Protein IMPACT (IMPACT)
The protein contains 320 amino acids for an estimated molecular weight of 36476 Da.
Translational regulator that ensures constant high levels of translation upon a variety of stress conditions, such as amino acid starvation, UV-C irradiation, proteasome inhibitor treatment and glucose deprivation. Plays a role as a negative regulator of the EIF2AK4/GCN2 kinase activity; impairs GCN1-mediated EIF2AK4/GCN2 activation, and hence EIF2AK4/GCN2-mediated eIF-2-alpha phosphorylation and subsequent down-regulation of protein synthesis. May be required to regulate translation in specific neuronal cells under amino acid starvation conditions by preventing GCN2 activation and therefore ATF4 synthesis. Through its inhibitory action on EIF2AK4/GCN2, plays a role in differentiation of neuronal cells by stimulating neurite outgrowth. (updated: Oct. 25, 2017)
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.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
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:rs582234 | |
| dbSNP:rs677688 | |
| dbSNP:rs544203385 |
Biological Process
Cellular response to acidic pH
Cellular response to amino acid starvation
Cellular response to benomyl
Cellular response to glucose starvation
Cellular response to hydrogen peroxide
Cellular response to leucine starvation
Cellular response to UV-C
GCN2-mediated signaling
Negative regulation of cell death
Negative regulation of protein autophosphorylation
Negative regulation of protein phosphorylation
Negative regulation of protein-containing complex assembly
Negative regulation of transcription by RNA polymerase II
Negative regulation of transcription from RNA polymerase II promoter in response to stress
Neuron projection extension
Positive regulation of neuron differentiation
Positive regulation of translational initiation in response to starvation
Regulation of eIF2 alpha phosphorylation by amino acid starvation
Regulation of translational initiation
Molecular Function
Actin binding
Polysome binding
Protein kinase inhibitor activity
Ribosome binding
The reference OMIM entry for this protein is 615319
Impact rwd domain protein; impact
Imprinted and ancient gene, mouse, homolog of
DESCRIPTION
IMPACT is the nonimprinted human homolog of an imprinted mouse gene (Okamura et al., 2000).CLONING
By searching an EST database for sequences similar to mouse Impact, followed by 5-prime and 3-prime RACE and RT-PCR of adult and fetal brain RNA, Okamura et al. (2000) cloned human IMPACT. The deduced 320-amino acid protein shares 82.2% identity with the mouse protein. The authors also identified a close ortholog in Xenopus, with weaker conservation in invertebrates, bacteria, and plants. Northern blot analysis detected variable expression of a major IMPACT transcript of about 3.9 kb and a minor transcript of about 2.1 kb in all 16 adult and 4 fetal human tissues examined. The 2 transcripts appeared to differ in their 3-prime UTRs. Unlike mouse Impact, the human gene was biallelically expressed. Using Western blot analysis, Pereira et al. (2005) found that mouse Impact was predominantly expressed in brain, with much weaker expression in lung, kidney, and testis, and little to no expression in spleen, heart, liver, and pancreas. Immunohistochemical analysis revealed abundant Impact expression in hypothalamic neurons, with scattered neuronal expression in other regions, including hippocampus and piriform cortex.GENE FUNCTION
Okamura et al. (2000) found that mouse Impact was imprinted and expressed from the paternal allele only. They identified a CpG island within intron 1 of the mouse gene that has a tandem repeat structure characteristic of imprinted genes, and this CpG island was highly methylated on the maternal allele. The human gene, which is biallelically expressed, lacks the intronic CpG island. Pereira et al. (2005) found that overexpression of Impact in mouse embryonic fibroblasts inhibited Gcn2 (EIF2AK4; 609280)-dependent phosphorylation of Eif2-alpha (EIF2S1; 603907) under leucine starvation conditions. Overexpression of Impact also abolished expression of the Eif2-alpha downstream targets Atf4 (604064) and Chop (DDIT3; 126337). Roffe et al. (2013) found that expression of Impact increased in primary mouse hippocampal neurons and N2a neuroblastoma cells upon differentiation, concomitant with reduction in Gcn2 phosphorylation. Upon differentiation, Impact associated with translating ribosomes, enhanced translation initiation, and downregulated expression of Atf4. Endogenous Impact promoted neurite outgrowth, whereas Gcn2 inhibited neurite outgrowth.GENE STRUCTURE
Okamura et al. (2000) determined that the IMPACT gene contains 11 exons and spans about 30 kb. The last exon is over 2 kb long. The upstream region contains an Alu element, and the promoter region and first exon contain a CpG island. The human IMPACT gene lacks the differentially methylated CpG island found in intron 1 of the mouse gene.MAPPING
Using FISH, Okamura et al. (2000) mapped the IMPACT gene to chromosome 18q11.2-q12.1. They mapped the mouse Impact gene to a region of chromosome 18A2-B1 that shares homology of synteny with human chromosome 18q11.2-q12.2. ... More on the omim web site
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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 615319 was added.