COX14

COX14
Identifiers
Aliases	COX14 , C12orf62, COX14 cytochrome c oxidase assembly factor, cytochrome c oxidase assembly factor, PCAG1, cytochrome c oxidase assembly factor MC4DN10
External IDs	OMIM: 614478 MGI: 1913629 HomoloGene: 50025 GeneCards: COX14
Gene location (Human)
Chr.	Chromosome 12 (human)
End	50,120,457 bp
Gene location (Mouse)
Chr.	Chromosome 15 (mouse)
End	99,627,413 bp
RNA expression pattern
	Top expressed in
	left ventricle; ; right adrenal gland; ; gastrocnemius muscle; ; anterior pituitary; ; left adrenal gland; ; islet of Langerhans; ; left coronary artery; ; right lobe of thyroid gland; ; left lobe of thyroid gland; ; right lobe of liver;
	Top expressed in
	extraocular muscle; ; digastric muscle; ; myocardium of ventricle; ; temporal muscle; ; morula; ; sternocleidomastoid muscle; ; soleus muscle; ; facial motor nucleus; ; cardiac muscles; ; right ventricle;
	More reference expression data
	n/a
Orthologs
	84987
	66379
	ENSG00000178449
	ENSMUSG00000023020
	Q96I36
	Q8BH51
	NM_001257133 ; NM_001257134 ; NM_032901
	NM_183256
	NP_001244062 ; NP_001244063 ; NP_116290
	NP_899079
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated August 17, 2023

Cytochrome c oxidase assembly factor COX14 is a protein that in humans is encoded by the COX14 gene. This gene encodes a small single-pass transmembrane protein that localizes to mitochondria. This protein may play a role in coordinating the early steps of cytochrome c oxidase (COX; also known as complex IV) subunit assembly and, in particular, the synthesis and assembly of the COX I subunit of the holoenzyme. Mutations in this gene have been associated with mitochondrial complex IV deficiency. Alternative splicing results in multiple transcript variants.^[5]

Structure

The COX14 gene is located on the q arm of chromosome 12 at position 13.12 and it spans 8,476 base pairs.^[5] The COX14 gene produces a 6.6 kDa protein composed of 57 amino acids.^[6]^[7] COX14 is a component of the enzyme MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, and the structure contains a central transmembrane domain.^[8]

Function

The COX14 gene encodes for a core protein component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, which is required for the proper regulation of complex IV assembly. Complex IV of the mitochondrial respiratory chain is essential in catalyzing the oxidation of cytochrome c by molecular oxygen. COX14 has been shown to contribute to the early stages of complex IV assembly by coelution with COX1 and COX4 for nucleation of the assembly. The protein participates in the coupling synthesis of COX1 followed by an assembly of nascent subunits into the holoenzyme complex IV.^[9]^[10]^[8] The knockdown of the protein COX14 involving small interfering RNA in regular human fibroblast has been shown to result in a complex IV defect with reduced activity.^[8]

Clinical significance

Variants of COX14 have been associated with the mitochondrial Complex IV deficiency, a deficiency in an enzyme complex of the mitochondrial respiratory chain which catalyzes the oxidation of cytochrome c utilizing molecular oxygen.^[11]^[9]^[10] The deficiency is characterized by heterogeneous phenotypes ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Other Clinical Manifestations include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, exercise intolerance, developmental delay, delayed motor development and mental retardation.^[12] A mutation in the homozygous missense mutation c.88G>A in the COX14 gene has resulted in the dysfunction of complex IV assembly and an unstable nascent enzyme complex.^[8]

Interactions

Like COA3, COX14 is a key component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex.^[13] In addition, it has interactions with proteins such as COX17, COX1, LMNA, COA3, SPPL2B, and others.^[14]^[9]

Related Research Articles

The enzyme cytochrome c oxidase or Complex IV, is a large transmembrane protein complex found in bacteria, archaea, and mitochondria of eukaryotes.

Cytochrome c oxidase II is a protein in eukaryotes that is encoded by the MT-CO2 gene. Cytochrome c oxidase subunit II, abbreviated COXII, COX2, COII, or MT-CO2, is the second subunit of cytochrome c oxidase. It is also one of the three mitochondrial DNA (mtDNA) encoded subunits of respiratory complex IV.

