Cytochrome c oxidase subunit 7B, mitochondrial (COX7B) is an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
that in humans is encoded by the ''COX7B''
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 ...
.
COX7B is a
nuclear
Nuclear may refer to:
Physics
Relating to the nucleus of the atom:
* Nuclear engineering
*Nuclear physics
*Nuclear power
*Nuclear reactor
*Nuclear weapon
*Nuclear medicine
*Radiation therapy
*Nuclear warfare
Mathematics
*Nuclear space
*Nuclear ...
-encoded subunit 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 ...
(COX). Cytochrome c oxidase (
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 ...
) is a multi-subunit enzyme complex that couples the transfer of
electron
The electron ( or ) is a subatomic particle with a negative one elementary electric charge. Electrons belong to the first generation of the lepton particle family,
and are generally thought to be elementary particles because they have no ...
s from
cytochrome c to molecular
oxygen
Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as ...
and contributes to a
proton electrochemical gradient
An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts, the chemical gradient, or difference in solute concentration across a membrane, and ...
across the
inner mitochondrial membrane
The inner mitochondrial membrane (IMM) is the mitochondrial membrane which separates the mitochondrial matrix from the intermembrane space.
Structure
The structure of the inner mitochondrial membrane is extensively folded and compartmentalized. ...
, acting as the terminal enzyme 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 ...
.
Work with
Oryzias latices has linked disruptions in COX7B with
microphthalmia with linear
skin lesions
A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this s ...
(MLS),
microcephaly
Microcephaly (from New Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it ...
, and
mitochondrial disease
Mitochondrial disease is a group of disorders caused by mitochondrial dysfunction. Mitochondria are the organelles that generate energy for the cell and are found in every cell of the human body except red blood cells. They convert the energy of ...
. Clinically,
mutation
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 replication, DNA or viral repl ...
s in ''COX7B'' have been associated with linear skin defects with multiple
congenital anomalies
A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can r ...
.
Structure
''COX7B'' 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 ...
of the
X chromosome
The X chromosome is one of the two sex-determining chromosomes (allosomes) in many organisms, including mammals (the other is the Y chromosome), and is found in both males and females. It is a part of the XY sex-determination system and XO sex ...
in position 21.1 and has 3
exons.
The ''COX7B'' gene produces a 9.2 kDa
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 ...
composed of 80
amino acid
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 a ...
s. COX7B is one of the nuclear-encoded polypeptide chains 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 ...
(COX), a
heteromer A heteromer is something that consists of different parts; the antonym of homomeric. Examples are:
Biology
* Spinal neurons that pass over to the opposite side of the spinal cord.
* A protein complex that contains two or more different polypeptide ...
ic complex consisting of 3 catalytic subunits encoded by
mitochondrial genes and multiple structural subunits encoded by
nuclear gene
A nuclear gene is a gene whose physical DNA nucleotide sequence is located in the cell nucleus of a eukaryote. The term is used to distinguish nuclear genes from genes found in mitochondria or chloroplasts. The vast majority of genes in eukary ...
s. The protein encoded by ''COX7B'' belongs to the cytochrome c oxidase VIIb family. ''COX7B'' has a 24 amino acid
transit peptide
A signal peptide (sometimes referred to as signal sequence, targeting signal, localization signal, localization sequence, transit peptide, leader sequence or leader peptide) is a short peptide (usually 16-30 amino acids long) present at the N-ter ...
domain from positions 1-24, an 8 amino acid topological
mitochondrial matrix
In the mitochondrion, the matrix is the space within the inner membrane. The word "matrix" stems from the fact that this space is viscous, compared to the relatively aqueous cytoplasm. The mitochondrial matrix contains the mitochondrial DNA, ribo ...
domain from positions 25–32, a helical, 27 amino acid
transmembrane domain
A transmembrane domain (TMD) is a membrane-spanning protein domain. TMDs generally adopt an alpha helix topological conformation, although some TMDs such as those in porins can adopt a different conformation. Because the interior of the lipid bi ...
from positions 33–59, and a 21 amino acid topological
intermembrane domain from positions 60–80.
''COX7B'' may also have several
pseudogenes on chromosomes
1,
2,
20 and
22.
Function
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 ...
(COX), the terminal enzyme 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 ...
, catalyzes the electron transfer from reduced
cytochrome c to
oxygen
Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as ...
. The mitochondrially-encoded subunits of COX function in
electron transfer
Electron transfer (ET) occurs when an electron relocates from an atom or molecule to another such chemical entity. ET is a mechanistic description of certain kinds of redox reactions involving transfer of electrons.
Electrochemical processes ar ...
, while the nuclear-encoded subunits may be involved in the regulation and assembly of the complex. The ''COX7B'' nuclear gene encodes subunit 7B, which is located on the
inner mitochondrial membrane
The inner mitochondrial membrane (IMM) is the mitochondrial membrane which separates the mitochondrial matrix from the intermembrane space.
Structure
The structure of the inner mitochondrial membrane is extensively folded and compartmentalized. ...
in association with several other proteins encompassing the COX complex. It is found in all tissues and has been shown to be highly similar to bovine COX VIIb protein.
COX7B is believed to be important for COX assembly and activity, the function of
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 ...
