UniProt functional annotation for Q16836



	UniProt functional annotation for Q16836

UniProt code: Q16836.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Mitochondrial fatty acid beta-oxidation enzyme that catalyzes the third step of the beta-oxidation cycle for medium and short-chain 3-hydroxy fatty acyl-CoAs (C4 to C10) (PubMed:10231530, PubMed:11489939, PubMed:16725361). Plays a role in the control of insulin secretion by inhibiting the activation of glutamate dehydrogenase 1 (GLUD1), an enzyme that has an important role in regulating amino acid-induced insulin secretion (By similarity). {ECO:0000250|UniProtKB:Q61425, ECO:0000269|PubMed:10231530, ECO:0000269|PubMed:11489939, ECO:0000269|PubMed:16725361}.

Catalytic activity: Reaction=a (3S)-3-hydroxyacyl-CoA + NAD(+) = a 3-oxoacyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:22432, ChEBI:CHEBI:15378, ChEBI:CHEBI:57318, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:90726; EC=1.1.1.35; Evidence={ECO:0000269|PubMed:10231530, ECO:0000269|PubMed:11489939, ECO:0000269|PubMed:16725361};

Catalytic activity: Reaction=(3S)-3-hydroxybutanoyl-CoA + NAD(+) = acetoacetyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:30799, ChEBI:CHEBI:15378, ChEBI:CHEBI:57286, ChEBI:CHEBI:57316, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:10231530, ECO:0000269|PubMed:16725361};

Catalytic activity: Reaction=(3S)-hydroxydecanoyl-CoA + NAD(+) = 3-oxodecanoyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:31187, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:62548, ChEBI:CHEBI:62616; Evidence={ECO:0000250|UniProtKB:P00348};

Catalytic activity: Reaction=(3S)-hydroxyhexadecanoyl-CoA + NAD(+) = 3-oxohexadecanoyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:31159, ChEBI:CHEBI:15378, ChEBI:CHEBI:57349, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:62613; Evidence={ECO:0000250|UniProtKB:P00348};

Biophysicochemical properties: Kinetic parameters: KM=34.5 uM for acetoacetyl-CoA at pH 5.0 {ECO:0000269|PubMed:10231530}; KM=45.0 uM for acetoacetyl-CoA at pH 6.0 {ECO:0000269|PubMed:10231530}; KM=18.7 uM for acetoacetyl-CoA at pH 7.0 {ECO:0000269|PubMed:10231530}; KM=13.8 uM for acetoacetyl-CoA at pH 8.0 {ECO:0000269|PubMed:10231530}; KM=11.9 uM for acetoacetyl-CoA {ECO:0000269|PubMed:16725361}; KM=24.2 uM for NADH {ECO:0000269|PubMed:16725361}; Vmax=281 umol/min/mg enzyme with acetoacetyl-CoA as substrate at PH 5.0 {ECO:0000269|PubMed:10231530}; Vmax=448 umol/min/mg enzyme with acetoacetyl-CoA as substrate at PH 6.0 {ECO:0000269|PubMed:10231530}; Vmax=459 umol/min/mg enzyme with acetoacetyl-CoA as substrate at PH 6.0 {ECO:0000269|PubMed:10231530}; Vmax=205 umol/min/mg enzyme with acetoacetyl-CoA as substrate at PH 8.0 {ECO:0000269|PubMed:10231530}; pH dependence: Optimum at neutral pH. {ECO:0000269|PubMed:10231530};

Pathway: Lipid metabolism; fatty acid beta-oxidation. {ECO:0000269|PubMed:11489939, ECO:0000269|PubMed:16725361}.

Subunit: Homodimer (PubMed:10231530, PubMed:10840044, PubMed:16725361). Interacts with GLUD1; this interaction inhibits the activation of glutamate dehydrogenase 1 (GLUD1) (By similarity). {ECO:0000250|UniProtKB:Q61425, ECO:0000269|PubMed:10231530, ECO:0000269|PubMed:10840044, ECO:0000269|PubMed:16725361}.

Subcellular location: Mitochondrion matrix {ECO:0000305|PubMed:8687463}.

Tissue specificity: Expressed in liver, kidney, pancreas, heart and skeletal muscle. {ECO:0000269|PubMed:8687463}.

Ptm: Succinylation at Lys-81, adjacent to a coenzyme A binding site. Desuccinylated by SIRT5. {ECO:0000250|UniProtKB:Q61425}.

Disease: 3-alpha-hydroxyacyl-CoA dehydrogenase deficiency (HADH deficiency) [MIM:231530]: An autosomal recessive, metabolic disorder with various clinical presentations including hypoglycemia, hepatoencephalopathy, myopathy or cardiomyopathy, and in some cases sudden death. {ECO:0000269|Ref.13}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Familial hyperinsulinemic hypoglycemia 4 (HHF4) [MIM:609975]: Most common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur. HHF4 should be easily recognizable by analysis of acylcarnitine species and that this disorder responds well to treatment with diazoxide. It provides the first 'experiment of nature' that links impaired fatty acid oxidation to hyperinsulinism and that provides support for the concept that a lipid signaling pathway is implicated in the control of insulin secretion. {ECO:0000269|PubMed:11489939}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the 3-hydroxyacyl-CoA dehydrogenase family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Mitochondrial fatty acid beta-oxidation enzyme that catalyzes the third step of the beta-oxidation cycle for medium and short-chain 3-hydroxy fatty acyl-CoAs (C4 to C10) (PubMed:10231530, PubMed:11489939, PubMed:16725361). Plays a role in the control of insulin secretion by inhibiting the activation of glutamate dehydrogenase 1 (GLUD1), an enzyme that has an important role in regulating amino acid-induced insulin secretion (By similarity). {ECO:0000250\|UniProtKB:Q61425, ECO:0000269\|PubMed:10231530, ECO:0000269\|PubMed:11489939, ECO:0000269\|PubMed:16725361}.