Surfeit locus protein 1 (SURF1) is a protein that in humans is encoded by the SURF1 gene. The protein encoded by SURF1 is a component of the mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex, which is involved in the regulation of cytochrome c oxidase assembly. Defects in this gene are a cause of Leigh syndrome, a severe neurological disorder that is commonly associated with systemic cytochrome c oxidase deficiency, and Charcot-Marie-Tooth disease 4K (CMT4K).

SCO2 cytochrome c oxidase assembly is a protein that in humans is encoded by the SCO2 gene. The encoded protein is one of the cytochrome c oxidase (COX)(Complex IV) assembly factors. Human COX is a multimeric protein complex that requires several assembly factors. Cytochrome c oxidase (COX) catalyzes the transfer of electrons from cytochrome c to molecular oxygen, which helps to maintain the proton gradient across the inner mitochondrial membrane that is necessary for aerobic ATP production. The encoded protein is a metallochaperone that is involved in the biogenesis of cytochrome c oxidase subunit II. Mutations in this gene are associated with fatal infantile encephalocardiomyopathy and myopia 6.

Protein SCO1 homolog, mitochondrial, also known as SCO1, cytochrome c oxidase assembly protein, is a protein that in humans is encoded by the SCO1 gene. SCO1 localizes predominantly to blood vessels, whereas SCO2 is barely detectable, as well as to tissues with high levels of oxidative phosphorylation. The expression of SCO2 is also much higher than that of SCO1 in muscle tissue, while SCO1 is expressed at higher levels in liver tissue than SCO2. Mutations in both SCO1 and SCO2 are associated with distinct clinical phenotypes as well as tissue-specific cytochrome c oxidase deficiency.

Cytochrome c oxidase subunit 4 isoform 2, mitochondrial is an enzyme that in humans is encoded by the COX4I2 gene. COX4I2 is a nuclear-encoded isoform of cytochrome c oxidase (COX) subunit 4. Cytochrome c oxidase is a multi-subunit enzyme complex that couples the transfer of electrons from cytochrome c to molecular oxygen and contributes to a proton electrochemical gradient across the inner mitochondrial membrane, acting as the terminal enzyme of the mitochondrial respiratory chain. Mutations in COX4I2 have been associated with exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis (EPIDACH).

Cytochrome c oxidase subunit 6B1 is an enzyme that in humans is encoded by the COX6B1 gene. Cytochrome c oxidase 6B1 is a subunit of the cytochrome c oxidase complex, also known as Complex IV, the last enzyme in the mitochondrial electron transport chain. Mutations of the COX6B1 gene are associated with severe infantile encephalomyopathy and mitochondrial complex IV deficiency (MT-C4D).

Protoheme IX farnesyltransferase, mitochondrial is an enzyme that in humans is encoded by the COX10 gene. Cytochrome c oxidase (COX), the terminal component of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. This component is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, and the nuclear-encoded subunits may function in the regulation and assembly of the complex. This nuclear gene, COX10, encodes heme A: farnesyltransferase, which is not a structural subunit but required for the expression of functional COX and functions in the maturation of the heme A prosthetic group of COX. A gene mutation, which results in the substitution of a lysine for an asparagine (N204K), is identified to be responsible for cytochrome c oxidase deficiency. In addition, this gene is disrupted in patients with CMT1A duplication and with HNPP deletion.

Cytochrome c oxidase subunit 7B, mitochondrial (COX7B) is an enzyme that in humans is encoded by the COX7B gene. COX7B is a nuclear-encoded subunit of cytochrome c oxidase (COX). Cytochrome c oxidase is a multi-subunit enzyme complex that couples the transfer of electrons from cytochrome c to molecular oxygen and contributes to a proton electrochemical gradient across the inner mitochondrial membrane, acting as the terminal enzyme of the mitochondrial respiratory chain. Work with Oryzias latices has linked disruptions in COX7B with microphthalmia with linear skin lesions (MLS), microcephaly, and mitochondrial disease. Clinically, mutations in COX7B have been associated with linear skin defects with multiple congenital anomalies.

Cytochrome c oxidase assembly protein COX15 homolog (COX15), also known as heme A synthase, is a protein that in humans is encoded by the COX15 gene. This protein localizes to the inner mitochondrial membrane and involved in heme A biosynthesis. COX15 is also part of a three-component mono-oxygenase that catalyses the hydroxylation of the methyl group at position eight of the protoheme molecule. Mutations in this gene has been reported in patients with hypertrophic cardiomyopathy as well as Leigh syndrome, and characterized by delayed onset of symptoms, hypotonia, feeding difficulties, failure to thrive, motor regression, and brain stem signs.

