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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...
that in humans is encoded by the ''CYC1''
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 b ...
. CYC1 is a respiratory
subunit
Subunit may refer to:
*Subunit HIV vaccine, a class of HIV vaccine
*Protein subunit, a protein molecule that assembles with other protein molecules
*Monomer, a molecule that may bind chemically to other molecules to form a polymer
*Sub-subunit, a ...
of
Ubiquinol Cytochrome c Reductase (
complex III), 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. ...
and is part of the
electron transport 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 couple ...
. 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 145 million base pairs (the building material of DNA) and represents between 4.5 and 5.0% of the total DNA ...
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 sequenc ...
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 hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...
s. ''CYC1'' belongs to the
cytochrome c family. 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, or haem (pronounced / hi:m/ ), is a precursor to hemoglobin, which is necessary to bind oxygen in the bloodstream. Heme is biosynthesized in both the bone marrow and the liver.
In biochemical terms, heme is a coordination complex "consis ...
groups. It has
helix
A helix () is a shape like a corkscrew or spiral staircase. 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 formed as two intertwined hel ...
,
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 ...
, and
transmembrane
A transmembrane protein (TP) 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 frequentl ...
domains and contains 9
alpha helix
The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues earl ...
es, 5
beta strands, and 3 turns. The transmembrane protein passes through 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. ...
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 ( 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 ele ...
iron-metal binding sites at positions 125 and 244.
Function
''CYC1'' encodes a protein that 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. ...
and is part of
Ubiquinol Cytochrome c Reductase (
complex III). The encoded protein, CYC1, is a respiratory
subunit
Subunit may refer to:
*Subunit HIV vaccine, a class of HIV vaccine
*Protein subunit, a protein molecule that assembles with other protein molecules
*Monomer, a molecule that may bind chemically to other molecules to form a polymer
*Sub-subunit, a ...
of the
cytochrome bc1 complex, which plays an important role in the
mitochondrial respiratory chain by transferring
electron
The electron (, or in nuclear reactions) is a subatomic particle with a negative one elementary electric charge. Electrons belong to the first generation of the lepton particle family,
and are generally thought to be elementary partic ...
s from the
Rieske iron-sulfur protein 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 ...
.
Species
''CYC1'' is a human gene that is
conserved in
chimpanzee,
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 that are split between two groups, the Chinese-derived and the Indian-derived. Generally b ...
, dog, cow, mouse, rat,
zebrafish
The zebrafish (''Danio rerio'') is a freshwater fish belonging to the minnow family (Cyprinidae) of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (and thus often c ...
,
fruit fly, mosquito,
''C. elegans'', ''
S. cerevisiae,'' ''
K. lactis'', ''
E. gossypii
(also known as Ashbya gossypii) is a filamentous fungus or mold closely related to yeast, but growing exclusively in a filamentous way. It was originally isolated from cotton as a pathogen causing stigmatomycosis by Ashby and Nowell in 192 ...
'', ''
S. pombe'', ''
N. crassa
''Neurospora crassa'' is a type of red bread mold of the phylum Ascomycota. The genus name, meaning "nerve spore" in Greek, refers to the characteristic striations on the spores. The first published account of this fungus was from an infestation ...
'', ''
A. thaliana
''Arabidopsis thaliana'', the thale cress, mouse-ear cress or arabidopsis, is a small flowering plant native to Eurasia and Africa. ''A. thaliana'' is considered a weed; it is found along the shoulders of roads and in disturbed land.
A winter ...
'', 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 spe ...
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 effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and ...
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 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 d ...
,
ketoacidosis,
insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabol ...
-responsive
hyperglycemia
Hyperglycemia is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200 mg/dL), but symptoms may not start to become noticeable until even ...
,
liver dysfunction,
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 ...
, 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 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.
...
,
cytochrome c1 (CYC1),
UQCRFS1, the core proteins
UQCRC1 and
UQCRC2, and the low-molecular weight proteins
UQCRH,
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.
References
External links
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{{NLM content
Human proteins