UQCRFS1
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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 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 ...
which in humans is encoded by the ''UQCRFS1''
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 ...
. UQCRFS1 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 both the product 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 the products of ten nuclear genes UQCRC1,
UQCRC2 Cytochrome b-c1 complex subunit 2, mitochondrial (UQCRC2), also known as QCR2, UQCR2, or MC3DN5 is a protein that in humans is encoded by the ''UQCRC2'' gene. The product of ''UQCRC2'' is a subunit of the respiratory chain protein Ubiquinol Cyto ...
,
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 (this protein, a type of
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), UCRC ("cyt. c1 associated protein"), and ("Rieske-associated protein").


Structure

''UQCRFS1'' is located on the q arm of
chromosome A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most import ...
19 in position 12, has 2
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, and spans 5,969 base pairs. The ''UQCRFS1'' gene produces a 29.7 kDa protein composed of 274
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. UQCRFS1 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). The structure of the complex is a symmetric homodimer composed of one
mitochondrial genome Mitochondrial DNA (mtDNA and mDNA) is the DNA located in the mitochondria organelles in a eukaryotic cell that converts chemical energy from food into adenosine triphosphate (ATP). Mitochondrial DNA is a small portion of the DNA contained in ...
encoded cytochrome b subunit and ten other nucleus encoded subunits. The primary structure of UQCRFS1 from cDNA analysis is composed of a 78 amino acid long
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 amin ...
extension sequence.


Function

The ''UQCRFS1'' gene encodes for an iron-sulfur protein, which is an essential subunit of the Ubiquinol Cytochrome c Reductase or Complex III in 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 ...
.
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 ...
is responsible for electron transfer from
coenzyme Q Coenzyme Q10 (CoQ10 ), also known as ubiquinone, is a naturally occurring biochemical cofactor (coenzyme) and an antioxidant produced by the human body. It can also be obtained from dietary sources, such as meat, fish, seed oils, vegetables, ...
to cytochrome c as well as the proton transfer from the
extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and bio ...
to the
intermembrane space The intermembrane space (IMS) is the space occurring between or involving two or more membranes. In cell biology, it is most commonly described as the region between the Inner mitochondrial membrane, inner membrane and the Outer mitochondrial memb ...
which leads to ATP-coupled
electrochemical potential Electrochemistry is the branch of physical chemistry concerned with the relationship between electrical potential difference and identifiable chemical change. These reactions involve electrons moving via an electronically conducting phase (typi ...
generation. Incorporation of the subunit UQCRFS1 is the second to last step in
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 ...
assembly. Once it is incorporated, UQCRFS1 undergoes
proteolytic processing Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Protein degradation is a major regulatory mechanism of gene expression and contributes substantially to shaping mammalian proteomes. Uncatalysed, the hydrolysis o ...
, which is essential for the correct insertion into
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 ...
. Preventions of the insertion may occur due to UQCRFS1-derived fragments, leading to a loss of
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 ...
structure and function.


Clinical significance

The ''UQCRFS1'' gene has been shown to be involved in
carcinogenesis Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cell (biology), cells are malignant transformation, transformed into cancer cells. The process is characterized by changes at the cellular, G ...
of some cancers. It is mainly associated with more aggressive
tumors A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
, and results in the development of more aggressive
phenotypes 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 properti ...
of
breast cancer Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...
s. The association was found with a grade 3 amplification of the UQCRFS1 gene. In addition,
Acute myeloid leukemia Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with haematopoiesis, normal blood cell production. Sympt ...
(AML) has been found to be associated with the amplification of ''UQCRFS1'' gene. In contrast, UQCRFS1 and complex III has been absent in renal cell
carcinoma Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesoder ...
, though the mechanism is unknown.


Interactions

In addition to co-complexes, UQCRFS1 has protein-protein interactions with UQCRB, BCS1L,
COX6B1 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 elect ...
, UQCRQ, NDUFA9, and other proteins.


References


Further reading

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