HCDH_PIG
ID HCDH_PIG Reviewed; 314 AA.
AC P00348; Q9XS66;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial;
DE Short=HCDH;
DE EC=1.1.1.35 {ECO:0000269|PubMed:2817332, ECO:0000269|PubMed:9593854};
DE AltName: Full=L-3-hydroxyacyl CoA dehydrogenase {ECO:0000303|PubMed:7409145};
DE AltName: Full=Medium and short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase;
DE AltName: Full=Short-chain 3-hydroxyacyl-CoA dehydrogenase;
DE Flags: Precursor;
GN Name=HADH; Synonyms=HAD, HADHSC, SCHAD;
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 [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT.
RC TISSUE=Liver;
RX PubMed=9593854; DOI=10.1016/s0005-2760(98)00031-9;
RA He X.-Y., Yang S.-Y.;
RT "Molecular cloning, expression in Escherichia coli, and characterization of
RT a novel L-3-hydroxyacyl coenzyme A dehydrogenase from pig liver.";
RL Biochim. Biophys. Acta 1392:119-126(1998).
RN [2]
RP PROTEIN SEQUENCE OF 13-314.
RC TISSUE=Heart;
RX PubMed=7409145; DOI=10.1016/0014-5793(80)80642-9;
RA Bitar K.G., Perez-Aranda A., Bradshaw R.A.;
RT "Amino acid sequence of L-3-hydroxyacyl CoA dehydrogenase from pig heart
RT muscle.";
RL FEBS Lett. 116:196-198(1980).
RN [3]
RP SEQUENCE REVISION TO 16 AND 21.
RA Fang J.-K., Bradshaw R.A.;
RL Submitted (OCT-1982) to the PIR data bank.
RN [4]
RP CATALYTIC ACTIVITY, FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=2817332; DOI=10.1016/0003-2697(89)90095-x;
RA He X.Y., Yang S.Y., Schulz H.;
RT "Assay of L-3-hydroxyacyl-coenzyme A dehydrogenase with substrates of
RT different chain lengths.";
RL Anal. Biochem. 180:105-109(1989).
RN [5]
RP SHOWS THAT HEART AND LIVER ENZYMES ARE IDENTICAL.
RX PubMed=10064895; DOI=10.1016/s1388-1981(98)00005-5;
RA He X.-Y., Zhang G., Blecha F., Yang S.-Y.;
RT "Identity of heart and liver L-3-hydroxyacyl coenzyme A dehydrogenase.";
RL Biochim. Biophys. Acta 1437:119-123(1999).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 13-314 IN COMPLEX WITH NAD.
RX PubMed=3479790; DOI=10.1073/pnas.84.23.8262;
RA Birktoff J.J., Holden H.M., Hamlin R., Xuong N.H., Banaszak L.J.;
RT "Structure of L-3-hydroxyacyl-coenzyme A dehydrogenase: preliminary chain
RT tracing at 2.8-A resolution.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:8262-8266(1987).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 13-314.
RC TISSUE=Heart;
RX PubMed=10548046; DOI=10.1110/ps.8.10.2010;
RA Barycki J.J., O'Brien L.K., Birktoft J.J., Strauss A.W., Banaszak L.J.;
RT "Pig heart short chain L-3-hydroxyacyl-CoA dehydrogenase revisited:
RT sequence analysis and crystal structure determination.";
RL Protein Sci. 8:2010-2018(1999).
CC -!- FUNCTION: Mitochondrial fatty acid beta-oxidation enzyme that catalyzes
CC the third step of the beta-oxidation cycle for medium and short-chain
CC 3-hydroxy fatty acyl-CoAs (C4 to C10) (PubMed:9593854, PubMed:2817332).