Cytochrome c oxidase subunit 8A (COX8A) is a protein that in humans is encoded by the COX8A gene. Cytochrome c oxidase 8A is a subunit of the cytochrome c oxidase complex, also known as Complex IV. Mutations in the COX8A gene have been associated with complex IV deficiency with Leigh syndrome and epilepsy.

Mitochondrial import inner membrane translocase subunit TIM16 also known as presequence translocated-associated motor subunit PAM16, mitochondria-associated granulocyte macrophage CSF-signaling molecule, or presequence translocated-associated motor subunit PAM16 is a protein that in humans is encoded by the PAM16 gene.

Chromosome 19 open reading frame 70, also known as QIL1, MICOS complex subunit MIC13 (MIC13) or Protein P117 is a protein that in humans is encoded by the C19orf70 gene.

Cytochrome c oxidase assembly factor 3, also known as Coiled-coil domain-containing protein 56, or Mitochondrial translation regulation assembly intermediate of cytochrome c oxidase protein of 12 kDa is a protein that in humans is encoded by the COA3 gene. This gene encodes a member of the cytochrome c oxidase assembly factor family. Studies of a related gene in fly suggest that the encoded protein is localized to mitochondria and is essential for cytochrome c oxidase function.

Cytochrome c oxidase assembly factor 5 is a protein that in humans is encoded by the COA5 gene. This gene encodes an ortholog of yeast Pet191, which in yeast is a subunit of a large oligomeric complex associated with the mitochondrial inner membrane, and required for the assembly of the cytochrome c oxidase complex. Mutations in this gene are associated with mitochondrial complex IV deficiency.

Cytochrome c oxidase assembly factor 7 (putative) (COA7), also known as Beta-lactamase hap-like protein, Respiratory chain assembly factor 1 (RESA1), Sel1 repeat-containing protein 1 (SELRC1), or C1orf163 is a protein that in humans is encoded by the COA7 gene. The protein encoded by COA7 is an assembly factor important for the mitochondrial respiratory chain. Mutations in COA7 have been associated with cytochrome c oxidase deficiency resulting in spinocerebellar ataxia with axonal neuropathy type 3 and mitochondrial myopathy.

Cytochrome c oxidase assembly factor COX20 is a protein that in humans is encoded by the COX20 gene. This gene encodes a protein that plays a role in the assembly of cytochrome c oxidase, an important component of the respiratory pathway. Mutations in this gene can cause mitochondrial complex IV deficiency. There are multiple pseudogenes for this gene. Alternative splicing results in multiple transcript variants.

Cytochrome c oxidase assembly factor 6 is a protein that in humans is encoded by the COA6 gene. Mitochondrial respiratory chain Complex IV, or cytochrome c oxidase, is the component of the respiratory chain that catalyzes the transfer of electrons from intermembrane space cytochrome c to molecular oxygen in the matrix and as a consequence contributes to the proton gradient involved in mitochondrial ATP synthesis. The COA6 gene encodes an assembly factor for mitochondrial complex IV and is a member of the cytochrome c oxidase subunit 6B family. This protein is located in the intermembrane space, associating with SCO2 and COX2. It stabilizes newly formed COX2 and is part of the mitochondrial copper relay system. Mutations in this gene result in fatal infantile cardioencephalomyopathy.

PET100 homolog is a protein that in humans is encoded by the PET100 gene. Mitochondrial complex IV, or cytochrome c oxidase, is a large transmembrane protein complex that is part of the respiratory electron transport chain of mitochondria. The small protein encoded by the PET100 gene plays a role in the biogenesis of mitochondrial complex IV. This protein localizes to the inner mitochondrial membrane and is exposed to the intermembrane space. Mutations in this gene are associated with mitochondrial complex IV deficiency. This gene has a pseudogene on chromosome 3. Alternative splicing results in multiple transcript variants.

Centrosomal protein 89, also known as Centrosomal protein of 89 kDa (CEP89), Centrosomal protein 123 (CEP123), or Coiled-coil domain-containing protein 123 is a protein that in humans is encoded by the CEP89 gene.

References

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