DHB8_PIG
ID DHB8_PIG Reviewed; 259 AA.
AC Q9XT00;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 2.
DT 03-AUG-2022, entry version 107.
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=Protein Ke6;
DE Short=Ke-6;
DE AltName: Full=Testosterone 17-beta-dehydrogenase 8;
DE EC=1.1.1.239 {ECO:0000250|UniProtKB:Q92506};
GN Name=HSD17B8; Synonyms=FABGL, HKE6;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Landrace X Pietrain;
RX PubMed=12030927; DOI=10.1046/j.1365-2052.2002.00849.x;
RA Jacobs K., Mattheeuws M., Van Poucke M., Van Zeveren A., Peelman L.J.;
RT "Characterization of the porcine FABGL gene.";
RL Anim. Genet. 33:220-223(2002).
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, acts as
CC 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(+)(H).
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 -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; AF146398; AAD44802.2; -; Genomic_DNA.
DR AlphaFoldDB; Q9XT00; -.
DR SMR; Q9XT00; -.
DR STRING; 9823.ENSSSCP00000030579; -.
DR PaxDb; Q9XT00; -.
DR PeptideAtlas; Q9XT00; -.
DR PRIDE; Q9XT00; -.
DR eggNOG; KOG1200; Eukaryota.
DR InParanoid; Q9XT00; -.
DR UniPathway; UPA00094; -.
DR UniPathway; UPA00660; -.
DR UniPathway; UPA00769; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
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; IEA:UniProtKB-EC.
DR GO; GO:0006703; P:estrogen biosynthetic process; ISS:UniProtKB.
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 3: Inferred from homology;
KW Fatty acid biosynthesis; Fatty acid metabolism; Lipid biosynthesis;
KW Lipid metabolism; Mitochondrion; NAD; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Steroid biosynthesis.
FT CHAIN 1..259
FT /note="(3R)-3-hydroxyacyl-CoA dehydrogenase"
FT /id="PRO_0000054600"
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: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; 26622 MW; E8A357BCCD26DD1C CRC64;
MASQLRLRSA LALVTGAGSG IGRAVSVRLA AEGAAVAACD LDGAAAQETV QLLGGPGSEK
GAPSGPMAAF QADVSEAETA RRLLEQVQAY FFRPPSVVVS CAGITRDEFL LRMSEDDWDK
VIAVNLKGIF LVTQAAAQAL VSSGCPGSII NISSIIGKVG NMGQTNYAAS KAGVIGLTQA
VARELGRYRI RCNSVLPGFI KTPMAQKVPQ KVLDKVVGMI PMGHLGGPPD VADVVAFLAS
EDSGYITGAS VEVTGGLFM