CC Plays a role in the control of insulin secretion by inhibiting the
CC activation of glutamate dehydrogenase 1 (GLUD1), an enzyme that has an
CC important role in regulating amino acid-induced insulin secretion (By
CC similarity). {ECO:0000250|UniProtKB:Q61425, ECO:0000269|PubMed:2817332,
CC ECO:0000269|PubMed:9593854}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3S)-3-hydroxyacyl-CoA + NAD(+) = a 3-oxoacyl-CoA + H(+) +
CC NADH; Xref=Rhea:RHEA:22432, ChEBI:CHEBI:15378, ChEBI:CHEBI:57318,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:90726; EC=1.1.1.35;
CC Evidence={ECO:0000269|PubMed:9593854};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-3-hydroxybutanoyl-CoA + NAD(+) = acetoacetyl-CoA + H(+) +
CC NADH; Xref=Rhea:RHEA:30799, ChEBI:CHEBI:15378, ChEBI:CHEBI:57286,
CC ChEBI:CHEBI:57316, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000269|PubMed:2817332};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxydecanoyl-CoA + NAD(+) = 3-oxodecanoyl-CoA + H(+) +
CC NADH; Xref=Rhea:RHEA:31187, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:62548, ChEBI:CHEBI:62616;
CC Evidence={ECO:0000269|PubMed:2817332};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxyhexadecanoyl-CoA + NAD(+) = 3-oxohexadecanoyl-CoA
CC + H(+) + NADH; Xref=Rhea:RHEA:31159, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57349, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:62613; Evidence={ECO:0000269|PubMed:2817332};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=7.2 uM for (3S)-hydroxybutanoyl-CoA {ECO:0000269|PubMed:2817332};
CC KM=2.9 uM for (3S)-hydroxydecanoyl-CoA {ECO:0000269|PubMed:2817332};
CC KM=3.0 uM for (3S)-hydroxyhexadecanoyl-CoA
CC {ECO:0000269|PubMed:2817332};
CC -!- PATHWAY: Lipid metabolism; fatty acid beta-oxidation. {ECO:0000305}.
CC -!- SUBUNIT: Homodimer (PubMed:3479790, PubMed:9593854). Interacts with
CC GLUD1; this interaction inhibits the activation of glutamate
CC dehydrogenase 1 (GLUD1) (By similarity). {ECO:0000250|UniProtKB:Q61425,
CC ECO:0000269|PubMed:3479790, ECO:0000269|PubMed:9593854}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC -!- PTM: Succinylation at Lys-81, adjacent to a coenzyme A binding site.
CC Desuccinylated by SIRT5. {ECO:0000250|UniProtKB:Q61425}.
CC -!- SIMILARITY: Belongs to the 3-hydroxyacyl-CoA dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; AF027652; AAD20939.1; -; mRNA.
DR PIR; T46866; T46866.
DR RefSeq; NP_999496.1; NM_214331.1.
DR PDB; 3HDH; X-ray; 2.80 A; A/B/C=13-314.
DR PDBsum; 3HDH; -.
DR AlphaFoldDB; P00348; -.
DR SMR; P00348; -.
DR STRING; 9823.ENSSSCP00000009757; -.
DR PaxDb; P00348; -.
DR PeptideAtlas; P00348; -.
DR PRIDE; P00348; -.
DR Ensembl; ENSSSCT00000049871; ENSSSCP00000053505; ENSSSCG00000009150.
DR Ensembl; ENSSSCT00015021821; ENSSSCP00015008559; ENSSSCG00015016364.
DR Ensembl; ENSSSCT00025056558; ENSSSCP00025023930; ENSSSCG00025041615.
DR Ensembl; ENSSSCT00030004417; ENSSSCP00030001758; ENSSSCG00030003353.
DR Ensembl; ENSSSCT00035031118; ENSSSCP00035012173; ENSSSCG00035023707.
DR Ensembl; ENSSSCT00040103510; ENSSSCP00040046934; ENSSSCG00040074801.
DR Ensembl; ENSSSCT00045041276; ENSSSCP00045028650; ENSSSCG00045024125.
DR Ensembl; ENSSSCT00050020134; ENSSSCP00050008385; ENSSSCG00050014864.
DR Ensembl; ENSSSCT00055013484; ENSSSCP00055010607; ENSSSCG00055006902.
DR Ensembl; ENSSSCT00060105557; ENSSSCP00060046413; ENSSSCG00060076804.
DR Ensembl; ENSSSCT00065008871; ENSSSCP00065003731; ENSSSCG00065006573.
DR Ensembl; ENSSSCT00070038976; ENSSSCP00070032640; ENSSSCG00070019666.
