Facilitates the differentiation and the cornification of keratinocytes. (updated: March 4, 2015)
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.
No sequence conservation computed yet.
Total structural coverage: 100%
No model available.
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The reference OMIM entry for this protein is 603114
S100 calcium-binding protein a11; s100a11
Calgizzarin
S100c
DESCRIPTION
S100 proteins, such as S100A11, are 10- to 12-kD molecules that have a canonical EF hand at their C termini and a modified, S100-specific EF hand at their N termini. Binding of Ca(2+) to EF-hand motifs changes the conformation and hence the function of S100 proteins (summary by Sakaguchi et al., 2008).
CLONING
Todoroki et al. (1991) purified an S100 protein from chicken gizzard that they called calgizzarin. Watanabe et al. (1991) isolated a cDNA encoding rabbit calgizzarin. Tanaka et al. (1995) identified and sequenced a cDNA encoding a human calgizzarin homolog. The deduced protein contains 105 amino acids. Using Northern blot analysis, Sakaguchi et al. (2003) found that S100A11 was variably expressed in human tissues, with highest expression in skin, followed by placenta, lung, peripheral blood leukocytes, kidney, and heart. Other tissues showed much lower expression, and there was little to no expression in brain. Immunohistochemical analysis of human skin detected S100A11 in nuclei of differentiating cells in the suprabasal layers, but not in nuclei of proliferating cells in the basal layer.
GENE FUNCTION
Tanaka et al. (1995) found that expression of human calgizzarin was elevated in colorectal cancers compared with normal colorectal mucosa. Tomasetto et al. (1995) reported that calgizzarin, or MLN70, is 1 of several genes expressed in breast cancer-derived metastatic axillary lymph nodes, but not in normal lymph nodes or breast fibroadenomas. High extracellular Ca(2+) concentration results in termination of cell growth in keratinocytes and induction of terminal differentiation. Sakaguchi et al. (2003) identified S100A11 as a key mediator of Ca(2+)-induced growth inhibition in cultured human epidermal keratinocytes. Elevated extracellular Ca(2+) resulted in phosphorylation of S100A11 on thr10 and ser94. Phosphorylated and Ca(2+)-bound S100A11 interacted with nucleolin (NCL;
164035) and was translocated to the nucleus. Binding of S100A11 to nucleolin resulted in induction of p21(CIP1/WAF1) (CDN1A;
116899) by SP1 (
189906) and SP3 (
601804), leading to inhibition of cell growth. Sakaguchi et al. (2008) noted that both high Ca(2+) levels and TGF-beta (TGFB1;
190180) activation suppress growth of human keratinocytes via S100A11. However, they found that secreted S100A11 could enhance cell growth via induction of EGF (
131530) and activation of EGFR (
131550) signaling. Addition of purified S100A11 to the culture medium stimulated growth of human keratinocytes by binding of S100A11 to the cell surface S100 receptor RAGE (AGER;
600214). Enhanced cell growth involved downregulation of p21(WAF1) and p27(KIP1) (CDKN1B
600778), activation of NF-kappa-B (see
164011) and ATK (see
164730), and phosphorylation of CREB (CREB1;
123810), culminating in AP1 (
165160)-mediated activation of the EGF promoter. Sakaguchi et al. (2008) also found that Ca(2+) induced S100A11 phosphorylation, but not its secretion, whereas EGF enhanced S100A11 secretion, but not its phosphorylation.
MAPPING
By in situ hybridization, Moog-Lutz et al. (1995) mapped the S100A11 gene to chromosome 1q21. By analysis of clones from this region, Wicki et al. (1996) determined that S100A11 is part of the S100 gene cluster and is located near S100A10 (
114085). ...
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Subscribe to this protein entry history
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 603114 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed