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Cytochrome c oxidase subunit III

"COX3" redirects here. For the cyclooxygenase isoenzyme, see COX-3.
COX3
Identifiers
AliasesCOX3, COIII, MTCO3, Cytochrome c oxidase subunit III, cytochrome c oxidase III
External IDsOMIM: 516050; MGI: 102502; HomoloGene: 5014; GeneCards: COX3; OMA:COX3 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

4514

17710

Ensembl

ENSG00000198938

ENSMUSG00000064358

UniProt

P00414

P00416

RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

NP_904334

Location (UCSC)Chr M: 0.01 – 0.01 MbChr M: 0.01 – 0.01 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
Location of the MT-CO3 gene in the human mitochondrial genome. MT-CO3 is one of the three cytochrome c oxidase subunit mitochondrial genes (orange boxes).
Cytochrome c oxidase subunit III
Structure of the 13-subunit oxidized cytochrome c oxidase.[5]
Identifiers
SymbolCOX3
PfamPF00510
InterProIPR000298
PROSITEPDOC50253
SCOP21occ / SCOPe / SUPFAM
TCDB3.D.4
OPM superfamily4
OPM protein1v55
CDDcd01665
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

Cytochrome c oxidase subunit III (COX3) is an enzyme that in humans is encoded by the MT-CO3 gene.[6] It is one of main transmembrane subunits of cytochrome c oxidase. It is also one of the three mitochondrial DNA (mtDNA) encoded subunits (MT-CO1, MT-CO2, MT-CO3) 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 .[7][8][9]

Structure

The MT-CO3 gene produces a 30 kDa protein composed of 261 amino acids.[10][11] COX3, the protein encoded by this gene, is a member of the cytochrome c oxidase subunit 3 family. This protein is located on the inner mitochondrial membrane. COX3 is a multi-pass transmembrane protein: in human, it contains 7 transmembrane domains at positions 15–35, 42–59, 81–101, 127–147, 159–179, 197–217, and 239–259.[8][9]

Function

Cytochrome c oxidase (EC 1.9.3.1) is the terminal enzyme of the respiratory chain of mitochondria and many aerobic bacteria. It catalyzes the transfer of electrons from reduced cytochrome c to molecular oxygen:

4 cytochrome c+2 + 4 H+ + O2 4 cytochrome c+3 + 2 H2O

This reaction is coupled to the pumping of four additional protons across the mitochondrial or bacterial membrane.[12][13]

Cytochrome c oxidase is an oligomeric enzymatic complex that is located in the mitochondrial inner membrane of eukaryotes and in the plasma membrane of aerobic prokaryotes. The core structure of prokaryotic and eukaryotic cytochrome c oxidase contains three common subunits, I, II and III. In prokaryotes, subunits I and III can be fused and a fourth subunit is sometimes found, whereas in eukaryotes there are a variable number of additional small subunits.[14]

As the bacterial respiratory systems are branched, they have a number of distinct terminal oxidases, rather than the single cytochrome c oxidase present in the eukaryotic mitochondrial systems. Although the cytochrome o oxidases do not catalyze the cytochrome c but the quinol (ubiquinol) oxidation they belong to the same haem-copper oxidase superfamily as cytochrome c oxidases. Members of this family share sequence similarities in all three core subunits: subunit I is the most conserved subunit, whereas subunit II is the least conserved.[15][16][17]

Clinical significance

Mutations in mtDNA-encoded cytochrome c oxidase subunit genes have been observed to be associated with isolated myopathy, severe encephalomyopathy, Leber hereditary optic neuropathy, mitochondrial complex IV deficiency, and recurrent myoglobinuria .[7][8][9]

Leber hereditary optic neuropathy (LHON)

LHON is a maternally inherited disease resulting in acute or subacute loss of central vision, due to optic nerve dysfunction. Cardiac conduction defects and neurological defects have also been described in some patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes. Mutations at positions 9438 and 9804, which result in glycine-78 to serine and alanine-200 to threonine amino acid changes, have been associated with this disease.[18][8][9]

Mitochondrial complex IV deficiency (MT-C4D)

Complex IV deficiency (COX deficiency) is a disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations, ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Features include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, exercise intolerance, developmental delay, delayed motor development, mental retardation, lactic acidemia, encephalopathy, ataxia, and cardiac arrhythmia. Some affected individuals manifest a fatal hypertrophic cardiomyopathy resulting in neonatal death and a subset of patients manifest Leigh syndrome. The mutations G7970T and G9952A have been associated with this disease.[7][19][8][9]

Recurrent myoglobinuria mitochondrial (RM-MT)

Recurrent myoglobinuria is characterized by recurrent attacks of rhabdomyolysis (necrosis or disintegration of skeletal muscle) associated with muscle pain and weakness, and followed by excretion of myoglobin in the urine. It has been associated with mitochondrial complex IV deficiency.[20][8][9]

