Cystatin-A (CSTA)
The protein contains 98 amino acids for an estimated molecular weight of 11006 Da.
This is an intracellular thiol proteinase inhibitor. Has an important role in desmosome-mediated cell-cell adhesion in the lower levels of the epidermis. (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.
- 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.
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| Variant | Description |
|---|---|
| dbSNP:rs34173813 |
Biological Process
Cell-cell adhesion
Cornification
Keratinocyte differentiation
Negative regulation of endopeptidase activity
Negative regulation of peptidase activity
Negative regulation of proteolysis
Peptide cross-linking
Single organismal cell-cell adhesion
The reference OMIM entry for this protein is 184600
Cystatin a; csta
Stefin a; stfa
Stf1
DESCRIPTION
Cystatin A is a cysteine proteinase inhibitor that belongs to family 1 of the cystatin superfamily. It was originally derived from the cytosol of human polymorphonuclear granulocytes (Strauss et al., 1988) but has also been isolated from the spleen, liver, and epidermis. Cystatin A is identical to keratolinin, one of the precursor proteins of the cornified cell envelope of keratinocytes (Takahashi et al., 1998).CLONING
Strauss et al. (1988) isolated a DNA containing the coding sequence for human stefin A by enzymic ligation of chemically synthesized deoxyoligonucleotides, using the Khorana ligation method. The deduced 98-residue protein has a molecular mass of 11 kDa. It forms tight complexes with papain and the cathepsins B, H, and L. Expression in E. coli resulted in secretion of a protein exhibiting biologic properties similar to those of the native protein isolated from human plasma. By immunostaining normal skin sections, Blaydon et al. (2011) demonstrated localization of cystatin A throughout all suprabasal layers of the epidermis with a diffuse cytoplasmic distribution and the strongest synthesis in the granular layer.GENE STRUCTURE
Takahashi et al. (1998) determined that the CSTA gene contains 3 exons.MAPPING
Hsieh et al. (1991) used PCR to amplify the human stefin A sequence in a panel of rodent-human somatic cell hybrid DNAs. They identified STF1 sequences on chromosome 3. Sublocalization to human 3q21 was accomplished using a deletion mapping panel for human chromosome 3.GENE FAMILY
Tsui et al. (1993) studied 3 members of the murine stefin gene family. Southern analysis suggested that the family comprises at least 6 and possibly 10 to 20 members, all of which appear to be clustered in the proximal region of mouse chromosome 16 in an area of conserved homology of synteny with human chromosome 3q.GENE FUNCTION
Takahashi et al. (1992) demonstrated that phosphorylated cystatin A is a component of the cornified envelope proteins in newborn rat skin. Incubation of both phosphorylated cystatin A and nonphosphorylated cystatin A with epidermal transglutaminase (TGM1; 190195) resulted in production of polymerized proteins formed by crosslinking peptide bonds between lysine residues of cystatin A and glutamine residues of the substrate protein. Inhibition of protein kinase C inhibited incorporation of cystatin A into keratohyaline granules, indicating that phosphorylation of cystatin A is necessary to target the polymerized protein to the cornified envelope. Blaydon et al. (2011) knocked down cystatin A in the HaCaT human keratinocyte cell line and studied the effects of mechanical stress on these cells. Upon intense stretching, thickening of keratin filaments was observed in both knockdown and control cells; however, in the knockdown cells, the monolayer of cells split into many fragments, whereas the monolayer was intact in control cells. At higher magnification, breakage of keratin filaments and widened intercellular spaces could be seen in the CSTA knockdown cells. In contrast, there were no obvious cell-cell adhesion defects in the stretched control cell monolayer. Knockdown cell monolayers subjected to agitation by inversion showed a high increase in the number of fragments, compared to the very few fragments obtained for the control monolayers. In an organotypic 3D culture model, Blaydon et al. (2011) demonstrated that there is no gross barrier de ... 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 184600 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed