Cytochrome b-c1 complex subunit 2, mitochondrial (UQCRC2), also known as QCR2, UQCR2, or MC3DN5 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''UQCRC2''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. The product of ''UQCRC2'' is a subunit of the respiratory chain protein Ubiquinol Cytochrome c Reductase (UQCR,

Complex III Complex commonly refers to: * Complexity, the behaviour of a system whose components interact in multiple ways so possible interactions are difficult to describe ** Complex system, a system composed of many components which may interact with each ...

or Cytochrome bc1 complex), which consists of the products of one mitochondrially encoded gene, MTCYTB (mitochondrial

cytochrome b Cytochrome b is a protein found in the membranes of aerobic cells. In eukaryotic mitochondria (inner membrane) and in aerobic prokaryotes, cytochrome b is a component of respiratory chain complex III () — also known as the bc1 complex or ubiq ...

) and ten

nuclear gene A nuclear gene is a gene whose DNA sequence is located within the cell nucleus of a eukaryotic organism. These genes are distinguished from extranuclear genes, such as those found in the genomes of mitochondria and chloroplasts, which reside ou ...

s: UQCRC1, UQCRC2,

Cytochrome c1 Cytochrome C1 (also known as Complex III subunit 4) is a protein encoded by the '' CYC1'' gene. Cytochrome is a heme-containing subunit of the cytochrome b-c1 complex, which accepts electrons from Rieske protein and transfers electrons to cytoc ...

, UQCRFS1 (

Rieske protein Rieske proteins are iron–sulfur protein (ISP) components of cytochrome ''bc''1 complexes and cytochrome b6f complexes and are responsible for electron transfer in some biological systems. John S. Rieske and co-workers first discovered the pro ...

), UQCRB, "11kDa protein",

UQCRH Cytochrome b-c1 complex subunit 6, mitochondrial is a protein that in humans is encoded by the ''UQCRH'' gene. Its gene product is a subunit of the respiratory chain protein ubiquinol-cytochrome-c reductase, Ubiquinol Cytochrome c Reductase (UQC ...

(cyt c1 Hinge protein),

Rieske Protein Rieske proteins are iron–sulfur protein (ISP) components of cytochrome ''bc''1 complexes and cytochrome b6f complexes and are responsible for electron transfer in some biological systems. John S. Rieske and co-workers first discovered the pro ...

presequence, "cyt. c1 associated protein", and "Rieske-associated protein." Defects in ''UQCRC2'' are associated with mitochondrial complex III deficiency, nuclear, type 5.

Structure

''UQCRC2'' is located on the

p arm In genetics, a locus (: 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 numb ...

chromosome 16 Chromosome 16 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 16 spans about 90 million base pairs (the building material of DNA) and represents just under 3% of the total DNA in cel ...

in position 12.2 and has 14

exon 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 ...

s. The ''UQCRC2'' gene produces a 48.4 kDa protein composed of 453

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

s. UQCRC2 belongs to the

peptidase A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products. They do ...

M16 family and UQCRC2/QCR2 subfamily. UQCRC2 has a

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-t ...

domain. Ubiquinol Cytochrome c Reductase ( b-c1 complex) contains 11 subunits: 3 respiratory subunits (

cytochrome c1 Cytochrome C1 (also known as Complex III subunit 4) is a protein encoded by the '' CYC1'' gene. Cytochrome is a heme-containing subunit of the cytochrome b-c1 complex, which accepts electrons from Rieske protein and transfers electrons to cytoc ...

and Rieske/ UQCRFS1), 2 core proteins ( UQCRC1/QCR1 and UQCRC2/QCR2) and 6 low-molecular weight proteins (

/QCR6, UQCRB/QCR7, UQCRQ/QCR8, UQCR10/QCR9, UQCR11/QCR10 and a cleavage product of Rieske/UQCRFS1). UQCRC2 is part of the

hydrophobic In chemistry, hydrophobicity is the chemical property of a molecule (called a hydrophobe) that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, thu ...

core of the b-c1 complex and is necessary for the stabilization of Ubiquinol Cytochrome c Reductase.

Function

The protein encoded by this gene is located in the

mitochondrion A mitochondrion () is an organelle found in the cell (biology), cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosine tri ...

, where it is part of the ubiquinol-cytochrome c reductase complex (also known as

complex III Complex commonly refers to: * Complexity, the behaviour of a system whose components interact in multiple ways so possible interactions are difficult to describe ** Complex system, a system composed of many components which may interact with each ...

). This complex constitutes a part of the

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

. The core protein UQCRC2 is required for the assembly and stabilization of the complex.

Clinical Significance

Variants of ''UQCRC2'' have been associated with mitochondrial complex III deficiency, nuclear, type 5. Mitochondrial complex III deficiency nuclear type 5 is a disorder of the mitochondrial respiratory chain resulting in a highly variable

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological propert ...

depending on which tissues are affected. Clinical features include mitochondrial

encephalopathy Encephalopathy (; ) means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of overall brain dysfunction; this syndrome ...

psychomotor retardation Psychomotor retardation involves a slowing down of thought and a reduction of physical movements in an individual. It can cause a visible slowing of physical and emotional reactions, including speech and affect. Psychomotor retardation is most ...

ataxia Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...

, severe

failure to thrive Failure to thrive (FTT), also known as weight faltering or faltering growth, indicates insufficient weight gain or absence of appropriate physical growth in children. FTT is usually defined in terms of weight, and can be evaluated either by a low ...

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. Liver diseases File:Ground glas ...

, renal tubulopathy,

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, includ ...

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 ...

lactic acidosis Lactic acidosis refers to the process leading to the production of lactate by anaerobic metabolism. It increases hydrogen ion concentration tending to the state of acidemia or low pH. The result can be detected with high levels of lactate and lo ...

and

hypoglycemia Hypoglycemia (American English), also spelled hypoglycaemia or hypoglycæmia (British English), sometimes called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's tria ...

. Homozygous mutations resulting in a change from

Arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidinium, guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) a ...

Tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromat ...

at position 183 have been associated with mitochondrial complex III deficiency due to UQCRC2 dysfunction.

Autosomal recessive inheritance In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

has been proposed as a transmission pattern.

Interactions

UQCRC2 has 98 protein-protein interactions with 90 of them being co-complex interactions. CAC1A, QCR1, UQCRC1, CACNA1A,

STOM Stomatin also known as human erythrocyte integral membrane protein band 7 is a protein that in humans is encoded by the ''STOM'' gene. Clinical significance Stomatin is a 31 kDa integral membrane protein, named after the rare human haemolyti ...

, a8k1f4,

HLA-B HLA-B (major histocompatibility complex, class I, B) is a human gene that provides instructions for making a protein that plays a critical role in the immune system. HLA-B is part of a family of genes called the human leukocyte antigen (HLA) comp ...

ARF6 ADP-ribosylation factor 6 (ARF6) is a member of the ADP ribosylation factor family of GTP-binding proteins. ARF6 has a variety of cellular functions that are frequently involved in trafficking of biological membranes and transmembrane protein c ...

, and

Mapk3 Mitogen-activated protein kinase 3, also known as p44MAPK and ERK1, is an enzyme that in humans is encoded by the ''MAPK3'' gene. Function The protein encoded by this gene is a member of the mitogen-activated protein kinase (MAP kinase) fam ...

have been found to interact with UQCRC2.

Structure

Function

Clinical Significance

Interactions

References

Further reading