Catalytic activity:		Reaction=a (3S)-3-hydroxyacyl-CoA + NAD(+) = a 3-oxoacyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:22432, ChEBI:CHEBI:15378, ChEBI:CHEBI:57318, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:90726; EC=1.1.1.35; Evidence={ECO:0000269\|PubMed:10231530, ECO:0000269\|PubMed:11489939, ECO:0000269\|PubMed:16725361};
Catalytic activity:		Reaction=(3S)-3-hydroxybutanoyl-CoA + NAD(+) = acetoacetyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:30799, ChEBI:CHEBI:15378, ChEBI:CHEBI:57286, ChEBI:CHEBI:57316, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269\|PubMed:10231530, ECO:0000269\|PubMed:16725361};
Catalytic activity:		Reaction=(3S)-hydroxydecanoyl-CoA + NAD(+) = 3-oxodecanoyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:31187, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:62548, ChEBI:CHEBI:62616; Evidence={ECO:0000250\|UniProtKB:P00348};
Catalytic activity:		Reaction=(3S)-hydroxyhexadecanoyl-CoA + NAD(+) = 3-oxohexadecanoyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:31159, ChEBI:CHEBI:15378, ChEBI:CHEBI:57349, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:62613; Evidence={ECO:0000250\|UniProtKB:P00348};
Biophysicochemical properties:		Kinetic parameters: KM=34.5 uM for acetoacetyl-CoA at pH 5.0 {ECO:0000269\|PubMed:10231530}; KM=45.0 uM for acetoacetyl-CoA at pH 6.0 {ECO:0000269\|PubMed:10231530}; KM=18.7 uM for acetoacetyl-CoA at pH 7.0 {ECO:0000269\|PubMed:10231530}; KM=13.8 uM for acetoacetyl-CoA at pH 8.0 {ECO:0000269\|PubMed:10231530}; KM=11.9 uM for acetoacetyl-CoA {ECO:0000269\|PubMed:16725361}; KM=24.2 uM for NADH {ECO:0000269\|PubMed:16725361}; Vmax=281 umol/min/mg enzyme with acetoacetyl-CoA as substrate at PH 5.0 {ECO:0000269\|PubMed:10231530}; Vmax=448 umol/min/mg enzyme with acetoacetyl-CoA as substrate at PH 6.0 {ECO:0000269\|PubMed:10231530}; Vmax=459 umol/min/mg enzyme with acetoacetyl-CoA as substrate at PH 6.0 {ECO:0000269\|PubMed:10231530}; Vmax=205 umol/min/mg enzyme with acetoacetyl-CoA as substrate at PH 8.0 {ECO:0000269\|PubMed:10231530}; pH dependence: Optimum at neutral pH. {ECO:0000269\|PubMed:10231530};
Pathway:		Lipid metabolism; fatty acid beta-oxidation. {ECO:0000269\|PubMed:11489939, ECO:0000269\|PubMed:16725361}.
Subunit:		Homodimer (PubMed:10231530, PubMed:10840044, PubMed:16725361). Interacts with GLUD1; this interaction inhibits the activation of glutamate dehydrogenase 1 (GLUD1) (By similarity). {ECO:0000250\|UniProtKB:Q61425, ECO:0000269\|PubMed:10231530, ECO:0000269\|PubMed:10840044, ECO:0000269\|PubMed:16725361}.
Subcellular location:		Mitochondrion matrix {ECO:0000305\|PubMed:8687463}.
Tissue specificity:		Expressed in liver, kidney, pancreas, heart and skeletal muscle. {ECO:0000269\|PubMed:8687463}.
Ptm:		Succinylation at Lys-81, adjacent to a coenzyme A binding site. Desuccinylated by SIRT5. {ECO:0000250\|UniProtKB:Q61425}.
Disease:		3-alpha-hydroxyacyl-CoA dehydrogenase deficiency (HADH deficiency) [MIM:231530]: An autosomal recessive, metabolic disorder with various clinical presentations including hypoglycemia, hepatoencephalopathy, myopathy or cardiomyopathy, and in some cases sudden death. {ECO:0000269\|Ref.13}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Familial hyperinsulinemic hypoglycemia 4 (HHF4) [MIM:609975]: Most common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur. HHF4 should be easily recognizable by analysis of acylcarnitine species and that this disorder responds well to treatment with diazoxide. It provides the first 'experiment of nature' that links impaired fatty acid oxidation to hyperinsulinism and that provides support for the concept that a lipid signaling pathway is implicated in the control of insulin secretion. {ECO:0000269\|PubMed:11489939}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the 3-hydroxyacyl-CoA dehydrogenase family. {ECO:0000305}.