HCDH_RAT
ID HCDH_RAT Reviewed; 314 AA.
AC Q9WVK7;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial;
DE Short=HCDH;
DE EC=1.1.1.35 {ECO:0000250|UniProtKB:P00348};
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 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 [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Heart muscle, and Liver;
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).
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) (By similarity). Plays a role in
CC the control of insulin secretion by inhibiting the activation of
CC glutamate dehydrogenase 1 (GLUD1), an enzyme that has an important role
CC in regulating amino acid-induced insulin secretion (By similarity).
CC {ECO:0000250|UniProtKB:Q16836, ECO:0000250|UniProtKB:Q61425}.
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:0000250|UniProtKB:P00348};
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:0000250|UniProtKB:P00348};
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:0000250|UniProtKB:P00348};
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:0000250|UniProtKB:P00348};
CC -!- PATHWAY: Lipid metabolism; fatty acid beta-oxidation.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with GLUD1; this
CC interaction inhibits the activation of glutamate dehydrogenase 1
CC (GLUD1) (By similarity). {ECO:0000250|UniProtKB:P00348,
CC ECO:0000250|UniProtKB:Q61425}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000250|UniProtKB:P00348}.
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; AF095449; AAD42162.1; -; mRNA.
DR PIR; S74114; S74114.
DR RefSeq; NP_476534.1; NM_057186.2.
DR AlphaFoldDB; Q9WVK7; -.
DR SMR; Q9WVK7; -.
DR BioGRID; 250240; 2.
DR IntAct; Q9WVK7; 2.
DR MINT; Q9WVK7; -.
DR STRING; 10116.ENSRNOP00000014658; -.
DR ChEMBL; CHEMBL2176821; -.
DR iPTMnet; Q9WVK7; -.
DR PhosphoSitePlus; Q9WVK7; -.
DR jPOST; Q9WVK7; -.
DR PaxDb; Q9WVK7; -.
DR PRIDE; Q9WVK7; -.
DR Ensembl; ENSRNOT00000014658; ENSRNOP00000014658; ENSRNOG00000010697.
DR GeneID; 113965; -.
DR KEGG; rno:113965; -.
DR CTD; 3033; -.
DR RGD; 69321; Hadh.
DR eggNOG; KOG2304; Eukaryota.
DR GeneTree; ENSGT00940000159984; -.
DR HOGENOM; CLU_009834_2_0_1; -.
DR InParanoid; Q9WVK7; -.
DR OMA; FYDYSES; -.
DR OrthoDB; 938257at2759; -.
DR PhylomeDB; Q9WVK7; -.
DR TreeFam; TF300886; -.
DR Reactome; R-RNO-77310; Beta oxidation of lauroyl-CoA to decanoyl-CoA-CoA.
DR Reactome; R-RNO-77346; Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA.
DR Reactome; R-RNO-77348; Beta oxidation of octanoyl-CoA to hexanoyl-CoA.
DR Reactome; R-RNO-77350; Beta oxidation of hexanoyl-CoA to butanoyl-CoA.
DR Reactome; R-RNO-77352; Beta oxidation of butanoyl-CoA to acetyl-CoA.
DR SABIO-RK; Q9WVK7; -.
DR UniPathway; UPA00659; -.
DR PRO; PR:Q9WVK7; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000010697; Expressed in heart and 19 other tissues.
DR Genevisible; Q9WVK7; RN.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0003857; F:3-hydroxyacyl-CoA dehydrogenase activity; IMP:RGD.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0070403; F:NAD+ binding; ISS:UniProtKB.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IMP:RGD.
DR GO; GO:0046676; P:negative regulation of insulin secretion; IMP:RGD.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0050796; P:regulation of insulin secretion; ISS:UniProtKB.
DR GO; GO:0014823; P:response to activity; IDA:RGD.
DR GO; GO:0009725; P:response to hormone; IEP:RGD.
DR GO; GO:0032868; P:response to insulin; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IDA:RGD.
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 2: Evidence at transcript level;
KW Acetylation; Fatty acid metabolism; Hydroxylation; Lipid metabolism;
KW Mitochondrion; NAD; 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_0000007409"
FT BINDING 34..39
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q16836"
FT BINDING 57
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q16836"
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:0000250|UniProtKB:Q16836"
FT BINDING 127
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q16836"
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:0000250|UniProtKB:Q16836"
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 75
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q61425"
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"
SQ SEQUENCE 314 AA; 34448 MW; B36518766D6C3828 CRC64;
MAFVTRQFVR SMSSSSSASA AAKKILIKHV TVIGGGLMGA GIAQVAAATG HTVVLVDQTE
DILAKSKKGI EESLKRMAKK KFTENPKAAD EFVEKTLSSL STSTDAASVV HSTDLVVEAI
VENLKLKNEL FQRLDKFAAE HTIFASNTSS LQITNIANAT TRQDRFAGLH FFNPVPMMKL
VEVIKTPMTS QKTFESLVDF CKTLGKHPVS CKDTPGFIVN RLLVPYLIEA IRLHERGDAS
KEDIDTAMKL GAGYPMGPFE LLDYVGLDTT KFILDGWHEM DPENPLFQPS PSMNNLVAQK
KLGKKTGEGF YKYK
