S100B

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S100 calcium binding protein B
Protein S100B PDB 1b4c.png
PDB rendering based on 1b4c.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols S100B ; NEF; S100; S100-B; S100beta
External IDs OMIM176990 MGI98217 HomoloGene4567 ChEMBL: 4300 GeneCards: S100B Gene
RNA expression pattern
PBB GE S100B 209686 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 6285 20203
Ensembl ENSG00000160307 ENSMUSG00000033208
UniProt P04271 P50114
RefSeq (mRNA) NM_006272 NM_009115
RefSeq (protein) NP_006263 NP_033141
Location (UCSC) Chr 21:
48.02 – 48.03 Mb
Chr 10:
76.25 – 76.26 Mb
PubMed search [1] [2]

S100 calcium binding protein B or 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[edit]

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.[1]

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[edit]

Chromosomal rearrangements and altered expression of this gene have been implicated in several neurological, neoplastic, and other types of diseases, including Alzheimer's disease, Down's syndrome, epilepsy, amyotrophic lateral sclerosis, melanoma, and type I diabetes.[2]

It has been suggested that the regulation of S100B by melittin has potential for the treatment of epilepsy.[3]

Diagnostic use[edit]

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 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. [4] 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.[5] 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.[6][7] In addition, S100B, which is also present in human melanocytes, is a reliable marker for melanoma malignancy both in bioptic tissue and in serum.[8][9]

Model organisms[edit]

Model organisms have been used in the study of S100B function. A conditional knockout mouse line, called S100btm1a(EUCOMM)Wtsi[14][15] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.[16][17][18]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[12][19] Twenty three tests were carried out on mutant mice, but no significant abnormalities have yet been observed.[12]

Interactions[edit]

S100B has been shown to interact with:

References[edit]

  1. ^ Wang DD, Bordey A (December 2008). "The astrocyte odyssey". Prog. Neurobiol. 86 (4): 342–67. doi:10.1016/j.pneurobio.2008.09.015. PMC 2613184. PMID 18948166. 
  2. ^ "Entrez Gene: S100B S100 calcium binding protein B". 
  3. ^ Verma N, Karmakar M, Singh KP, Smita S (February 2013). "Structural and Dynamic Insights into S100B Protein Activity Inhibition by Melittin for the Treatment of Epilepsy". International journal of Computer Application. NSAAILS (0975 – 8887): 55–60. 
  4. ^ Marchi N, Angelov L, Masaryk T, et al. (April 2007). "Seizure-promoting effect of blood–brain barrier disruption". Epilepsia 48 (4): 732–42. doi:10.1111/j.1528-1167.2007.00988.x. PMID 17319915. 
  5. ^ Zongo, D., Ribéreau-Gayon, R., Masson, F., Laborey, M., Contrand, B., Salmi, L.R., Montaudon, D., Beaudeux, J.L., Meurin, A., Dousset, V., Loiseau, H., Lagarde, E (2012). "S100-B protein as a screening tool for the early assessment of minor head injury". Annals of Emergency Medicine 59 (1): 209–218. doi:10.1016/j.annemergmed.2011.07.027. 
  6. ^ Czeisler BM, Janigro D (June 2006). "Reading and writing the blood–brain barrier: relevance to therapeutics". Recent patents on CNS drug discovery 1 (2): 157–73. doi:10.2174/157488906777452712. PMID 18221201. 
  7. ^ Marchi N, Cavaglia M, Fazio V, Bhudia S, Hallene K, Janigro D (April 2004). "Peripheral markers of blood–brain barrier damage". Clinica Chimica Acta 342 (1–2): 1–12. doi:10.1016/j.cccn.2003.12.008. PMID 15026262. 
  8. ^ Michetti F, Corvino V, Geloso MC, Lattanzi W, Bernardini C, Serpero L, Gazzolo D (March 2012). "The S100B protein in biological fluids: more than a lifelong biomarker of brain distress". J. Neurochem. 120 (5): 644–59. doi:10.1111/j.1471-4159.2011.07612.x. PMID 22145907. 
  9. ^ Cocchia D, Michetti F, Donato R (November 1981). "Immunochemical and immuno-cytochemical localization of S-100 antigen in normal human skin". Nature 294 (5836): 85–7. doi:10.1038/294085a0. PMID 7290214. 
  10. ^ "Salmonella infection data for S100b". Wellcome Trust Sanger Institute. 
  11. ^ "Citrobacter infection data for S100b". Wellcome Trust Sanger Institute. 
  12. ^ a b c Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88 (S248). doi:10.1111/j.1755-3768.2010.4142.x. 
  13. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  14. ^ "International Knockout Mouse Consortium". 
  15. ^ "Mouse Genome Informatics". 
  16. ^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750. 
  17. ^ Dolgin E (June 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718. 
  18. ^ Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. 
  19. ^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353. 
  20. ^ Gentil BJ, Delphin C, Mbele GO, Deloulme JC, Ferro M, Garin J, Baudier J (June 2001). "The giant protein AHNAK is a specific target for the calcium- and zinc-binding S100B protein: potential implications for Ca2+ homeostasis regulation by S100B". J. Biol. Chem. 276 (26): 23253–61. doi:10.1074/jbc.M010655200. PMID 11312263. 
  21. ^ Vig PJ, Shao Q, Subramony SH, Lopez ME, Safaya E (September 2009). "Bergmann glial S100B activates myo-inositol monophosphatase 1 and Co-localizes to purkinje cell vacuoles in SCA1 transgenic mice". Cerebellum 8 (3): 231–44. doi:10.1007/s12311-009-0125-5. PMC 3351107. PMID 19593677. 
  22. ^ Mbele GO, Deloulme JC, Gentil BJ, Delphin C, Ferro M, Garin J, Takahashi M, Baudier J (December 2002). "The zinc- and calcium-binding S100B interacts and co-localizes with IQGAP1 during dynamic rearrangement of cell membranes". J. Biol. Chem. 277 (51): 49998–50007. doi:10.1074/jbc.M205363200. PMID 12377780. 
  23. ^ Yu WH, Fraser PE (April 2001). "S100beta interaction with tau is promoted by zinc and inhibited by hyperphosphorylation in Alzheimer's disease". J. Neurosci. 21 (7): 2240–6. PMID 11264299. 
  24. ^ Baudier J, Cole RD (April 1988). "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. PMID 2833519. 
  25. ^ Lin J, Yang Q, Yan Z, Markowitz J, Wilder PT, Carrier F, Weber DJ (August 2004). "Inhibiting S100B restores p53 levels in primary malignant melanoma cancer cells". J. Biol. Chem. 279 (32): 34071–7. doi:10.1074/jbc.M405419200. PMID 15178678. 
  26. ^ Landar A, Caddell G, Chessher J, Zimmer DB (September 1996). "Identification of an S100A1/S100B target protein: phosphoglucomutase". Cell Calcium 20 (3): 279–85. doi:10.1016/S0143-4160(96)90033-0. PMID 8894274. 
  27. ^ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514. 
  28. ^ a b Yang Q, O'Hanlon D, Heizmann CW, Marks A (February 1999). "Demonstration of heterodimer formation between S100B and S100A6 in the yeast two-hybrid system and human melanoma". Exp. Cell Res. 246 (2): 501–9. doi:10.1006/excr.1998.4314. PMID 9925766. 
  29. ^ a b Deloulme JC, Assard N, Mbele GO, Mangin C, Kuwano R, Baudier J (November 2000). "S100A6 and S100A11 are specific targets of the calcium- and zinc-binding S100B protein in vivo". J. Biol. Chem. 275 (45): 35302–10. doi:10.1074/jbc.M003943200. PMID 10913138. 
  30. ^ Fackler OT, Luo W, Geyer M, Alberts AS, Peterlin BM (June 1999). "Activation of Vav by Nef induces cytoskeletal rearrangements and downstream effector functions". Mol. Cell 3 (6): 729–39. doi:10.1016/S1097-2765(01)80005-8. PMID 10394361. 

Further reading[edit]

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