COX6A2

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]

COX6A2
Identifiers
AliasesCOX6A2, COX6AH, COXVIAH, cytochrome c oxidase subunit 6A2, MC4DN18, COXVIa-M
External IDsOMIM: 602009 MGI: 104649 HomoloGene: 38020 GeneCards: COX6A2
Orthologs
SpeciesHumanMouse
Entrez

1339

12862

Ensembl

ENSG00000156885

ENSMUSG00000030785

UniProt

Q02221

P43023

RefSeq (mRNA)

NM_005205

NM_009943

RefSeq (protein)

NP_005196

NP_034073

Location (UCSC)Chr 16: 31.43 – 31.43 MbChr 7: 127.8 – 127.81 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Structure

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

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

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 (ΔΨm) occurs with submicromolar doses of Tat, and cytochrome c is released from the mitochondria.[9]

References
  1. GRCh38: Ensembl release 89: ENSG00000156885 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000030785 - 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. "Entrez Gene: Cytochrome c oxidase subunit VIa polypeptide 2".
  6. ]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.
  7. "Cytochrome c oxidase subunit 6A2, mitochondrial". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Archived from the original on 2018-07-19. Retrieved 2018-07-18.
  8. 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.
  9. 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.

Further reading

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

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