Q64428 · ECHA_RAT
- ProteinTrifunctional enzyme subunit alpha, mitochondrial
- GeneHadha
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids763 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Mitochondrial trifunctional enzyme catalyzes the last three of the four reactions of the mitochondrial beta-oxidation pathway. The mitochondrial beta-oxidation pathway is the major energy-producing process in tissues and is performed through four consecutive reactions breaking down fatty acids into acetyl-CoA. Among the enzymes involved in this pathway, the trifunctional enzyme exhibits specificity for long-chain fatty acids. 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. Independently of the subunit beta, the trifunctional enzyme subunit alpha/HADHA also has a monolysocardiolipin acyltransferase activity. It acylates monolysocardiolipin into cardiolipin, a major mitochondrial membrane phospholipid which plays a key role in apoptosis and supports mitochondrial respiratory chain complexes in the generation of ATP. Allows the acylation of monolysocardiolipin with different acyl-CoA substrates including oleoyl-CoA for which it displays the highest activity.
Catalytic activity
- a (3S)-3-hydroxyacyl-CoA = a (2E)-enoyl-CoA + H2OThis reaction proceeds in the backward direction.
- (3S)-hydroxyoctanoyl-CoA = (2E)-octenoyl-CoA + H2OThis reaction proceeds in the backward direction.
- (3S)-3-hydroxydodecanoyl-CoA = (2E)-dodecenoyl-CoA + H2OThis reaction proceeds in the backward direction.
- (3S)-hydroxyhexadecanoyl-CoA = (2E)-hexadecenoyl-CoA + H2OThis reaction proceeds in the backward direction.
- (3S)-hydroxyoctanoyl-CoA + NAD+ = 3-oxooctanoyl-CoA + H+ + NADHThis reaction proceeds in the forward direction.
- (3S)-hydroxydecanoyl-CoA + NAD+ = 3-oxodecanoyl-CoA + H+ + NADHThis reaction proceeds in the forward direction.
- (3S)-3-hydroxydodecanoyl-CoA + NAD+ = 3-oxododecanoyl-CoA + H+ + NADHThis reaction proceeds in the forward direction.
- (3S)-hydroxytetradecanoyl-CoA + NAD+ = 3-oxotetradecanoyl-CoA + H+ + NADHThis reaction proceeds in the forward direction.
- (3S)-hydroxyhexadecanoyl-CoA + NAD+ = 3-oxohexadecanoyl-CoA + H+ + NADHThis reaction proceeds in the forward direction.
- 1'-[1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-3'-[1-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-glycerol + hexadecanoyl-CoA = 1'-[1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-3'-[1-(9Z,12Z-octadecadienoyl)-2-hexadecanoyl-sn-glycero-3-phospho]-glycerol + CoAThis reaction proceeds in the forward direction.
- (9Z)-octadecenoyl-CoA + 1'-[1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-3'-[1-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-glycerol = 1'-[1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-3'-[1-(9Z,12Z-octadecadienoyl)-2-(9Z-octadecenoyl)-sn-glycero-3-phospho]-glycerol + CoAThis reaction proceeds in the forward direction.
- (9Z,12Z)-octadecadienoyl-CoA + 1'-[1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-3'-[1-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-glycerol = 1',3'-bis-[1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-glycerol + CoAThis reaction proceeds in the forward direction.
Pathway
Lipid metabolism; fatty acid beta-oxidation.
Features
Showing features for site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 151 | Important for long-chain enoyl-CoA hydratase activity | ||||
Sequence: E | ||||||
Site | 173 | Important for long-chain enoyl-CoA hydratase activity | ||||
Sequence: E | ||||||
Site | 498 | Important for hydroxyacyl-coenzyme A dehydrogenase activity | ||||
Sequence: H | ||||||
Active site | 510 | For hydroxyacyl-coenzyme A dehydrogenase activity | ||||
Sequence: E |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | mitochondrial fatty acid beta-oxidation multienzyme complex | |
Cellular Component | mitochondrial inner membrane | |
Cellular Component | mitochondrial nucleoid | |
Cellular Component | mitochondrion | |
Molecular Function | 3-hydroxyacyl-CoA dehydratase activity | |
Molecular Function | 3-hydroxyacyl-CoA dehydrogenase activity | |
Molecular Function | acetyl-CoA C-acyltransferase activity | |
Molecular Function | enoyl-CoA hydratase activity | |
Molecular Function | fatty-acyl-CoA binding | |
Molecular Function | long-chain-3-hydroxyacyl-CoA dehydrogenase activity | |
Molecular Function | NAD binding | |
Molecular Function | NAD+ binding | |
Molecular Function | protein-containing complex binding | |
Biological Process | cardiolipin acyl-chain remodeling | |
Biological Process | fatty acid beta-oxidation | |
Biological Process | response to insulin | |
Biological Process | response to xenobiotic stimulus |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTrifunctional enzyme subunit alpha, mitochondrial
- Alternative names
Including 2 domains:
- Recommended nameLong-chain enoyl-CoA hydratase
- EC number
- Recommended nameLong chain 3-hydroxyacyl-CoA dehydrogenase
- EC number
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionQ64428
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Protein stability and association with mitochondrion inner membrane do not require HADHB.
