DHB8_RAT
ID DHB8_RAT Reviewed; 259 AA.
AC Q6MGB5;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=(3R)-3-hydroxyacyl-CoA dehydrogenase;
DE EC=1.1.1.n12 {ECO:0000250|UniProtKB:Q92506};
DE AltName: Full=17-beta-hydroxysteroid dehydrogenase 8;
DE Short=17-beta-HSD 8;
DE AltName: Full=3-ketoacyl-[acyl-carrier-protein] reductase alpha subunit {ECO:0000250|UniProtKB:Q92506};
DE Short=KAR alpha subunit {ECO:0000250|UniProtKB:Q92506};
DE AltName: Full=3-oxoacyl-[acyl-carrier-protein] reductase;
DE AltName: Full=Estradiol 17-beta-dehydrogenase 8;
DE EC=1.1.1.62 {ECO:0000250|UniProtKB:Q92506};
DE AltName: Full=Testosterone 17-beta-dehydrogenase 8;
DE EC=1.1.1.239 {ECO:0000250|UniProtKB:Q92506};
GN Name=Hsd17b8;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15060004; DOI=10.1101/gr.1987704;
RA Hurt P., Walter L., Sudbrak R., Klages S., Mueller I., Shiina T., Inoko H.,
RA Lehrach H., Guenther E., Reinhardt R., Himmelbauer H.;
RT "The genomic sequence and comparative analysis of the rat major
RT histocompatibility complex.";
RL Genome Res. 14:631-639(2004).
RN [2]
RP TISSUE SPECIFICITY.
RX PubMed=9712896; DOI=10.1074/jbc.273.35.22664;
RA Fomitcheva J., Baker M.E., Anderson E., Lee G.Y., Aziz N.;
RT "Characterization of Ke 6, a new 17beta-hydroxysteroid dehydrogenase, and
RT its expression in gonadal tissues.";
RL J. Biol. Chem. 273:22664-22671(1998).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Required for the solubility and assembly of the
CC heterotetramer 3-ketoacyl-[acyl carrier protein] (ACP) reductase
CC functional complex (KAR or KAR1) that forms part of the mitochondrial
CC fatty acid synthase (mtFAS). Alpha-subunit of the KAR complex that acts
CC as scaffold protein required for the stability of carbonyl reductase
CC type-4 (CBR4, beta-subunit of the KAR complex) and for its 3-ketoacyl-
CC ACP reductase activity, thereby participating in mitochondrial fatty
CC acid biosynthesis. Catalyzes the NAD-dependent conversion of (3R)-3-
CC hydroxyacyl-CoA into 3-ketoacyl-CoA (3-oxoacyl-CoA) with no chain
CC length preference; this enzymatic activity is not needed for the KAR
CC function. Prefers (3R)-3-hydroxyacyl-CoA over (3S)-3-hydroxyacyl-CoA
CC and displays enzymatic activity only in the presence of NAD(+).
CC Cooperates with enoyl-CoA hydratase 1 in mitochondria, together they
CC constitute an alternative route to the auxiliary enzyme pathways for
CC the breakdown of Z-PUFA (cis polyunsaturated fatty acid) enoyl-esters.
CC NAD-dependent 17-beta-hydroxysteroid dehydrogenase with highest
CC activity towards estradiol (17beta-estradiol or E2). Has very low
CC activity towards testosterone and dihydrotestosterone (17beta-hydroxy-
CC 5alpha-androstan-3-one). Primarily an oxidative enzyme, it can switch
CC to a reductive mode determined in the appropriate physiologic milieu
CC and catalyze the reduction of estrone (E1) to form biologically active
CC 17beta-estradiol. {ECO:0000250|UniProtKB:Q92506}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3R)-3-hydroxyacyl-CoA + NAD(+) = a 3-oxoacyl-CoA + H(+) +
CC NADH; Xref=Rhea:RHEA:32711, ChEBI:CHEBI:15378, ChEBI:CHEBI:57319,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:90726;
CC EC=1.1.1.n12; Evidence={ECO:0000250|UniProtKB:Q92506};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32712;
CC Evidence={ECO:0000250|UniProtKB:Q92506};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol + NAD(+) = estrone + H(+) + NADH;
CC Xref=Rhea:RHEA:24612, ChEBI:CHEBI:15378, ChEBI:CHEBI:16469,
CC ChEBI:CHEBI:17263, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.62;
CC Evidence={ECO:0000250|UniProtKB:Q92506};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24613;
CC Evidence={ECO:0000250|UniProtKB:Q92506};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:24614;
CC Evidence={ECO:0000250|UniProtKB:Q92506};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+) + testosterone = androst-4-ene-3,17-dione + H(+) +
CC NADH; Xref=Rhea:RHEA:14929, ChEBI:CHEBI:15378, ChEBI:CHEBI:16422,
CC ChEBI:CHEBI:17347, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC EC=1.1.1.239; Evidence={ECO:0000250|UniProtKB:Q92506};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14930;
CC Evidence={ECO:0000250|UniProtKB:Q92506};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-hydroxy-5alpha-androstan-3-one + NAD(+) = 5alpha-
CC androstan-3,17-dione + H(+) + NADH; Xref=Rhea:RHEA:41992,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15994, ChEBI:CHEBI:16330,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000250|UniProtKB:Q92506};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41993;
CC Evidence={ECO:0000250|UniProtKB:Q92506};
CC -!- PATHWAY: Steroid biosynthesis; estrogen biosynthesis.
