NDUFAF3

NDUFAF3
Identifiers
Aliases	NDUFAF3, 2P1, C3orf60, E3-3, NADH:ubiquinone oxidoreductase complex assembly factor 3, MC1DN18
External IDs	OMIM: 612911; MGI: 1913956; HomoloGene: 32460; GeneCards: NDUFAF3; OMA:NDUFAF3 - orthologs
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3p21.31 Start 49,020,459 bp[1] End 49,023,495 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9|9 F2 Start 108,442,736 bp[2] End 108,444,633 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in left testis right testis apex of heart right auricle C1 segment right adrenal gland anterior pituitary left adrenal gland left adrenal cortex right adrenal cortex Top expressed in left ventricle interventricular septum spermatocyte adrenal gland proximal tubule right kidney striatum of neuraxis white adipose tissue dentate gyrus of hippocampal formation granule cell testicle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding Cellular component mitochondrial inner membrane membrane mitochondrion nucleus Biological process mitochondrial respiratory chain complex I assembly Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 25915 66706 Ensembl ENSG00000178057 ENSMUSG00000070283 UniProt Q9BU61 Q9JKL4 RefSeq (mRNA) NM_199417 NM_199069 NM_199070 NM_199073 NM_199074 NM_023247 RefSeq (protein) NP_951032 NP_951033 NP_951047 NP_951056 NP_075736 Location (UCSC) Chr 3: 49.02 – 49.02 Mb Chr 9: 108.44 – 108.44 Mb PubMed search [3] [4]
Wikidata
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NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 3, also known as 2P1, E3-3, or C3orf60, is a protein that in humans is encoded by the NDUFAF3 gene.^[5][6][7] NDUFAF3 is a mitochondrial assembly protein involved in the assembly of NADH dehydrogenase (ubiquinone) also known as complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.^[8][9] Mutations in this gene have been associated with severe complex I deficiency and Leigh syndrome.^[5][9][10]

NDUFAF3 is located on the p arm of chromosome 3 in position 21.31 and has 7 exons.^[5] The NDUFAF3 gene produces a 20.4 kDa protein composed of 184 amino acids.^[11][12] NDUFAF3 encodes two isoforms which have a common DUF498 domain. Predictions indicate that isoform A contains an additional 35 amino acid N-terminal sequence and is thus longer than isoform B. The extra sequence may be involved in mitochondrial targeting, supporting NDUFAF3's function in mitochondrial assembly.^[9]

NADH:ubiquinone oxidoreductase (complex I) catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q) in the first step of the mitochondrial respiratory chain, resulting in the translocation of protons across the mitochondrial inner membrane.^[13] The NDUFAF3 gene encodes a mitochondrial complex I assembly protein that localizes to the mitochondrial inner membrane and interacts with complex I subunits and is important for the correct function of the mitochondrial respiratory chain.^[5][9]

NDUFAF3 colocalizes, comigrates to several assembly intermediates, and is codependent with NDUFAF4 from the early to late stages of complex I assembly. In addition to their close interactions with each other, NDUFAF3 and NDUFAF4 interact with NDUFS2, NDUFS3, NDUFS8, and NDUFA5 in a translation-dependent early assembly mechanism. It is also suggested that NDUFAF3 is involved in coupling mitochondrial translation with membrane insertion in the process of complex I assembly.^[9]

Mutations in NDUFAF3 have been associated with complex I deficiency and mitochondrial diseases. These disorders are a result of the dysfunction of the mitochondrial respiratory chain and can cause a wide range of clinical manifestations from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease.^[6][7] Mutations have included the homozygous variants c.494C > T; p.(Ala165Val),^[10] c.365 G→C resulting in R122P, and c.2 T→C resulting in M1T.^[9] Clinically, NDUFAF3 mutations have been associated with Leigh syndrome^[10] and severe complex I deficiency.^[9] Some common signs and symptoms include lactic acidosis, nystagmus, hypotonia, and cerebral lesions.^[9][10]

In addition to co-complexes, NDUFAF3 has protein-protein interactions with NDUFAF4^[14] and SNRPA.^[15]

• Human NDUFAF3 genome location and NDUFAF3 gene details page in the UCSC Genome Browser.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.