Peflin (PEF1)
The protein contains 284 amino acids for an estimated molecular weight of 30381 Da.
Calcium-binding protein that acts as an adapter that bridges unrelated proteins or stabilizes weak protein-protein complexes in response to calcium. Together with PDCD6, acts as calcium-dependent adapter for the BCR(KLHL12) complex, a complex involved in endoplasmic reticulum (ER)-Golgi transport by regulating the size of COPII coats (PubMed:27716508). In response to cytosolic calcium increase, the heterodimer formed with PDCD6 interacts with, and bridges together the BCR(KLHL12) complex and SEC31 (SEC31A or SEC31B), promoting monoubiquitination of SEC31 and subsequent collagen export, which is required for neural crest specification (PubMed:27716508). Its role in the heterodimer formed with PDCD6 is however unclear: some evidence shows that PEF1 and PDCD6 work together and promote association between PDCD6 and SEC31 in presence of calcium (PubMed:27716508). Other reports show that PEF1 dissociates from PDCD6 in presence of calcium, and may act as a negative regulator of PDCD6 (PubMed:11278427). Also acts as a negative regulator of ER-Golgi transport; possibly by inhibiting interaction between PDCD6 and SEC31 (By similarity). (updated: May 8, 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.
- 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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Biological Process
COPII vesicle coating
Endoplasmic reticulum to Golgi vesicle-mediated transport
Neural crest cell development
Neural crest formation
Positive regulation of protein monoubiquitination
Proteolysis
Response to calcium ion
Cellular Component
COPII vesicle coat
Cul3-RING ubiquitin ligase complex
Cytoplasm
Endoplasmic reticulum
Extracellular exosome
Golgi membrane
Membrane
Molecular Function
Calcium ion binding
Calcium-dependent cysteine-type endopeptidase activity
Calcium-dependent protein binding
Identical protein binding
Molecular adaptor activity
Poly(A) RNA binding
Protein dimerization activity
Protein heterodimerization activity
RNA binding
Ubiquitin ligase-substrate adaptor activity
The reference OMIM entry for this protein is 610033
Penta-ef-hand domain-containing protein 1; pef1
Peflin
DESCRIPTION
PEF1 is a Ca(2+)-binding protein that belongs to the penta-EF-hand (PEF) protein family, which includes the calpain small subunit (CAPNS1; 114170), sorcin (SRI; 182520), grancalcin (GCA; 607030), and ALG2 (PDCD6; 601057) (Kitaura et al., 2001).CLONING
By searching databases for novel PEF proteins, followed by RT-PCR and 5-prime and 3-prime RACE, Kitaura et al. (1999) cloned full-length PEF1, which they designated peflin. The deduced 284-amino acid protein has a calculated molecular mass of 30.3 kD. PEF1 contains an N-terminal hydrophobic domain, 5 C-terminal EF-hand motifs, and several potential phosphorylation sites. It shares about 30% amino acid identity with ALG2. Northern blot analysis detected a 1.8-kb PEF1 transcript in several human cell lines. Western blot analysis showed endogenous PEF1 with an apparent molecular mass of 30 kD.GENE FUNCTION
Kitaura et al. (2001) found that ALG2 coimmunoprecipitated with peflin from Jurkat human T cells and from transfected HEK293 cells. Peflin dissociated from ALG2 in the presence of Ca(2+), and the N-terminal hydrophobic domain of peflin was not essential for heterodimerization. Peflin and ALG2 colocalized in the cytoplasm, but ALG2 was also detected in nuclei, as revealed by immunofluorescence staining and subcellular fractionation. Peflin was recovered in the cytosolic fraction in the absence of Ca(2+) and in the membrane/cytoskeletal fraction in the presence of Ca(2+). Kitaura et al. (2001) concluded that peflin may modulate the function of ALG2 in Ca(2+) signaling.MAPPING
The International Radiation Mapping Consortium mapped the PEF1 gene to chromosome 1 (TMAP RH79572). ... More on the omim web site
May 11, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
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
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 610033 was added.