Cytochrome c oxidase assembly factor 3, also known as Coiled-coil domain-containing protein 56, or Mitochondrial

translation Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...

regulation assembly intermediate of

cytochrome c oxidase The enzyme cytochrome c oxidase or Complex IV, (was , now reclassified as a translocasEC 7.1.1.9 is a large transmembrane protein complex found in bacteria, archaea, and mitochondria of eukaryotes. It is the last enzyme in the respiratory elect ...

protein of 12 kDa is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

that in humans is encoded by the COA3

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. This gene encodes a member of the

assembly factor family. Studies of a related gene in fly suggest that the encoded protein is localized to mitochondria and is essential for

function.

Structure

The ''COA3'' gene is located on the

q arm In genetics, a locus (plural loci) is a specific, fixed position on a chromosome where a particular gene or genetic marker is located. Each chromosome carries many genes, with each gene occupying a different position or locus; in humans, the total ...

chromosome 17 Chromosome 17 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 17 spans more than 83 million base pairs (the building material of DNA) and represents between 2.5 and 3% of the total D ...

at position 21.2 and it spans 1,107 base pairs. The ''COA3'' gene produces a 7.8 kDa protein composed of 71 amino acids. COA3 is a component of the enzyme MITRAC (mitochondrial

regulation assembly intermediate of

complex) complex, and the structure contains a

C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...

coiled-coil domain as well as a central single pass transmembrane domain.

Function

The ''COA3'' gene encodes for a Core

of the MITRAC (mitochondrial

regulation assembly intermediate of

complex) complex. The MITRAC complex is essential in the assembly of

(complex IV) of the

mitochondrial respiratory chain An electron transport chain (ETC) is a series of protein complexes and other molecules that transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples thi ...

, which is responsible for the

catalysis Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

of oxidation of cytochrome c by

molecular oxygen There are several known allotropes of oxygen. The most familiar is molecular oxygen (O2), present at significant levels in Earth's atmosphere and also known as dioxygen or triplet oxygen. Another is the highly reactive ozone (O3). Others are: * ...

. The MITRAC complex regulates both

of mitochondrial encoded components and assembly of nuclear-encoded components imported in mitochondrion. In addition, COA3 is required for efficient

MT-CO1 Cytochrome c oxidase I (COX1) also known as mitochondrially encoded cytochrome c oxidase I (MT-CO1) is a protein that in humans is encoded by the ''MT-CO1'' gene. In other eukaryotes, the gene is called ''COX1'', ''CO1'', or ''COI''. Cytochrom ...

and assembly of the

complex IV The enzyme cytochrome c oxidase or Complex IV, (was , now reclassified as a translocasEC 7.1.1.9 is a large transmembrane protein complex found in bacteria, archaea, and mitochondria of eukaryotes. It is the last enzyme in the respiratory electr ...

Clinical significance

Variants of ''COA3'' have been associated with the mitochonrdial

Complex IV The enzyme cytochrome c oxidase or Complex IV, (was , now reclassified as a translocasEC 7.1.1.9 is a large transmembrane protein complex found in bacteria, archaea, and mitochondria of eukaryotes. It is the last enzyme in the respiratory electr ...

deficiency, a deficiency in an enzyme complex of the

which catalyzes the oxidation of cytochrome c utilizing

. The deficiency is characterized by heterogeneous

phenotypes In genetics, the phenotype () is the set of observable characteristics or phenotypic trait, traits of an organism. The term covers the organism's morphology (biology), morphology or physical form and structure, its Developmental biology, dev ...

ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Other Clinical Manifestations include hypertrophic cardiomyopathy,

hepatomegaly Hepatomegaly is the condition of having an enlarged liver. It is a non-specific medical sign having many causes, which can broadly be broken down into infection, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdo ...

and

liver dysfunction Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Signs and symptoms Some of the s ...

hypotonia Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases ...

, muscle weakness,

exercise intolerance Exercise intolerance is a condition of inability or decreased ability to perform physical exercise at the normally expected level or duration for people of that age, size, sex, and muscle mass. It also includes experiences of unusually severe pos ...

developmental delay Global developmental delay is an umbrella term used when children are significantly delayed in their cognitive and physical development. It can be diagnosed when a child is delayed in one or more milestones, categorised into motor skills, speech ...

, delayed motor development and

mental retardation Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation, Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signifi ...

. A missense mutation of c.215A>G in the ''COA3'' gene has been found to result in a severe decrease in protein levels with symptoms of

and

peripheral neuropathy Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or or ...

Interactions

Like COX14, COA3 is a key component of the MITRAC (mitochondrial

regulation assembly intermediate of

complex) complex. In addition, it has interactions with proteins such as

, COX1,

SMIM20 Small integral membrane protein (SMIM) 20 is a protein that in humans is encoded by the SMIM20 gene. SMIM20 acts as a prohormone to the peptide hormone phoenixin which was discovered for the first time in 2013 in rodent sensory ganglia. In the s ...

SURF1 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 (MITRAC ...

, TIMM21, and others.

Structure

Function

Clinical significance

Interactions

References

Further reading