Q9H845 · ACAD9_HUMAN
- ProteinComplex I assembly factor ACAD9, mitochondrial
- GeneACAD9
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids621 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
As part of the MCIA complex, primarily participates in the assembly of the mitochondrial complex I and therefore plays a role in oxidative phosphorylation (PubMed:20816094, PubMed:24158852, PubMed:32320651).
This moonlighting protein has also a dehydrogenase activity toward a broad range of substrates with greater specificity for long-chain unsaturated acyl-CoAs (PubMed:12359260, PubMed:16020546, PubMed:21237683, PubMed:24158852).
However, in vivo, it does not seem to play a primary role in fatty acid oxidation (PubMed:20816094, PubMed:24158852).
In addition, the function in complex I assembly is independent of the dehydrogenase activity of the protein (PubMed:24158852).
This moonlighting protein has also a dehydrogenase activity toward a broad range of substrates with greater specificity for long-chain unsaturated acyl-CoAs (PubMed:12359260, PubMed:16020546, PubMed:21237683, PubMed:24158852).
However, in vivo, it does not seem to play a primary role in fatty acid oxidation (PubMed:20816094, PubMed:24158852).
In addition, the function in complex I assembly is independent of the dehydrogenase activity of the protein (PubMed:24158852).
Catalytic activity
- eicosanoyl-CoA + H+ + oxidized [electron-transfer flavoprotein] = (2E)-eicosenoyl-CoA + reduced [electron-transfer flavoprotein]This reaction proceeds in the forward direction.
- H+ + octadecanoyl-CoA + oxidized [electron-transfer flavoprotein] = (2E)-octadecenoyl-CoA + reduced [electron-transfer flavoprotein]This reaction proceeds in the forward direction.
- H+ + hexadecanoyl-CoA + oxidized [electron-transfer flavoprotein] = (2E)-hexadecenoyl-CoA + reduced [electron-transfer flavoprotein]This reaction proceeds in the forward direction.
- decanoyl-CoA + H+ + oxidized [electron-transfer flavoprotein] = (2E)-decenoyl-CoA + reduced [electron-transfer flavoprotein]This reaction proceeds in the forward direction.
- H+ + nonanoyl-CoA + oxidized [electron-transfer flavoprotein] = (2E)-nonenoyl-CoA + reduced [electron-transfer flavoprotein]This reaction proceeds in the forward direction.
- H+ + oxidized [electron-transfer flavoprotein] + pentadecanoyl-CoA = (2E)-pentadecenoyl-CoA + reduced [electron-transfer flavoprotein]This reaction proceeds in the forward direction.
- H+ + oxidized [electron-transfer flavoprotein] + undecanoyl-CoA = reduced [electron-transfer flavoprotein] + trans-2-undecenoyl-CoAThis reaction proceeds in the forward direction.
- (9Z)-hexadecenoyl-CoA + H+ + oxidized [electron-transfer flavoprotein] = (2E,9Z)-hexadecadienoyl-CoA + reduced [electron-transfer flavoprotein]This reaction proceeds in the forward direction.
- H+ + heptadecanoyl-CoA + oxidized [electron-transfer flavoprotein] = reduced [electron-transfer flavoprotein] + trans-2-heptadecenoyl-CoAThis reaction proceeds in the forward direction.
- (9E)-octadecenoyl-CoA + H+ + oxidized [electron-transfer flavoprotein] = (2E,9E)-octadecadienoyl-CoA + reduced [electron-transfer flavoprotein]This reaction proceeds in the forward direction.
- (9Z)-octadecenoyl-CoA + H+ + oxidized [electron-transfer flavoprotein] = (2E,9Z)-octadecadienoyl-CoA + reduced [electron-transfer flavoprotein]This reaction proceeds in the forward direction.
- (9Z,12Z)-octadecadienoyl-CoA + H+ + oxidized [electron-transfer flavoprotein] = (2E,9Z,12Z)-octadecatrienoyl-CoA + reduced [electron-transfer flavoprotein]This reaction proceeds in the forward direction.