DR Ensembl; ENSSSCT00070039014; ENSSSCP00070032672; ENSSSCG00070019666.
DR GeneID; 397604; -.
DR KEGG; ssc:397604; -.
DR CTD; 3033; -.
DR VGNC; VGNC:88771; HADH.
DR eggNOG; KOG2304; Eukaryota.
DR GeneTree; ENSGT00940000159984; -.
DR HOGENOM; CLU_009834_2_0_1; -.
DR InParanoid; P00348; -.
DR OMA; FYDYSES; -.
DR OrthoDB; 938257at2759; -.
DR TreeFam; TF300886; -.
DR Reactome; R-SSC-77310; Beta oxidation of lauroyl-CoA to decanoyl-CoA-CoA.
DR Reactome; R-SSC-77346; Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA.
DR Reactome; R-SSC-77348; Beta oxidation of octanoyl-CoA to hexanoyl-CoA.
DR Reactome; R-SSC-77350; Beta oxidation of hexanoyl-CoA to butanoyl-CoA.
DR Reactome; R-SSC-77352; Beta oxidation of butanoyl-CoA to acetyl-CoA.
DR SABIO-RK; P00348; -.
DR UniPathway; UPA00659; -.
DR EvolutionaryTrace; P00348; -.
DR Proteomes; UP000008227; Chromosome 8.
DR Proteomes; UP000314985; Chromosome 8.
DR Bgee; ENSSSCG00000009150; Expressed in adult mammalian kidney and 46 other tissues.
DR ExpressionAtlas; P00348; baseline.
DR Genevisible; P00348; SS.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0003857; F:3-hydroxyacyl-CoA dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0070403; F:NAD+ binding; ISS:UniProtKB.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IDA:UniProtKB.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IEA:Ensembl.
DR GO; GO:0050796; P:regulation of insulin secretion; ISS:UniProtKB.
DR Gene3D; 1.10.1040.10; -; 1.
DR InterPro; IPR022694; 3-OHacyl-CoA_DH.
DR InterPro; IPR006180; 3-OHacyl-CoA_DH_CS.
DR InterPro; IPR006176; 3-OHacyl-CoA_DH_NAD-bd.
DR InterPro; IPR006108; 3HC_DH_C.
DR InterPro; IPR008927; 6-PGluconate_DH-like_C_sf.
DR InterPro; IPR013328; 6PGD_dom2.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF00725; 3HCDH; 1.
DR Pfam; PF02737; 3HCDH_N; 1.
DR PIRSF; PIRSF000105; HCDH; 1.
DR SUPFAM; SSF48179; SSF48179; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00067; 3HCDH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Direct protein sequencing;
KW Fatty acid metabolism; Hydroxylation; Lipid metabolism; Mitochondrion; NAD;
KW Oxidoreductase; Reference proteome; Transit peptide.
FT TRANSIT 1..12
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:Q16836"
FT CHAIN 13..314
FT /note="Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial"
FT /id="PRO_0000007408"
FT BINDING 34..39
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:3479790"
FT BINDING 57
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:3479790"
FT BINDING 73
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:Q16836"
FT BINDING 80
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:Q16836"
FT BINDING 122
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:3479790"
FT BINDING 127
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:3479790"
FT BINDING 149
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:Q16836"
FT BINDING 149
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:3479790"
FT BINDING 173
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q16836"
FT BINDING 305
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q16836"
FT SITE 170
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250|UniProtKB:Q16836"
FT MOD_RES 80
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q61425"
FT MOD_RES 81
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q61425"
FT MOD_RES 81
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q61425"
FT MOD_RES 87
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q61425"
FT MOD_RES 87
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q61425"
FT MOD_RES 125