Subfamilies

Interactions

COX3 has been shown to have 15 binary protein-protein interactions including 8 co-complex interactions. COX3 appears to interact with SNCA, KRAS, RAC1, and HSPB2.[21]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000198938 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000064358 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Miki K, Sogabe S, Uno A, Ezoe T, Kasai N, Saeda M, Matsuura Y, Miki M (May 1994). "Application of an automatic molecular-replacement procedure to crystal structure analysis of cytochrome c2 from Rhodopseudomonas viridis". Acta Crystallographica Section D. 50 (Pt 3): 271–5. Bibcode:1994AcCrD..50..271M. doi:10.1107/S0907444993013952. PMID 15299438.
  6. ^ "Entrez Gene: COX3 cytochrome c oxidase subunit III".Public Domain This article incorporates text from this source, which is in the public domain.
  7. ^ a b c Horváth R, Schoser BG, Müller-Höcker J, Völpel M, Jaksch M, Lochmüller H (December 2005). "Mutations in mtDNA-encoded cytochrome c oxidase subunit genes causing isolated myopathy or severe encephalomyopathy". Neuromuscular Disorders. 15 (12): 851–7. doi:10.1016/j.nmd.2005.09.005. PMID 16288875. S2CID 11683931.
  8. ^ a b c d e f "MT-CO3 - Cytochrome c oxidase subunit 3 - Homo sapiens (Human) - MT-CO3 gene & protein". www.uniprot.org. Retrieved 2018-08-21. This article incorporates text available under the CC BY 4.0 license.
  9. ^ a b c d e f "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622.
  10. ^ Yao, Daniel. "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information". amino.heartproteome.org. Archived from the original on 2018-08-22. Retrieved 2018-08-21.
  11. ^ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
  12. ^ Michel H (November 1999). "Cytochrome c oxidase: catalytic cycle and mechanisms of proton pumping--a discussion". Biochemistry. 38 (46): 15129–40. doi:10.1021/bi9910934. PMID 10563795.
  13. ^ Belevich I, Verkhovsky MI, Wikström M (April 2006). "Proton-coupled electron transfer drives the proton pump of cytochrome c oxidase". Nature. 440 (7085): 829–32. Bibcode:2006Natur.440..829B. doi:10.1038/nature04619. PMID 16598262. S2CID 4312050.
  14. ^ Mather MW, Springer P, Hensel S, Buse G, Fee JA (March 1993). "Cytochrome oxidase genes from Thermus thermophilus. Nucleotide sequence of the fused gene and analysis of the deduced primary structures for subunits I and III of cytochrome caa3". The Journal of Biological Chemistry. 268 (8): 5395–408. doi:10.1016/S0021-9258(18)53335-4. PMID 8383670.
  15. ^ Santana M, Kunst F, Hullo MF, Rapoport G, Danchin A, Glaser P (May 1992). "Molecular cloning, sequencing, and physiological characterization of the qox operon from Bacillus subtilis encoding the aa3-600 quinol oxidase". The Journal of Biological Chemistry. 267 (15): 10225–31. doi:10.1016/S0021-9258(19)50007-2. PMID 1316894.
  16. ^ Chepuri V, Lemieux L, Au DC, Gennis RB (July 1990). "The sequence of the cyo operon indicates substantial structural similarities between the cytochrome o ubiquinol oxidase of Escherichia coli and the aa3-type family of cytochrome c oxidases". The Journal of Biological Chemistry. 265 (19): 11185–92. doi:10.1016/S0021-9258(19)38574-6. PMID 2162835.
  17. ^ García-Horsman JA, Barquera B, Rumbley J, Ma J, Gennis RB (September 1994). "The superfamily of heme-copper respiratory oxidases". Journal of Bacteriology. 176 (18): 5587–600. doi:10.1128/jb.176.18.5587-5600.1994. PMC 196760. PMID 8083153.
  18. ^ Johns DR, Neufeld MJ (October 1993). "Cytochrome c oxidase mutations in Leber hereditary optic neuropathy". Biochemical and Biophysical Research Communications. 196 (2): 810–5. doi:10.1006/bbrc.1993.2321. PMID 8240356.
  19. ^ Hanna MG, Nelson IP, Rahman S, Lane RJ, Land J, Heales S, Cooper MJ, Schapira AH, Morgan-Hughes JA, Wood NW (July 1998). "Cytochrome c oxidase deficiency associated with the first stop-codon point mutation in human mtDNA". American Journal of Human Genetics. 63 (1): 29–36. doi:10.1086/301910. PMC 1377234. PMID 9634511.
  20. ^ Keightley JA, Hoffbuhr KC, Burton MD, Salas VM, Johnston WS, Penn AM, Buist NR, Kennaway NG (April 1996). "A microdeletion in cytochrome c oxidase (COX) subunit III associated with COX deficiency and recurrent myoglobinuria". Nature Genetics. 12 (4): 410–6. doi:10.1038/ng0496-410. PMID 8630495. S2CID 13314201.
  21. ^ "2 binary interactions found for search term COX3". IntAct Molecular Interaction Database. EMBL-EBI. Retrieved 2018-08-21.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


Quelle: https://en.wikipedia.org/wiki/MT-CO3