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 A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is use ...

electron transport 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 th ...

. Mutations of the COX6B1 gene are associated with severe infantile

encephalomyopathy Encephalopathy (; from grc, ἐνκέφαλος "brain" + πάθος "suffering") means any disorder or disease of the brain, especially chronic Neurodegeneration, degenerative conditions. In modern usage, encephalopathy does not refer to a sin ...

and mitochondrial complex IV deficiency (MT-C4D).

Structure

The COX6B1 gene, located on the q arm of chromosome 19 in position 13.1, contains 4

exons An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence ...

and is 10,562

base pairs A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...

in length. The COX6B1 protein weighs 10 kDa and is composed of 86 amino acids. The protein is a subunit of Complex IV, a heteromeric complex consisting of 3 catalytic subunits encoded by

genes, and multiple structural subunits encoded by nuclear genes.

Function

Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. It 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 be involved in the regulation and assembly of the complex. This nuclear gene encodes subunit VIb. Three pseudogenes COX6BP-1, COX6BP-2 and COX6BP-3 have been found on chromosomes 7, 17 and 22q13.1-13.2, respectively. Summary reaction: : 4 Fe²⁺-cytochrome ''c'' + 8 H⁺_in + O₂ → 4 Fe³⁺-cytochrome ''c'' + 2 H₂O + 4 H⁺_out

Clinical significance

Mutations affecting the ''COX6B1'' gene are associated with mitochondrial complex IV deficiency (MT-C4D), a disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations, 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 affecting several tissues and organs. Features include hypertrophic

cardiomyopathy Cardiomyopathy is a group of diseases that affect the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. A ...

, 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, and mental retardation. Some affected individuals manifest a fatal

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 ...

resulting in neonatal death. A subset of patients manifest Leigh's syndrome. A ''COX6B1'' R20C missense mutation has been linked to complex IV deficiency with

, hydrocephalus, and hypertrophic cardiomyopathy.

Interactions

COX6B1 has been shown to have 548 binary protein-protein interactions including 547 co-complex interactions.

References

External links