Q9H845 · ACAD9_HUMAN

  • Protein
    Complex I assembly factor ACAD9, mitochondrial
  • Gene
    ACAD9
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

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-CoA
    This 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-CoA
    This 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

FAD (UniProtKB | Rhea| CHEBI:57692 )

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
2.8 μMhexadecanoyl-CoA
0.7 μM(9Z)-hexadecenoyl-CoA
2.1 μM(9Z,12Z)-octadecadienoyl-CoA

Features

Showing features for active site.

TypeIDPosition(s)Description
Active site426Proton acceptor

GO annotations

AspectTerm
Cellular Componentdendrite
Cellular Componentmitochondrial inner membrane
Cellular Componentmitochondrial membrane
Cellular Componentmitochondrion
Cellular Componentnucleus
Molecular Functionacyl-CoA dehydrogenase activity
Molecular Functionflavin adenine dinucleotide binding
Molecular Functionlong-chain fatty acyl-CoA dehydrogenase activity
Molecular Functionmedium-chain fatty acyl-CoA dehydrogenase activity
Biological Processlong-chain fatty acid metabolic process
Biological Processmedium-chain fatty acid metabolic process
Biological Processmitochondrial respiratory chain complex I assembly

Keywords

Enzyme and pathway databases

Chemistry

Names & Taxonomy

Protein names

  • Recommended name
    Complex I assembly factor ACAD9, mitochondrial
  • Alternative names
    • Acyl-CoA dehydrogenase family member 9
      (ACAD-9
      ) (EC:1.3.8.-
      ) . EC:1.3.8.- (UniProtKB | ENZYME | Rhea)

Gene names

    • Name
      ACAD9

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    Q9H845
  • Secondary accessions
    • D3DNB8
    • Q8WXX3

Proteomes

Organism-specific databases

Subcellular Location

Mitochondrion inner membrane
; Peripheral membrane protein
Note: Essentially associated with membranes.

Keywords

Disease & Variants

Involvement in disease

Mitochondrial complex I deficiency, nuclear type 20 (MC1DN20)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    An 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 also
    MIM:611126
Natural variants in MC1DN20
Variant IDPosition(s)ChangeDescription
VAR_07189244F>Iin MC1DN20; dbSNP:rs387907041
VAR_071893127R>Kin MC1DN20
VAR_071894193R>Win MC1DN20; uncertain significance; dbSNP:rs377547811
VAR_071895220A>Vin MC1DN20
VAR_071896234S>Fin MC1DN20; uncertain significance
VAR_071897266R>Qin MC1DN20; dbSNP:rs387907042
VAR_076177271C>Gin MC1DN20
VAR_071898303G>Sin MC1DN20; uncertain significance; dbSNP:rs143383023
VAR_071899326A>Tin MC1DN20; uncertain significance; dbSNP:rs115532916
VAR_076178384V>Min MC1DN20; dbSNP:rs1447947184
VAR_071900413E>Kin MC1DN20; uncertain significance; dbSNP:rs149753643
VAR_071901414R>Cin MC1DN20; dbSNP:rs777282696
VAR_071902417R>Cin MC1DN20; dbSNP:rs368949613
VAR_071903469R>Win MC1DN20; dbSNP:rs139145143
VAR_071904518R>Hin MC1DN20; dbSNP:rs781149699
VAR_071905532R>Win MC1DN20; dbSNP:rs377022708
VAR_076179606L>Hin MC1DN20

Features

Showing features for natural variant, mutagenesis.

TypeIDPosition(s)Description
Natural variantVAR_07189244in MC1DN20; dbSNP:rs387907041
Natural variantVAR_071893127in MC1DN20
Natural variantVAR_071894193in MC1DN20; uncertain significance; dbSNP:rs377547811
Natural variantVAR_071895220in MC1DN20
Natural variantVAR_071896234in MC1DN20; uncertain significance
Natural variantVAR_071897266in MC1DN20; dbSNP:rs387907042
Natural variantVAR_076177271in MC1DN20
Natural variantVAR_071898303in MC1DN20; uncertain significance; dbSNP:rs143383023
Natural variantVAR_071899326in MC1DN20; uncertain significance; dbSNP:rs115532916
Natural variantVAR_076178384in MC1DN20; dbSNP:rs1447947184
Natural variantVAR_071900413in MC1DN20; uncertain significance; dbSNP:rs149753643
Natural variantVAR_071901414in MC1DN20; dbSNP:rs777282696
Natural variantVAR_071902417in MC1DN20; dbSNP:rs368949613
Mutagenesis426Loss of long-chain-acyl-CoA dehydrogenase activity. Does not affect mitochondrial complex I assembly.
Natural variantVAR_071903469in MC1DN20; dbSNP:rs139145143
Natural variantVAR_033459477in dbSNP:rs4494951
Natural variantVAR_071904518in MC1DN20; dbSNP:rs781149699
Natural variantVAR_071905532in MC1DN20; dbSNP:rs377022708
Natural variantVAR_076179606in MC1DN20