CC {ECO:0000250|UniProtKB:Q92506}.
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC {ECO:0000250|UniProtKB:Q92506}.
CC -!- PATHWAY: Lipid metabolism; mitochondrial fatty acid beta-oxidation.
CC {ECO:0000250|UniProtKB:Q92506}.
CC -!- SUBUNIT: Heterotetramer with CBR4; contains two molecules of HSD17B8
CC and CBR4. {ECO:0000250|UniProtKB:Q92506}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000250|UniProtKB:Q92506}.
CC -!- TISSUE SPECIFICITY: Expressed in ovary at protein level.
CC {ECO:0000269|PubMed:9712896}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; BX883042; CAE83931.1; -; Genomic_DNA.
DR RefSeq; NP_997694.1; NM_212529.1.
DR AlphaFoldDB; Q6MGB5; -.
DR SMR; Q6MGB5; -.
DR IntAct; Q6MGB5; 1.
DR STRING; 10116.ENSRNOP00000000542; -.
DR iPTMnet; Q6MGB5; -.
DR PhosphoSitePlus; Q6MGB5; -.
DR PaxDb; Q6MGB5; -.
DR PRIDE; Q6MGB5; -.
DR GeneID; 361802; -.
DR KEGG; rno:361802; -.
DR UCSC; RGD:1303158; rat.
DR CTD; 7923; -.
DR RGD; 1303158; Hsd17b8.
DR eggNOG; KOG1200; Eukaryota.
DR HOGENOM; CLU_010194_1_3_1; -.
DR InParanoid; Q6MGB5; -.
DR OrthoDB; 1226147at2759; -.
DR PhylomeDB; Q6MGB5; -.
DR TreeFam; TF313099; -.
DR Reactome; R-RNO-75105; Fatty acyl-CoA biosynthesis.
DR UniPathway; UPA00094; -.
DR UniPathway; UPA00660; -.
DR UniPathway; UPA00769; -.
DR PRO; PR:Q6MGB5; -.
DR Proteomes; UP000002494; Chromosome 20.
DR Bgee; ENSRNOG00000000466; Expressed in ovary and 20 other tissues.
DR ExpressionAtlas; Q6MGB5; baseline and differential.
DR Genevisible; Q6MGB5; RN.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0005740; C:mitochondrial envelope; ISO:RGD.
DR GO; GO:0005759; C:mitochondrial matrix; ISO:RGD.
DR GO; GO:1990204; C:oxidoreductase complex; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0106386; F:(3R)-hydroxyacyl-CoA dehydrogenase (NAD) activity; ISS:UniProtKB.
DR GO; GO:0044594; F:17-beta-hydroxysteroid dehydrogenase (NAD+) activity; IEA:RHEA.
DR GO; GO:0004303; F:estradiol 17-beta-dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0070404; F:NADH binding; ISS:UniProtKB.
DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IBA:GO_Central.
DR GO; GO:0048038; F:quinone binding; IBA:GO_Central.
DR GO; GO:0047035; F:testosterone dehydrogenase (NAD+) activity; ISO:RGD.
DR GO; GO:0008209; P:androgen metabolic process; ISO:RGD.
DR GO; GO:0006703; P:estrogen biosynthetic process; ISS:UniProtKB.
DR GO; GO:0008210; P:estrogen metabolic process; ISO:RGD.
DR GO; GO:0006633; P:fatty acid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0051290; P:protein heterotetramerization; 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 1: Evidence at protein level;
KW Acetylation; Fatty acid biosynthesis; Fatty acid metabolism;
KW Lipid biosynthesis; Lipid metabolism; Mitochondrion; NAD; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Steroid biosynthesis.
FT CHAIN 1..259
FT /note="(3R)-3-hydroxyacyl-CoA dehydrogenase"
FT /id="PRO_0000304877"
FT ACT_SITE 167
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 13..21
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 40..41
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 72..74
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 154
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 167..171
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 200..202
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT MOD_RES 58
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 66
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P50171"
FT MOD_RES 158
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P50171"
FT MOD_RES 171
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P50171"
SQ SEQUENCE 259 AA; 26791 MW; 5E23ECCE525E6781 CRC64;
MASQLRLRSA LALVTGAGSG IGRAISVRLA AEGAAVAACD LDGAAAQDTV RLLGNPGSED
REPRGKHAAF QADVSEGPAA KRLLEQVQAC FFRPPSVVVS CAGITRDEFL LHMSEEDWDR
VIAVNLKGTF LVTQAAAQAL VSSGGRGSII NISSIVGKVG NIGQTNYASS KAGVIGLTQT
AARELGRHGI RCNSVLPGFI ATPMTQKMPE KVKDKVTAMI PLGHMGDPED VADVVAFLAS
EDSGYITGAS VEVSGGLFM
