BDH2_BOVIN
ID BDH2_BOVIN Reviewed; 245 AA.
AC Q3T046;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=3-hydroxybutyrate dehydrogenase type 2;
DE EC=1.1.1.30 {ECO:0000250|UniProtKB:Q9BUT1};
DE AltName: Full=4-oxo-L-proline reductase {ECO:0000250|UniProtKB:Q9BUT1};
DE EC=1.1.1.104 {ECO:0000250|UniProtKB:D4A1J4, ECO:0000250|UniProtKB:Q9BUT1};
DE AltName: Full=Dehydrogenase/reductase SDR family member 6;
DE AltName: Full=R-beta-hydroxybutyrate dehydrogenase;
GN Name=BDH2; Synonyms=DHRS6;
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 [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Testis;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: NAD(H)-dependent dehydrogenase/reductase with a preference
CC for cyclic substrates (By similarity). Catalyzes stereoselective
CC conversion of 4-oxo-L-proline to cis-4-hydroxy-L-proline, likely a
CC detoxification mechanism for ketoprolines (By similarity). Mediates the
CC formation of 2,5-dihydroxybenzoate (2,5-DHBA), a siderophore that
CC chelates free cytoplasmic iron and associates with LCN2, thereby
CC regulating iron transport and homeostasis while protecting cells
CC against free radical-induced oxidative stress. The iron-siderophore
CC complex is imported into mitochondria, providing an iron source for
CC mitochondrial metabolic processes in particular heme synthesis (By
CC similarity). May act as a 3-hydroxybutyrate dehydrogenase (By
CC similarity). {ECO:0000250|UniProtKB:Q8JZV9,
CC ECO:0000250|UniProtKB:Q9BUT1}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cis-4-hydroxy-L-proline + NAD(+) = 4-oxo-L-proline + H(+) +
CC NADH; Xref=Rhea:RHEA:13601, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:63727, ChEBI:CHEBI:84813;
CC EC=1.1.1.104; Evidence={ECO:0000250|UniProtKB:Q9BUT1};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:13603;
CC Evidence={ECO:0000250|UniProtKB:Q9BUT1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-3-hydroxybutanoate + NAD(+) = acetoacetate + H(+) + NADH;
CC Xref=Rhea:RHEA:20521, ChEBI:CHEBI:10983, ChEBI:CHEBI:13705,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.30;
CC Evidence={ECO:0000250|UniProtKB:Q9BUT1};
CC -!- PATHWAY: Amino-acid metabolism. {ECO:0000250|UniProtKB:Q9BUT1}.
CC -!- PATHWAY: Siderophore biosynthesis. {ECO:0000250|UniProtKB:Q8JZV9}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:Q9BUT1}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9BUT1}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
CC -!- CAUTION: Postulated to act as a 3-hydroxybutyrate dehydrogenase,
CC however its contribution to ketone body formation appears to be
CC physiologically irrelevant since it has very low affinity for the
CC substrate. {ECO:0000250|UniProtKB:Q8JZV9,
CC ECO:0000250|UniProtKB:Q9BUT1}.
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DR EMBL; BC102567; AAI02568.1; -; mRNA.
DR RefSeq; NP_001029660.1; NM_001034488.2.
DR AlphaFoldDB; Q3T046; -.
DR SMR; Q3T046; -.
DR STRING; 9913.ENSBTAP00000003277; -.
DR PaxDb; Q3T046; -.
DR PeptideAtlas; Q3T046; -.
DR GeneID; 515321; -.
DR KEGG; bta:515321; -.
DR CTD; 56898; -.
DR eggNOG; KOG0725; Eukaryota.
DR InParanoid; Q3T046; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0003858; F:3-hydroxybutyrate dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0016628; F:oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor; ISS:UniProtKB.
DR GO; GO:0042168; P:heme metabolic process; ISS:UniProtKB.
DR GO; GO:0055072; P:iron ion homeostasis; ISS:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0019290; P:siderophore biosynthetic process; ISS:UniProtKB.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; Lipid metabolism; NAD; Oxidoreductase; Reference proteome.
FT CHAIN 1..245
FT /note="3-hydroxybutyrate dehydrogenase type 2"
FT /id="PRO_0000247551"
FT ACT_SITE 147
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 16..18
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9BUT1"
FT BINDING 37
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9BUT1"
FT BINDING 58
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9BUT1"
FT BINDING 144
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 151
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9BUT1"
FT BINDING 180..184
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9BUT1"
FT BINDING 188
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 205
FT /ligand="substrate"
FT /evidence="ECO:0000250"
SQ SEQUENCE 245 AA; 26662 MW; A846933ACBA6F83C CRC64;
MGRLDGKVIV LTAAAQGIGR AAALAFAKEG AKVIATDIND SKLQELDKYP GIHTRVLDVT
KKKQIDQFAN DIERLDVLFN VAGFVHHGTI LDCEETDWDF SMNLNVRSMY LMIKAFLPKM
MAQKSGNIIN MSSVASSIKG VVNRCVYSTT KAAVIGLTKS VAADFIQQGI RCNCVCPGTV
DTPSLQERIQ ARPNPEEALS DFLKRQKTGR FATAEEVALL CVYLASDESA YITGNPVIID
GGWSL
