S100PBP (S100P binding protein)

2012-07-01 Kate E Lines , Tatjana Crnogorac-Jurcevic Affiliation

Barts Cancer Institute, Queen Mary University of London, London, UK

Identity

HGNC

S100PBP

LOCATION

1p35.1

LOCUSID

64766

ALIAS

S100PBPR

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).

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).

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.

Disease

Pancreatic cancer.

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

Gene ID	Transcript ID	Uniprot
ENSG00000116497	ENST00000373475	Q96BU1
ENSG00000116497	ENST00000373475	A0A0S2Z5M0
ENSG00000116497	ENST00000373476	Q96BU1
ENSG00000116497	ENST00000373476	A0A0S2Z5M0
ENSG00000116497	ENST00000482212	E9PL86
ENSG00000116497	ENST00000526230	E9PIY5
ENSG00000116497	ENST00000529027	E9PIZ7
ENSG00000116497	ENST00000530710	E9PMK1
ENSG00000116497	ENST00000531256	E9PSA0

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
25156441	2015	Novel functions and targets of miR-944 in human cervical cancer cells.	20
15632002	2005	Expression of S100P and its novel binding partner S100PBPR in early pancreatic cancer.	18
18089492	2008	Usefulness of S100P in diagnosis of adenocarcinoma of pancreas on fine-needle aspiration biopsy specimens.	12
22330678	2012	S100P-binding protein, S100PBP, mediates adhesion through regulation of cathepsin Z in pancreatic cancer cells.	9

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)