- (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA + H+ + oxidized [electron-transfer flavoprotein] = (2E,4Z,7Z,10Z,13Z,16Z,19Z)-docosaheptaenoyl-CoA + reduced [electron-transfer flavoprotein]This reaction proceeds in the forward direction.
- H+ + oxidized [electron-transfer flavoprotein] + tetradecanoyl-CoA = (2E)-tetradecenoyl-CoA + reduced [electron-transfer flavoprotein]This reaction proceeds in the forward direction.
Cofactor
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
2.8 μM | hexadecanoyl-CoA | |||||
0.7 μM | (9Z)-hexadecenoyl-CoA | |||||
2.1 μM | (9Z,12Z)-octadecadienoyl-CoA |
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 426 | Proton acceptor | ||||
Sequence: E |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | dendrite | |
Cellular Component | mitochondrial inner membrane | |
Cellular Component | mitochondrial membrane | |
Cellular Component | mitochondrion | |
Cellular Component | nucleus | |
Molecular Function | acyl-CoA dehydrogenase activity | |
Molecular Function | flavin adenine dinucleotide binding | |
Molecular Function | long-chain fatty acyl-CoA dehydrogenase activity | |
Molecular Function | medium-chain fatty acyl-CoA dehydrogenase activity | |
Biological Process | long-chain fatty acid metabolic process | |
Biological Process | medium-chain fatty acid metabolic process | |
Biological Process | mitochondrial respiratory chain complex I assembly |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Chemistry
Names & Taxonomy
Protein names
- Recommended nameComplex I assembly factor ACAD9, mitochondrial
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9H845
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Mitochondrion inner membrane ; Peripheral membrane protein
Note: Essentially associated with membranes.
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Mitochondrial complex I deficiency, nuclear type 20 (MC1DN20)
- Note
- DescriptionAn autosomal recessive metabolic disorder associated with mitochondrial complex I deficiency, resulting in multisystemic and variable manifestations. Clinical features include infantile onset of acute metabolic acidosis, Reye-like episodes (brain edema and vomiting that may rapidly progress to seizures, coma and death), exercise intolerance, hypertrophic cardiomyopathy, liver failure, muscle weakness, and neurologic dysfunction.
- See alsoMIM:611126
Natural variants in MC1DN20
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_071892 | 44 | F>I | in MC1DN20; dbSNP:rs387907041 | |
VAR_071893 | 127 | R>K | in MC1DN20 | |
VAR_071894 | 193 | R>W | in MC1DN20; uncertain significance; dbSNP:rs377547811 | |
VAR_071895 | 220 | A>V | in MC1DN20 | |
VAR_071896 | 234 | S>F | in MC1DN20; uncertain significance | |
VAR_071897 | 266 | R>Q | in MC1DN20; dbSNP:rs387907042 | |
VAR_076177 | 271 | C>G | in MC1DN20 | |
VAR_071898 | 303 | G>S | in MC1DN20; uncertain significance; dbSNP:rs143383023 | |
VAR_071899 | 326 | A>T | in MC1DN20; uncertain significance; dbSNP:rs115532916 | |
VAR_076178 | 384 | V>M | in MC1DN20; dbSNP:rs1447947184 | |
VAR_071900 | 413 | E>K | in MC1DN20; uncertain significance; dbSNP:rs149753643 | |
VAR_071901 | 414 | R>C | in MC1DN20; dbSNP:rs777282696 | |
VAR_071902 | 417 | R>C | in MC1DN20; dbSNP:rs368949613 | |
VAR_071903 | 469 | R>W | in MC1DN20; dbSNP:rs139145143 | |
VAR_071904 | 518 | R>H | in MC1DN20; dbSNP:rs781149699 | |
VAR_071905 | 532 | R>W | in MC1DN20; dbSNP:rs377022708 | |
VAR_076179 | 606 | L>H | in MC1DN20 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_071892 | 44 | in MC1DN20; dbSNP:rs387907041 | |||
