| CEP89 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | CEP89 , CCDC123, CEP123, centrosomal protein 89 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 615470 MGI: 1919390 HomoloGene: 12444 GeneCards: CEP89 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Centrosomal protein 89, also known as Centrosomal protein of 89 kDa (CEP89), Centrosomal protein 123 (CEP123), or Coiled-coil domain-containing protein 123 is a protein that in humans is encoded by the CEP89 gene. [4] [5] [6]
The CEP89 gene is located on the q arm of chromosome 19 at position 13.11 and it spans 96,104 base pairs. [4] The CEP89 gene produces a 54.4 kDa protein composed of 476 amino acids. [7] [8] The structure of the protein has been found to be similar to a ring. It is associated and dependent on the orientation of centrioles, which are attached in the exterior region. The protein contains two coiled-coil domains and a putative mitochondrial-targeting signal. [9] [10] Experiments have shown that CEP89 is found within the intermembrane space, as well as the cytosol of the mitochondria. [9]
The CEP89 gene encodes for a protein required for ciliogenesis. It plays a role in mitochondrial metabolism by modulating complex IV activity. [6] [5] CEP89 has also been shown to be responsible for the integrity of the mitochondria, membrane depolarization, synaptic transmission of photoreceptor neurons and for the synaptic organization of the larval neuromuscular junction. [9]
Variants of CEP89 have been associated with the mitochondrial Complex IV deficiency, a deficiency in an enzyme complex of the mitochondrial respiratory chain which catalyzes the oxidation of cytochrome c utilizing molecular oxygen. [11] The deficiency is characterized by heterogeneous phenotypes ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Other Clinical Manifestations include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, exercise intolerance, developmental delay, delayed motor development and mental retardation. [12] Pathogenic mutations of CEP89 has also been found to be associated with intellectual disability and multisystemic disorders such as cystinuria, cataract, broad based walking pattern, deafness, and others. [9] [5] [6] A CEP89 loss-of-function has been shown to lead to a severe decrease in complex activity and altered mobility, which are signs of dysfunction in the complex IV resulting in complete lethality. [9] A Homozygous deletion in the CEP89 gene has resulted in an isolated complex IV deficiency confirmed by decreased ATP production and reduced oxidation of pyruvate (1-[14C]) and malate. [9]
CEP89 has interactions with proteins such as PICK1, LATS2, ERC1, CEP72, ADSL and others. [13] [5] [6]
Cytochrome c oxidase II is a protein in eukaryotes that is encoded by the MT-CO2 gene. Cytochrome c oxidase subunit II, abbreviated COXII, COX2, COII, or MT-CO2, is the second subunit of cytochrome c oxidase. It is also one of the three mitochondrial DNA (mtDNA) encoded subunits of respiratory complex IV.
Cytochrome c oxidase subunit III (COX3) is an enzyme that in humans is encoded by the MT-CO3 gene. It is one of main transmembrane subunits of cytochrome c oxidase. It is also one of the three mitochondrial DNA (mtDNA) encoded subunits of respiratory complex IV. Variants of it have been associated with isolated myopathy, severe encephalomyopathy, Leber hereditary optic neuropathy, mitochondrial complex IV deficiency, and recurrent myoglobinuria.
Surfeit locus protein 1 (SURF1) is a protein that in humans is encoded by the SURF1 gene. The protein encoded by SURF1 is a component of the mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex, which is involved in the regulation of cytochrome c oxidase assembly. Defects in this gene are a cause of Leigh syndrome, a severe neurological disorder that is commonly associated with systemic cytochrome c oxidase deficiency, and Charcot-Marie-Tooth disease 4K (CMT4K).
Protein SCO1 homolog, mitochondrial, also known as SCO1, cytochrome c oxidase assembly protein, is a protein that in humans is encoded by the SCO1 gene. SCO1 localizes predominantly to blood vessels, whereas SCO2 is barely detectable, as well as to tissues with high levels of oxidative phosphorylation. The expression of SCO2 is also much higher than that of SCO1 in muscle tissue, while SCO1 is expressed at higher levels in liver tissue than SCO2. Mutations in both SCO1 and SCO2 are associated with distinct clinical phenotypes as well as tissue-specific cytochrome c oxidase deficiency.
Mitochondrial chaperone BCS1 (BCS1L), also known as BCS1 homolog, ubiquinol-cytochrome c reductase complex chaperone (h-BCS1), is a protein that in humans is encoded by the BCS1L gene. BCS1L is a chaperone protein involved in the assembly of Ubiquinol Cytochrome c Reductase, which is located in the inner mitochondrial membrane and is part of the electron transport chain. Mutations in this gene are associated with mitochondrial complex III deficiency, GRACILE syndrome, and Bjoernstad syndrome.
NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial (NDUFS2) also known as NADH-ubiquinone oxidoreductase 49 kDa subunit is an enzyme that in humans is encoded by the NDUFS2 gene. The protein encoded by this gene is a core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase. Mutations in this gene are associated with mitochondrial complex I deficiency.
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 electron transport chain. Mutations of the COX6B1 gene are associated with severe infantile encephalomyopathy and mitochondrial complex IV deficiency (MT-C4D).
Protoheme IX farnesyltransferase, mitochondrial is an enzyme that in humans is encoded by the COX10 gene. Cytochrome c oxidase (COX), the terminal component of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. This component is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, and the nuclear-encoded subunits may function in the regulation and assembly of the complex. This nuclear gene, COX10, encodes heme A: farnesyltransferase, which is not a structural subunit but required for the expression of functional COX and functions in the maturation of the heme A prosthetic group of COX. A gene mutation, which results in the substitution of a lysine for an asparagine (N204K), is identified to be responsible for cytochrome c oxidase deficiency. In addition, this gene is disrupted in patients with CMT1A duplication and with HNPP deletion.
ATP synthase subunit delta, mitochondrial, also known as ATP synthase F1 subunit delta or F-ATPase delta subunit is an enzyme that in humans is encoded by the ATP5F1D gene. This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation.
Cytochrome c oxidase assembly protein COX15 homolog (COX15), also known as heme A synthase, is a protein that in humans is encoded by the COX15 gene. This protein localizes to the inner mitochondrial membrane and involved in heme A biosynthesis. COX15 is also part of a three-component mono-oxygenase that catalyses the hydroxylation of the methyl group at position eight of the protoheme molecule. Mutations in this gene has been reported in patients with hypertrophic cardiomyopathy as well as Leigh syndrome, and characterized by delayed onset of symptoms, hypotonia, feeding difficulties, failure to thrive, motor regression, and brain stem signs.
Mitochondrial import inner membrane translocase subunit TIM16 also known as presequence translocated-associated motor subunit PAM16, mitochondria-associated granulocyte macrophage CSF-signaling molecule, or presequence translocated-associated motor subunit PAM16 is a protein that in humans is encoded by the PAM16 gene.
Coiled-coil-helix-coiled-coil-helix domain-containing protein 10, mitochondrial, also known as Protein N27C7-4 is a protein that in humans is encoded by the CHCHD10 gene.
Ubiquinol-cytochrome c reductase complex assembly factor 3 is a protein that in humans is encoded by the UQCC3 gene. Located in mitochondria, this protein is involved in the assembly of mitochondrial Complex III, stabilizing supercomplexes containing Complex III. Mutations in the UQCC3 gene cause Complex III deficiency with symptoms of hypoglycemia, hypotonia, lactic acidosis, and developmental delays. This protein plays an important role as an antiviral factor, bolstering the ability of cells to inhibit viral replication, independent of interferon production. The UQCC3 protein can be cleaved by OMA1 metalloprotease during mitochondrial depolarization, targeting the cell for apoptosis. Depletion of this protein alters cardiolipin composition, causing cellular and mitochondrial defects.
Cytochrome c oxidase assembly factor 3, also known as Coiled-coil domain-containing protein 56, or Mitochondrial translation regulation assembly intermediate of cytochrome c oxidase protein of 12 kDa is a protein that in humans is encoded by the COA3 gene. This gene encodes a member of the cytochrome c oxidase assembly factor family. Studies of a related gene in fly suggest that the encoded protein is localized to mitochondria and is essential for cytochrome c oxidase function.
Cytochrome c oxidase assembly factor 5 is a protein that in humans is encoded by the COA5 gene. This gene encodes an ortholog of yeast Pet191, which in yeast is a subunit of a large oligomeric complex associated with the mitochondrial inner membrane, and required for the assembly of the cytochrome c oxidase complex. Mutations in this gene are associated with mitochondrial complex IV deficiency.
Cytochrome c oxidase assembly factor COX14 is a protein that in humans is encoded by the COX14 gene. This gene encodes a small single-pass transmembrane protein that localizes to mitochondria. This protein may play a role in coordinating the early steps of cytochrome c oxidase subunit assembly and, in particular, the synthesis and assembly of the COX I subunit of the holoenzyme. Mutations in this gene have been associated with mitochondrial complex IV deficiency. Alternative splicing results in multiple transcript variants.
Cytochrome c oxidase assembly factor COX20 is a protein that in humans is encoded by the COX20 gene. This gene encodes a protein that plays a role in the assembly of cytochrome c oxidase, an important component of the respiratory pathway. Mutations in this gene can cause mitochondrial complex IV deficiency. There are multiple pseudogenes for this gene. Alternative splicing results in multiple transcript variants.
PET100 homolog is a protein that in humans is encoded by the PET100 gene. Mitochondrial complex IV, or cytochrome c oxidase, is a large transmembrane protein complex that is part of the respiratory electron transport chain of mitochondria. The small protein encoded by the PET100 gene plays a role in the biogenesis of mitochondrial complex IV. This protein localizes to the inner mitochondrial membrane and is exposed to the intermembrane space. Mutations in this gene are associated with mitochondrial complex IV deficiency. This gene has a pseudogene on chromosome 3. Alternative splicing results in multiple transcript variants.
PET117 homolog is a protein that in humans is encoded by the PET117 gene. Localized to mitochondria, this protein is a chaperone protein involved in the assembly of mitochondrial Complex IV, or Cytochrome C Oxidase. Mutations in this gene can cause Complex IV deficiency with symptoms including medulla oblongata lesions and lactic acidosis.
Solute carrier family 25 member 46 is a protein that in humans is encoded by the SLC25A46 gene. This protein is a member of the SLC25 mitochondrial solute carrier family. It is a transmembrane protein located in the mitochondrial outer membrane involved in lipid transfer from the endoplasmic reticulum (ER) to mitochondria. Mutations in this gene result in neuropathy and optic atrophy.
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This article incorporates text available under the CC BY 4.0 license.This article incorporates text from the United States National Library of Medicine, which is in the public domain.