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.

Go to variant viewer

Keywords

Organism-specific databases

Miscellaneous

Genetic variation databases

PTM/Processing

Features

Showing features for transit peptide, chain, modified residue, modified residue (large scale data).

TypeIDPosition(s)SourceDescription
Transit peptide1-37UniProtMitochondrion
ChainPRO_000000052438-621UniProtComplex I assembly factor ACAD9, mitochondrial
Modified residue41UniProtN6-acetyllysine
Modified residue92UniProtN6-succinyllysine
Modified residue (large scale data)187PRIDEPhosphoserine
Modified residue (large scale data)461PRIDEPhosphoserine
Modified residue478UniProtPhosphothreonine
Modified residue521UniProtN6-acetyllysine; alternate
Modified residue521UniProtN6-succinyllysine; alternate

Keywords

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).

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).
View interactors in UniProtKB
View CPX-6322 in Complex Portal

Protein-protein interaction databases

Miscellaneous

Family & Domains

Sequence similarities

Belongs to the acyl-CoA dehydrogenase family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    621
  • Mass (Da)
    68,760
  • Last updated
    2001-03-01 v1
  • Checksum
    064BCE0378877F54
MSGCGLFLRTTAAARACRGLVVSTANRRLLRTSPPVRAFAKELFLGKIKKKEVFPFPEVSQDELNEINQFLGPVEKFFTEEVDSRKIDQEGKIPDETLEKLKSLGLFGLQVPEEYGGLGFSNTMYSRLGEIISMDGSITVTLAAHQAIGLKGIILAGTEEQKAKYLPKLASGEHIAAFCLTEPASGSDAASIRSRATLSEDKKHYILNGSKVWITNGGLANIFTVFAKTEVVDSDGSVKDKITAFIVERDFGGVTNGKPEDKLGIRGSNTCEVHFENTKIPVENILGEVGDGFKVAMNILNSGRFSMGSVVAGLLKRLIEMTAEYACTRKQFNKRLSEFGLIQEKFALMAQKAYVMESMTYLTAGMLDQPGFPDCSIEAAMVKVFSSEAAWQCVSEALQILGGLGYTRDYPYERILRDTRILLIFEGTNEILRMYIALTGLQHAGRILTTRIHELKQAKVSTVMDTVGRRLRDSLGRTVDLGLTGNHGVVHPSLADSANKFEENTYCFGRTVETLLLRFGKTIMEEQLVLKRVANILINLYGMTAVLSRASRSIRIGLRNHDHEVLLANTFCVEAYLQNLFSLSQLDKYAPENLDEQIKKVSQQILEKRAYICAHPLDRTC

Computationally mapped potential isoform sequences

There are 14 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
D6RJA8D6RJA8_HUMANACAD993
D6RGK6D6RGK6_HUMANACAD969
D6RDK9D6RDK9_HUMANACAD993
D6RCD8D6RCD8_HUMANACAD9173
A0A7P0T9N9A0A7P0T9N9_HUMANACAD9388
D6R9Z3D6R9Z3_HUMANACAD999
A0A7P0T8U3A0A7P0T8U3_HUMANACAD9643
A0A7P0T871A0A7P0T871_HUMANACAD9660
A0A7P0T7Z1A0A7P0T7Z1_HUMANACAD9626
H0Y8Z9H0Y8Z9_HUMANACAD9384
A0A7P0TB58A0A7P0TB58_HUMANACAD9476
A0A7P0TB68A0A7P0TB68_HUMANACAD9234
A0A7P0Z450A0A7P0Z450_HUMANACAD9240
Q9H9W4Q9H9W4_HUMANACAD9498

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict397in Ref. 1; AAL56011

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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