/0006-291x(92)92373-6;
RA Obeid J., White P.C.;
RT "Tyr-179 and Lys-183 are essential for enzymatic activity of 11 beta-
RT hydroxysteroid dehydrogenase.";
RL Biochem. Biophys. Res. Commun. 188:222-227(1992).
CC -!- FUNCTION: Controls the reversible conversion of biologically active
CC glucocorticoids such as 11-dehydrocorticosterone to corticosterone
CC using NADP(H) (PubMed:12460758, PubMed:8613810, PubMed:14973125).
CC Participates in the corticosteroid receptor-mediated anti-inflammatory
CC response, as well as metabolic and homeostatic processes (By
CC similarity). Bidirectional in vitro, predominantly functions as a
CC reductase in vivo, thereby increasing the concentration of active
CC glucocorticoids (PubMed:12460758). It has broad substrate specificity,
CC besides glucocorticoids, it accepts other steroid and sterol substrates
CC (PubMed:14973125). Interconverts 7-oxo- and 7-hydroxy-neurosteroids
CC such as 7-oxopregnenolone and 7beta-hydroxypregnenolone, 7-
CC oxodehydroepiandrosterone (3beta-hydroxy-5-androstene-7,17-dione) and
CC 7beta-hydroxydehydroepiandrosterone (3beta,7beta-dihydroxyandrost-5-en-
CC 17-one), among others (By similarity). Catalyzes the stereo-specific
CC conversion of the major dietary oxysterol, 7-ketocholesterol (7-
CC oxocholesterol), into the more polar 7-beta-hydroxycholesterol
CC metabolite (PubMed:14973125). 7-oxocholesterol is one of the most
CC important oxysterols, it participates in several events such as
CC induction of apoptosis, accumulation in atherosclerotic lesions, lipid
CC peroxidation, and induction of foam cell formation (By similarity).
CC Mediates the 7-oxo reduction of 7-oxolithocholate mainly to
CC chenodeoxycholate, and to a lesser extent to ursodeoxycholate, both in
CC its free form and when conjugated to glycine or taurine, providing a
CC link between glucocorticoid activation and bile acid metabolism (By
CC similarity). Catalyzes the synthesis of 7-beta-25-dihydroxycholesterol
CC from 7-oxo-25-hydroxycholesterol in vitro, which acts as ligand for the
CC G-protein-coupled receptor (GPCR) Epstein-Barr virus-induced gene 2
CC (EBI2) and may thereby regulate immune cell migration (By similarity).
CC {ECO:0000250|UniProtKB:P28845, ECO:0000250|UniProtKB:P50172,
CC ECO:0000269|PubMed:12460758, ECO:0000269|PubMed:14973125,
CC ECO:0000269|PubMed:8613810, ECO:0000303|PubMed:12460758}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an 11beta-hydroxysteroid + NADP(+) = an 11-oxosteroid + H(+) +
CC NADPH; Xref=Rhea:RHEA:11388, ChEBI:CHEBI:15378, ChEBI:CHEBI:35346,
CC ChEBI:CHEBI:47787, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC EC=1.1.1.146; Evidence={ECO:0000269|PubMed:12460758,
CC ECO:0000269|PubMed:14973125, ECO:0000269|PubMed:2808402,
CC ECO:0000269|PubMed:8613810};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11389;
CC Evidence={ECO:0000269|PubMed:12460758, ECO:0000269|PubMed:14973125,
CC ECO:0000269|PubMed:2808402};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:11390;
CC Evidence={ECO:0000269|PubMed:12460758, ECO:0000269|PubMed:14973125,
CC ECO:0000269|PubMed:2808402, ECO:0000269|PubMed:8613810};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=corticosterone + NADP(+) = 11-dehydrocorticosterone + H(+) +
CC NADPH; Xref=Rhea:RHEA:42200, ChEBI:CHEBI:15378, ChEBI:CHEBI:16827,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:78600;
CC Evidence={ECO:0000269|PubMed:12460758, ECO:0000269|PubMed:14973125,
CC ECO:0000269|PubMed:2808402, ECO:0000269|PubMed:8613810};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42201;
CC Evidence={ECO:0000269|PubMed:12460758, ECO:0000269|PubMed:14973125,
CC ECO:0000269|PubMed:2808402};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42202;
