DHI1_SAISC
ID DHI1_SAISC Reviewed; 291 AA.
AC Q29608;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=11-beta-hydroxysteroid dehydrogenase 1 {ECO:0000303|PubMed:8319583};
DE Short=11-DH;
DE Short=11-beta-HSD1 {ECO:0000303|PubMed:8319583};
DE EC=1.1.1.146 {ECO:0000269|PubMed:8319583};
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 Saimiri sciureus (Common squirrel monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Platyrrhini; Cebidae;
OC Saimiriinae; Saimiri.
OX NCBI_TaxID=9521;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, TISSUE
RP SPECIFICITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=8319583; DOI=10.1210/endo.133.1.8319583;
RA Moore C.C., Mellon S.H., Murai J., Siiteri P.K., Miller W.L.;
RT "Structure and function of the hepatic form of 11 beta-hydroxysteroid
RT dehydrogenase in the squirrel monkey, an animal model of glucocorticoid
RT resistance.";
RL Endocrinology 133:368-375(1993).
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:8319583). Participates in the corticosteroid receptor-mediated
CC anti-inflammatory response, as well as metabolic and homeostatic
CC processes (PubMed:8319583). Bidirectional in vitro, predominantly
CC functions as a reductase in vivo, thereby increasing the concentration
CC of active glucocorticoids (PubMed:8319583). It has broad substrate
CC specificity, besides glucocorticoids, it accepts other steroid and
CC sterol substrates. 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. 7-oxocholesterol is one of the most important oxysterols,
CC it participates in several events such as induction of apoptosis,
CC accumulation in atherosclerotic lesions, lipid peroxidation, and
CC induction of foam cell formation (By similarity). Mediates the 7-oxo
CC reduction of 7-oxolithocholate mainly to chenodeoxycholate, and to a
CC lesser extent to ursodeoxycholate, both in its free form and when
CC conjugated to glycine or taurine, providing a link between
CC glucocorticoid activation and bile acid metabolism (By similarity).
CC Catalyzes the synthesis of 7-beta-25-dihydroxycholesterol from 7-oxo-
CC 25-hydroxycholesterol in vitro, which acts as ligand for the G-protein-
CC coupled receptor (GPCR) Epstein-Barr virus-induced gene 2 (EBI2) and
CC may thereby regulate immune cell migration (By similarity).
CC {ECO:0000250|UniProtKB:P28845, ECO:0000250|UniProtKB:P50172,
CC ECO:0000269|PubMed:8319583, ECO:0000303|PubMed:8319583}.
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:8319583};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11389;
CC Evidence={ECO:0000269|PubMed:8319583};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:11390;
CC Evidence={ECO:0000269|PubMed:8319583};
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:8319583};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68617;
CC Evidence={ECO:0000269|PubMed:8319583};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:68618;
CC Evidence={ECO:0000269|PubMed:8319583};
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=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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.89 uM for cortisol {ECO:0000269|PubMed:8319583};
CC KM=0.272 uM for cortisone {ECO:0000269|PubMed:8319583};
CC Vmax=2490.0 nmol/h/ug enzyme with cortisol as substrate
CC {ECO:0000269|PubMed:8319583};
CC Vmax=0.376 nmol/h/ug enzyme with cortisone as substrate
CC {ECO:0000269|PubMed:8319583};
CC -!- PATHWAY: Steroid metabolism. {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: Abundantly expressed in the liver, followed by
CC fibroblasts, also detected in the brain, lung, heart, and ovary, and in
CC smaller amounts in kidney, skin, and spleen.
CC {ECO:0000269|PubMed:8319583}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; S63400; AAB27374.1; -; mRNA.
DR AlphaFoldDB; Q29608; -.
DR SMR; Q29608; -.
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 1: Evidence at protein level;
KW Endoplasmic reticulum; Glycoprotein; Lipid metabolism; Membrane; NADP;
KW Oxidoreductase; Signal-anchor; Steroid metabolism; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..291
FT /note="11-beta-hydroxysteroid dehydrogenase 1"
FT /id="PRO_0000054624"
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..291
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 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:0000255"
FT CARBOHYD 162
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 291 AA; 32364 MW; 33DB15EB381C3B88 CRC64;
MAFMKTHLLP ILGLFMAYYY YSAYEEFRPE MLQGKKVIVT GASKGIGREM AYHLAKMGAH
VVVTARSKET LQKVVSHCLE LGAASAHYIA GTMEDMTFAE QFVAQAGKLM GGLDMLILNH
ITNTSLNFFH DDIHHVRKSM EVNFLSYVVL TVAAMPMLKQ SNGSIVIVSS VAGKVAYPMI
SAYSASKFAL YGFFSSIRKE YLMSEVNVSI TLCVLGLIDT DTAMKAVSGI IKMQAARKEE
CALEIIKGGV LRQEEVYYDR SLWTTLLLRN PSRKILEFLR STSYSTDGLI N