Sequence: F → I | ||||||
Natural variant | VAR_071893 | 127 | in MC1DN20 | |||
Sequence: R → K | ||||||
Natural variant | VAR_071894 | 193 | in MC1DN20; uncertain significance; dbSNP:rs377547811 | |||
Sequence: R → W | ||||||
Natural variant | VAR_071895 | 220 | in MC1DN20 | |||
Sequence: A → V | ||||||
Natural variant | VAR_071896 | 234 | in MC1DN20; uncertain significance | |||
Sequence: S → F | ||||||
Natural variant | VAR_071897 | 266 | in MC1DN20; dbSNP:rs387907042 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_076177 | 271 | in MC1DN20 | |||
Sequence: C → G | ||||||
Natural variant | VAR_071898 | 303 | in MC1DN20; uncertain significance; dbSNP:rs143383023 | |||
Sequence: G → S | ||||||
Natural variant | VAR_071899 | 326 | in MC1DN20; uncertain significance; dbSNP:rs115532916 | |||
Sequence: A → T | ||||||
Natural variant | VAR_076178 | 384 | in MC1DN20; dbSNP:rs1447947184 | |||
Sequence: V → M | ||||||
Natural variant | VAR_071900 | 413 | in MC1DN20; uncertain significance; dbSNP:rs149753643 | |||
Sequence: E → K | ||||||
Natural variant | VAR_071901 | 414 | in MC1DN20; dbSNP:rs777282696 | |||
Sequence: R → C | ||||||
Natural variant | VAR_071902 | 417 | in MC1DN20; dbSNP:rs368949613 | |||
Sequence: R → C | ||||||
Mutagenesis | 426 | Loss of long-chain-acyl-CoA dehydrogenase activity. Does not affect mitochondrial complex I assembly. | ||||
Sequence: E → Q | ||||||
Natural variant | VAR_071903 | 469 | in MC1DN20; dbSNP:rs139145143 | |||
Sequence: R → W | ||||||
Natural variant | VAR_033459 | 477 | in dbSNP:rs4494951 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_071904 | 518 | in MC1DN20; dbSNP:rs781149699 | |||
Sequence: R → H | ||||||
Natural variant | VAR_071905 | 532 | in MC1DN20; dbSNP:rs377022708 | |||
Sequence: R → W | ||||||
Natural variant | VAR_076179 | 606 | in MC1DN20 | |||
Sequence: L → H |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 787 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for transit peptide, chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Transit peptide | 1-37 | UniProt | Mitochondrion | ||||
Sequence: MSGCGLFLRTTAAARACRGLVVSTANRRLLRTSPPVR | |||||||
Chain | PRO_0000000524 | 38-621 | UniProt | Complex I assembly factor ACAD9, mitochondrial | |||
Sequence: AFAKELFLGKIKKKEVFPFPEVSQDELNEINQFLGPVEKFFTEEVDSRKIDQEGKIPDETLEKLKSLGLFGLQVPEEYGGLGFSNTMYSRLGEIISMDGSITVTLAAHQAIGLKGIILAGTEEQKAKYLPKLASGEHIAAFCLTEPASGSDAASIRSRATLSEDKKHYILNGSKVWITNGGLANIFTVFAKTEVVDSDGSVKDKITAFIVERDFGGVTNGKPEDKLGIRGSNTCEVHFENTKIPVENILGEVGDGFKVAMNILNSGRFSMGSVVAGLLKRLIEMTAEYACTRKQFNKRLSEFGLIQEKFALMAQKAYVMESMTYLTAGMLDQPGFPDCSIEAAMVKVFSSEAAWQCVSEALQILGGLGYTRDYPYERILRDTRILLIFEGTNEILRMYIALTGLQHAGRILTTRIHELKQAKVSTVMDTVGRRLRDSLGRTVDLGLTGNHGVVHPSLADSANKFEENTYCFGRTVETLLLRFGKTIMEEQLVLKRVANILINLYGMTAVLSRASRSIRIGLRNHDHEVLLANTFCVEAYLQNLFSLSQLDKYAPENLDEQIKKVSQQILEKRAYICAHPLDRTC | |||||||
Modified residue | 41 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 92 | UniProt | N6-succinyllysine | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 187 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 461 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 478 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 521 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 521 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Ubiquitously expressed in most normal human tissues and cancer cell lines with high level of expression in heart, skeletal muscles, brain, kidney and liver (PubMed:12359260).
