HADHA
entrez
3030
canonical
uniprot
P40939
canonical
ensembl
ENSG00000084754
resolver
ensp
ENSP00000370023
resolver
genesymbol
HADHA
resolver
genesymbol_syn
HADH
resolver
hgnc
HGNC:4801
resolver
uniprot
B2R7L4
resolver
uniprot
B4DYP2
resolver
uniprot
E9KL44
resolver
uniprot
Q16679
resolver
uniprot
Q53T69
resolver
uniprot
Q53TA2
resolver
uniprot
Q96GT7
resolver
uniprot
Q9UQC5
resolver
uniprot_entry
E9KL44_HUMAN
resolver
uniprot_entry
ECHA_HUMAN
resolver
uniprot_sec
B2R7L4
resolver
uniprot_sec
B4DYP2
resolver
uniprot_sec
Q16679
resolver
uniprot_sec
Q53T69
resolver
uniprot_sec
Q53TA2
resolver
uniprot_sec
Q96GT7
resolver
uniprot_sec
Q9UQC5
resolver
amino_acid_sequence
MVACRAIGILSRFSAFRILRSRGYICRNFTGSSALLTRTHINYGVKGDVAVVRINSPNSKVNTLSKELHSEFSEVMNEIWASDQIRSAVLISSKPGCFIAGADINMLAACKTLQEVTQLSQEAQRIVEKLEKSTKPIVAAINGSCLGGGLEVAISCQYRIATKDRKTVLGTPEVLLGALPGAGGTQRLPKMVGVPAALDMMLTGRSIRADRAKKMGLVDQLVEPLGPGLKPPEERTIEYLEEVAITFAKGLADKKISPKRDKGLVEKLTAYAMTIPFVRQQVYKKVEEKVRKQTKGLYPAPLKIIDVVKTGIEQGSDAGYLCESQKFGELVMTKESKALMGLYHGQVLCKKNKFGAPQKDVKHLAILGAGLMGAGIAQVSVDKGLKTILKDATLTALDRGQQQVFKGLNDKVKKKALTSFERDSIFSNLTGQLDYQGFEKADMVIEAVFEDLSLKHRVLKEVEAVIPDHCIFASNTSALPISEIAAVSKRPEKVIGMHYFSPVDKMQLLEIITTEKTSKDTSASAVAVGLKQGKVIIVVKDGPGFYTTRCLAPMMSEVIRILQEGVDPKKLDSLTTSFGFPVGAATLVDEVGVDVAKHVAEDLGKVFGERFGGGNPELLTQMVSKGFLGRKSGKGFYIYQEGVKRKDLNSDMDSILASLKLPPKSEVSSDEDIQFRLVTRFVNEAVMCLQEGILATPAEGDIGAVFGLGFPPCLGGPFRFVDLYGAQKIVDRLKKYEAAYGKQFTPCQLLADHANSPNKKFYQ
uniprot
proteins
disease_involvement
DISEASE: Mitochondrial trifunctional protein deficiency 1 (MTPD1) [MIM:609015]: An autosomal recessive metabolic disorder of long-chain fatty acid oxidation, biochemically characterized by loss of all enzyme activities of the mitochondrial trifunctional protein complex. The disease phenotype ranges from a fatal form characterized by early-onset cardiomyopathy, cardiac failure and early death to less severe, late-onset forms with myopathy, recurrent rhabdomyolysis, and sensorimotor axonal neuropathy as key features. {ECO:0000269|PubMed:9739053}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Long-chain 3-hydroxyl-CoA dehydrogenase deficiency (LCHAD deficiency) [MIM:609016]: The clinical features are very similar to TFP deficiency. Biochemically, LCHAD deficiency is characterized by reduced long-chain 3-hydroxyl-CoA dehydrogenase activity, while the other enzyme activities of the TFP complex are normal or only slightly reduced. {ECO:0000269|PubMed:7811722, ECO:0000269|PubMed:9266371}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Maternal acute fatty liver of pregnancy (AFLP) [MIM:609016]: Severe maternal illness occurring during pregnancies with affected fetuses. This disease is associated with LCHAD deficiency and characterized by sudden unexplained infant death or hypoglycemia and abnormal liver enzymes (Reye-like syndrome). {ECO:0000269|PubMed:7846063}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
1.1.1.211
uniprot
proteins
ec_number
2.3.1.-
uniprot
proteins
ec_number
4.2.1.17
uniprot
proteins
function
FUNCTION: Mitochondrial trifunctional enzyme catalyzes the last three of the four reactions of the mitochondrial beta-oxidation pathway (PubMed:1550553, PubMed:29915090, PubMed:30850536, PubMed:8135828, PubMed:31604922). The mitochondrial beta-oxidation pathway is the major energy-producing process in tissues and is performed through cycles of four consecutive reactions (PubMed:29915090). Each beta-oxidation cycle shortens the fatty acyl-CoA by two carbons, yielding one acetyl-CoA (for the citric acid cycle), one FADH(2), and one NADH (which donate electrons to the respiratory chain for ATP production) (PubMed:29915090). These