Alternative titles; symbols
HGNC Approved Gene Symbol: S100A4
Cytogenetic location: 1q21.3 Genomic coordinates (GRCh38): 1:153,543,621-153,545,806 (from NCBI)
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).
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.
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.
Ambartsumian et al. (1995) showed that the S100A4 gene contains of 4 exons.
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 revised nomenclature, CAPL became S100A4.
Ambartsumian, N., Tarabykina, S., Grigorian, M., Tulchinsky, E., Hulgaard, E., Georgiev, G., Lukanidin, E. Characterization of two splice variants of metastasis-associated human mts1 gene. Gene 159: 125-130, 1995. [PubMed: 7607566] [Full Text: https://doi.org/10.1016/0378-1119(94)00778-q]
Dorin, J. R., Emslie, E., van Heyningen, V. Related calcium-binding proteins map to the same subregion of chromosome 1q and to an extended region of synteny on mouse chromosome 3. Genomics 8: 420-426, 1990. [PubMed: 2149559] [Full Text: https://doi.org/10.1016/0888-7543(90)90027-r]
Engelkamp, D., Schafer, B. W., Erne, P., Heizmann, C. W. S100-alpha, CAPL, and CACY: molecular cloning and expression analysis of three calcium-binding proteins from human heart. Biochemistry 31: 10258-10264, 1992. [PubMed: 1384693] [Full Text: https://doi.org/10.1021/bi00157a012]
Fernandez-Fernandez, M. R., Veprintsev, D. B., Fersht, A. R. Proteins of the S100 family regulate the oligomerization of p53 tumor suppressor. Proc. Nat. Acad. Sci. 102: 4735-4740, 2005. [PubMed: 15781852] [Full Text: https://doi.org/10.1073/pnas.0501459102]
Jackson-Grusby, L. L., Swiergiel, J., Linzer, D. I. A growth-related mRNA in cultured mouse cells encodes a placental calcium binding protein. Nucleic Acids Res. 15: 6677-6690, 1987. [PubMed: 3628004] [Full Text: https://doi.org/10.1093/nar/15.16.6677]
Mandinova, A., Atar, D., Schafer, B. W., Spiess, M., Aebi, U., Heizmann, C. W. Distinct subcellular localization of calcium binding S100 proteins in human smooth muscle cells and their relocation in response to rises in intracellular calcium. J. Cell Sci. 111: 2043-2054, 1998. [PubMed: 9645951] [Full Text: https://doi.org/10.1242/jcs.111.14.2043]
Saris, C. J., Kristensen, T., D'Eustachio, P., Hicks, L. J., Noonan, D. J., Hunter, T., Tack, B. F. cDNA sequence and tissue distribution of the mRNA for bovine and murine p11, the S100-related light chain of the protein-tyrosine kinase substrate p36 (calpactin I). J. Biol. Chem. 262: 10663-10671, 1987. [PubMed: 3038891]
Schafer, B. W., Wicki, R., Engelkamp, D., Mattei, M.-G., Heizmann, C. W. Isolation of a YAC clone covering a cluster of nine S100 genes on human chromosome 1q21: rationale for a new nomenclature of the S100 calcium-binding protein family. Genomics 25: 638-643, 1995. [PubMed: 7759097] [Full Text: https://doi.org/10.1016/0888-7543(95)80005-7]
van Heyningen, V., Emslie, E., Dorin, J. R. Related calcium binding proteins map to the same sub-region of chromosome 1q and to an extended region of synteny on mouse chromosome 3. (Abstract) Cytogenet. Cell Genet. 51: 1095, 1989.