Profilin-1 (PFN1)
The protein contains 140 amino acids for an estimated molecular weight of 15054 Da.
Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. Inhibits androgen receptor (AR) and HTT aggregation and binding of G-actin is essential for its inhibition of AR. (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.
- 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.
- 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.
Biological Process
Actin cytoskeleton organization
Blood coagulation
Cellular response to growth factor stimulus
Modification of postsynaptic actin cytoskeleton
Negative regulation of actin filament bundle assembly
Negative regulation of actin filament polymerization
Negative regulation of stress fiber assembly
Neural tube closure
Platelet activation
Platelet degranulation
Positive regulation of actin filament bundle assembly
Positive regulation of actin filament polymerization
Positive regulation of ATPase activity
Positive regulation of DNA metabolic process
Positive regulation of epithelial cell migration
Positive regulation of ruffle assembly
Positive regulation of stress fiber assembly
Positive regulation of transcription by RNA polymerase II
Positive regulation of viral transcription
Protein stabilization
Regulation of actin filament polymerization
Regulation of transcription by RNA polymerase II
Synapse maturation
Wnt signaling pathway, planar cell polarity pathway
The reference OMIM entry for this protein is 176610
Profilin 1; pfn1
DESCRIPTION
Profilin-1 is a 140-amino acid protein and major growth regulator of filamentous (F)-actin through its binding of monomeric (G)-actin (Mockrin and Korn, 1980).CLONING
Profilin is a ubiquitous 12- to 15-kD protein which inhibits the polymerization of actin. It is thought to function by complexing with unpolymerized actin in vivo. Dissociation of the profilin-actin complex is caused by binding of phosphatidylinositol 4,5-bisphosphate to profilin. Ampe et al. (1988) described the amino acid sequence of human platelet profilin and found it to have 95% homology to the sequence of calf spleen profilin.GENE FUNCTION
Goldschmidt-Clermont and Janmey (1991) reviewed the function of profilin, partly on the basis of work in the S. cerevisiae, homolog, PFY (Vojtek et al., 1991). Theriot and Mitchison (1993) reviewed the multiple functions of profilin.MAPPING
By Southern blot analysis of somatic cell hybrid DNA, Kwiatkowski and Bruns (1988) found that at least 4 dispersed genetic loci in the human genome hybridize with the profilin cDNA as well as the untranslated region fragments, suggesting that several of these loci represent pseudogenes of recent evolutionary origin. Chromosomes 1, 6, 13, and 17 were implicated. In addition, 5-prime and 3-prime untranslated regions were found to be conserved between humans and rodents, implying a functional role for these regions of the profilin gene. Kwiatkowski et al. (1990) localized the functional profilin gene to 17p13 by analysis of somatic cell hybrids and by in situ hybridization. By study of patients with deletions and by use of somatic cell hybrids containing a deleted chromosome 17, Kwiatkowski et al. (1990) sublocalized the PFN1 gene to 17p13.3. This is the same region as that deleted in the Miller-Dieker syndrome (MDLS; 247200). They found that the gene indeed was deleted in some patients with MDLS but that other patients had smaller deletions not affecting the profilin locus. Thus, a single allelic deletion of the profilin locus may contribute to the clinical phenotype of MDLS in some patients but does not play a major role in the essential phenotype. In the mouse, Klingenspor et al. (1997) mapped the Pfn1 gene to chromosome 11 and a profilin-1 related sequence to chromosome 15.MOLECULAR GENETICS
Wu et al. (2012) identified 4 different mutations in the PFN1 gene in 7 of 274 familial ALS cases. One mutation (E117G; 176610.0004), was found in 3 of 1,090 ALS cases and 3 of 7,560 controls. Wu et al. (2012) performed in vitro assays and showed that mutant PFN1 produces ubiquitinated, insoluble aggregates in transfected cells. In many cases the aggregates contained the ALS-associated protein TDP43 (605078). The E117G mutation (176610.0004) displayed a pattern more similar to wildtype PFN1, with most of the expressed protein in the soluble fraction. Wu et al. (2012) found that mutant PFN1 inhibited axon outgrowth. Wu et al. (2012) concluded that mutations in the PFN1 gene account for approximately 1 to 2% of familial ALS and suggested that disruption of cytoskeletal pathways contribute importantly to ALS pathogenicity.ANIMAL MODEL
To examine the function of profilin-1 in vivo, Witke et al. (2001) generated Pfn1 knockout mice. Homozygotes were not viable; they died as early as the 2-cell stage, and no homozygous knockout blastocysts were detectable. Adult heterozygotes showed a 50% reduction in profilin-1 expression with no a ... 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 176610 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed