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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

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

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 ba ...

. 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 within both molecular and cell biology, is a protein found in the mitochondria of eukaryotic cells. It functions as part of the electron transport chain and is the main subunit of transmembrane cytochrome bc1 and b6f complexes. F ...

) and ten

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 eukaryote ...

UQCRC1 Cytochrome b-c1 complex subunit 1, mitochondrial is a protein that in humans is encoded by the ''UQCRC1'' gene. Its gene product is a subunit of the respiratory chain protein Ubiquinol Cytochrome c Reductase (UQCR, Complex III or Cytochrome bc1 c ...

, 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 cytochr ...

UQCRFS1 Ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1, also known as UQCRFS1, Rieske iron-sulfur (Fe-S) protein, Cytochrome b-c1 complex subunit 5, or Complex III subunit 5 is a protein which in humans is encoded by the ''UQCRFS1'' ge ...

(

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 Ubiquinol-cytochrome c reductase binding protein, also known as UQCRB, Complex III subunit 7, QP-C, or Ubiquinol-cytochrome c reductase complex 14 kDa protein is a protein which in humans is encoded by the UQCRB gene. This gene encodes a subunit o ...

, "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 (UQCR, Complex III or Cytochrome bc1 c ...

(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 (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 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 pair A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting ...

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 sequen ...

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 hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

s. UQCRC2 belongs to the

peptidase A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the fo ...

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-ter ...

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 cytochr ...

and Rieske/

), 2 core proteins (

/QCR1 and UQCRC2/QCR2) and 6 low-molecular weight proteins (

/QCR6,

/QCR7,

UQCRQ Ubiquinol-cytochrome c reductase, complex III subunit VII, 9.5kDa is a protein that in humans is encoded by the ''UQCRQ'' gene. This ubiqinone-binding protein is a subunit of mitochondrial Complex III in the electron transport chain. A mutation i ...

/QCR8, UQCR10/QCR9,

UQCR11 UQCR11 (ubiquinol-cytochrome c reductase, complex III sub-unit XI) is a protein that in humans is encoded by the ''UQCR11'' gene. UQCR11 is the smallest known component of Complex III in the mitochondrial respiratory chain. Structure The UQCR1 ...

/QCR10 and a cleavage product of Rieske/UQCRFS1). UQCRC2 is part of the

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

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 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 used ...

, 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 that transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples thi ...

. 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 or physical form and structure, its developmental processes, its biochemical and physiological proper ...

depending on which tissues are affected. Clinical features include mitochondrial

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

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 ...

ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...

, 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. Signs and symptoms Some of the s ...

, 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, includi ...

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 post ...

lactic acidosis Lactic acidosis is a medical condition characterized by a build-up of lactate (especially -lactate) in the body, with formation of an excessively low pH in the bloodstream. It is a form of metabolic acidosis, in which excessive acid accumulates ...

and

hypoglycemia Hypoglycemia, also 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 triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose belo ...

. 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 guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the am ...

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 aromatic ...

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 effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

has been proposed as a transmission pattern.

Interactions

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

CACNA1A Cav2.1, also called the P/ Q voltage-dependent calcium channel, is a calcium channel found mainly in the brain. Specifically, it is found on the presynaptic terminals of neurons in the brain and cerebellum. Cav2.1 plays an important role in con ...

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 haemolytic an ...

, 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) compl ...

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 ...

, 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) famil ...

have been found to interact with UQCRC2.

Structure

Function

Clinical Significance

Interactions

References

Further reading