Protein mono-ADP-ribosyltransferase PARP10 (PARP10)
The protein contains 1025 amino acids for an estimated molecular weight of 109998 Da.
ADP-ribosyltransferase that mediates mono-ADP-ribosylation of glutamate and aspartate residues on target proteins (PubMed:18851833, PubMed:23332125, PubMed:23474714, PubMed:25043379). In contrast to PARP1 and PARP2, it is not able to mediate poly-ADP-ribosylation (PubMed:18851833). Catalyzes mono-ADP-ribosylation of GSK3B, leading to negatively regulate GSK3B kinase activity (PubMed:23332125). Involved in translesion DNA synthesis in response to DNA damage via its interaction with PCNA (PubMed:24695737). (updated: Jan. 16, 2019)
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.
- 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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| Variant | Description |
|---|---|
| dbSNP:rs11136344 | |
| dbSNP:rs11136343 | |
| dbSNP:rs11544989 |
Biological Process
NAD biosynthesis via nicotinamide riboside salvage pathway
Negative regulation of fibroblast proliferation
Negative regulation of gene expression
Negative regulation of NF-kappaB transcription factor activity
Negative regulation of protein import into nucleus, translocation
Negative regulation of protein K63-linked ubiquitination
Negative regulation of viral genome replication
Protein ADP-ribosylation
Protein auto-ADP-ribosylation
Protein mono-ADP-ribosylation
Protein poly-ADP-ribosylation
Regulation of chromatin assembly
Translesion synthesis
Viral protein processing
Cellular Component
Cytoplasm
Cytosol
Golgi apparatus
Intracellular membrane-bounded organelle
Nucleolus
Nucleoplasm
Nucleus
The reference OMIM entry for this protein is 609564
Poly(adp-ribose) polymerase 10; parp10
DESCRIPTION
Poly(ADP-ribose) polymerases (PARPs), such as PARP10, regulate gene transcription by altering chromatin organization by adding ADP-ribose to histones. PARPs can also function as transcriptional cofactors (Yu et al., 2005).CLONING
Yu et al. (2005) identified PARP10 as a MYC (190080)-interacting protein by immunopurifying MYC-containing complexes from human Jurkat T cells. By searching an EST database using PARP10 peptide sequences, they identified a PARP10 cDNA. The deduced 1,025-amino acid protein had an apparent molecular mass of 150 kD by SDS-PAGE. PARP10 contains an N-terminal RNA recognition motif, followed by a glycine-rich domain, a glutamic acid-rich domain, and a PARP catalytic domain. The glutamic acid-rich domain has a potential leucine-rich nuclear export signal (NES) and 2 ubiquitin-interacting motifs. Northern blot analysis detected a 3.8-kb PARP10 transcript in all tissues analyzed, with highest expression in spleen and thymus. PARP10 localized predominantly to the cytoplasm of transfected human osteosarcoma cells, but mutation of the NES or use of a nuclear export inhibitor resulted in PARP10 accumulation in the nuclear compartment.GENE FUNCTION
Yu et al. (2005) found that the C-terminal half of PARP10 showed PARP activity. The PARP domain possessed auto-PARP activity and modified all 4 core histones (see 142711) tested, with preference for histone H2A, but it did not modify MYC, MAX (154950), histone H1, or YY1 (600013). The full-length protein also exhibited PARP activity. Point mutation of his887 or gly888 inactivated the enzyme, and point mutation of lys916 strongly reduced the catalytic activity. By coimmunoprecipitations and in vitro protein pull-down assays, Yu et al. (2005) confirmed a direct interaction between PARP10 and MYC. Mutation analysis indicated that the C-terminal half of PARP10 interacted with both N- and C-terminal regions of MYC. PARP10 overexpression inhibited MYC/HRAS (190020)- and adenovirus E1A/HRAS-mediated cotransformation of rat embryo fibroblasts, and it inhibited entry into S phase in serum-stimulated mouse fibroblasts. The effects of PARP10 on cell proliferation were independent of the PARP domain. Kleine et al. (2008) demonstrated that, unlike PARP1 (173870), which catalyzed poly-ADP-ribosylation, PARP10 catalyzed only mono-ADP-ribosylation. Core secondary structural elements and critical residues involved in NAD+ binding are conserved in PARP1 and PARP10, but PARP10 has an isoleucine (I987) in place of the catalytic glutamate found in PARP1 (E988). PARP10 catalyzed auto-ADP-ribosylation, predominantly on E882. Structural analysis revealed that E882 lies near the catalytic center of the molecule, and Kleine et al. (2008) showed that E882, via substrate-assisted catalysis, behaved as the catalytic glutamate. They concluded that automodification of the catalytic glutamate prevents PARP10 from functioning as a poly-ADP-ribose polymerase.GENE STRUCTURE
Lesniewicz et al. (2005) determined that the mouse Parp10 gene contains at least 11 exons. All introns are small except intron 9, which spans more than 6 kb. A potential TATA box is located upstream of the most 5-prime sequence. The 3-prime sequence of the Parp10 gene overlaps on the same strand with the 5-prime sequence of the Plec1 gene (601282). Exons 10 and 11 of the Parp10 gene, which encode the last 109 amino acids and the 3-prime UTR of Parp10, are spliced at different sites to fo ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Jan. 21, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
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 609564 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed