S100B (S100 calcium binding protein B)

2007-05-01   M Rosario Fernandez-Fernandez , Alan R Fersht 

Centre for Protein Engineering, Medical Research Council, Hills Road, Cambridge CB2 2QH, United Kingdom

Identity

HGNC
LOCATION
21q22.3
LOCUSID
ALIAS
NEF,S100,S100-B,S100beta
FUSION GENES

DNA/RNA

Description

The gene encompasses 17.3 Kb of DNA; 3 exons (the first one contains the 5 untranslated region).

Transcription

1135 b mRNA; 279 b coding sequence.

Proteins

Description

92 amino acids (including initial methionine that is generally processed in vivo);
10.5 kDa monomer (S100B can form homodimers and heterodimers with other proteins of the S100 family, described for S100A1).

Expression

S100B highest levels are found in brain. The protein is primarily found in astrocytes. Outside the central nervous system it can be found in chondrocytes and melanocytes.

Localisation

Nuclear and cytoplasmic. It has both intracellular and extracellular roles.

Function

The exact function of S100B is not fully understood. It inhibits microtubule assembly, has been involved in the regulation of cell cycle progression and differentiation and is able to induce neurite extension. This latest effect seems to be dependent on the concentration of S100B and occurs at nanomolar concentrations.
But micromolar levels of extracellular S100B stimulate apoptosis in vitro. Calcium binding induces a conformational change in S100B that allows the interaction with a variety of target proteins. These include p53 tumour suppressor, the microtubule-associated protein tau, the cytoskeletal protein tubulin (and its prokaryotic ancestor FtsZ), the scaffold protein IQGAP1, the intermediate filament protein glial fibrillary acidic protein (GFAP),the actin capping protein CapZ and the giant phosphoprotein AHNAK. Over-expression of S100B has been proposed to play a role in different neuro-pathologies.

Homology

S100B belongs to the S100 family of calcium binding proteins, a highly homologous family. These proteins contain two EF-hand calcium binding domains. The S100 genes are present exclusively in vertebrates.

Mutations

Note

Have not been reported.

Implicated in

Disease
Overexpression of S100B has been generally linked to neurodegeneration. It is over-expressed in the brain of patients suffering from Alzheimers disease, epilepsy or amyotrophic lateral sclerosis. The gene coding for S100B maps in the Downs syndrome region of chromosome 21, and its over-expression, due to the trisomic state, may be responsible for the neurological disturbances in Downs syndrome.
Oncogenesis
S100B may be involved in the proliferation of melanoma cells. It has been shown to be elevated in primary malignant melanomas. However, S100B is used as a predictor of survival prognosis as elevated levels of S100B in serum are associated with the survival rate.

Bibliography

Pubmed IDLast YearTitleAuthors
29640861988Gene encoding the beta subunit of S100 protein is on chromosome 21: implications for Down syndrome.Allore R et al
26047191989The Ca2+-binding sequence in bovine brain S100b protein beta-subunit. A spectroscopic study.Baudier J et al
14548551992Characterization of the tumor suppressor protein p53 as a protein kinase C substrate and a S100b-binding protein.Baudier J et al
66157781983Ions binding to S100 proteins: structural changes induced by calcium and zinc on S100a and S100b proteins.Baudier J et al
31115271987Comparison of S100b protein with calmodulin: interactions with melittin and microtubule-associated tau proteins and inhibition of phosphorylation of tau proteins by protein kinase C.Baudier J et al
101878471999Calcium-dependent interaction of S100B with the C-terminal domain of the tumor suppressor p53.Delphin C et al
87947371996Solution structure of rat apo-S100B(beta beta) as determined by NMR spectroscopy.Drohat AC et al
94854231998Solution structure of calcium-bound rat S100B(betabeta) as determined by nuclear magnetic resonance spectroscopy,.Drohat AC et al
157818522005Proteins of the S100 family regulate the oligomerization of p53 tumor suppressor.Fernandez-Fernandez MR et al
173625032007Expression of S100B during embryonic development of the mouse cerebellum.Hachem S et al
94292221997S100B protein, 5-S-cysteinyldopa and 6-hydroxy-5-methoxyindole-2-carboxylic acid as biochemical markers for survival prognosis in patients with malignant melanoma.Kärnell R et al
94165991997Identification of the binding site on S100B protein for the actin capping protein CapZ.Kilby PM et al
156592252005S100B-induced microglial and neuronal IL-1 expression is mediated by cell type-specific transcription factors.Liu L et al
69472521981Calcium-dependent interaction of S100b, troponin C, and calmodulin with an immobilized phenothiazine.Marshak DR et al
97743361998Calcium regulation of Ndr protein kinase mediated by S100 calcium-binding proteins.Millward TA et al
118912902002Glial protein S100B modulates long-term neuronal synaptic plasticity.Nishiyama H et al
165516282006Key role of Src kinase in S100B-induced activation of the receptor for advanced glycation end products in vascular smooth muscle cells.Reddy MA et al
82024931994Astrocytosis and axonal proliferation in the hippocampus of S100b transgenic mice.Reeves RH et al
108762432000Structure of the negative regulatory domain of p53 bound to S100B(betabeta).Rustandi RR et al
104906521999Concerted regulation of wild-type p53 nuclear accumulation and activation by S100B and calcium-dependent protein kinase C.Scotto C et al
99204181998Association of S100B with intermediate filaments and microtubules in glial cells.Sorci G et al
128324732003S100B inhibits myogenic differentiation and myotube formation in a RAGE-independent manner.Sorci G et al
171998892007Evidence for a wide extra-astrocytic distribution of S100B in human brain.Steiner J et al

