DHI1_BOVIN
ID DHI1_BOVIN Reviewed; 292 AA.
AC Q8HZJ8; F6PTG3;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=11-beta-hydroxysteroid dehydrogenase 1;
DE Short=11-DH;
DE Short=11-beta-HSD1;
DE Short=11HSD1 {ECO:0000303|PubMed:12773125};
DE EC=1.1.1.146 {ECO:0000269|PubMed:17470521};
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;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1] {ECO:0000312|EMBL:AAN40687.2}
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=12773125; DOI=10.1677/joe.0.1770445;
RA Tetsuka M., Yamamoto S., Hayashida N., Hayashi K.G., Hayashi M.,
RA Acosta T.J., Miyamoto A.;
RT "Expression of 11beta-hydroxysteroid dehydrogenases in bovine follicle and
RT corpus luteum.";
RL J. Endocrinol. 177:445-452(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=19393038; DOI=10.1186/gb-2009-10-4-r42;
RA Zimin A.V., Delcher A.L., Florea L., Kelley D.R., Schatz M.C., Puiu D.,
RA Hanrahan F., Pertea G., Van Tassell C.P., Sonstegard T.S., Marcais G.,
RA Roberts M., Subramanian P., Yorke J.A., Salzberg S.L.;
RT "A whole-genome assembly of the domestic cow, Bos taurus.";
RL Genome Biol. 10:R42.01-R42.10(2009).
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=17470521; DOI=10.1677/joe.1.07025;
RA Thurston L.M., Abayasekara D.R., Michael A.E.;
RT "11beta-Hydroxysteroid dehydrogenase expression and activities in bovine
RT granulosa cells and corpora lutea implicate corticosteroids in bovine
RT ovarian physiology.";
RL J. Endocrinol. 193:299-310(2007).
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:17470521). Participates in the corticosteroid receptor-mediated
CC anti-inflammatory response, as well as metabolic and homeostatic
CC processes (By similarity). Plays a role in the secretion of aqueous
CC humor in the eye, maintaining a normotensive, intraocular environment
CC (By 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 ECO:0000250|UniProtKB:P51975, ECO:0000269|PubMed:17470521}.
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:17470521};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11389;
CC Evidence={ECO:0000305|PubMed:17470521};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:11390;
CC Evidence={ECO:0000305|PubMed:17470521};
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:0000269|PubMed:17470521};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68617;
CC Evidence={ECO:0000305|PubMed:17470521};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:68618;
CC Evidence={ECO:0000305|PubMed:17470521};
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
CC {ECO:0000250|UniProtKB:P51975}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:P51975}.
CC -!- TISSUE SPECIFICITY: Expressed highest in liver and ovaries (corpora
CC lutea, granulosa cells, thecal, uterine caruncle and intercarunculer
CC tissues), lower expression in kidney and spleen, and lowest in the
CC adrenal. {ECO:0000269|PubMed:12773125}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; AF548027; AAN40687.2; -; mRNA.
DR RefSeq; NP_001116504.1; NM_001123032.1.
DR RefSeq; XP_010811843.1; XM_010813541.2.
DR RefSeq; XP_010811844.1; XM_010813542.2.
DR SMR; Q8HZJ8; -.
DR STRING; 9913.ENSBTAP00000020078; -.
DR PaxDb; Q8HZJ8; -.
DR GeneID; 282589; -.
DR KEGG; bta:282589; -.
DR CTD; 3290; -.
DR VEuPathDB; HostDB:ENSBTAG00000015086; -.
DR eggNOG; KOG1205; Eukaryota.
DR HOGENOM; CLU_010194_2_1_1; -.
DR InParanoid; Q8HZJ8; -.
DR OMA; SMEDMTF; -.
DR OrthoDB; 906746at2759; -.
DR TreeFam; TF329114; -.
DR Reactome; R-BTA-194002; Glucocorticoid biosynthesis.
DR Proteomes; UP000009136; Chromosome 16.
DR Bgee; ENSBTAG00000015086; Expressed in liver and 89 other tissues.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IEA:Ensembl.
DR GO; GO:0070524; F:11-beta-hydroxysteroid dehydrogenase (NADP+) activity; IEA:Ensembl.
DR GO; GO:0050661; F:NADP binding; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0030324; P:lung development; IEA:Ensembl.
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; Membrane; Oxidoreductase; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..292
FT /note="11-beta-hydroxysteroid dehydrogenase 1"
FT /id="PRO_0000455006"
FT TRANSMEM 7..24
FT /note="Helical"
FT /evidence="ECO:0000255"
SQ SEQUENCE 292 AA; 32309 MW; 065C4D70C669C2DB CRC64;
MAFMKKYLLP ILGIFLAYYY YSANEEFRPE MLRGKRVIVT GASKGIGREM AYHLARMGAH
VVVTARSEES LKKVVSRCLE LGAASAHYVA GTMENMTFAE QFVAKAGELV GGLDMLILNH
IHYTPLGVFS NDIHLLRRTL EVNLLSYVVL STAALPMLKQ TNGSIVVVSS IAGKIACPLV
AAYSASKFAL DGFFSSLRME YEATKVNVSI TLCILGLIDT DTAMKAVAGI FNAKASPKEE
CALEIIKGGT LRQDEVYYDS SILTPLLLRN PGRKIMEFFF LKKYNMERFI NN
