DHI1_MESAU
ID DHI1_MESAU Reviewed; 292 AA.
AC Q6R0J2;
DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=11-beta-hydroxysteroid dehydrogenase 1 {ECO:0000303|PubMed:14973125};
DE Short=11-DH;
DE Short=11-beta-HSD1 {ECO:0000303|PubMed:14973125};
DE EC=1.1.1.146 {ECO:0000269|PubMed:14973125, ECO:0000269|PubMed:9632680};
DE AltName: Full=7-alpha-hydroxycholesterol dehydrogenase {ECO:0000303|PubMed:9632680};
DE Short=7-alpha-HCD {ECO:0000303|PubMed:9632680};
DE AltName: Full=7-oxosteroid reductase;
DE EC=1.1.1.201 {ECO:0000269|PubMed:14973125, ECO:0000269|PubMed:9632680};
DE AltName: Full=Corticosteroid 11-beta-dehydrogenase isozyme 1;
GN Name=HSD11B1;
OS Mesocricetus auratus (Golden hamster).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Mesocricetus.
OX NCBI_TaxID=10036;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RC TISSUE=Liver;
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 [2]
RP PROTEIN SEQUENCE OF 2-31, FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR
RP LOCATION, NADP REQUIREMENT, TISSUE SPECIFICITY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=9632680; DOI=10.1074/jbc.273.26.16223;
RA Song W., Chen J., Dean W.L., Redinger R.N., Prough R.A.;
RT "Purification and characterization of hamster liver microsomal 7alpha-
RT hydroxycholesterol dehydrogenase. Similarity to type I 11beta-
RT hydroxysteroid dehydrogenase.";
RL J. Biol. Chem. 273:16223-16228(1998).
CC -!- FUNCTION: Controls the reversible conversion of biologically active
CC glucocorticoids such as 11-dehydrocorticosterone to corticosterone in
CC the presence of NADP(H) (PubMed:14973125). Participates in the
CC corticosteroid receptor-mediated anti-inflammatory response, as well as
CC metabolic and homeostatic processes (By similarity). Bidirectional in
CC vitro, predominantly functions as a reductase in vivo, thereby
CC increasing the concentration of active glucocorticoids (By similarity).
CC It has broad substrate specificity, besides glucocorticoids, it accepts
CC other steroid and sterol substrates (PubMed:14973125, PubMed:9632680).
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 reversibly the
CC conversion of the major dietary oxysterol, 7-ketocholesterol (7-
CC oxocholesterol), into the more polar 7-beta-hydroxycholesterol and 7-
CC alpha-hhydroxycholesterol metabolites (PubMed:14973125,
CC PubMed:9632680). 7-oxocholesterol is one of the most important
CC oxysterols, it participates in several events such as induction of
CC apoptosis, accumulation in atherosclerotic lesions, lipid peroxidation,
CC and induction of foam cell formation (By similarity). Mediates the 7-
CC oxo reduction of 7-oxolithocholate mainly to chenodeoxycholate, and to
CC a 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:14973125, ECO:0000269|PubMed:9632680}.
