Protein PAXX (C9orf142)
The protein contains 204 amino acids for an estimated molecular weight of 21640 Da.
Involved in non-homologous end joining (NHEJ), a major pathway to repair double-strand breaks in DNA. May act as a scaffold required to stabilize the Ku heterodimer, composed of XRCC5/Ku80 and XRCC6/Ku70, at double-strand break sites and promote the assembly and/or stability of the NHEJ machinery. (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.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
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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No binding partner found
Biological Process
Cellular response to DNA damage stimulus
DNA ligation involved in DNA repair
Double-strand break repair via nonhomologous end joining
The reference OMIM entry for this protein is 616315
Chromosome 9 open reading frame 142; c9orf142
Paralog of xrcc4 and xlf; paxx
DESCRIPTION
DNA double-strand breaks (DSBs) arise in cells exposed to DNA-damaging agents and are also generated as intermediates during V(D)J and class-switch recombination at immune receptor gene loci (see 147020). Nonhomologous end joining (NHEJ) is a key DNA repair pathway that involves recognition of DSBs and assembly of repair proteins. PAXX promotes DSB repair by stabilizing NHEJ protein assembly (Ochi et al., 2015).CLONING
By searching databases using the DSB repair protein XRCC4 (194363) as query, Ochi et al. (2015) identified PAXX. The deduced 204-amino acid protein has a domain structure similar to that of XRCC4, including an N-terminal head domain, a central coiled-coil region, and a C-terminal domain of low complexity. The head domain contains a PISA (present in SAS6, 609321) motif that is conserved throughout the XRCC4 superfamily. Fluorescence-tagged PAXX predominantly localized to nuclei in transfected U2OS cells. Database analysis revealed orthologs of PAXX in vertebrates, invertebrates, and unicellular organisms, but not in insects or fungi.BIOCHEMICAL FEATURES
Ochi et al. (2015) solved the crystal structure of PAXX and found that it resembled that of XRCC4. Electrospray mass spectroscopy indicated that PAXX formed dimers in solution.GENE FUNCTION
Using protein pull-down assays, coimmunoprecipitation analysis, and mutation analysis, Ochi et al. (2015) found that the C terminus of human PAXX interacted directly with the DSB repair proteins Ku70 (XRCC6; 152690) and Ku80 (XRCC5; 194364). Fluorescence-tagged PAXX was recruited to DNA-damage sites in U2OS cells. RNA interference in U2OS cells and generation of PAXX-null RPE-1 cells showed that PAXX functioned with XRCC4 and XLF (NHEJ1; 611290) to mediate DSB repair and cell survival in response to DSB-inducing agents. Ochi et al. (2015) also found that PAXX promoted Ku-dependent DNA ligation in vitro and assembly of core NHEJ factors on damaged chromatin in human cells. They concluded that PAXX is a novel component of the NHEJ machinery.MAPPING
Hartz (2015) mapped the PAXX gene to chromosome 9q34.3 based on an alignment of the PAXX sequence (GenBank GENBANK BC002613) with the genomic sequence (GRCh38). ... More on the omim web site
Feb. 10, 2018: Protein entry updated
Automatic update: OMIM entry 616315 was added.
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
June 20, 2017: Protein entry updated
Automatic update: comparative model 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. 25, 2016: Protein entry updated
Automatic update: model status changed