COX6A2 Knowpia

COX6A2
Identifiers
Aliases	COX6A2, COX6AH, COXVIAH, cytochrome c oxidase subunit 6A2, MC4DN18, COXVIa-M
External IDs	OMIM: 602009 MGI: 104649 HomoloGene: 38020 GeneCards: COX6A2
Gene location (Human)
Chr.	Chromosome 16 (human)
End	31,428,360 bp
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)
End	127,805,559 bp
RNA expression pattern
	Top expressed in
	gastrocnemius muscle; ; triceps brachii muscle; ; left ventricle; ; thoracic diaphragm; ; biceps brachii; ; right ventricle; ; quadriceps femoris muscle; ; tibialis anterior muscle; ; body of tongue; ; vastus lateralis muscle;
	Top expressed in
	digastric muscle; ; right ventricle; ; interventricular septum; ; sternocleidomastoid muscle; ; plantaris muscle; ; extensor digitorum longus muscle; ; soleus muscle; ; temporal muscle; ; triceps brachii muscle; ; myocardium of ventricle;
	More reference expression data
	n/a
Gene ontology
Molecular function	cytochrome-c oxidase activity; enzyme regulator activity;
Cellular component	membrane; mitochondrion; mitochondrial inner membrane; mitochondrial respiratory chain complex IV;
Biological process	proton transmembrane transport; generation of precursor metabolites and energy; mitochondrial electron transport, cytochrome c to oxygen; aerobic respiration; regulation of catalytic activity;
	Sources:Amigo / QuickGO
Orthologs
	1339
	12862
	ENSG00000156885
	ENSMUSG00000030785
	Q02221
	P43023
	NM_005205
	NM_009943
	NP_005196
	NP_034073
	Wikidata
View/Edit Human	View/Edit Mouse

Cytochrome c oxidase subunit VIa polypeptide 2 is a protein that in humans is encoded by the COX6A2 gene. Cytochrome c oxidase 6A2 is a subunit of the cytochrome c oxidase complex, also known as Complex IV, the last enzyme in the mitochondrial electron transport chain.^[5]

Structure edit

The COX6A2 gene, located on the p arm of chromosome 16 in position 11.12, contains 3 exons and is 698 base pairs in length.^[5] The COX6A1 protein weighs 11 kDa and is composed of 97 amino acids.^[6]^[7] The protein is a subunit of Complex IV, a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. This nuclear gene encodes polypeptide 2 (heart/muscle isoform) of subunit VIa, and polypeptide 2 is present only in striated muscles. Polypeptide 1 (liver isoform) of subunit VIa is encoded by a different gene, COX6A1, and is found in all non-muscle tissues. These two polypeptides share 66% amino acid sequence identity.^[5]

Function edit

Cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial respiratory chain. It is a multi-subunit enzyme complex that couples the transfer of electrons from cytochrome c to molecular oxygen and contributes to a proton electrochemical gradient across the inner mitochondrial membrane to drive ATP synthesis via protonmotive force. The mitochondrially-encoded subunits perform the electron transfer of proton pumping activities. The functions of the nuclear-encoded subunits are unknown but they may play a role in the regulation and assembly of the complex.^[5]

Summary reaction:

4 Fe²⁺-cytochrome c + 8 H⁺_in + O₂ → 4 Fe³⁺-cytochrome c + 2 H₂O + 4 H⁺_out^[8]

Clinical significance edit

The Trans-activator of transcription protein (Tat) of human immunodeficiency virus (HIV) inhibits cytochrome c oxidase (COX) activity in permeabilized mitochondria isolated from both mouse and human liver, heart, and brain samples. Rapid loss of membrane potential (ΔΨ_m) occurs with submicromolar doses of Tat, and cytochrome c is released from the mitochondria.^[9]

References edit

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000156885 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000030785 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b ^c ^d "Entrez Gene: Cytochrome c oxidase subunit VIa polypeptide 2".
^ ]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 (Oct 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.
^ "Cytochrome c oxidase subunit 6A2, mitochondrial". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Archived from the original on 2018-07-19. Retrieved 2018-07-18.
^ Voet D, Voet JG, Pratt CW (2013). "Chapter 18". Fundamentals of Biochemistry: Life at the Molecular Level (4th ed.). Hoboken, NJ: Wiley. pp. 581–620. ISBN 978-0-470-54784-7.
^ Lecoeur H, Borgne-Sanchez A, Chaloin O, El-Khoury R, Brabant M, Langonné A, Porceddu M, Brière JJ, Buron N, Rebouillat D, Péchoux C, Deniaud A, Brenner C, Briand JP, Muller S, Rustin P, Jacotot E (2012). "HIV-1 Tat protein directly induces mitochondrial membrane permeabilization and inactivates cytochrome c oxidase". Cell Death & Disease. 3 (3): e282. doi:10.1038/cddis.2012.21. PMC 3317353. PMID 22419111.