Protein S100-A4 (S100A4)
The protein contains 101 amino acids for an estimated molecular weight of 11729 Da.
Calcium-binding protein that plays a role in various cellular processes including motility, angiogenesis, cell differentiation, apoptosis, and autophagy (PubMed:16707441, PubMed:23752197, PubMed:30713770). Increases cell motility and invasiveness by interacting with non-muscle myosin heavy chain (NMMHC) IIA/MYH9 (PubMed:16707441). Mechanistically, promotes filament depolymerization and increases the amount of soluble myosin-IIA, resulting in the formation of stable protrusions facilitating chemotaxis (By similarity). Modulates also the pro-apoptotic function of TP53 by binding to its C-terminal transactivation domain within the nucleus and reducing its protein levels (PubMed:23752197). Within the extracellular space, stimulates cytokine production including granulocyte colony-stimulating factor and CCL24 from T-lymphocytes (By similarity). In addition, stimulates T-lymphocyte chemotaxis by acting as a chemoattractant complex with PGLYRP1 that promotes lymphocyte migration via CCR5 and CXCR3 receptors (PubMed:30713770, PubMed:26654597). (updated: April 7, 2021)
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.
- 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
Epithelial to mesenchymal transition
Positive regulation of I-kappaB kinase/NF-kappaB signaling
The reference OMIM entry for this protein is 114210
S100 calcium-binding protein a4; s100a4
Calcium placental protein; capl
Fibroblast-specific protein 1; fsp1
DESCRIPTION
S100 proteins, such as S100A4, are small, acidic calcium-binding proteins that transduce Ca(2+)-signals via interaction with intracellular target proteins (Mandinova et al., 1998).CLONING
Engelkamp et al. (1992) cloned S100A4, which they called CAPL, from a human heart cDNA library. The deduced 101-amino acid protein has the domain structure of an S100 protein, with N- and C-terminal hydrophobic regions and 2 central calcium loops. Northern blot analysis detected ubiquitous expression of a 650-bp transcript, with highest expression in thymus, lung, and heart. Ambartsumian et al. (1995) described 2 alternative splice variants of S100A4 that differ in their 5-prime untranslated regions. Using immunofluorescence analysis and confocal laser scanning microscopy, Mandinova et al. (1998) showed that S100A1 (176940), S100A2 (176993), S100A4, and S100A6 (114110) localized to distinct intracellular compartments in cultured human vascular and intestinal smooth muscle cells. S100A1 and S100A4 were associated predominantly with the sarcoplasmic reticulum and with actin stress fibers.GENE FUNCTION
Mandinova et al. (1998) showed that elevated cytosolic Ca(2+) led to relocalization of S100A1, S100A4, and S100A6 from sarcoplasmic reticulum to vesicle-like structures around the nucleus in human vascular smooth muscle cells. The localization of stress fiber-associated S100A1 and S100A4 remained unchanged. Fernandez-Fernandez et al. (2005) found that S100B (176990) and S100A4 bound the C-terminal tetramerization domain of p53 (191170) when the domain was exposed in lower oligomerization states, disrupting p53 tetramerization. S100B bound to the negative regulatory and nuclear localization domains of p53, resulting in very tight binding. Because trafficking of p53 depends on its oligomerization state, Fernandez-Fernandez et al. (2005) proposed that S100B and S100A4 may regulate subcellular localization of p53 but with different effects on p53 function in cell cycle control due to their differences in binding p53.GENE STRUCTURE
Ambartsumian et al. (1995) showed that the S100A4 gene contains of 4 exons.MAPPING
Jackson-Grusby et al. (1987) isolated a probe for the mouse placental protein for which the human equivalent was symbolized CAPL by van Heyningen et al. (1989). By Southern blot analysis of DNAs from somatic cell hybrids, van Heyningen et al. (1989) and Dorin et al. (1990) showed that the CAPL gene in man cosegregates with CAGA (123885), CAGB (123886), and calcyclin (114110). In the hands of van Heyningen et al. (1989), Southern blot analysis of DNA from BxD recombinant inbred strain mice showed a TaqI polymorphism for CAPL probe 18A2 to distinguish the parental strains. CAPL cosegregated in the BxD mice with a fifth member of this gene family, the p11 protein (mouse symbol Cal11) which had been mapped to chromosome 3 by Saris et al. (1987). In the mouse Capl is within 8 kb of Cacy; thus, by homology, the CAPL gene in man is probably in region 1q21-q25 where the CACY gene has been mapped. Schafer et al. (1995) isolated a YAC clone from the 1q21 region on which 9 different genes coding for S100 calcium-binding proteins could be localized. The clustered organization of S100 genes allowed introduction of a new logical nomenclature based on their physical arrangement on the chromosome, with S100A1 (176940) being closest to the telomere and S100A9 being closest to the centromere. In this ... More on the omim web site
April 10, 2021: 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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 114210 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed