S100PBP (S100P binding protein)
2012-07-01 Kate E Lines , Tatjana Crnogorac-Jurcevic AffiliationBarts Cancer Institute, Queen Mary University of London, London, UK
DNA/RNA
Description
There are two different transcript variants of S100PBP. Variant 1 is 4317 base pairs and contains 7 exons. Variant 2 is 1483 base pairs and also contains 7 exons. This is shown in the above alignment. The coding sequence for each isoform is indicated in red, with the non-coding sequence in grey. Unmatched base pairs between the two isoforms are highlighted in green and the position of a missing CAG codon in isoform B is circled. The end of the isoform B sequence is indicated by a bold line.
Proteins
Description
S100PBP isoform A codes for a 45 kDa protein and isoform B for 37 kDa protein.
Secondary structure analysis of the S100PBP protein sequence was performed using the secondary structure consensus prediction tool (NPS@, Lyon, France). Based on three different methods: DSC (Discrimination of protein Secondary structure Class), MLRC (Multivariate Linear Regression Combination) and PHD neural network system, S100PBP was shown to be largely unstructured and unfolded, as seen above ("h" represents a helix, "c" a coil and "e" an extended strand).
Secondary structure analysis of the S100PBP protein sequence was performed using the secondary structure consensus prediction tool (NPS@, Lyon, France). Based on three different methods: DSC (Discrimination of protein Secondary structure Class), MLRC (Multivariate Linear Regression Combination) and PHD neural network system, S100PBP was shown to be largely unstructured and unfolded, as seen above ("h" represents a helix, "c" a coil and "e" an extended strand).
Expression
S100PBP is expressed in various normal tissues including prostate and lung and in both the endocrine and exocrine pancreas. S100PBP is also expressed in malignant tissues such as liver hepatocellular carcinoma and thyroid carcinoma (Lines et al., 2012).
In pancreas, S100PBP is expressed in decreasing levels as cancer develops and progresses, which is an inverse pattern of expression of its binding partner, S100P. This is shown on picture below (a= acinar cells, d= ducts; PanIN= pancreatic intraepithelial neoplasia, a precursor lesion to pancreatic cancer, black arrows= PanIN-1, red arrows= PanIN-2; PDAC= pancreatic cancer).
In pancreas, S100PBP is expressed in decreasing levels as cancer develops and progresses, which is an inverse pattern of expression of its binding partner, S100P. This is shown on picture below (a= acinar cells, d= ducts; PanIN= pancreatic intraepithelial neoplasia, a precursor lesion to pancreatic cancer, black arrows= PanIN-1, red arrows= PanIN-2; PDAC= pancreatic cancer).
Localisation
Predominantly nuclear.
Function
The exact functions of S100PBP are currently unknown, however it has been shown that S100PBP can bind to the metastasis related protein S100P (Dowen et al., 2005).
Homology
No homology to any currently described protein is seen.
Mutations
Note
No mutations have yet been reported.
Implicated in
Entity name
Pancreatic ductal adenocarcinoma (PDAC)
Note
Overexpression of S100PBP in FA6 pancreatic cancer cells that show low levels of endogenous S100PBP expression and silencing of S100PBP in MiaPaCa2 cells (high levels of endogenous S100PBP) showed no effect on proliferation or wound healing. While cell migration was not affected in majority of tested pancreatic cancer cell lines after modulation of S100PBP expression, significant changes in invasion (increase in MiaPaCa2 and Panc1 cells after S100PBP silencing and decrease in RwP1 cells after overexpression) were seen. However, the most affected cellular function after modulation of S100PBP expression was adhesion. Loss of S100PBP causes an increase in pancreatic cancer cell adhesion to extracellular matrix proteins which was mediated by cysteine protease Cathepsin Z (CTSZ) and the integrin ανβ5 (Lines et al., 2012).
Schematic and simplified diagram of the putative mechanism behind S100PBP mediated changes in pancreatic cell adhesion is shown below: in normal cells where S100PBP is highly expressed, low levels of CTSZ are present; no or very little ανβ5 is seen on the cellular surface. In cancer cells (PDAC), S100PBP levels decrease, which results in an increase in CTSZ expression; CTSZ is then secreted and can interact with ανβ5, promoting thus the adhesion.
Schematic and simplified diagram of the putative mechanism behind S100PBP mediated changes in pancreatic cell adhesion is shown below: in normal cells where S100PBP is highly expressed, low levels of CTSZ are present; no or very little ανβ5 is seen on the cellular surface. In cancer cells (PDAC), S100PBP levels decrease, which results in an increase in CTSZ expression; CTSZ is then secreted and can interact with ανβ5, promoting thus the adhesion.
Disease
Pancreatic cancer.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 15632002 | 2005 | Expression of S100P and its novel binding partner S100PBPR in early pancreatic cancer. | Dowen SE et al |
| 22330678 | 2012 | S100P-binding protein, S100PBP, mediates adhesion through regulation of cathepsin Z in pancreatic cancer cells. | Lines KE et al |
Other Information
Locus ID:
NCBI: 64766
MIM: 611889
HGNC: 25768
Ensembl: ENSG00000116497
Variants:
dbSNP: 64766
ClinVar: 64766
TCGA: ENSG00000116497
COSMIC: S100PBP
RNA/Proteins
Expression (GTEx)
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37794133 | 2023 | S100PBP is regulated by mutated KRAS and plays a tumour suppressor role in pancreatic cancer. | 2 |
| 37794133 | 2023 | S100PBP is regulated by mutated KRAS and plays a tumour suppressor role in pancreatic cancer. | 2 |
| 25156441 | 2015 | Novel functions and targets of miR-944 in human cervical cancer cells. | 30 |
| 25156441 | 2015 | Novel functions and targets of miR-944 in human cervical cancer cells. | 30 |
| 22330678 | 2012 | S100P-binding protein, S100PBP, mediates adhesion through regulation of cathepsin Z in pancreatic cancer cells. | 20 |
| 22330678 | 2012 | S100P-binding protein, S100PBP, mediates adhesion through regulation of cathepsin Z in pancreatic cancer cells. | 20 |
| 18089492 | 2008 | Usefulness of S100P in diagnosis of adenocarcinoma of pancreas on fine-needle aspiration biopsy specimens. | 15 |
| 18089492 | 2008 | Usefulness of S100P in diagnosis of adenocarcinoma of pancreas on fine-needle aspiration biopsy specimens. | 15 |
| 15632002 | 2005 | Expression of S100P and its novel binding partner S100PBPR in early pancreatic cancer. | 26 |
| 15632002 | 2005 | Expression of S100P and its novel binding partner S100PBPR in early pancreatic cancer. | 26 |
Citation
Kate E Lines ; Tatjana Crnogorac-Jurcevic
S100PBP (S100P binding protein)
Atlas Genet Cytogenet Oncol Haematol. 2012-07-01
Online version: http://atlasgeneticsoncology.org/gene/44308/s100pbp-(s100p-binding-protein)
