Cytochrome c1, heme protein, mitochondrial (CYC1), also known as UQCR4, MC3DN6, Complex III subunit 4, Cytochrome b-c1 complex subunit 4, or Ubiquinol-cytochrome-c reductase complex cytochrome c1 subunit 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 ''CYC1''

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 ...

. CYC1 is a respiratory subunit of Ubiquinol Cytochrome c Reductase (

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 ...

), which is located in 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. T ...

and is part of the

electron transport 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 th ...

. Mutations in this gene may cause mitochondrial complex III deficiency, nuclear, type 6.

Structure

''CYC1'' is located on the q arm of

chromosome 8 Chromosome 8 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 8 spans about 146 million base pairs (the building material of DNA) and represents between 4.5 and 5.0% of the total DNA i ...

in position 24.3 and has 8

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 ''CYC1'' gene produces a 13.5 kDa protein composed of 130

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. ''CYC1'' belongs to the

cytochrome c family Cytochromes ''c'' (cyt ''c'', c-type cytochromes) cytochromes, or heme-containing proteins, that have heme C covalently attached to the peptide backbone via one or two thioether bonds. These bonds are in most cases part of a specific Cys-X-X-C ...

. CYC1 is a

phosphoprotein A phosphoprotein is a protein that is posttranslationally modified by the attachment of either a single phosphate group, or a complex molecule such as 5'-phospho-DNA, through a phosphate group. The target amino acid is most often serine, threonin ...

and subunit of Ubiquinol Cytochrome c Reductase that binds

heme Heme (American English), or haem (Commonwealth English, both pronounced /Help:IPA/English, hi:m/ ), is a ring-shaped iron-containing molecule that commonly serves as a Ligand (biochemistry), ligand of various proteins, more notably as a Prostheti ...

groups. It has

helix A helix (; ) is a shape like a cylindrical coil spring or the thread of a machine screw. It is a type of smooth space curve with tangent lines at a constant angle to a fixed axis. Helices are important in biology, as the DNA molecule is for ...

, transit peptide, and

transmembrane A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently u ...

domains and contains 9

alpha helix An alpha helix (or α-helix) is a sequence of amino acids in a protein that are twisted into a coil (a helix). The alpha helix is the most common structural arrangement in the Protein secondary structure, secondary structure of proteins. It is al ...

es, 5 beta strands, and 3 turns. The transmembrane protein passes through the

once and the majority of the protein is found on the intermembrane side. CYC1 contains

covalent A covalent bond is a chemical bond that involves the sharing of electrons to form electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs. The stable balance of attractive and repulsive forces between atom ...

heme bindings sites at positions 121 and 124 and heme axial

ligand In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...

iron-metal binding sites at positions 125 and 244.

Function

''CYC1'' encodes a protein that is located in the

and is part of Ubiquinol Cytochrome c Reductase (

). The encoded protein, CYC1, is a respiratory subunit of the

cytochrome bc1 complex Cytochromes are redox-active proteins containing a heme, with a central iron (Fe) atom at its core, as a cofactor. They are involved in the electron transport chain and redox catalysis. They are classified according to the type of heme and its ...

, which plays an important role 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 ...

by transferring

electron The electron (, or in nuclear reactions) is a subatomic particle with a negative one elementary charge, elementary electric charge. It is a fundamental particle that comprises the ordinary matter that makes up the universe, along with up qua ...

s from the Rieske iron-sulfur protein to cytochrome c.

Species

''CYC1'' is a human gene that is conserved in

chimpanzee The chimpanzee (; ''Pan troglodytes''), also simply known as the chimp, is a species of Hominidae, great ape native to the forests and savannahs of tropical Africa. It has four confirmed subspecies and a fifth proposed one. When its close rel ...

Rhesus monkey The rhesus macaque (''Macaca mulatta''), colloquially rhesus monkey, is a species of Old World monkey. There are between six and nine recognised subspecies split between two groups, the Chinese-derived and the Indian-derived. Generally brown or g ...

, dog, cow, mouse, rat,

zebrafish The zebrafish (''Danio rerio'') is a species of freshwater ray-finned fish belonging to the family Danionidae of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (an ...

, fruit fly, mosquito, ''C. elegans'', '' S. cerevisiae,'' '' K. lactis'', '' E. gossypii'', ''

S. pombe ''Schizosaccharomyces pombe'', also called "fission yeast", is a species of yeast used in traditional brewing and as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically measu ...

'', '' N. crassa'', '' A. thaliana'', rice, and frog. There are

orthologs 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 spec ...

of CYC1 in 137 known organisms.

Clinical Significance

Variants of ''CYC1'' have been associated with mitochondrial complex III deficiency, nuclear, type 6. Mitochondrial complex III deficiency, nuclear, type 6 is an

autosomal recessive 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 ...

disorder of the mitochondrial respiratory chain resulting from a defect in Ubiquinol Cytochrome c Reductase (complex III) that leads to reduced complex III activity. Clinical features tend to emerge in early childhood and include episodic acute

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 ...

ketoacidosis Ketoacidosis is a metabolic state caused by uncontrolled production of ketone bodies that cause a metabolic acidosis. While ketosis refers to any elevation of blood ketones, ketoacidosis is a specific pathologic condition that results in changes i ...

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...

-responsive

hyperglycemia Hyperglycemia is a condition where unusually high amount of glucose is present in blood. It is defined as blood glucose level exceeding 6.9 mmol/L (125 mg/dL) after fasting for 8 hours or 10 mmol/L (180 mg/dL) 2 hours after eating. Blood gluc ...

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 ...

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 ...

, and associated infection, although psychomotor development may remain normal. Pathogenic mutations have included c.288G>T, p.Trp96Cys and c.643C>T p. Leu215Phe.

Interactions

CYC1 has 78 protein-protein interactions with 72 of them being co-complex interactions. CYC1 is one of 11 subunits of Ubiquinol Cytochrome c Reductase (b1-c complex) that includes the respiratory subunits

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 ...

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 ...

(CYC1), UQCRFS1, the core proteins UQCRC1 and UQCRC2, and the low-molecular weight proteins

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 ...

, UQCRB, UQCRQ, UQCR10, UQCR11, as well as an additional cleavage product of UQCRFS1. Additionally, CCP1, CDKA-1, and CDKB1-1 have also been found to interact with CYC1.

Structure

Function

Species

Clinical Significance

Interactions

References

External links

Further reading