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q61425"
FT MOD_RES 127
FT /note="N6-(2-hydroxyisobutyryl)lysine"
FT /evidence="ECO:0000250|UniProtKB:Q16836"
FT MOD_RES 136
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q61425"
FT MOD_RES 136
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q61425"
FT MOD_RES 179
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q61425"
FT MOD_RES 185
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q16836"
FT MOD_RES 185
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q61425"
FT MOD_RES 192
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q61425"
FT MOD_RES 192
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q61425"
FT MOD_RES 202
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q16836"
FT MOD_RES 202
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q61425"
FT MOD_RES 206
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q61425"
FT MOD_RES 212
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q61425"
FT MOD_RES 212
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q61425"
FT MOD_RES 241
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q16836"
FT MOD_RES 241
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q61425"
FT MOD_RES 312
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q16836"
FT MOD_RES 312
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q61425"
FT CONFLICT 108
FT /note="S -> A (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 122
FT /note="E -> EQLKVVGE (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 172..174
FT /note="FNP -> N (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 29..33
FT /evidence="ECO:0007829|PDB:3HDH"
FT HELIX 37..48
FT /evidence="ECO:0007829|PDB:3HDH"
FT STRAND 52..56
FT /evidence="ECO:0007829|PDB:3HDH"
FT HELIX 60..81
FT /evidence="ECO:0007829|PDB:3HDH"
FT TURN 82..84
FT /evidence="ECO:0007829|PDB:3HDH"
FT HELIX 86..98
FT /evidence="ECO:0007829|PDB:3HDH"
FT STRAND 100..104
FT /evidence="ECO:0007829|PDB:3HDH"
FT HELIX 106..108
FT /evidence="ECO:0007829|PDB:3HDH"
FT STRAND 110..112
FT /evidence="ECO:0007829|PDB:3HDH"
FT STRAND 114..118
FT /evidence="ECO:0007829|PDB:3HDH"
FT HELIX 124..137
FT /evidence="ECO:0007829|PDB:3HDH"
FT STRAND 143..146
FT /evidence="ECO:0007829|PDB:3HDH"
FT STRAND 149..151
FT /evidence="ECO:0007829|PDB:3HDH"
FT HELIX 153..157
FT /evidence="ECO:0007829|PDB:3HDH"
FT HELIX 163..165
FT /evidence="ECO:0007829|PDB:3HDH"
FT STRAND 166..170
FT /evidence="ECO:0007829|PDB:3HDH"
FT TURN 175..177
FT /evidence="ECO:0007829|PDB:3HDH"
FT STRAND 180..185
FT /evidence="ECO:0007829|PDB:3HDH"
FT HELIX 191..203
FT /evidence="ECO:0007829|PDB:3HDH"
FT STRAND 207..213
FT /evidence="ECO:0007829|PDB:3HDH"
FT TURN 215..218
FT /evidence="ECO:0007829|PDB:3HDH"
FT HELIX 219..235
FT /evidence="ECO:0007829|PDB:3HDH"
FT HELIX 241..252
FT /evidence="ECO:0007829|PDB:3HDH"
FT HELIX 258..265
FT /evidence="ECO:0007829|PDB:3HDH"
FT HELIX 267..279
FT /evidence="ECO:0007829|PDB:3HDH"
FT TURN 280..283
FT /evidence="ECO:0007829|PDB:3HDH"
FT HELIX 285..287
FT /evidence="ECO:0007829|PDB:3HDH"
FT HELIX 291..298
FT /evidence="ECO:0007829|PDB:3HDH"
FT TURN 304..307
FT /evidence="ECO:0007829|PDB:3HDH"
FT STRAND 308..312
FT /evidence="ECO:0007829|PDB:3HDH"
SQ SEQUENCE 314 AA; 34161 MW; 596CBFD227214C3B CRC64;
MAFATRQLVR SLSSSSTAAA SAKKILVKHV TVIGGGLMGA GIAQVAAATG HTVVLVDQTE
DILAKSKKGI EESLRKVAKK KFAENPKAGD EFVEKTLSSI STSTDAASVV HSTDLVVEAI
VENLKVKSEL FKRLDKFAAE HTIFASNTSS LQITSLANAT TRQDRFAGLH FFNPVPLMKL
VEVVKTPMTS QKTLESLVDF SKTLGKHPVS CKDTPGFIVN RLLVPYLIEA VRLYERGDAS
KEDIDTAMKL GAGYPMGPFE LLDYVGLDTT KFIIDGWHEM DSQNPLFQPS PAMNKLVAEN
KFGKKTGEGF YKYK