Keywords
- Cellular component
PTM/Processing
Features
Showing features for transit peptide, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transit peptide | 1-36 | Mitochondrion | ||||
Sequence: MVASRAIGSLSRFSAFRILRSRGCICHSFTTSSALL | ||||||
Chain | PRO_0000007405 | 37-763 | Trifunctional enzyme subunit alpha, mitochondrial | |||
Sequence: SRTHINYGVKGDVAVIRINSPNSKVNTLNKEVQSEFVEVMNEIWANDQIRSAVLISSKPGCFVAGADINMLASCTTPQEAARISQEGQKMFEKLEKSPKPVVAAISGSCLGGGLELAIACQYRIATKDRKTVLGVPEVLLGILPGAGGTQRLPKMVGVPAAFDMMLTGRNIRADRAKKMGLVDQLVDPLGPGIKSPEERTIEYLEEVAVNFAKGLADRKVSAKQSKGLMEKLTSYAMTIPFVRQQVYKTVEEKVKKQTKGLYPAPLKIIDAVKTGLEQGNDAGYLAESEKFGELALTKESKALMGLYNGQVLCKKNKFGAPQKTVQQLAILGAGLMGAGIAQVSVDKGLKTLLKDTTVTGLGRGQQQVFKGLNDKVKKKALTSFERDSIFSNLIGQLDYKGFEKADMVIEAVFEDLAVKHKVLKEVESVTPEHCIFASNTSALPINQIAAVSQRPEKVIGMHYFSPVDKMQLLEIITTDKTSKDTTASAVAVGLKQGKVIIVVKDGPGFYTTRCLAPMMSEVIRILQEGVDPKKLDALTTGFGFPVGAATLADEVGIDVAQHVAEDLGKAFGERFGGGSVELLKLMVSKGFLGRKSGKGFYIYQSGSKNKNLNSEIDNILVNLRLPAKPEVSSDEDIQYRVITRFVNEAVLCLQEGILATPEEGDIGAVFGLGFPPCLGGPFRFVDLYGAQKVVDRLRKYESAYGTQFTPCQLLRDLANNSSKKFYQ | ||||||
Modified residue | 46 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 46 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 60 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 60 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 129 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 166 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 166 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 213 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 214 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 214 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 230 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 231 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 249 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 249 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 289 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 295 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 303 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 303 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 326 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 326 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 334 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 334 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 350 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 350 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 353 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 395 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 399 | Omega-N-methylarginine | ||||
Sequence: R | ||||||
Modified residue | 406 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 406 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 411 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 411 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 415 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 419 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 436 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 436 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 440 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 460 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 460 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 505 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 505 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 519 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 519 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 540 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 569 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 569 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 620 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 634 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 644 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 644 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 646 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 650 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 664 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 664 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 728 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 728 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 735 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 759 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 759 | N6-succinyllysine; alternate | ||||
Sequence: K |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
Heterotetramer of 2 alpha/HADHA and 2 beta/HADHB subunits; forms the mitochondrial trifunctional enzyme (By similarity).
Also purified as higher order heterooligomers including a 4 alpha/HADHA and 4 beta/HADHB heterooligomer which physiological significance remains unclear (PubMed:1730633).
The mitochondrial trifunctional enzyme interacts with MTLN (By similarity).
Also purified as higher order heterooligomers including a 4 alpha/HADHA and 4 beta/HADHB heterooligomer which physiological significance remains unclear (PubMed:1730633).
The mitochondrial trifunctional enzyme interacts with MTLN (By similarity).
Protein-protein interaction databases
Structure
Family & Domains
Sequence similarities
In the N-terminal section; belongs to the enoyl-CoA hydratase/isomerase family.
In the central section; belongs to the 3-hydroxyacyl-CoA dehydrogenase family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length763
- Mass (Da)82,665
- Last updated2008-03-18 v2
- ChecksumA16648B82AE7D62E
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A8I6A8P4 | A0A8I6A8P4_RAT | Hadha | 718 |
Sequence caution
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
D16478 EMBL· GenBank· DDBJ | BAA03939.1 EMBL· GenBank· DDBJ | mRNA | Frameshift | |
BC091697 EMBL· GenBank· DDBJ | AAH91697.1 EMBL· GenBank· DDBJ | mRNA |