MICOS complex subunit MIC19 (CHCHD3)
The protein contains 227 amino acids for an estimated molecular weight of 26152 Da.
Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane. Has also been shown to function as a transcription factor which binds to the BAG1 promoter and represses BAG1 transcription. Plays an important role in the maintenance of the MICOS complex stability and the mitochondrial cristae morphology (PubMed:25781180). (updated: Jan. 31, 2018)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- 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.
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
Cristae formation
Inner mitochondrial membrane organization
Mitochondrial fusion
Negative regulation of transcription by RNA polymerase II
Transcription, DNA-templated
The reference OMIM entry for this protein is 613748
Coiled-coil-helix-coiled-coil-helix domain-containing protein 3; chchd3
CLONING
Using mass spectrometry and database analysis, Schauble et al. (2007) identified Chchd3 as a substrate for protein kinase A (PKA; see 176911) in mouse mitochondria. The deduced 226-amino acid protein contains a coiled-coil-helix-coiled-coil-helix (CHCH) motif and 3 putative PKA phosphorylation sites. Epitope-tagged Chchd3 localized to mitochondria in transfected HEK293 cells. Darshi et al. (2011) reported that the deduced 227-amino acid human CHCHD3 protein contains an N-myristoylation motif, followed by a DUF737 domain and a CHCH domain, which is predominantly found in mitochondrial proteins. Human CHCHD3 shares 92% amino acid identity with mouse Chchd3. CHCHD3 orthologs are present throughout metazoans, but not in fungi or plants.GENE FUNCTION
Schauble et al. (2007) showed that cAMP treatment increased phosphorylation of mouse Chchd3 following transfection in HEK293 cells. Using a monoclonal antibody directed against the mitochondrial inner membrane protein mitofilin (IMMT; 600378), followed by SDS-PAGE and mass spectrometry, Xie et al. (2007) identified a protein complex in human heart mitochondria that, in addition to mitofilin, included SAMM50 (612058), metaxin-1 (MTX1; 600605), metaxin-2 (MTX2; 608555), CHCHD3, CHCHD6 (615634), and DNAJC11 (614827). By limited proteolysis and by detergent and salt extraction of fractionated mouse liver mitochondria, Darshi et al. (2011) found that Chchd3 was located on the inner mitochondrial membrane facing the intermembrane space. Knockdown of CHCHD3 in HeLa cells via RNA interference resulted in fragmentation of mitochondria and clustering of mitochondria around nuclei. CHCHD3 knockdown led to a significant increase in DRP1 (DNM1L; 603850), which mediates mitochondrial fission, and reduced OPA1 (605290), which mediates mitochondrial fusion. Use of a dominant-negative DRP1 mutant revealed that mitochondria were unable to fuse in the absence of CHCHD3. Loss of CHCHD3 also reduced mitochondrial capacity to generate ATP, with reduced rate of oxygen consumption and lactate production, indicating diminished respiratory and glycolytic capacity. Transmission electron microscopy revealed defects in mitochondrial crista content and remodeling. Immunoprecipitation analysis, mass spectroscopy, and sequence analysis revealed that mouse Chchd3 interacted with the mitochondrial proteins mitofilin, SAM50, OPA1, and HSP70 (see HSPA1A; 140550) in transfected HEK293 cells. Loss of CHCHD3 also led to reduced cell proliferation and increased autophagy, likely due to removal of defective mitochondria. Darshi et al. (2011) concluded that CHCHD3 is a scaffolding protein that stabilizes protein complexes involved in maintaining crista architecture and protein import into mitochondria.GENE STRUCTURE
Darshi et al. (2011) determined that the CHCHD3 gene contains 8 coding exons.MAPPING
Darshi et al. (2011) stated that the CHCHD3 gene maps to chromosome 7q32.3-q33. ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
Oct. 27, 2017: Protein entry updated
Automatic update: model status changed
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 613748 was added.
Feb. 25, 2016: Protein entry updated
Automatic update: model status changed
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed