DHI2_BOVIN
ID DHI2_BOVIN Reviewed; 404 AA.
AC O77667;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=11-beta-hydroxysteroid dehydrogenase type 2 {ECO:0000303|PubMed:10822012};
DE Short=11-DH2;
DE Short=11-beta-HSD2 {ECO:0000303|PubMed:10822012, ECO:0000303|PubMed:17470521};
DE EC=1.1.1.- {ECO:0000269|PubMed:10822012, ECO:0000269|PubMed:17470521, ECO:0000305|PubMed:26519454};
DE AltName: Full=Corticosteroid 11-beta-dehydrogenase isozyme 2;
DE AltName: Full=NAD-dependent 11-beta-hydroxysteroid dehydrogenase;
GN Name=HSD11B2;
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]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=10822012; DOI=10.1016/s0960-0760(00)00034-0;
RA Romero D.G., Zhou M.-Y., Gomez-Sanchez C.E.;
RT "Cloning and expression of the bovine 11beta-hydroxysteroid dehydrogenase
RT type-2.";
RL J. Steroid Biochem. Mol. Biol. 72:231-237(2000).
RN [2]
RP 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 [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).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=26519454; DOI=10.1530/rep-15-0363;
RA Tetsuka M., Takagi R., Ambo N., Myat T.S., Zempo Y., Onuma A.;
RT "Glucocorticoid metabolism in the bovine cumulus-oocyte complex matured in
RT vitro.";
RL Reproduction 151:73-82(2016).
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:10822012, PubMed:17470521,
CC PubMed:26519454). Functions as a dehydrogenase (oxidase), thereby
CC decreasing the concentration of active glucocorticoids, thus protecting
CC the nonselective mineralocorticoid receptor from occupation by
CC glucocorticoids (PubMed:10822012). Affinity towards corticosterone is
CC higher than cortisol or dexamethasone (PubMed:10822012). Plays an
CC important role in maintaining glucocorticoids balance during
CC preimplantation and protects the fetus from excessive maternal
CC corticosterone exposure (By similarity). Catalyzes the oxidation of
CC 11beta-hydroxytestosterone (11beta,17beta-dihydroxyandrost-4-ene-3-one)
CC to 11-ketotestosterone (17beta-hydroxyandrost-4-ene-3,11-dione), a
CC major bioactive androgen. Catalyzes the conversion of 11beta-
CC hydroxyandrostenedione (11beta-hydroxyandrost-4-ene-3,17-dione) to 11-
CC ketoandrostenedione (androst-4-ene-3,11,17-trione), which can be
CC further metabolized to 11-ketotestosterone. Converts 7-beta-25-
CC dihydroxycholesterol to 7-oxo-25-hydroxycholesterol in vitro. 7-beta-
CC 25-dihydroxycholesterol (not 7-oxo-25-hydroxycholesterol) acts as
CC ligand for the G-protein-coupled receptor (GPCR) Epstein-Barr virus-
CC induced gene 2 (EBI2) and may thereby regulate immune cell migration
CC (By similarity). May protect ovulating oocytes and fertilizing
CC spermatozoa from the adverse effects of cortisol (PubMed:17470521,
CC PubMed:26519454). {ECO:0000250|UniProtKB:P51661,
CC ECO:0000250|UniProtKB:P80365, ECO:0000269|PubMed:10822012,
CC ECO:0000269|PubMed:17470521, ECO:0000269|PubMed:26519454,
CC ECO:0000303|PubMed:17470521, ECO:0000303|PubMed:26519454}.
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:10822012, ECO:0000269|PubMed:17470521,
CC ECO:0000305|PubMed:26519454};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53117;
CC Evidence={ECO:0000269|PubMed:10822012, ECO:0000305|PubMed:17470521,
CC ECO:0000305|PubMed:26519454};
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:10822012};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42205;
CC Evidence={ECO:0000269|PubMed:10822012};
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:10822012, ECO:0000269|PubMed:17470521,
CC ECO:0000305|PubMed:26519454};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50209;
CC Evidence={ECO:0000269|PubMed:10822012, ECO:0000305|PubMed:17470521,
CC ECO:0000305|PubMed:26519454};
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:0000269|PubMed:10822012}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=45.6 nM for cortisol {ECO:0000269|PubMed:10822012};
CC KM=5.5 nM for corticosterone {ECO:0000269|PubMed:10822012};
CC KM=71.8 nM for dexamethasone {ECO:0000269|PubMed:10822012};
CC Vmax=106.3 pmol/min/mg enzyme with cortisol as substrate
CC {ECO:0000269|PubMed:10822012};
CC Vmax=31.6 pmol/min/mg enzyme using corticosterone as substrate
CC {ECO:0000269|PubMed:10822012};
CC Vmax=36 pmol/min/mg enzyme using dexamethasone as substrate
CC {ECO:0000269|PubMed:10822012};
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 kidney, adrenal and colon;
CC detected at lower levels on lung, liver, and spleen (PubMed:10822012,
CC PubMed:12773125). Expressed in oocytes (PubMed:26519454). Expressed in
CC uterine tissues and in corpora lutea (PubMed:12773125).
CC {ECO:0000269|PubMed:10822012, ECO:0000269|PubMed:12773125,
CC ECO:0000269|PubMed:26519454}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF074706; AAC26137.1; -; mRNA.
DR RefSeq; NP_777067.1; NM_174642.2.
DR AlphaFoldDB; O77667; -.
DR SMR; O77667; -.
DR STRING; 9913.ENSBTAP00000007470; -.
DR PaxDb; O77667; -.
DR GeneID; 282434; -.
DR KEGG; bta:282434; -.
DR CTD; 3291; -.
DR eggNOG; KOG1610; Eukaryota.
DR InParanoid; O77667; -.
DR OrthoDB; 1313182at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0070523; F:11-beta-hydroxysteroid dehydrogenase (NAD+) activity; IBA:GO_Central.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0016229; F:steroid dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0008211; P:glucocorticoid metabolic process; IBA:GO_Central.
DR GO; GO:0008202; P:steroid metabolic process; IBA:GO_Central.
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..404
FT /note="11-beta-hydroxysteroid dehydrogenase type 2"
FT /id="PRO_0000054626"
FT REGION 383..404
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 404 AA; 43987 MW; E04C2852CFD4D064 CRC64;
MESWPWPSGG AWLLVPARAL LQLLRADLRL GRPLLAALAL LAALDWLCQR LLPPLAALAV
LAATGWIVLS RLARPQRLPV ATRAVLITGC DSGFGNATAK KLDTMGFTVL ATVLDLNSPG
ALELRACCSS RLKLLQMDLT KPGDISRVLE FTKVHTPSTG LWGLVNNAGQ NIFVADAELC
PVATFRTCME VNFFGALEMT KGLLPLLRRS SGRIVTVSSP AGDMPFPCLA AYGTSKAALA
LLMGNFSCEL LPWGVKVSII QPACFKTESV KDVHQWEERK QQLLATLPQE LLQAYGEDYI
EHLNGQFLHS LSQALPDLSP VVDAITDALL AAQPLRRYYP GHGLGLIYFI HYYLPEGLRQ
RFLQSFFISP YVPRALQAGQ PGLTSARDIA QDQGPRPDPS PTAQ