cycles repeat until the chain is fully degraded to acetyl-CoA units (PubMed:29915090). Among the enzymes involved in this pathway, the trifunctional protein--responsible for the hydration, dehydrogenation, and thiolysis steps, shows specificity for long-chain fatty acids, such as those from dietary and stored fats (PubMed:30850536, PubMed:31604922). Mitochondrial trifunctional enzyme is a heterotetrameric complex composed of two proteins, the trifunctional enzyme subunit alpha/HADHA described here carries the 2,3-enoyl-CoA hydratase and the 3-hydroxyacyl-CoA dehydrogenase activities while the trifunctional enzyme subunit beta/HADHB bears the 3-ketoacyl-CoA thiolase activity (Probable) (PubMed:29915090, PubMed:30850536, PubMed:8135828). These activities have been experimentally confirmed on a few substrates derived from beta-oxidation of long-chain saturated fatty acids such as palmitate (hexadecanoate) and laurate (dodecanoate) (PubMed:1550553, PubMed:8135828, PubMed:8163672, PubMed:8651282). In addition, based on its established catalytic mechanism, and combined genetic interaction or mutant phenotype evidence, it is predicted to act also on other substrates, including long-chain unsaturated fatty acids such as oleate (9Z-octadecenoate), linoleate (9Z,12Z-octadecadienoate), linolenate (9Z,12Z,15Z-octadecatrienoate), and others (Probable) (PubMed:26474213). Independently of subunit beta, HADHA also exhibits a cardiolipin acyltransferase activity that participates in cardiolipin remodeling; cardiolipin is a major mitochondrial membrane phospholipid (PubMed:23152787, PubMed:31604922). HADHA may act downstream of Tafazzin/TAZ, that remodels monolysocardiolipin (MLCL) to a cardiolipin intermediate, and then HADHA may continue to remodel this species into mature tetralinoleoyl-cardiolipin (PubMed:31604922). Has also been proposed to act directly on MLCL; capable of acylating MLCL using different acyl-CoA substrates, with highest activity for oleoyl-CoA (PubMed:23152787). {ECO:0000269|PubMed:1550553, ECO:0000269|PubMed:23152787, ECO:0000269|PubMed:29915090, ECO:0000269|PubMed:30850536, ECO:0000269|PubMed:31604922, ECO:0000269|PubMed:8135828, ECO:0000269|PubMed:8163672, ECO:0000269|PubMed:8651282, ECO:0000303|PubMed:26474213, ECO:0000303|PubMed:29915090, ECO:0000303|PubMed:30850536, ECO:0000305|PubMed:38372965}.
uniprot
proteins
mass_dalton
83000
uniprot
proteins
pathway_participation
PATHWAY: Lipid metabolism; fatty acid beta-oxidation. {ECO:0000269|PubMed:1550553, ECO:0000269|PubMed:8135828}.
uniprot
proteins
protein_family
Enoyl-CoA hydratase/isomerase family; 3-hydroxyacyl-CoA dehydrogenase family
uniprot
proteins
pubmed
10075708
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
1550553
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
23152787
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26474213
uniprot
proteins
pubmed
29915090
uniprot
proteins
pubmed
30850536
uniprot
proteins
pubmed
31604922
uniprot
proteins
pubmed
32385292
uniprot
proteins
pubmed
38372965
uniprot
proteins
pubmed
7811722
uniprot
proteins
pubmed
7846063
uniprot
proteins
pubmed
7918661
uniprot
proteins
pubmed
8135828
uniprot
proteins
pubmed
8163672
uniprot
proteins
pubmed
8651282
uniprot
proteins
pubmed
8770876
uniprot
proteins
pubmed
9266371
uniprot
proteins
pubmed
9739053
uniprot
proteins
sequence_length
763
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:29915090}. Mitochondrion inner membrane {ECO:0000269|PubMed:29915090}. Note=Protein stability and association with mitochondrion inner membrane do not require HADHB. {ECO:0000269|PubMed:29915090}.
uniprot
proteins