Other Information

Locus ID:

NCBI: 6285
MIM: 176990
HGNC: 10500
Ensembl: ENSG00000160307

Variants:

dbSNP: 6285
ClinVar: 6285
TCGA: ENSG00000160307
COSMIC: S100B

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000160307ENST00000291700P04271
ENSG00000160307ENST00000291700A0A0S2Z4C5
ENSG00000160307ENST00000367071A8MRB1
ENSG00000160307ENST00000397648P04271
ENSG00000160307ENST00000397648A0A0S2Z4C5

Expression (GTEx)

0
500
1000
1500
2000
2500
3000
3500
4000

Pathways

PathwaySourceExternal ID
Immune SystemREACTOMER-HSA-168256
Innate Immune SystemREACTOMER-HSA-168249
Toll-Like Receptors CascadesREACTOMER-HSA-168898
Toll Like Receptor 10 (TLR10) CascadeREACTOMER-HSA-168142
MyD88 cascade initiated on plasma membraneREACTOMER-HSA-975871
TAK1 activates NFkB by phosphorylation and activation of IKKs complexREACTOMER-HSA-445989
Toll Like Receptor 3 (TLR3) CascadeREACTOMER-HSA-168164
MyD88-independent TLR3/TLR4 cascadeREACTOMER-HSA-166166
TRIF-mediated TLR3/TLR4 signalingREACTOMER-HSA-937061
Toll Like Receptor 5 (TLR5) CascadeREACTOMER-HSA-168176
Toll Like Receptor 7/8 (TLR7/8) CascadeREACTOMER-HSA-168181
MyD88 dependent cascade initiated on endosomeREACTOMER-HSA-975155
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activationREACTOMER-HSA-975138
Toll Like Receptor 9 (TLR9) CascadeREACTOMER-HSA-168138
Toll Like Receptor 4 (TLR4) CascadeREACTOMER-HSA-166016
Activated TLR4 signallingREACTOMER-HSA-166054
MyD88:Mal cascade initiated on plasma membraneREACTOMER-HSA-166058
Toll Like Receptor 2 (TLR2) CascadeREACTOMER-HSA-181438
Toll Like Receptor TLR1:TLR2 CascadeREACTOMER-HSA-168179
Toll Like Receptor TLR6:TLR2 CascadeREACTOMER-HSA-168188
Advanced glycosylation endproduct receptor signalingREACTOMER-HSA-879415
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathwaysREACTOMER-HSA-168928
TRAF6 mediated NF-kB activationREACTOMER-HSA-933542
Cytosolic sensors of pathogen-associated DNAREACTOMER-HSA-1834949
ZBP1(DAI) mediated induction of type I IFNsREACTOMER-HSA-1606322
RIP-mediated NFkB activation via ZBP1REACTOMER-HSA-1810476
DEx/H-box helicases activate type I IFN and inflammatory cytokines productionREACTOMER-HSA-3134963
Signal TransductionREACTOMER-HSA-162582
Signaling by ERBB4REACTOMER-HSA-1236394
Nuclear signaling by ERBB4REACTOMER-HSA-1251985

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
126450092003S100B in brain damage and neurodegeneration.102
210791802010GFAP and S100B are biomarkers of traumatic brain injury: an observational cohort study.89
176607472007Structural and functional insights into RAGE activation by multimeric S100B.74
171998892007Evidence for a wide extra-astrocytic distribution of S100B in human brain.71
209470222010Structural basis for ligand recognition and activation of RAGE.71
177260192007S100B and S100A6 differentially modulate cell survival by interacting with distinct RAGE (receptor for advanced glycation end products) immunoglobulin domains.70
184549412008Biological and methodological features of the measurement of S100B, a putative marker of brain injury.60
152570812004Changes in CSF S100B and cytokine concentrations in early-phase severe traumatic brain injury.58
197054612010Overexpression of human S100B exacerbates cerebral amyloidosis and gliosis in the Tg2576 mouse model of Alzheimer's disease.57
173480382007S100B in neuropathologic states: the CRP of the brain?56

Citation

M Rosario Fernandez-Fernandez ; Alan R Fersht

S100B (S100 calcium binding protein B)

Atlas Genet Cytogenet Oncol Haematol. 2007-05-01

Online version: http://atlasgeneticsoncology.org/gene/42195/s100b-(s100-calcium-binding-protein-b)