14-3-3 protein sigma (SFN)
The protein contains 248 amino acids for an estimated molecular weight of 27774 Da.
Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway. May also regulate MDM2 autoubiquitination and degradation and thereby activate p53/TP53.', 'p53-regulated inhibitor of G2/M progression. (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.
- 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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| Variant | Description |
|---|---|
| dbSNP:rs11542705 |
Biological Process
Apoptotic process
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
Establishment of skin barrier
Intrinsic apoptotic signaling pathway
Intrinsic apoptotic signaling pathway in response to DNA damage
Keratinization
Keratinocyte development
Membrane organization
Negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
Negative regulation of keratinocyte proliferation
Negative regulation of protein kinase activity
Negative regulation of protein serine/threonine kinase activity
Positive regulation of cell growth
Positive regulation of epidermal cell differentiation
Positive regulation of protein export from nucleus
Positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
Regulation of cyclin-dependent protein serine/threonine kinase activity
Regulation of epidermal cell division
Release of cytochrome c from mitochondria
Signal transduction
The reference OMIM entry for this protein is 601290
Stratifin; sfn
14-3-3-sigma
DESCRIPTION
SFN, or 14-3-3-sigma, is a regulator of mitotic translation that interacts with a variety of translation and initiation factors (Wilker et al., 2007).CLONING
Leffers et al. (1993) obtained peptide sequence and subsequently cloned a T-cell cDNA of the 14-3-3 family (see 113508) of conserved proteins. The protein, called stratifin, was shown to be diffusely distributed in the cytoplasm and was present in cultured epithelial cells. It was most abundant in tissues enriched in stratified keratinizing epithelium.MAPPING
Hermeking et al. (1997) mapped the SFN gene to chromosome 1p35 using fluorescence in situ hybridization.GENE FUNCTION
Through a quantitative analysis of gene expression patterns in colorectal cancer cell lines, Hermeking et al. (1997) discovered that 14-3-3-sigma, or stratifin, is strongly induced by gamma irradiation and other DNA-damaging agents. The induction of 14-3-3-sigma is mediated by a p53 (191170)-responsive element located 1.8 kb upstream of its transcription start site. Exogenous introduction of 14-3-3-sigma into cycling cells results in a G2 arrest. As the fission yeast 14-3-3 homologs rad24 and rad25 mediate similar checkpoint effects, Hermeking et al. (1997) concluded that the results document a molecular mechanism for G2/M control that is conserved throughout eukaryotic evolution and regulated in human cells by p53. Chan et al. (1999) described an improved approach to the generation of human somatic cell knockouts, which they used to generate human colorectal cancer cells in which both 14-3-3-sigma alleles were inactivated. After DNA damage, these cells initially arrested in the G2 phase of the cell cycle, but unlike cells containing 14-3-3-sigma, the 14-3-3-sigma -/- cells were unable to maintain cell cycle arrest. The 14-3-3-sigma -/- cells died (mitotic catastrophe) as they entered mitosis. This process was associated with a failure of the 14-3-3-sigma-deficient cells to sequester the proteins (cyclin B, 123836; CDC2, 116940) that initiate mitosis and prevent them from entering the nucleus. Chan et al. (1999) concluded that these results indicated a mechanism for maintaining the G2 checkpoint and preventing mitotic death. Expression of 14-3-3-sigma is induced in response to DNA damage, and causes cells to arrest in G2. By SAGE, Ferguson et al. (2000) identified sigma as a gene whose expression is 7-fold lower in breast carcinoma cells than in normal breast epithelium. Although genetic alterations at the SFN locus such as loss of heterozygosity were rare and no mutations were detected, the authors found that hypermethylation of CpG islands in the SFN gene could be detected in 91% of breast tumors and was associated with lack of gene expression. Treatment of sigma-nonexpressing breast cancer cell lines with the drug 5-aza-2-prime-deoxycytidine resulted in demethylation of the gene and synthesis of sigma mRNA. Breast cancer cells lacking sigma expression showed an increased number of chromosomal breaks and gaps when exposed to gamma-irradiation. Ferguson et al. (2000) thought it possible that loss of sigma expression contributes to malignant transformation by impairing the G2 cell cycle checkpoint function, thus allowing an accumulation of genetic defects. They suggested that hypermethylation and loss of sigma expression were the most consistent molecular alterations identified in breast cancer. Urano et al. (2002) demonstrated that EFP (600453) is a RI ... 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 15, 2016: Protein entry updated
Automatic update: OMIM entry 601290 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed