DHI1_RABIT
ID DHI1_RABIT Reviewed; 292 AA.
AC Q7M3I4;
DT 04-JAN-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 95.
DE RecName: Full=11-beta-hydroxysteroid dehydrogenase 1 {ECO:0000303|PubMed:7836463};
DE Short=11-DH {ECO:0000303|PubMed:7836463};
DE Short=11-beta-HSD1 {ECO:0000303|PubMed:19456256};
DE EC=1.1.1.146 {ECO:0000269|PubMed:19456256, ECO:0000269|PubMed:7836463};
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 {ECO:0000250|UniProtKB:P28845};
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1] {ECO:0000305, ECO:0000312|PIR:A55573}
RP PROTEIN SEQUENCE OF 2-292, FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR
RP LOCATION, DISULFIDE BOND, AND GLYCOSYLATION AT ASN-123; ASN-162 AND
RP ASN-207.
RC STRAIN=New Zealand {ECO:0000269|PubMed:7836463};
RC TISSUE=Liver {ECO:0000269|PubMed:7836463};
RX PubMed=7836463; DOI=10.1074/jbc.270.5.2305;
RA Ozols J.;
RT "Lumenal orientation and post-translational modifications of the liver
RT microsomal 11beta-hydroxysteroid dehydrogenase.";
RL J. Biol. Chem. 270:2305-2312(1995).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=19456256; DOI=10.1089/jop.2008.0120;
RA Anderson S., Carreiro S., Quenzer T., Gale D., Xiang C., Gukasyan H.,
RA Lafontaine J., Cheng H., Krauss A., Prasanna G.;
RT "In vivo evaluation of 11beta-hydroxysteroid dehydrogenase activity in the
RT rabbit eye.";
RL J. Ocul. Pharmacol. Ther. 25:215-222(2009).
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)
CC (PubMed:7836463, PubMed:19456256). Participates in the corticosteroid
CC receptor-mediated anti-inflammatory response, as well as metabolic and
CC homeostatic processes (By similarity). Plays a role in the secretion of
CC aqueous humor in the eye, maintaining a normotensive, intraocular
CC environment (By similarity). Bidirectional in vitro, predominantly
CC functions as a reductase in vivo, thereby increasing the concentration
CC of active glucocorticoids (By similarity). It has broad substrate
CC specificity, besides glucocorticoids, it accepts other steroid and
CC sterol substrates. It has broad substrate specificity, besides
CC glucocorticoids, it accepts other steroid and sterol substrates.
CC 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 ECO:0000269|PubMed:19456256, ECO:0000269|PubMed:7836463}.
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:19456256,
CC ECO:0000269|PubMed:7836463};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11389;
CC Evidence={ECO:0000305|PubMed:19456256, ECO:0000305|PubMed:7836463};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:11390;
CC Evidence={ECO:0000269|PubMed:19456256, ECO:0000269|PubMed:7836463};
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:7836463};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42201;
CC Evidence={ECO:0000269|PubMed:7836463};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42202;
CC Evidence={ECO:0000305|PubMed:7836463};
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:0000269|PubMed:19456256};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68617;
CC Evidence={ECO:0000269|PubMed:19456256};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:68618;
CC Evidence={ECO:0000305|PubMed:19456256};
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 -!- PATHWAY: Steroid metabolism. {ECO:0000250|UniProtKB:P28845}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P28845}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:7836463}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:7836463}. Microsome membrane
CC {ECO:0000269|PubMed:7836463}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:7836463}.
CC -!- TISSUE SPECIFICITY: Expressed in the eye.
CC {ECO:0000269|PubMed:19456256}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:7836463}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000255}.
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DR PIR; A55573; A55573.
DR AlphaFoldDB; Q7M3I4; -.
DR SMR; Q7M3I4; -.
DR STRING; 9986.ENSOCUP00000003489; -.
DR iPTMnet; Q7M3I4; -.
DR eggNOG; KOG1205; Eukaryota.
DR InParanoid; Q7M3I4; -.
DR Proteomes; UP000001811; 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; IDA:GO_Central.
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 1: Evidence at protein level;
KW Direct protein sequencing; Endoplasmic reticulum; Glycoprotein;
KW Lipid metabolism; Membrane; Microsome; NADP; Oxidoreductase;
KW Reference proteome; Signal-anchor; Steroid metabolism; Transmembrane;
KW Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:7836463"
FT CHAIN 2..292
FT /note="11-beta-hydroxysteroid dehydrogenase 1"
FT /id="PRO_0000054622"
FT TOPO_DOM 2..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 BINDING 92..93
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT BINDING 119..121
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT BINDING 170
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 183..187
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT BINDING 218..222
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P28845"
FT CARBOHYD 123
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:7836463"
FT CARBOHYD 162
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:7836463"
FT CARBOHYD 207
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:7836463"
SQ SEQUENCE 292 AA; 32125 MW; 9C1F22DF787FD49D CRC64;
MAFMKKYLLP LLGLFLAYYY YSANEEFRPE MLQGKKVIVT GASKGIGKEI AFHLAKMGAH
VVVTARSKET LQEVVAHCLK LGAASAHYIA GTMEDMTFAE QFVAKAGKLM GGLDMLILNH
ITNASLMFFN NDIHHVRKEM EVNFLSYVVL TVAALPMLKQ SNGSIVVVSS LAGKIAHPLI
APYSASKFAL DGFFSAIRKE HALTNVNVSI TLCVLGLIDT DTAMKEVSGK IDMKAAPKEE
CALEIIKGGA LRQDEVYYGN LQWTPLLLGN PGKRLIEFLH LRKFDISKLV NN
