SCO2 cytochrome c oxidase assembly (also known as SCO2 homolog, mitochondrial and SCO cytochrome oxidase deficient homolog 2) 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 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 ...

the transfer of electrons from

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 ...

to molecular oxygen, which helps to maintain the proton gradient across the inner mitochondrial membrane that is necessary for aerobic

ATP ATP may refer to: Companies and organizations * Association of Tennis Professionals, men's professional tennis governing body * American Technical Publishers, employee-owned publishing company * ', a Danish pension * Armenia Tree Project, non ...

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 Near-sightedness, also known as myopia and short-sightedness, is an eye disease where light focuses in front of, instead of on, the retina. As a result, distant objects appear blurry while close objects appear normal. Other symptoms may include ...

Structure

The ''SCO2'' gene is located on the q arm of chromosome 22 at position 13.33 and it spans 2,871 base pairs. The ''SCO2'' gene produces a 15.1 kDa protein composed of 136

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 ...

. The protein contains an

N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...

mitochondrial targeting presequence of 41

, and shares identity with the yeast protein in regions between glycine-102 and glycine-242 in human SCO2. SCO2 is a subunit of the enzyme Mammalian cytochrome c oxidase (COX)(Complex IV).

Function

The ''SCO2'' gene encodes for a protein essential for the assembly and function of Mammalian cytochrome c oxidase (COX)(Complex IV) of the mitochondrial respiratory chain. SCO2 acts as a metallochaperone involved in the biogenesis of cytochrome c oxidase subunit II, an essential subunit of Complex IV which transfers the electrons from

to the bimetallic center of the catalytic subunit 1 via its binuclear copper A center. The biogenesis involves the transport of copper to the Cu(A) site on the cytochrome c oxidase subunit II leading to the proper synthesis and maturation of the subunit. In addition, SCO2 acts as a thiol- disulfide oxidoreductase to regulate the redox state of the cysteines in SCO1 during maturation of the cytochrome c oxidase subunit II. The maturation and synthesis of cytochrome c oxidase subunit II is required for the function of Mammalian cytochrome c oxidase (COX)(Complex IV). Complex IV, a multimeric protein complex that requires several assembly factors,

the transfer of reducing equivalents from

to molecular oxygen and pumps protons across the inner mitochondrial membrane.

Clinical significance

Mutations in ''SCO2'' that alter the regulation of copper and oxygen have been found to be associated with fatal infantile Cardioencephalomyopathy due to cytochrome c oxidase deficiency 1 (CEMCOX1), Myopia 6 (MYP6), and Leigh syndrome (LS). CEMCOX1 is characterized by disorders characterized by hypotonia, developmental delay,

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 ...

, lactic acidosis, gliosis, neuronal loss in basal ganglia,

brainstem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is cont ...

and spinal cord, and cytochrome c oxidase deficiency. Myopia 6 is characterized by a refractive error of the eye, in which parallel rays from a distant object come to focus in front of the retina, vision being better for near objects than for far. Lastly, leigh syndrome is an early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the

, thalamus, basal ganglia,

cerebellum The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cerebel ...

and spinal cord. Clinical manifestations may include

psychomotor retardation Psychomotor may refer to: * Psychomotor learning, the relationship between cognitive functions and physical movement * Psychomotor retardation, a slowing-down of thought and a reduction of physical movements in an individual * Psychomotor agitatio ...

, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, and dysphagia. A pathogenic mutation of G1541A in a patient has shown strong evidence in neonatal hypotonia with an SMA 1 phenotype, and has been found to result in less COX deficiencies. A mutation of 1602T>G has been found to result in rapidly progressive disease phenotypes. Other pathogenic mutations have included a missense mutation of E140K, a nonsense mutation Q53X, and a 1541G > A mutation which resulted in a severe protein instability.

Interactions

In addition to co-complex interactions, SCO2 has been found to interact with

COA6 Cytochrome c oxidase assembly factor 6 is a protein that in humans is encoded by the ''COA6'' gene. Electron transport chain#In mitochondria, Mitochondrial respiratory chain Cytochrome c oxidase, Complex IV, or cytochrome c oxidase, is the compone ...

, THEM177 in a

COX20 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. Mutat ...

-dependent manner,

, COX16, SCO1, and others.

References

External links