HADHA

Protein identityUniProt · HPA

UniProt accession

P40939

Gene

HADHA

Ensembl

ENSG00000084754

Chromosome

2

Canonical length

763 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Mitochondria

OverviewNCBI Gene

This gene encodes the alpha subunit of the mitochondrial trifunctional protein, which catalyzes the last three steps of mitochondrial beta-oxidation of long chain fatty acids. The mitochondrial membrane-bound heterocomplex is composed of four alpha and four beta subunits, with the alpha subunit catalyzing the 3-hydroxyacyl-CoA dehydrogenase and enoyl-CoA hydratase activities. Mutations in this gene result in trifunctional protein deficiency or LCHAD deficiency. The genes of the alpha and beta subunits of the mitochondrial trifunctional protein are located adjacent to each other in the human genome in a head-to-head orientation. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

763 residues, UniProt reviewed canonical sequence.

>P40939|HADHA
     1  MVACRAIGIL SRFSAFRILR SRGYICRNFT GSSALLTRTH INYGVKGDVA VVRINSPNSK
    61  VNTLSKELHS EFSEVMNEIW ASDQIRSAVL ISSKPGCFIA GADINMLAAC KTLQEVTQLS
   121  QEAQRIVEKL EKSTKPIVAA INGSCLGGGL EVAISCQYRI ATKDRKTVLG TPEVLLGALP
   181  GAGGTQRLPK MVGVPAALDM MLTGRSIRAD RAKKMGLVDQ LVEPLGPGLK PPEERTIEYL
   241  EEVAITFAKG LADKKISPKR DKGLVEKLTA YAMTIPFVRQ QVYKKVEEKV RKQTKGLYPA
   301  PLKIIDVVKT GIEQGSDAGY LCESQKFGEL VMTKESKALM GLYHGQVLCK KNKFGAPQKD
   361  VKHLAILGAG LMGAGIAQVS VDKGLKTILK DATLTALDRG QQQVFKGLND KVKKKALTSF
   421  ERDSIFSNLT GQLDYQGFEK ADMVIEAVFE DLSLKHRVLK EVEAVIPDHC IFASNTSALP
   481  ISEIAAVSKR PEKVIGMHYF SPVDKMQLLE IITTEKTSKD TSASAVAVGL KQGKVIIVVK
   541  DGPGFYTTRC LAPMMSEVIR ILQEGVDPKK LDSLTTSFGF PVGAATLVDE VGVDVAKHVA
   601  EDLGKVFGER FGGGNPELLT QMVSKGFLGR KSGKGFYIYQ EGVKRKDLNS DMDSILASLK
   661  LPPKSEVSSD EDIQFRLVTR FVNEAVMCLQ EGILATPAEG DIGAVFGLGF PPCLGGPFRF
   721  VDLYGAQKIV DRLKKYEAAY GKQFTPCQLL ADHANSPNKK FYQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HADHA can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.24

Highest tissue expression

468 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HADHA.

Disease | AllUniProt

Conditions HADHA is implicated in, by any mechanism.

• Mitochondrial trifunctional protein deficiency 1 (MTPD1) MIM:609015
• Long-chain 3-hydroxyl-CoA dehydrogenase deficiency (LCHAD deficiency) MIM:609016
• Maternal acute fatty liver of pregnancy (AFLP) MIM:609016

Disease | GeneticClinVar

239 pathogenic / likely-pathogenic of 1,196 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency
• Mitochondrial trifunctional protein deficiency
• Mitochondrial trifunctional protein deficiency 1
• Thyroid cancer, nonmedullary, 1
• HADHA-related disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.62

gnomAD pLI

0

gnomAD missense Z

0.82

DepMap mean gene effect

-0.22

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cardiolipin acyl-chain remodeling
• fatty acid beta-oxidation
• response to insulin

Molecular functions

• (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity
• 3-hydroxyacyl-CoA dehydratase activity
• acetyl-CoA C-acetyltransferase activity
• enoyl-CoA hydratase activity
• long-chain (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity
• long-chain fatty acyl-CoA hydrolase activity
• NAD+ binding

Cellular components

• mitochondrial fatty acid beta-oxidation multienzyme complex
• mitochondrial inner membrane
• mitochondrial nucleoid
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Enoyl-CoA hydratase/isomerase-like domain
• 3-hydroxyacyl-CoA dehydrogenase, C-terminal
• 3-hydroxyacyl-CoA dehydrogenase, NAD binding
• 3-hydroxyacyl-CoA dehydrogenase, conserved site
• 6-phosphogluconate dehydrogenase-like, C-terminal domain superfamily
• Enoyl-CoA hydratase/isomerase, conserved site
• ClpP/crotonase-like domain superfamily
• NAD(P)-binding domain superfamily
• Enoyl-CoA hydratase/isomerase
• 3-hydroxyacyl-CoA dehydrogenase, C-terminal domain
• 3-hydroxyacyl-CoA dehydrogenase, NAD binding domain
• Fatty acid oxidation complex, alpha subunit, mitochondrial
• Fatty acid oxidation complex subunit alpha

KeywordsUniProt

• Acetylation
• Fatty acid metabolism
• Lipid metabolism
• Lyase
• Membrane
• Methylation
• Mitochondrion
• Mitochondrion inner membrane
• Multifunctional enzyme
• NAD
• Oxidoreductase
• Phosphoprotein
• Transferase
• Transit peptide

InteractionsUniProt · HPA

Protein binding partners of HADHA in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MTLN
• CD74
• CSNK2A2
• HADHB
• MAP1LC3B