CC Evidence={ECO:0000269|PubMed:12460758, ECO:0000269|PubMed:14973125,
CC ECO:0000269|PubMed:2808402, ECO:0000269|PubMed:8613810};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 7beta-hydroxysteroid + NADP(+) = a 7-oxosteroid + H(+) +
CC NADPH; Xref=Rhea:RHEA:20233, ChEBI:CHEBI:15378, ChEBI:CHEBI:35349,
CC ChEBI:CHEBI:47789, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC EC=1.1.1.201; Evidence={ECO:0000250|UniProtKB:P28845};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:20235;
CC Evidence={ECO:0000250|UniProtKB:P28845};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7-oxocholesterol + H(+) + NADPH = 7beta-hydroxycholesterol +
CC NADP(+); Xref=Rhea:RHEA:68656, ChEBI:CHEBI:15378, ChEBI:CHEBI:42989,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:64294;
CC Evidence={ECO:0000269|PubMed:14973125};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68657;
CC Evidence={ECO:0000269|PubMed:14973125};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chenodeoxycholate + NADP(+) = 7-oxolithocholate + H(+) +
CC NADPH; Xref=Rhea:RHEA:53820, ChEBI:CHEBI:15378, ChEBI:CHEBI:36234,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:78605;
CC Evidence={ECO:0000250|UniProtKB:P28845};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:53822;
CC Evidence={ECO:0000250|UniProtKB:P28845};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7-oxolithocholate + H(+) + NADPH = NADP(+) + ursodeoxycholate;
CC Xref=Rhea:RHEA:47540, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:78604, ChEBI:CHEBI:78605;
CC Evidence={ECO:0000250|UniProtKB:P28845};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47541;
CC Evidence={ECO:0000250|UniProtKB:P28845};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycochenodeoxycholate + NADP(+) = 7-oxoglycolithocholate +
CC H(+) + NADPH; Xref=Rhea:RHEA:65056, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:36252, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:137818; Evidence={ECO:0000250|UniProtKB:P28845};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:65058;
CC Evidence={ECO:0000250|UniProtKB:P28845};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADP(+) + taurochenodeoxycholate = 7-oxotaurolithocholate +
CC H(+) + NADPH; Xref=Rhea:RHEA:65060, ChEBI:CHEBI:9407,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:137724; Evidence={ECO:0000250|UniProtKB:P28845};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:65062;
CC Evidence={ECO:0000250|UniProtKB:P28845};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADP(+) + tauroursodeoxycholate = 7-oxotaurolithocholate +
CC H(+) + NADPH; Xref=Rhea:RHEA:68980, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:132028,
CC ChEBI:CHEBI:137724; Evidence={ECO:0000250|UniProtKB:P28845};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:68982;
CC Evidence={ECO:0000250|UniProtKB:P28845};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycoursodeoxycholate + NADP(+) = 7-oxoglycolithocholate +
CC H(+) + NADPH; Xref=Rhea:RHEA:68976, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:132030,
CC ChEBI:CHEBI:137818; Evidence={ECO:0000250|UniProtKB:P28845};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:68978;
CC Evidence={ECO:0000250|UniProtKB:P28845};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7-oxopregnenolone + H(+) + NADPH = 7beta-hydroxypregnenolone +
CC NADP(+); Xref=Rhea:RHEA:69436, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:183806, ChEBI:CHEBI:183807;
CC Evidence={ECO:0000250|UniProtKB:P28845};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69437;
CC Evidence={ECO:0000250|UniProtKB:P28845};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta,7alpha-dihydroxyandrost-5-en-17-one + NADP(+) = 3beta-
