Phosphatidylethanolamine-binding protein 1 (PEBP1)
The protein contains 187 amino acids for an estimated molecular weight of 21057 Da.
Binds ATP, opioids and phosphatidylethanolamine. Has lower affinity for phosphatidylinositol and phosphatidylcholine. Serine protease inhibitor which inhibits thrombin, neuropsin and chymotrypsin but not trypsin, tissue type plasminogen activator and elastase (By similarity). Inhibits the kinase activity of RAF1 by inhibiting its activation and by dissociating the RAF1/MEK complex and acting as a competitive inhibitor of MEK phosphorylation.', 'HCNP may be involved in the function of the presynaptic cholinergic neurons of the central nervous system. HCNP increases the production of choline acetyltransferase but not acetylcholinesterase. Seems to be mediated by a specific receptor (By similarity). (updated: March 4, 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.
- 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.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| empty |
The reference OMIM entry for this protein is 604591
Phosphatidylethanolamine-binding protein 1; pebp1
Pbp
Raf kinase inhibitor protein; rkip
Hippocampal cholinergic neurostimulating peptide precursor protein
Hcnp precursor protein
CLONING
Yeung et al. (1999) used a yeast 2-hybrid screen to identify RAF1 (164760)-interacting proteins. They identified a protein, designated RKIP (RAF kinase inhibitor protein), that inhibits the phosphorylation and activation of MEK (176872) by RAF1. MEK is a kinase that activates the extracellular signal-regulated kinases (ERKs; see 176872). This kinase cascade controls the proliferation and differentiation of different cell types. RKIP is identical to the phosphatidylethanolamine-binding protein (PBP) with a relative molecular mass of 23 kD. Seddiqi et al. (1994) determined that the human RKIP cDNA encodes a protein of 186 amino acids, the sequence of which is 95% identical to the bovine 21- to 23-kD protein. The rat protein shows 85.5% identity with the human protein. Schoentgen and Jolles (1995) demonstrated that the bovine protein was highly expressed in the brain and associated with cytosolic proteins and small GTP-binding proteins. Multiple tissue Northern blots revealed the presence of a single mRNA in the different tissues of each species; a single band of 1.8 kb was identified in human, 1.45 kb in mouse, and 1.2 kb in rat tissues. The mRNA is particularly highly expressed in rat and mouse testis, where the level was 30 times higher than that in the brain. The mRNA was not observed in human testis by Northern blot analysis, and was detected only by PCR. Tohdoh et al. (1995) cloned phosphatidylethanolamine-binding protein, which they called the hippocampal cholinergic neurostimulating peptide, or HCNP, precursor protein. Hori et al. (1994) sequenced about 1,000 3-prime-directed cDNA clones from the human HepG2 cell line and found that 1 of the cDNAs encoded the human homolog of bovine PBP. They found that the cDNA consists of 1,434 nucleotides with a 91-nucleotide 5-prime noncoding sequence followed by a 187-amino acid coding region and a 779-nucleotide 3-prime noncoding sequence. Moore et al. (1996) cloned the brain phosphatidylethanolamine-binding protein and found it to be identical in sequence to the protein cloned by Hori et al. (1994). Moore et al. (1996) used polyclonal antibodies in immunohistochemical studies in brain tissue and found that PBP is expressed strongly in the cell bodies of oligodendrocytes but only weakly elsewhere. Schwann cells and spinal nerve roots showed intense cytoplasmic PBP immunoreactivity.GENE FUNCTION
Yeung et al. (1999) demonstrated that, in vitro, RKIP binds to RAF1, MEK, and ERK, but not to RAS (190020). RKIP coimmunoprecipitates with RAF1 and MEK from cell lysates and colocalizes with RAF1 when examined by confocal microscopy. RKIP is not a substrate for RAF1 or MEK but competitively disrupts the interaction between these kinases. RKIP overexpression interferes with the activation of MEK and ERK, induction of AP1 (165160)-dependent reporter genes, and transformation elicited by an oncogenically activated RAF1 kinase. Downregulation of endogenous RKIP by expression of antisense RNA or antibody microinjection induces the activation of MEK-, ERK-, and AP1-dependent transcription. Yeung et al. (1999) concluded that RKIP represents a class of protein kinase inhibitor protein that regulates the activity of the Raf/MEK/ERK module. Hengst et al. (2001) determined that the residual thrombin (176930) inhibitory activity in the brains of nexin (PI7; 177010)-null mice was due to Pbp. By coimmunoprecipitation and mobility shift assays, they demonstrated direct binding between r ... 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 604591 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed