Biology:S100B

Short description: Human protein and coding gene

Generic protein structure example

S100 calcium-binding protein B (S100B) is a protein of the S-100 protein family.

S100 proteins are localized in the cytoplasm and nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21; however, this gene is located at 21q22.3.

Function

S100B is glial-specific and is expressed primarily by astrocytes, but not all astrocytes express S100B. It has been shown that S100B is only expressed by a subtype of mature astrocytes that ensheath blood vessels and by NG2-expressing cells.

This protein may function in neurite extension, proliferation of melanoma cells, stimulation of Ca²⁺ fluxes, inhibition of PKC-mediated phosphorylation, astrocytosis and axonal proliferation, and inhibition of microtubule assembly. In the developing CNS it acts as a neurotrophic factor and neuronal survival protein. In the adult organism it is usually elevated due to nervous system damage, which makes it a potential clinical marker.

Clinical significance

Chromosomal rearrangements and altered expression of this gene have been implicated in several neurological, neoplastic, and other types of diseases, including Alzheimer disease, Down syndrome, epilepsy, amyotrophic lateral sclerosis, schwannoma, melanoma, and type I diabetes mellitus.

It has been suggested that the regulation of S100B by melittin has potential for the treatment of epilepsy.

Diagnostic use

S100B is secreted by astrocytes or can spill from injured cells and enter the extracellular space or bloodstream. Serum levels of S100B increase in patients during the acute phase of brain damage. Over the last decade, S100B has emerged as a candidate peripheral biomarker of blood–brain barrier (BBB) permeability and CNS injury. Elevated S100B levels accurately reflect the presence of neuropathological conditions including traumatic head injury or neurodegenerative diseases. Normal S100B levels reliably exclude major CNS pathology. Its potential clinical use in the therapeutic decision making process is substantiated by a vast body of literature (citation?) validating variations in serum 100B levels with standard modalities for prognosticating the extent of CNS damage: alterations in neuroimaging, cerebrospinal pressure, and other brain molecular markers (neuron specific enolase and glial fibrillary acidic protein). However, more importantly, S100B levels have been reported to rise prior to any detectable changes in intracerebral pressure, neuroimaging, and neurological examination findings. Thus, the major advantage of using S100B is that elevations in serum or CSF levels provide a sensitive measure for determining CNS injury at the molecular level before gross changes develop, enabling timely delivery of crucial medical intervention before irreversible damage occurs. S100B serum levels are elevated before seizures suggesting that BBB leakage may be an early event in seizure development. An extremely important application of serum S100B testing is in the selection of patients with minor head injury who do not need further neuroradiological evaluation, as studies comparing CT scans and S100B levels have demonstrated S100B values below 0.12 ng/mL are associated with low risk of obvious neuroradiological changes (such as intracranial hemorrhage or brain swelling) or significant clinical sequelae. The excellent negative predictive value of S100B in several neurological conditions is due to the fact that serum S100B levels reflect blood–brain barrier permeability changes even in absence of neuronal injury. In addition, S100B, which is also present in human melanocytes, is a reliable marker for melanoma malignancy both in bioptic tissue and in serum.

Interactions

S100B has been shown to interact with:

• AHNAK,
• IMPA1,
• IQGAP1,
• MAPT, and
• P53,
• PGM1,
• S100A1,
• S100A6,
• S100A11,
• VAV1.

Further reading

• "The S100 family of EF-hand calcium-binding proteins: functions and pathology". Trends Biochem. Sci. 21 (4): 134–40. 1996. doi:10.1016/S0968-0004(96)80167-8. PMID 8701470. 
• "The calcium-modulated proteins, S100A1 and S100B, as potential regulators of the dynamics of type III intermediate filaments". Braz. J. Med. Biol. Res. 32 (10): 1177–85. 2000. doi:10.1590/s0100-879x1999001000001. PMID 10510252. 
• "S100B in brain damage and neurodegeneration". Microsc. Res. Tech. 60 (6): 614–32. 2003. doi:10.1002/jemt.10303. PMID 12645009. 
• "S100B testing in pregnancy". Clin. Chim. Acta 335 (1–2): 1–7. 2004. doi:10.1016/S0009-8981(03)00243-2. PMID 12927678. 
• "Serum S-100B protein as a molecular marker in severe traumatic brain injury". Restor. Neurol. Neurosci. 21 (3–4): 159–69. 2004. PMID 14530578. 
• "S100B in neuropathologic states: the CRP of the brain?". J. Neurosci. Res. 85 (7): 1373–80. 2007. doi:10.1002/jnr.21211. PMID 17348038. 
• "Structure and chromosome assignment of human S100 alpha and beta subunit genes". Biochem. Biophys. Res. Commun. 175 (1): 185–91. 1991. doi:10.1016/S0006-291X(05)81218-5. PMID 1998503. 
• "Cloning and expression of the human S100 beta gene". J. Biol. Chem. 265 (26): 15537–43. 1990. doi:10.1016/S0021-9258(18)55430-2. PMID 2394738. 
• "Refined sublocalization of the human gene encoding the beta subunit of the S100 protein (S100B) and confirmation of a subtle t(9;21) translocation using in situ hybridization". Cytogenet. Cell Genet. 50 (4): 234–5. 1989. doi:10.1159/000132767. PMID 2530061. 
• "Interactions between the microtubule-associated tau proteins and S100b regulate tau phosphorylation by the Ca2+/calmodulin-dependent protein kinase II". J. Biol. Chem. 263 (12): 5876–83. 1988. doi:10.1016/S0021-9258(18)60647-7. PMID 2833519. 
• "Gene encoding the beta subunit of S100 protein is on chromosome 21: implications for Down syndrome". Science 239 (4845): 1311–3. 1988. doi:10.1126/science.2964086. PMID 2964086. Bibcode: 1988Sci...239.1311A. 
• "Characterization of human brain S100 protein fraction: amino acid sequence of S100 beta". J. Neurochem. 45 (3): 700–5. 1985. doi:10.1111/j.1471-4159.1985.tb04048.x. PMID 4031854. 
• "Purification, characterization and ion binding properties of human brain S100b protein". Biochim. Biophys. Acta 790 (2): 164–73. 1984. doi:10.1016/0167-4838(84)90220-6. PMID 6487634. 
• "Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence". Nature 377 (6547 Suppl): 3–174. 1995. PMID 7566098. http://www.columbia.edu/itc/biology/pollack/w4065/client_edit/readings/nature377_3.pdf. 
• "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 (3): 638–43. 1995. doi:10.1016/0888-7543(95)80005-7. PMID 7759097. 
• "Astrocytosis and axonal proliferation in the hippocampus of S100b transgenic mice". Proc. Natl. Acad. Sci. U.S.A. 91 (12): 5359–63. 1994. doi:10.1073/pnas.91.12.5359. PMID 8202493. Bibcode: 1994PNAS...91.5359R. 
• "Six S100 genes are clustered on human chromosome 1q21: identification of two genes coding for the two previously unreported calcium-binding proteins S100D and S100E". Proc. Natl. Acad. Sci. U.S.A. 90 (14): 6547–51. 1993. doi:10.1073/pnas.90.14.6547. PMID 8341667. Bibcode: 1993PNAS...90.6547E. 
• "beta-Amyloid regulates gene expression of glial trophic substance S100 beta in C6 glioma and primary astrocyte cultures". Brain Res. Mol. Brain Res. 34 (1): 118–26. 1997. doi:10.1016/0169-328X(95)00145-I. PMID 8750867. 
• "Physical exercise is required for environmental enrichment to offset the quantitative effects of dark-rearing on the S-100β astrocytic density in the rat visual cortex". Journal of Anatomy 215 (2): 132–40. 2009. doi:10.1111/j.1469-7580.2009.01103.x. PMID 19500177. 
• "Identification of an S100A1/S100B target protein: phosphoglucomutase". Cell Calcium 20 (3): 279–85. 1997. doi:10.1016/S0143-4160(96)90033-0. PMID 8894274. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.