CC hydroxy-5-androstene-7,17-dione + H(+) + NADPH; Xref=Rhea:RHEA:69440,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:81471, ChEBI:CHEBI:183808;
CC Evidence={ECO:0000250|UniProtKB:P28845};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69441;
CC Evidence={ECO:0000250|UniProtKB:P28845};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta-hydroxy-5-androstene-7,17-dione + H(+) + NADPH =
CC 3beta,7beta-dihydroxyandrost-5-en-17-one + NADP(+);
CC Xref=Rhea:RHEA:69452, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:183368, ChEBI:CHEBI:183808;
CC Evidence={ECO:0000250|UniProtKB:P28845};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69453;
CC Evidence={ECO:0000250|UniProtKB:P28845};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta-hydroxy-5alpha-androstane-7,17-dione + H(+) + NADPH =
CC 3beta,7beta-dihydroxy-5alpha-androstan-17-one + NADP(+);
CC Xref=Rhea:RHEA:69456, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:79834, ChEBI:CHEBI:183809;
CC Evidence={ECO:0000250|UniProtKB:P28845};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69457;
CC Evidence={ECO:0000250|UniProtKB:P28845};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=367 nM for corticosterone {ECO:0000269|PubMed:14973125};
CC KM=681 nM for 11-dehydrocorticosterone {ECO:0000269|PubMed:14973125};
CC KM=776 nM for 7-oxocholesterol {ECO:0000269|PubMed:14973125};
CC KM=3.1 uM for 11-dehydrocorticosterone {ECO:0000269|PubMed:12460758};
CC KM=2.5 uM for corticosterone {ECO:0000269|PubMed:12460758};
CC Vmax=42.5 nmol/min/mg enzyme with 11-dehydrocorticosterone as
CC substrate {ECO:0000269|PubMed:12460758};
CC Vmax=89.9 nmol/min/mg enzyme with corticosterone as substrate
CC {ECO:0000269|PubMed:12460758};
CC Vmax=0.97 nmol/min/mg enzyme with corticosterone as substrate
CC {ECO:0000269|PubMed:14973125};
CC Vmax=0.57 nmol/min/mg enzyme with 11-dehydrocorticosterone as
CC substrate {ECO:0000269|PubMed:14973125};
CC Vmax=0.14 nmol/min/mg enzyme with 7-oxocholesterol as substrate
CC {ECO:0000269|PubMed:14973125};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P28845}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass type
CC II membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage; Named isoforms=2;
CC Name=11-HSD1A;
CC IsoId=P16232-1; Sequence=Displayed;
CC Name=11-HSD1B;
CC IsoId=P16232-2; Sequence=VSP_012616;
CC -!- TISSUE SPECIFICITY: Liver, kidney, lung and testis (PubMed:2808402).
CC Brain (PubMed:2387261). Expressed in liver (at protein level)
CC (PubMed:21453287). {ECO:0000269|PubMed:21453287,
CC ECO:0000269|PubMed:2387261, ECO:0000269|PubMed:2808402}.
CC -!- DEVELOPMENTAL STAGE: Expression of both isoforms is found in 1 week-old
CC rats. Expression increases exponentially up to 4 weeks but after this
CC time there is no further increase up to 16 weeks.
CC -!- PTM: Glycosylated.
CC -!- MISCELLANEOUS: [Isoform 11-HSD1B]: Kidney-specific. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC 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; J05107; AAA40886.1; -; mRNA.
DR EMBL; BC078865; AAH78865.1; -; mRNA.
DR EMBL; S43333; AAB22993.1; -; Genomic_DNA.
DR EMBL; Y10420; CAA71447.1; -; Genomic_DNA.
DR EMBL; M77835; AAA40600.1; -; mRNA.
DR PIR; A34430; DXRTBH.
DR RefSeq; NP_058776.2; NM_017080.2. [P16232-1]
DR RefSeq; XP_006250535.1; XM_006250473.3. [P16232-1]
DR AlphaFoldDB; P16232; -.
DR SMR; P16232; -.
DR IntAct; P16232; 1.
DR BindingDB; P16232; -.
DR ChEMBL; CHEMBL2391; -.
DR DrugCentral; P16232; -.
DR GuidetoPHARMACOLOGY; 2763; -.
DR GlyGen; P16232; 2 sites.
DR iPTMnet; P16232; -.
DR PhosphoSitePlus; P16232; -.
DR PRIDE; P16232; -.
DR GeneID; 25116; -.
DR KEGG; rno:25116; -.
DR CTD; 3290; -.
DR RGD; 2834; Hsd11b1.
DR VEuPathDB; HostDB:ENSRNOG00000005861; -.