, and the proper development of the
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
in
vertebrate
Vertebrates () comprise all animal taxa within the subphylum Vertebrata () (chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, with c ...
s.
Model organisms
Oryzias latices (also known as
medaka
The Japanese rice fish (''Oryzias latipes''), also known as the medaka, is a member of genus ''Oryzias'' ( ricefish), the only genus in the subfamily Oryziinae. This small (up to about ) native of East Asia is a denizen of rice paddies, marshes, ...
) is a Japanese rice fish that has been used as a
model organism in COX7B studies. By using a
morpholino
A Morpholino, also known as a Morpholino oligomer and as a phosphorodiamidate Morpholino oligomer (PMO), is a type of oligomer molecule (colloquially, an oligo) used in molecular biology to modify gene expression. Its molecular structure contain ...
knockdown technique, COX7B has been shown to be indispensable for COX assembly, COX activity, and mitochondrial respiration. Additionally, the
down-regulation
In the biological context of organisms' production of gene products, downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external stimulus. The complementary pr ...
of an
ortholog
Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a s ...
of COX7B has suggested that there may be an association between COX7B dysfunction and
microphthalmia with linear
skin lesions
A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this s ...
(MLS),
microcephaly
Microcephaly (from New Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it ...
, and
mitochondrial disease
Mitochondrial disease is a group of disorders caused by mitochondrial dysfunction. Mitochondria are the organelles that generate energy for the cell and are found in every cell of the human body except red blood cells. They convert the energy of ...
. Work with Oryzias latices could also indicate an evolutionary conserved role for the mitochondrial respiratory chain complexes in
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
development.
Clinical significance
Mutations in ''COX7B'' have been associated with linear skin defects with multiple
congenital anomalies
A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can r ...
. This disorder is a distinct form of
aplasia cutis congenita
Aplasia cutis congenita is a rare disorder characterized by congenital absence of skin. Ilona J. Frieden classified ACC in 1986 into 9 groups on the basis of location of the lesions and associated congenital anomalies.Moss C, Shahidulla H. Naevi a ...
presenting as multiple linear skin defects on the face and neck associated with poor growth and
short stature
Short stature refers to a height of a human which is below typical. Whether a person is considered short depends on the context. Because of the lack of preciseness, there is often disagreement about the degree of shortness that should be called ' ...
,
microcephaly
Microcephaly (from New Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it ...
, and
facial dysmorphism
A dysmorphic feature is an abnormal difference in body structure. It can be an isolated finding in an otherwise normal individual, or it can be related to a congenital disorder, genetic syndrome or birth defect. Dysmorphology is the study of dysm ...
. Additional clinical features include
intellectual disability
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 signif ...
,
nail dystrophy
A nail disease or onychosis is a disease or deformity of the nail. Although the nail is a structure produced by the skin and is a skin appendage, nail diseases have a distinct classification as they have their own signs and symptoms which may r ...
, cardiac abnormalities,
diaphragmatic hernia
Diaphragmatic hernia is a defect or hole in the diaphragm that allows the abdominal contents to move into the chest cavity. Treatment is usually surgical.
Types
* Congenital diaphragmatic hernia
** Morgagni's hernia
** Bochdalek hernia
* Hiatal ...
,
genitourinary
The genitourinary system, or urogenital system, are the organs of the reproductive system and the urinary system. These are grouped together because of their proximity to each other, their common embryological origin and the use of common pathw ...
abnormalities,
pale optic discs and altered
visual-evoked potentials,
agenesis of the corpus callosum, and other
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
abnormalities.
The ''COX7B'' mutations associated with disease include c.196delC, a
heterozygous
Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism.
Mo ...
mutation leading to a
frameshift
Ribosomal frameshifting, also known as translational frameshifting or translational recoding, is a biological phenomenon that occurs during translation that results in the production of multiple, unique proteins from a single mRNA. The process can ...
in exon 3, c.41-2A>G, a heterozygous
splice mutation in a novel acceptor site in
intron 1, and c.55C>T, a heterozygous
nonsense mutation
In genetics, a nonsense mutation is a point mutation in a sequence of DNA that results in a premature stop codon, or a ''nonsense codon'' in the transcribed mRNA, and in leading to a truncated, incomplete, and usually nonfunctional protein produc ...
in exon 2. Additionally, experiments with
Oryzias latices suggest ''COX7B'' may be associated with
microphthalmia with linear skin lesions (MLS), an
X-linked, dominant, male-lethal
mitochondrial disorder
Mitochondrial disease is a group of disorders caused by mitochondrial dysfunction. Mitochondria are the organelles that generate energy for the cell and are found in every cell of the human body except red blood cells. They convert the energy of ...
.
Interactions
COX7B has been shown to have 6 binary
protein-protein interactions including 3 co-complex interactions.
GNMT,
MYB
MyB (Hangul: 마이비) was a South Korean girl group formed by Maroo Entertainment. The group debuted on August 25, 2015 with ''My Oh My'' and made a comeback on November 13, 2015 with ''Ddoddo'', before the group officially disbanded on December ...
,
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 ...
, HSCB, and
SLC25A13 have all been found to interact with COX7B.
References
External links
*
Further reading
*
*
*
*
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