DHI2_SHEEP
ID DHI2_SHEEP Reviewed; 427 AA.
AC P50168;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=11-beta-hydroxysteroid dehydrogenase type 2;
DE Short=11-DH2;
DE Short=11-beta-HSD2;
DE EC=1.1.1.- {ECO:0000269|PubMed:7929304};
DE AltName: Full=Corticosteroid 11-beta-dehydrogenase isozyme 2;
DE AltName: Full=NAD-dependent 11-beta-hydroxysteroid dehydrogenase;
GN Name=HSD11B2; Synonyms=HSD11K;
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], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=7929304; DOI=10.1016/s0021-9258(18)47142-6;
RA Agarwal A.K., Mune T., Monder C., White P.C.;
RT "NAD(+)-dependent isoform of 11 beta-hydroxysteroid dehydrogenase. Cloning
RT and characterization of cDNA from sheep kidney.";
RL J. Biol. Chem. 269:25959-25962(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Kidney;
RX PubMed=7588402; DOI=10.3109/07435809509030455;
RA Agarwal A.K., Mune T., Monder C., White P.C.;
RT "Cloning of cDNA encoding an NAD(+)-dependent isoform of 11 beta-
RT hydroxysteroid dehydrogenase in sheep kidney.";
RL Endocr. Res. 21:389-397(1995).
CC -!- FUNCTION: Catalyzes the conversion of biologically active 11beta-
CC hydroxyglucocorticoids (11beta-hydroxysteroid) such as cortisol, to
CC inactive 11-ketoglucocorticoids (11-oxosteroid) such as cortisone, in
CC the presence of NAD(+) (PubMed:7929304, PubMed:7588402). Functions as a
CC dehydrogenase (oxidase), thereby decreasing the concentration of active
CC glucocorticoids, thus protecting the nonselective mineralocorticoid
CC receptor from occupation by glucocorticoids (PubMed:7929304,
CC PubMed:7588402). Plays an important role in maintaining glucocorticoids
CC balance during preimplantation and protects the fetus from excessive
CC maternal corticosterone exposure (By similarity). Catalyzes the
CC oxidation of 11beta-hydroxytestosterone (11beta,17beta-
CC dihydroxyandrost-4-ene-3-one) to 11-ketotestosterone (17beta-
CC hydroxyandrost-4-ene-3,11-dione), a major bioactive androgen.Catalyzes
CC the conversion of 11beta-hydroxyandrostenedione (11beta-hydroxyandrost-
CC 4-ene-3,17-dione) to 11-ketoandrostenedione (androst-4-ene-3,11,17-
CC trione), which can be further metabolized to 11-ketotestosterone.
CC Converts 7-beta-25-dihydroxycholesterol to 7-oxo-25-hydroxycholesterol
CC in vitro. 7-beta-25-dihydroxycholesterol (not 7-oxo-25-
CC hydroxycholesterol) acts as ligand for the G-protein-coupled receptor
CC (GPCR) Epstein-Barr virus-induced gene 2 (EBI2) and may thereby
CC regulate immune cell migration (By similarity). May protect ovulating
CC oocytes and fertilizing spermatozoa from the adverse effects of
CC cortisol (By similarity). {ECO:0000250|UniProtKB:O77667,
CC ECO:0000250|UniProtKB:P51661, ECO:0000250|UniProtKB:P80365,
CC ECO:0000269|PubMed:7588402, ECO:0000269|PubMed:7929304,
CC ECO:0000303|PubMed:7588402, ECO:0000303|PubMed:7929304}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an 11beta-hydroxysteroid + NAD(+) = an 11-oxosteroid + H(+) +
CC NADH; Xref=Rhea:RHEA:53116, ChEBI:CHEBI:15378, ChEBI:CHEBI:35346,
CC ChEBI:CHEBI:47787, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000269|PubMed:7929304};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53117;
CC Evidence={ECO:0000305|PubMed:7929304};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=corticosterone + NAD(+) = 11-dehydrocorticosterone + H(+) +
CC NADH; Xref=Rhea:RHEA:42204, ChEBI:CHEBI:15378, ChEBI:CHEBI:16827,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78600;
CC Evidence={ECO:0000269|PubMed:7929304};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42205;
CC Evidence={ECO:0000305|PubMed:7929304};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cortisol + NAD(+) = cortisone + H(+) + NADH;
CC Xref=Rhea:RHEA:50208, ChEBI:CHEBI:15378, ChEBI:CHEBI:16962,
CC ChEBI:CHEBI:17650, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000269|PubMed:7929304};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50209;
CC Evidence={ECO:0000305|PubMed:7929304};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=11beta,17beta-dihydroxyandrost-4-ene-3-one + NAD(+) = 17beta-
CC hydroxyandrost-4-ene-3,11-dione + H(+) + NADH; Xref=Rhea:RHEA:69368,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:34133, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:81481;
CC Evidence={ECO:0000250|UniProtKB:P80365};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69369;
CC Evidence={ECO:0000250|UniProtKB:P80365};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=11beta-hydroxyandrost-4-ene-3,17-dione + NAD(+) = androst-4-
CC ene-3,11,17-trione + H(+) + NADH; Xref=Rhea:RHEA:69408,
CC ChEBI:CHEBI:2495, ChEBI:CHEBI:15378, ChEBI:CHEBI:27967,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000250|UniProtKB:P80365};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69409;
CC Evidence={ECO:0000250|UniProtKB:P80365};
CC -!- ACTIVITY REGULATION: Inhibited by glycyrrhetinic acid, carbenoloxone,
CC 11-alpha-OH-progesterone and 11-beta-OH-progesterone.