In the cerebellum uniquely expressed in the granular layer (at protein level) (PubMed:21237683).
In the cerebellum uniquely expressed in the granular layer (at protein level) (PubMed:21237683).
Gene expression databases
Organism-specific databases
Interaction
Subunit
Homodimer (PubMed:16020546).
Interacts with NDUFAF1 and ECSIT (PubMed:20816094).
Part of the mitochondrial complex I assembly/MCIA complex that comprises at least the core subunits TMEM126B, NDUFAF1, ECSIT and ACAD9 and complement subunits such as COA1 and TMEM186 (PubMed:32320651).
Interacts with TMEM70 and TMEM242 (PubMed:33753518).
Interacts with NDUFAF1 and ECSIT (PubMed:20816094).
Part of the mitochondrial complex I assembly/MCIA complex that comprises at least the core subunits TMEM126B, NDUFAF1, ECSIT and ACAD9 and complement subunits such as COA1 and TMEM186 (PubMed:32320651).
Interacts with TMEM70 and TMEM242 (PubMed:33753518).
Protein-protein interaction databases
Miscellaneous
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length621
- Mass (Da)68,760
- Last updated2001-03-01 v1
- Checksum064BCE0378877F54
Computationally mapped potential isoform sequences
There are 14 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
D6RJA8 | D6RJA8_HUMAN | ACAD9 | 93 | ||
D6RGK6 | D6RGK6_HUMAN | ACAD9 | 69 | ||
D6RDK9 | D6RDK9_HUMAN | ACAD9 | 93 | ||
D6RCD8 | D6RCD8_HUMAN | ACAD9 | 173 | ||
A0A7P0T9N9 | A0A7P0T9N9_HUMAN | ACAD9 | 388 | ||
D6R9Z3 | D6R9Z3_HUMAN | ACAD9 | 99 | ||
A0A7P0T8U3 | A0A7P0T8U3_HUMAN | ACAD9 | 643 | ||
A0A7P0T871 | A0A7P0T871_HUMAN | ACAD9 | 660 | ||
A0A7P0T7Z1 | A0A7P0T7Z1_HUMAN | ACAD9 | 626 | ||
H0Y8Z9 | H0Y8Z9_HUMAN | ACAD9 | 384 | ||
A0A7P0TB58 | A0A7P0TB58_HUMAN | ACAD9 | 476 | ||
A0A7P0TB68 | A0A7P0TB68_HUMAN | ACAD9 | 234 | ||
A0A7P0Z450 | A0A7P0Z450_HUMAN | ACAD9 | 240 | ||
Q9H9W4 | Q9H9W4_HUMAN | ACAD9 | 498 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 397 | in Ref. 1; AAL56011 | ||||
Sequence: A → V |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF327351 EMBL· GenBank· DDBJ | AAL56011.1 EMBL· GenBank· DDBJ | mRNA | ||
AK024012 EMBL· GenBank· DDBJ | BAB14775.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471052 EMBL· GenBank· DDBJ | EAW79295.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471052 EMBL· GenBank· DDBJ | EAW79296.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC013354 EMBL· GenBank· DDBJ | AAH13354.1 EMBL· GenBank· DDBJ | mRNA | ||
BC007970 EMBL· GenBank· DDBJ | AAH07970.1 EMBL· GenBank· DDBJ | mRNA |