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:14973125,
CC ECO:0000269|PubMed:9632680};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11389;
CC Evidence={ECO:0000269|PubMed:14973125, ECO:0000269|PubMed:9632680};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:11390;
CC Evidence={ECO:0000269|PubMed:14973125};
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:14973125, ECO:0000269|PubMed:9632680};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42201;
CC Evidence={ECO:0000269|PubMed:14973125, ECO:0000269|PubMed:9632680};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42202;
CC Evidence={ECO:0000269|PubMed:14973125};
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=7-oxocholesterol + H(+) + NADPH = 7alpha-hydroxycholesterol +
CC NADP(+); Xref=Rhea:RHEA:68740, ChEBI:CHEBI:15378, ChEBI:CHEBI:17500,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:64294;
CC Evidence={ECO:0000269|PubMed:14973125, ECO:0000269|PubMed:9632680};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68741;
CC Evidence={ECO:0000269|PubMed:14973125};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:68742;
CC Evidence={ECO:0000269|PubMed:9632680};
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=321 nM for corticosterone {ECO:0000269|PubMed:14973125};
CC KM=726 nM for 11-dehydrocorticosterone {ECO:0000269|PubMed:14973125};
CC KM=549 nM for 7-oxocholesterol {ECO:0000269|PubMed:14973125};
CC KM=1.2 uM for corticosterone {ECO:0000269|PubMed:9632680};
CC KM=1.9 uM for 7-alpha-hydroxycholesterol
CC {ECO:0000269|PubMed:9632680};
CC KM=1.8 uM for 7-beta-hydroxycholesterol {ECO:0000269|PubMed:9632680};
CC Vmax=180 nmol/min/mg enzyme with corticosterone as substrate
CC {ECO:0000269|PubMed:9632680};
CC Vmax=160 nmol/min/mg enzyme with 7-alpha-hydroxycholesterol as
CC substrate {ECO:0000269|PubMed:9632680};
CC Vmax=140 nmol/min/mg enzyme with 7-beta-hydroxycholesterol as
CC substrate {ECO:0000269|PubMed:9632680};
CC Vmax=1.2 nmol/min/mg enzyme with corticosterone as substrate
CC {ECO:0000269|PubMed:14973125};
CC Vmax=0.56 nmol/min/mg enzyme with 11-dehydrocorticosterone as
CC substrate {ECO:0000269|PubMed:14973125};
CC Vmax=0.20 nmol/min/mg enzyme with 7-oxocholesterol as substrate
CC {ECO:0000269|PubMed:14973125};
CC -!- PATHWAY: Steroid metabolism. {ECO:0000305}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P28845}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:9632680}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:9632680}.
CC -!- TISSUE SPECIFICITY: Detected in adrenal gland, liver, kidney, testis,
CC and at lower levels in brain and lung (at protein level).
CC {ECO:0000269|PubMed:9632680}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; AY519498; AAR99903.1; -; mRNA.
DR RefSeq; NP_001268282.1; NM_001281353.1.
DR AlphaFoldDB; Q6R0J2; -.
DR SMR; Q6R0J2; -.
DR STRING; 10036.XP_005082905.1; -.
DR GeneID; 101835279; -.
DR CTD; 3290; -.
DR eggNOG; KOG1205; Eukaryota.
DR OrthoDB; 906746at2759; -.
DR BRENDA; 1.1.1.146; 3239.
DR BRENDA; 1.1.1.B40; 3239.
DR SABIO-RK; Q6R0J2; -.
DR Proteomes; UP000189706; 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 1: Evidence at protein level;
KW Direct protein sequencing; Endoplasmic reticulum; Glycoprotein;
KW Lipid metabolism; Membrane; NADP; Oxidoreductase; Reference proteome;
KW Signal-anchor; Steroid metabolism; Transmembrane; Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:9632680"
FT CHAIN 2..292
FT /note="11-beta-hydroxysteroid dehydrogenase 1"
FT /id="PRO_0000054620"
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 /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 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 292 AA; 32305 MW; A64B39F22C11ACAE CRC64;
MHFMKKYLLP ILVLFLAYYY YSTKEEFRPE MLQGKKVIVT GASKGIGREM AYHLSEMGAH
VVLTARSEEG LQKVASRCLE LGAASAHYIA GTMEDMTFAE QFVLKAGKLM GGLDMLILNH
ITYTSMNFFR DEIHALRKAM EVNFISYVVM SVAALPMLKQ SNGSIVVVSS IAGKMAHPLV
ASYSASKFAL DGFFSSLRRE HGVTNVNVSI TLCVLGLINT ETAMKATSGV FNAPASPKEE
CALEIIKGGA LRQEEVYYDS WSWTPILLGN PGRKIMEFLS MKSFTFDKLI SS
