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 27-MAR-2024, entry version 178. 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 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}. 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; 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.ENSSSCP00000053505; -. DR PaxDb; 9823-ENSSSCP00000009757; -. DR PeptideAtlas; P00348; -. DR Ensembl; ENSSSCT00000049871.3; ENSSSCP00000053505.1; ENSSSCG00000009150.4. DR Ensembl; ENSSSCT00015021821.1; ENSSSCP00015008559.1; ENSSSCG00015016364.1. DR Ensembl; ENSSSCT00025056558.1; ENSSSCP00025023930.1; ENSSSCG00025041615.1. DR Ensembl; ENSSSCT00030004417.1; ENSSSCP00030001758.1; ENSSSCG00030003353.1. DR Ensembl; ENSSSCT00035031118.1; ENSSSCP00035012173.1; ENSSSCG00035023707.1. DR Ensembl; ENSSSCT00040103510.1; ENSSSCP00040046934.1; ENSSSCG00040074801.1. DR Ensembl; ENSSSCT00045041276.1; ENSSSCP00045028650.1; ENSSSCG00045024125.1. DR Ensembl; ENSSSCT00050020134.1; ENSSSCP00050008385.1; ENSSSCG00050014864.1. DR Ensembl; ENSSSCT00055013484.1; ENSSSCP00055010607.1; ENSSSCG00055006902.1. DR Ensembl; ENSSSCT00060105557.1; ENSSSCP00060046413.1; ENSSSCG00060076804.1. DR Ensembl; ENSSSCT00065008871.1; ENSSSCP00065003731.1; ENSSSCG00065006573.1. DR Ensembl; ENSSSCT00070038976.1; ENSSSCP00070032640.1; ENSSSCG00070019666.1. DR Ensembl; ENSSSCT00070039014.1; ENSSSCP00070032672.1; ENSSSCG00070019666.1. 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; NGIAHTF; -. DR OrthoDB; 314530at2759; -. 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 Proteomes; UP000694570; Unplaced. DR Proteomes; UP000694571; Unplaced. DR Proteomes; UP000694720; Unplaced. DR Proteomes; UP000694722; Unplaced. DR Proteomes; UP000694723; Unplaced. DR Proteomes; UP000694724; Unplaced. DR Proteomes; UP000694725; Unplaced. DR Proteomes; UP000694726; Unplaced. DR Proteomes; UP000694727; Unplaced. DR Proteomes; UP000694728; Unplaced. DR Bgee; ENSSSCG00000009150; Expressed in adult mammalian kidney and 46 other cell types or tissues. DR ExpressionAtlas; P00348; baseline and differential. 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; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 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 PANTHER; PTHR43561; -; 1. DR PANTHER; PTHR43561:SF3; HYDROXYACYL-COENZYME A DEHYDROGENASE, MITOCHONDRIAL; 1. DR Pfam; PF00725; 3HCDH; 1. DR Pfam; PF02737; 3HCDH_N; 1. DR PIRSF; PIRSF000105; HCDH; 1. DR SUPFAM; SSF48179; 6-phosphogluconate dehydrogenase C-terminal domain-like; 1. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. DR PROSITE; PS00067; 3HCDH; 1. DR Genevisible; P00348; SS. 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 //