Proliferation-associated protein 2G4 (PA2G4)
The protein contains 394 amino acids for an estimated molecular weight of 43787 Da.
May play a role in a ERBB3-regulated signal transduction pathway. Seems be involved in growth regulation. Acts a corepressor of the androgen receptor (AR) and is regulated by the ERBB3 ligand neuregulin-1/heregulin (HRG). Inhibits transcription of some E2F1-regulated promoters, probably by recruiting histone acetylase (HAT) activity. Binds RNA. Associates with 28S, 18S and 5.8S mature rRNAs, several rRNA precursors and probably U3 small nucleolar RNA. May be involved in regulation of intermediate and late steps of rRNA processing. May be involved in ribosome assembly. Mediates cap-independent translation of specific viral IRESs (internal ribosomal entry site) (By similarity). Regulates cell proliferation, differentiation, and survival. Isoform 1 suppresses apoptosis whereas isoform 2 promotes cell differentiation (By similarity). (updated: April 1, 2015)
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.
- 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.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- 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
Cell cycle arrest
Cell population proliferation
Negative regulation of apoptotic process
Negative regulation of transcription, DNA-templated
Neutrophil degranulation
Positive regulation of cell differentiation
Regulation of translation
RRNA processing
Transcription, DNA-templated
The reference OMIM entry for this protein is 602145
Proliferation-associated 2g4, 38-kd; pa2g4
Erbb3-binding protein 1; ebp1
CLONING
The mouse Pa2g4 gene was isolated by Radomski and Jost (1995) by screening a cDNA expression library from a murine macrophage cell line with the antibody mAb2G4. This monoclonal antibody was generated against a single-stranded DNA-binding protein to identify proteins showing cell cycle specific variation in nuclear localization. The protein encoded by Pa2g4, p38-2G4, was shown to be confined to the nucleus during interphase and early prophase, but distributed throughout the cytoplasm from metaphase through to telophase. In addition, p38-2G4 was found to be highly expressed between G1 and mid-S phase, decreasing toward the end of S phase and ceasing at the S/G2 transition. As the protein is expressed in response to mitogen stimulation, it may belong to a large family of cell cycle regulatory proteins or replication proteins that maintain the cell cycle activities of proliferating cells. It appears to be a proliferation-dependent gene that probably encodes a nuclear DNA-binding protein involved in the control of cell replication. Lamartine et al. (1997) isolated and characterized human PA2G4. A cDNA of 1,697 nucleotides was predicted to encode a protein of 394 amino acids. The deduced amino acid sequence of this human protein showed very strong homology to the mouse protein p38-2G4. Liu et al. (2006) identified isoforms of Ebp1 with apparent molecular masses of 48 and 42 kD by SDS-PAGE in the rat PC12 pheochromocytoma cell line. The 48-kD isoform (p48) localized to both the cytoplasm and nucleus of PC12 cells, whereas the 42-kD isoform (p42) was predominantly localized in the cytoplasm.GENE FUNCTION
Liu et al. (2006) found that the p48 isoform of Ebp1 suppressed apoptosis in rat PC12 cells, whereas the cytoplasmic p42 isoform promoted cell differentiation. EGF (131530) stimulated p42 to bind ERBB3 (190151) in transfected human embryonic kidney cells, and the association depended on PKC (see PRKCA; 176960)-mediated phosphorylation of p42. p48 did not bind ERBB3 regardless of EGF treatment. Overexpression of p48 induced PC12 cell proliferation, which was inhibited by p42. Nerve growth factor (NGFB; 162030) elicited extensive sprouting in p42-transfected PC12 cells, whereas p48 induced only modest neurite outgrowth. Akt (AKT1; 164730) was more active in p48 cells than in p42 cells. Liu et al. (2006) concluded that EBP1 may regulate cell survival and differentiation through 2 distinctive isoforms.MAPPING
Lamartine et al. (1997) concluded that PA2G4 belongs to a gene family with members in several chromosome regions: 3q24-q25, 6q22, 9q21, 12q13, 18q12, 20p12, and Xq25. They suggested that the human PA2G4 cDNA they analyzed probably corresponds to a functional copy at chromosome 12q13. ... More on the omim web site
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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602145 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed