DHI1_SHEEP
ID DHI1_SHEEP Reviewed; 292 AA.
AC P51975;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=11-beta-hydroxysteroid dehydrogenase 1 {ECO:0000303|PubMed:1425412};
DE Short=11-DH;
DE Short=11-beta-HSD1 {ECO:0000303|PubMed:1425412};
DE EC=1.1.1.146;
DE AltName: Full=7-oxosteroid reductase;
DE EC=1.1.1.201 {ECO:0000250|UniProtKB:P28845};
DE AltName: Full=Corticosteroid 11-beta-dehydrogenase isozyme 1;
GN Name=HSD11B1;
OS Ovis aries (Sheep).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Ovis.
OX NCBI_TaxID=9940;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Liver;
RX PubMed=1425412; DOI=10.1210/endo.131.5.1425412;
RA Yang K., Smith C.L., Dales D., Hammond G.L., Challis J.R.;
RT "Cloning of an ovine 11 beta-hydroxysteroid dehydrogenase complementary
RT deoxyribonucleic acid: tissue and temporal distribution of its messenger
RT ribonucleic acid during fetal and neonatal development.";
RL Endocrinology 131:2120-2126(1992).
CC -!- FUNCTION: Controls the reversible conversion of biologically active
CC glucocorticoids such as cortisone to cortisol, and 11-
CC dehydrocorticosterone to corticosterone in the presence of NADP(H) (By
CC similarity). Participates in the corticosteroid receptor-mediated anti-
CC inflammatory response, as well as metabolic and homeostatic processes
CC (By similarity). Plays a role in the secretion of aqueous humor in the
CC eye, maintaining a normotensive, intraocular environment (By
CC similarity). Bidirectional in vitro, predominantly functions as a
CC reductase in vivo, thereby increasing the concentration of active
CC glucocorticoids (By similarity). It has broad substrate specificity,
CC besides glucocorticoids, it accepts other steroid and sterol
CC substrates. Interconverts 7-oxo- and 7-hydroxy-neurosteroids such as 7-
CC 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 (By similarity). 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 -!- 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:0000250|UniProtKB:P28845};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11389;
CC Evidence={ECO:0000250|UniProtKB:P28845};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:11390;
CC Evidence={ECO:0000250|UniProtKB:P28845};
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:0000250|UniProtKB:P28845};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42201;
CC Evidence={ECO:0000250|UniProtKB:P28845};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42202;
CC Evidence={ECO:0000250|UniProtKB:P28845};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cortisone + H(+) + NADPH = cortisol + NADP(+);
CC Xref=Rhea:RHEA:68616, ChEBI:CHEBI:15378, ChEBI:CHEBI:16962,
CC ChEBI:CHEBI:17650, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000250|UniProtKB:P28845};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68617;
CC Evidence={ECO:0000250|UniProtKB:P28845};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:68618;
CC Evidence={ECO:0000250|UniProtKB:P28845};
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:0000250|UniProtKB:P28845};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68657;
CC Evidence={ECO:0000250|UniProtKB:P28845};
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 -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P28845}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass type
CC II membrane protein.
CC -!- TISSUE SPECIFICITY: Liver, kidney, lung, hypothalamus, anterior
CC pituitary and placenta. {ECO:0000269|PubMed:1425412}.
CC -!- DEVELOPMENTAL STAGE: Expression in the liver during fetal development
CC increases between day 125 and term, and rises further in the newborn,
CC being highest in the adult liver. {ECO:0000269|PubMed:1425412}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; X69561; CAA49290.1; -; mRNA.
DR PIR; S33117; S33117.
DR RefSeq; NP_001009395.1; NM_001009395.2.
DR AlphaFoldDB; P51975; -.
DR SMR; P51975; -.
DR STRING; 9940.ENSOARP00000013948; -.
DR GeneID; 443409; -.
DR KEGG; oas:443409; -.
DR CTD; 3290; -.
DR eggNOG; KOG1205; Eukaryota.
DR OrthoDB; 906746at2759; -.
DR BRENDA; 1.1.1.146; 2668.
DR Proteomes; UP000002356; Unplaced.
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:0070524; F:11-beta-hydroxysteroid dehydrogenase (NADP+) activity; IEA:UniProtKB-EC.
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:0008202; P:steroid metabolic process; IEA:UniProtKB-KW.
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 2: Evidence at transcript level;
KW Endoplasmic reticulum; Glycoprotein; Lipid metabolism; Membrane; NADP;
KW Oxidoreductase; Reference proteome; Signal-anchor; Steroid metabolism;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..292
FT /note="11-beta-hydroxysteroid dehydrogenase 1"
FT /id="PRO_0000054625"
FT TOPO_DOM 1..7
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 8..24
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 25..292
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT ACT_SITE 183
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 41..67
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P28845"
FT BINDING 92..93
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P28845"
FT BINDING 119..121
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P28845"
FT BINDING 170
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 183..187
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P28845"
FT BINDING 216..222
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 218..222
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P28845"
FT CARBOHYD 95
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 207
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 292 AA; 32154 MW; ADBD024E73EB95E3 CRC64;
MAFMKKYLLP ILGIFLAYYY YSANEEFRPE MLRGKRVIVT GASKGIGREM AYHLARMGAH
VVVTARSEES LKKVVSRCLE LGAASAHYVA GTMENMTFAE QFVAKAGELV GGLDMLILNH
INYTPLRVFS NDIHLLRRSL EVNLLSYVVL STAALPMLKQ TSGSIVVVSS VAGKIACPLA
AAYSASKFAL DGFFSSLRTE YEATKVNVSI TLCILGLIDT DTAMKAVAGI YNAEASPKEE
CALEIIKGGA LRQDEVYYDN SILTSLLLKN PGRKIMEFLS LKKYNMERFI NN
