DHI2_RABIT
ID DHI2_RABIT Reviewed; 406 AA.
AC P51976;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=11-beta-hydroxysteroid dehydrogenase type 2;
DE Short=11-DH2;
DE Short=11-beta-HSD2;
DE Short=11beta-OHSD type 2 {ECO:0000303|PubMed:7750480};
DE EC=1.1.1.- {ECO:0000269|PubMed:7750480};
DE AltName: Full=Corticosteroid 11-beta-dehydrogenase isozyme 2;
DE AltName: Full=NAD-dependent 11-beta-hydroxysteroid dehydrogenase;
GN Name=HSD11B2;
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]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC STRAIN=New Zealand white; TISSUE=Kidney cortex;
RX PubMed=7750480; DOI=10.1210/endo.136.6.7750480;
RA Naray-Fejes-Toth A., Fejes-Toth G.;
RT "Expression cloning of the aldosterone target cell-specific 11 beta-
RT hydroxysteroid dehydrogenase from rabbit collecting duct cells.";
RL Endocrinology 136:2579-2586(1995).
CC -!- FUNCTION: Catalyzes the conversion of biologically active 11beta-
CC hydroxyglucocorticoids (11beta-hydroxysteroid) such as corticosterone,
CC to inactive 11-ketoglucocorticoids (11-oxosteroid) such as 11-
CC dehydrocorticosterone, in the presence of NAD(+) (PubMed:7750480).
CC Functions as a dehydrogenase (oxidase), thereby decreasing the
CC concentration of active glucocorticoids, thus protecting the
CC nonselective mineralocorticoid receptor from occupation by
CC glucocorticoids (By similarity). Plays an important role in maintaining
CC glucocorticoids balance during preimplantation and protects the fetus
CC from excessive maternal corticosterone exposure (By similarity).
CC Catalyzes the 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:7750480}.
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:7750480};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53117;
CC Evidence={ECO:0000305|PubMed:7750480};
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:7750480};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42205;
CC Evidence={ECO:0000305|PubMed:7750480};
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:0000250|UniProtKB:P80365};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50209;
CC Evidence={ECO:0000250|UniProtKB:P80365};
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 carbenoloxone.
CC {ECO:0000305|PubMed:7750480}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.6 nM for corticosterone {ECO:0000269|PubMed:7750480};
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.
CC {ECO:0000269|PubMed:7750480}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; U23835; AAA86387.1; -; mRNA.
DR PIR; I46535; I46535.
DR RefSeq; NP_001076221.1; NM_001082752.1.
DR AlphaFoldDB; P51976; -.
DR SMR; P51976; -.
DR STRING; 9986.ENSOCUP00000010179; -.
DR PRIDE; P51976; -.
DR GeneID; 100009531; -.
DR KEGG; ocu:100009531; -.
DR CTD; 3291; -.
DR eggNOG; KOG1610; Eukaryota.
DR InParanoid; P51976; -.
DR OrthoDB; 1313182at2759; -.
DR BRENDA; 1.1.1.B40; 1749.
DR Proteomes; UP000001811; 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..406
FT /note="11-beta-hydroxysteroid dehydrogenase type 2"
FT /id="PRO_0000054629"
FT REGION 379..406
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 406 AA; 44182 MW; F14579663918425D CRC64;
MERWPWPSGG AWLLVAARAL IQLLRADLRL GRPLLAALAL LAALDWLCQS LLPPSAALAV
LAAAGWIALS RLARPQRLPV ATRAVLITGC DSGFGKETAK KLDAMGFTVL ATVLEMNGPG
ALELRACCSP RLKLLQMDLT KPADISRALE FTKAHTTSTG LWGLVNNAGH NDVVADVELS
PVATFRNCME VNFFGALELT KGLLPLLHHS RGRIVTLGSP AGEMPYPCLA AYGTSKAAMA
LLMDAFSCEL LPWGVKVSVI QPGCFKTESV SNVSHWEQRK QLLLANLPGE LRQAYGEDYI
EHLHREFLHS LRLALPDLSP VVDAITDALL AARPRPRYYP GRGLGLMYFI HYYLPEGLRR
RFLQSFFIIP CLPRALRPGQ PGATPAPDTA QDNPNPNPDP SLVGAR
