Cytochrome b-c1 complex subunit 2, mitochondrial (UQCRC2)
The protein contains 453 amino acids for an estimated molecular weight of 48443 Da.
Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. The cytochrome b-c1 complex catalyzes electron transfer from ubiquinol to cytochrome c, linking this redox reaction to translocation of protons across the mitochondrial inner membrane, with protons being carried across the membrane as hydrogens on the quinol. In the process called Q cycle, 2 protons are consumed from the matrix, 4 protons are released into the intermembrane space and 2 electrons are passed to cytochrome c (By similarity). The 2 core subunits UQCRC1/QCR1 and UQCRC2/QCR2 are homologous to the 2 mitochondrial-processing peptidase (MPP) subunits beta-MPP and alpha-MPP respectively, and they seem to have preserved their MPP processing properties (By similarity). May be involved in the in situ processing of UQCRFS1 into the mature Rieske protein and its mitochondrial targeting sequence (MTS)/subunit 9 when incorporated into complex III (Probable). (updated: Feb. 26, 2020)
Protein identification was indicated in the following studies:
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Aerobic respiration
Mitochondrial electron transport, ubiquinol to cytochrome c
Oxidative phosphorylation
Protein processing involved in protein targeting to mitochondrion
Proteolysis
Response to drug
Cellular Component
Mitochondrial inner membrane
Mitochondrial processing peptidase complex
Mitochondrial respiratory chain complex III
Mitochondrial respiratory chain complex IV
Mitochondrion
Nucleoplasm
Molecular Function
Metal ion binding
Metalloendopeptidase activity
Protein-containing complex binding
The reference OMIM entry for this protein is 191329
Ubiquinol-cytochrome c reductase core protein ii; uqcrc2
DESCRIPTION
The UQCRC2 gene encodes a subunit of mitochondrial complex III (Duncan et al., 1993). See also UQCRC1 (191328).MAPPING
By in situ hybridization to metaphase chromosomes, Duncan et al. (1993) assigned the UQCRC2 gene to human chromosome 16p12, thus confirming that it is encoded by the nuclear rather than the mitochondrial genome. Two other subunits of mitochondrial complex III (CYC1, 123980; UQPC, 191330) map to chromosome 8.GENE FUNCTION
Wisloff et al. (2005) hypothesized that artificial selection of rats based on low and high intrinsic exercise capacity would yield models that also contrast for cardiovascular disease risk. After 11 generations, rats with low aerobic capacity scored higher on cardiovascular risk factors that constitute the metabolic syndrome. The decrease in aerobic capacity was associated with decreases in the amounts of transcription factors required for mitochondrial biogenesis and in the amounts of oxidative enzymes in skeletal muscle. Wisloff et al. (2005) found that the amount of PPARG (601487), PPARG coactivator-1-alpha (PPARGC1A; 604517), ubiquinol-cytochrome c oxidoreductase core 2 subunit (UQCRC2), cytochrome c oxidase subunit I (MTCO1; 516030), uncoupling protein-2 (UCP2; 601693), and ATP synthase H(+)-transporting mitochondrial F1 complex (F1-ATP synthase; see 108729) were markedly reduced in the low capacity runner rats in comparison with the high capacity runners. The uniform decline in these proteins was consistent with the hypothesis that reduced aerobic metabolism plays a causal role in the development of the differences between the low capacity runner and high capacity runner rats. Wisloff et al. (2005) concluded that impairment of mitochondrial function may link reduced fitness to cardiovascular and metabolic disease.MOLECULAR GENETICS
In 3 affected individuals from a large consanguineous Mexican kindred with mitochondrial complex III deficiency nuclear type 5 (MC3DN5; 615160), Miyake et al. (2013) identified a homozygous mutation in the UQCRC2 gene (R183W; 191329.0001). Structural analysis indicated that the substitution would disrupt the hydrophobic core at the interface of the UQCRC2-containing complex, resulting in destabilization of complex III. In vitro studies showed that the mutant protein localized properly to the mitochondria but had decreased expression compared to wildtype, suggesting protein instability. Complex III activity in one of the patient's cells was decreased to 50% of normal, whereas complex I activity was increased and complex IV activity was normal. The patient's cells also showed severely decreased levels of complex III assembly and decreased levels of the supercomplex formed from complexes I, III, and IV. The patients had neonatal onset of severe metabolic acidosis associated with hyperammonemia and hypoglycemia. Physical signs included tachypnea and poor sucking. Two of the patients showed normal growth and development by early childhood despite multiple episodes of metabolic decompensation, usually associated with illness. The third patient had a similar disease course, but showed mild development delay at age 18 months. ... More on the omim web site
March 3, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
May 12, 2019: Protein entry updated
Automatic update: OMIM entry 191329 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).