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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
which in humans is encoded by the ''UQCRFS1''
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 ...
.
UQCRFS1 is a subunit of the respiratory chain protein
Ubiquinol Cytochrome c Reductase (UQCR,
Complex III or Cytochrome bc1 complex), which consists of the products of one mitochondrially encoded gene,
MTCYTB (mitochondrial
cytochrome b) and ten nuclear genes
UQCRC1,
UQCRC2,
Cytochrome C1, UQCRFS1 (this protein, a type of
Rieske protein),
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 (cyt c1 Hinge protein),
UCRC
Ubiquinol-cytochrome c reductase complex (7.2 kD), also known as UCRC or UQCR10, is a human gene.
Its gene product is a subunit of the respiratory chain protein Ubiquinol Cytochrome c Reductase (UQCR, Complex III or Cytochrome bc1 complex), whi ...
("cyt. c1 associated protein"), and ("Rieske-associated protein").
Structure
''UQCRFS1'' 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
chromosome
A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
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 sequen ...
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 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. UQCRFS1 is a subunit of the respiratory chain protein
Ubiquinol Cytochrome c Reductase (UQCR,
Complex III or Cytochrome bc1 complex). The structure of the complex is a symmetric homodimer composed of one
mitochondrial genome
Mitochondrial DNA (mtDNA or mDNA) is the DNA located in mitochondria, cellular organelles within eukaryotic cells that convert chemical energy from food into a form that cells can use, such as adenosine triphosphate (ATP). Mitochondrial D ...
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 ami ...
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.
Complex III is responsible for electron transfer from
coenzyme Q
Coenzyme Q, also known as ubiquinone and marketed as CoQ10, is a coenzyme family that is ubiquitous in animals and most bacteria (hence the name ubiquinone). In humans, the most common form is coenzyme Q10 or ubiquinone-10.
It is a 1,4-benzoq ...
to
cytochrome c
The cytochrome complex, or cyt ''c'', is a small hemeprotein found loosely associated with the inner membrane of the mitochondrion. It belongs to the cytochrome c family of proteins and plays a major role in cell apoptosis. Cytochrome c is hig ...
as well as the proton transfer from the
extracellular matrix
In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...
to the
intermembrane space which leads to ATP-coupled
electrochemical potential generation. Incorporation of the subunit UQCRFS1 is the second to last step in
complex III assembly.
Once it is incorporated, UQCRFS1 undergoes
proteolytic processing, which is essential for the correct insertion into
Complex III. Preventions of the insertion may occur due to UQCRFS1-derived fragments, leading to a loss of
Complex III 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 cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnor ...
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 or physical form and structure, its developmental processes, its biochemical and physiological proper ...
of
breast cancer
Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...
s. The association was found with a grade 3 amplification of the UQCRFS1 gene. In addition,
Acute myeloid leukemia (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, mesodermal ...
, though the mechanism is unknown.
Interactions
In addition to co-complexes, UQCRFS1 has
protein-protein interactions with
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 ...
,
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 ele ...
,
UQCRQ,
NDUFA9
NADH dehydrogenase biquinone1 alpha subcomplex subunit 9 is an enzyme that in humans is encoded by the NDUFA9 gene. The NDUFA9 protein is a subunit of NADH:ubiquinone oxidoreductase (Complex I of the electron transport chain), which is located i ...
, and other proteins.
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References
Further reading
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