CC {ECO:0000250|UniProtKB:O77667}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=15 nM for cortisol {ECO:0000269|PubMed:7929304};
CC KM=0.7 nM for corticosterone {ECO:0000269|PubMed:7929304};
CC Vmax=1.9 nmol/h/ug enzyme using cortisol as substrate
CC {ECO:0000269|PubMed:7929304};
CC Vmax=1.2 nmol/h/ug enzyme using corticosterone as substrate
CC {ECO:0000269|PubMed:7929304};
CC -!- PATHWAY: Steroid metabolism. {ECO:0000305}.
CC -!- SUBUNIT: Interacts with ligand-free cytoplasmic NR3C2.
CC {ECO:0000250|UniProtKB:P80365}.
CC -!- SUBCELLULAR LOCATION: Microsome {ECO:0000250|UniProtKB:P80365}.
CC Endoplasmic reticulum {ECO:0000250|UniProtKB:P80365}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the kidney and adrenal and at
CC lower levels in the colon. {ECO:0000269|PubMed:7929304}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; U14128; AAA93156.1; ALT_SEQ; mRNA.
DR PIR; A55353; A55353.
DR RefSeq; NP_001009460.1; NM_001009460.1.
DR AlphaFoldDB; P50168; -.
DR SMR; P50168; -.
DR STRING; 9940.ENSOARP00000003179; -.
DR GeneID; 443530; -.
DR KEGG; oas:443530; -.
DR CTD; 3291; -.
DR eggNOG; KOG1610; Eukaryota.
DR OrthoDB; 1313182at2759; -.
DR BRENDA; 1.1.1.146; 2668.
DR Proteomes; UP000002356; Unplaced.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0070523; F:11-beta-hydroxysteroid dehydrogenase (NAD+) activity; IEA:RHEA.
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; Lipid metabolism; Microsome; NAD; Oxidoreductase;
KW Reference proteome; Steroid metabolism.
FT CHAIN 1..427
FT /note="11-beta-hydroxysteroid dehydrogenase type 2"
FT /id="PRO_0000054631"
FT ACT_SITE 232
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 82..111
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 219
FT /ligand="substrate"
FT /evidence="ECO:0000250"
SQ SEQUENCE 427 AA; 46669 MW; 4641749BE408E2B1 CRC64;
MESWPWPSGG AWLLVAARAL LQLLRADLRL GRPLLAALAL LAALDWLCQR LLPPLAALAV
LAATGWIVLS RLARPQRLPV ATRAVLITGC DSGFGNATAK KLDAMGFTVL ATVLDLNSPG
ALELRACCSS RLQLLQMDLT KPADISRVLE FTKVHTASTG LWGLVNNAGQ NIFVADAELC
PVATFRTCME VNFFGALEMT KGLLPLLRRS SGRIVTVSSP AGDMPFPCLA AYGTSKAALA
LLMGNFSCEL LPWGVKVSII LPACFKTESV KDVHQWEERK QQLLATLPQE LLQAYGEDYI
EHLNGQFLHS LSQALPDLSP VVDAITDALL AAQPRRRYYP GHGLGLIYFI HYYLPEGCGR
VSCSPSSSVP MCQEHYRLPA WPYLCPGHSP GPRPQTGPLS HCPVSRAHVE QLQQRRFLVP
LLFFQVF