DR HOGENOM; CLU_010194_2_1_1; -.
DR InParanoid; P16232; -.
DR OMA; SMEDMTF; -.
DR OrthoDB; 906746at2759; -.
DR PhylomeDB; P16232; -.
DR BRENDA; 1.1.1.146; 5301.
DR BRENDA; 1.1.1.B40; 5301.
DR Reactome; R-RNO-194002; Glucocorticoid biosynthesis.
DR SABIO-RK; P16232; -.
DR PRO; PR:P16232; -.
DR Proteomes; UP000002494; Chromosome 13.
DR Bgee; ENSRNOG00000005861; Expressed in liver and 19 other tissues.
DR ExpressionAtlas; P16232; baseline and differential.
DR Genevisible; P16232; RN.
DR GO; GO:0045177; C:apical part of cell; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISO:RGD.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
DR GO; GO:0031965; C:nuclear membrane; IDA:RGD.
DR GO; GO:0005791; C:rough endoplasmic reticulum; IDA:RGD.
DR GO; GO:0070524; F:11-beta-hydroxysteroid dehydrogenase (NADP+) activity; ISO:RGD.
DR GO; GO:0047022; F:7-beta-hydroxysteroid dehydrogenase (NADP+) activity; IEA:RHEA.
DR GO; GO:0102196; F:cortisol dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0050661; F:NADP binding; IDA:RGD.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0005496; F:steroid binding; IPI:RGD.
DR GO; GO:0071392; P:cellular response to estradiol stimulus; IEP:RGD.
DR GO; GO:0006704; P:glucocorticoid biosynthetic process; IDA:RGD.
DR GO; GO:0006713; P:glucocorticoid catabolic process; IDA:RGD.
DR GO; GO:0030324; P:lung development; ISO:RGD.
DR GO; GO:0008212; P:mineralocorticoid metabolic process; IDA:RGD.
DR GO; GO:0043456; P:regulation of pentose-phosphate shunt; IDA:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0006706; P:steroid catabolic 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 Alternative promoter usage; Direct protein sequencing;
KW Endoplasmic reticulum; Glycoprotein; Lipid metabolism; Membrane; NADP;
KW Oxidoreductase; Reference proteome; Signal-anchor; Steroid metabolism;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..288
FT /note="11-beta-hydroxysteroid dehydrogenase 1"
FT /id="PRO_0000054623"
FT TOPO_DOM 1..4
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 5..20
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 21..288
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT ACT_SITE 179
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 37..63
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P28845"
FT BINDING 88..89
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P28845"
FT BINDING 115..117
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P28845"
FT BINDING 166
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 179..183
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P28845"
FT BINDING 212..218
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 214..218
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P28845"
FT CARBOHYD 158
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 203
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..26
FT /note="Missing (in isoform 11-HSD1B)"
FT /evidence="ECO:0000305"
FT /id="VSP_012616"
FT MUTAGEN 110
FT /note="D->N: Slight loss of activity."
FT MUTAGEN 179
FT /note="Y->F,S: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:1417845"
FT MUTAGEN 183
FT /note="K->R: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:1417845"
FT CONFLICT 31
FT /note="K -> N (in Ref. 4; CAA71447)"
FT /evidence="ECO:0000305"
FT CONFLICT 235
FT /note="E -> Q (in Ref. 1; AAA40886)"
FT /evidence="ECO:0000305"
FT CONFLICT 241
FT /note="Missing (in Ref. 1; AAA40886)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 288 AA; 31883 MW; AC445C0D92004808 CRC64;
MKKYLLPVLV LCLGYYYSTN EEFRPEMLQG KKVIVTGASK GIGREMAYHL SKMGAHVVLT
ARSEEGLQKV VSRCLELGAA SAHYIAGTME DMAFAERFVV EAGKLLGGLD MLILNHITQT
TMSLFHDDIH SVRRSMEVNF LSYVVLSTAA LPMLKQSNGS IAIISSMAGK MTQPLIASYS
ASKFALDGFF STIRKEHLMT KVNVSITLCV LGFIDTETAL KETSGIILSQ AAPKEECALE
IIKGTVLRKD EVYYDKSSWT PLLLGNPGRR IMEFLSLRSY NRDLFVSN
