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
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
. 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 biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
in this gene have been associated with
mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
l
complex IV deficiency.
Alternative splicing
Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be ...
results in multiple
transcript variants.
[
]
Structure
The ''COX14'' gene is located on the
q arm of
chromosome 12 at position 13.12 and it spans 8,476 base pairs.
The ''COX14'' gene produces a 6.6 kDa protein composed of 57
amino acids
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
.
[
] 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.
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
The cytochrome complex, or cyt ''c'', is a small hemeprotein found loosely associated with the inner membrane of the mitochondrion. It belongs to the cytochrome c family of proteins and plays a major role in cell apoptosis. Cytochrome c is hig ...
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.
[
][
] The knockdown of the protein COX14 involving
small interfering RNA in regular human
fibroblast
A fibroblast is a type of cell (biology), biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and plays a critical role in wound ...
has been shown to result in a
complex IV defect with reduced activity.
Clinical significance
Variants of ''COX14'' have been associated with the
mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
l
Complex IV deficiency, a deficiency in an enzyme complex of the
mitochondrial respiratory chain which catalyzes the oxidation of
cytochrome c
The cytochrome complex, or cyt ''c'', is a small hemeprotein found loosely associated with the inner membrane of the mitochondrion. It belongs to the cytochrome c family of proteins and plays a major role in cell apoptosis. Cytochrome c is hig ...
utilizing
molecular oxygen.
[
] The deficiency is characterized by
heterogeneous
Homogeneity and heterogeneity are concepts often used in the sciences and statistics relating to the uniformity of a substance or organism. A material or image that is homogeneous is uniform in composition or character (i.e. color, shape, siz ...
phenotypes ranging from isolated
myopathy
In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. This results in muscular weakness. ''Myopathy'' means muscle disease (Greek : myo- ''muscle'' + patheia '' -pathy'' : ''suffering''). This meani ...
to severe
multisystem disease
A systemic disease is one that affects a number of Organ (anatomy), organs and Tissue (biology), tissues, or affects the Human body, body as a whole.
Examples
* Mastocytosis, including mast cell activation syndrome and eosinophilic esophagitis
...
affecting several tissues and organs. Other Clinical Manifestations include
hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy (HCM, or HOCM when obstructive) is a condition in which the heart becomes thickened without an obvious cause. The parts of the heart most commonly affected are the interventricular septum and the ventricles. This r ...
,
hepatomegaly and
liver dysfunction,
hypotonia,
muscle weakness
Muscle weakness is a lack of muscle strength. Its causes are many and can be divided into conditions that have either true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, includi ...
,
exercise intolerance,
developmental delay, delayed
motor development
A motor neuron (or motoneuron or efferent neuron) is a neuron whose cell body is located in the motor cortex, brainstem or the spinal cord, and whose axon (fiber) projects to the spinal cord or outside of the spinal cord to directly or indirectly ...
and
mental retardation.
[
]
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.
Interactions
Like
COA3, COX14 is a key component of the MITRAC (mitochondrial
translation regulation assembly intermediate of
cytochrome c oxidase complex) complex.
[
] In addition, it has interactions with proteins such as
COX17
Cytochrome c oxidase copper chaperone is a protein that in humans is encoded by the ''COX17'' gene.
Function
Cytochrome c oxidase (COX), the terminal component of the electron transport chain, mitochondrial respiratory chain, catalyzes the e ...
,
COX1,
LMNA,
COA3,
SPPL2B
Signal peptide peptidase-like 2B, also known as SPPL2B, is a human gene.
This gene is a member of the signal peptide peptidase-like protease (SPPL) family with the conserved active site motifs 'YD' and 'GxGD' in adjacent transmembrane domains (TM ...
, and others.
[
]
References
Further reading
*
*
{{NLM content
Human proteins
Genes on human chromosome 12