S100P (S100 calcium binding protein P)

2008-07-01 Sayka Barry , Tatjana Crnogorac-Jurcevic Affiliation

Institute of Cancer, Barts, The London, Queen Marys School of Medicine, Dentistry, Queen Mary, University of London, Charterhouse Square, London EC1M 6BQ, United Kingdom

Identity

HGNC

S100P

LOCATION

4p16.1

LOCUSID

6286

ALIAS

MIG9

FUSION GENES

Show Gene Fusions

DNA/RNA

Description

S100P gene contains two exons and one intron. Genomic size of 3,332 bases.

Transcription

1279 bases mRNA; 288 bases coding sequences. The transcript is on Chromosome 4 at location 6,745,697-6,749,797.

Pseudogene

None identified.

Proteins

Description

S100P protein consists of 95 amino acids with a molecular weight of 10.4 kDa.
S100P is a Ca²⁺ binding protein that belongs to S100 family ("Soluble in 100% saturated solution with ammonium sulfate") which was first isolated from human placenta and is therefore designated as "P". S100 family includes at least 26 members, which are thought to be expressed only in vertebrates and are present in a tissue and cell-specific manner. S100 proteins are characterized by common structural motifs including 2 EF-hands (helix-loop-helix calcium binding domains) with different affinities for calcium ions, a central hinge region and the C-terminal extension. The N-terminal half of the protein contains an unconventional EF hand that binds calcium with lower affinity, while the C-terminal is canonical and binds calcium with high affinity. The connecting hinge region and the C-terminal extension are the most variable regions and thus determine the functional specificity of S100 family members, including S100P. In addition to Ca²⁺, S100P also binds Zn²⁺ and Mg²⁺ and can form homo- and heterodimers.

Expression

S100P is expressed in various normal tissues including placenta, lung, heart, kidney, bladder, skeletal muscle, bone marrow, spleen, mammary epithelium, epidermis, prostate gland, gastric and intestinal mucosa, and malignant tissues such as pancreatic ductal adenocarcinoma, pancreatic intraductal papillary mucinous neoplasm, non-small-cell lung cancer, melanoma, gastric adenocarcinoma, ovarian, breast, colon and prostate carcinoma as well as in the body fluids such as tear, pancreatic juice, blood and urine.

Localisation

Cytoplasm, nucleus, also secreted in the culture media.

Function

S100P is involved in diverse biological functions but the exact role or mechanism of its action is still largely unknown. Upon binding of calcium ions S100P undergoes a conformational change that results in an exposure of a hydrophobic surface which allows the interaction with specific target proteins. To date, several S100P interacting partners have been identified including S100P binding protein S100PBP, EZR, S100A1, ECD, CacyBP, RAGE, S100Z and S100A6, but the consequences of their interactions are not fully understood.

Homology

S100P shares 50% sequence identity with human S100A1 and 44% identity with S100B.

Mutations

Note

Mutations have not been reported.

Implicated in

Entity name

Cancers

Disease

S100P has been associated with the progression of several types of cancer including pancreatic, prostate, non-small cell lung, breast, and colorectal cancer.

Oncogenesis

S100P has been implicated in migration, invasion, proliferation and survival of cancer cells in vitro and increased tumour growth in vivo. In fibroblasts, S100P has been shown to function as an autocrine growth and survival factor that enhanced cell proliferation and survival by activating RAGE receptor through MAPK and NF-kB signaling.

Entity name

Pancreatic cancer

Oncogenesis

The up-regulation of S100P is an early event in the development of pancreatic cancer and its expression increases throughout the progression of pancreatic intraepithelial neoplasia (PanINs) to invasive pancreatic ductal adenocarcinoma. S100P plays a critical role in the maintenance of the structural organization of intermediate filaments (cytokeratins 8, 18 and 19) and actin cytoskeleton, and its over-expression changes the phosphorylation status of the actin regulatory protein cofilin. Over-expression of S100P also increases the expression of S100A6 and cathepsin D, both of which are involved in cellular invasion. As S100P is expressed early in pancreatic ductal adenocarcinoma and is secreted into body fluids, it can serve as an useful diagnostic marker.

Entity name

Prostate cancer

Oncogenesis

In prostate cancer over-expression of S100P increases cell growth both in vitro and in vivo. S100P over-expression also up-regulates androgen receptor that leads to prostate cancer progression. Its expression has also been associated with poor clinical prognosis of patients with this malignancy.

Entity name

Non-small-cell lung cancer

Oncogenesis

Higher levels of S100P have been correlated with progression to metastasis and decreased survival in patients with lung cancer. This may also serve as a predictor of distant metastasis and poor survival in non-small cell lung carcinomas.

Entity name

Colorectal cancer

Oncogenesis

In colon cancer, expression of S100P correlates with resistance to chemotherapy and has also been associated with doxorubicin resistance in colon cancer cell lines.

Entity name

Breast cancer

Oncogenesis

S100P has been associated with immortalization of breast cancer cells in vitro and tumour progression in vivo. Higher level of S100P expression has also been correlated with decreased survival in patients with breast cancer.

Entity name

Other cancer types

Note

S100P is also expressed at higher levels in gastric, ovarian and cervical carcinomas.

Article Bibliography

Pubmed ID	Last Year	Title	Authors
16948836	2006	The human urinary proteome contains more than 1500 proteins, including a large proportion of membrane proteins.	Adachi J et al
16061848	2005	S100P promotes pancreatic cancer growth, survival, and invasion.	Arumugam T et al
18452169	2008	Functional evidence implicating S100P in prostate cancer progression.	Basu GD et al
1633809	1992	S100P, a novel Ca(2+)-binding protein from human placenta. cDNA cloning, recombinant protein expression and Ca2+ binding properties.	Becker T et al
12118244	2002	Gene-expression profiles predict survival of patients with lung adenocarcinoma.	Beer DG et al
9635921	1998	Elevated expression of S100P, CAPL and MAGE 3 in doxorubicin-resistant cell lines: comparison of mRNA differential display reverse transcription-polymerase chain reaction and subtractive suppressive hybridization for the analysis of differential gene expression.	Bertram J et al
12950018	2003	Molecular alterations in pancreatic carcinoma: expression profiling shows that dysregulated expression of S100 genes is highly prevalent.	Crnogorac-Jurcevic T et al
15313892	2004	S100 family members and trypsinogens are predictors of distant metastasis and survival in early-stage non-small cell lung cancer.	Diederichs S et al
12645002	2003	Intracellular and extracellular roles of S100 proteins.	Donato R et al
15632002	2005	Expression of S100P and its novel binding partner S100PBPR in early pancreatic cancer.	Dowen SE et al
12042313	2002	CacyBP/SIP, a calcyclin and Siah-1-interacting protein, binds EF-hand proteins of the S100 family.	Filipek A et al
17587138	2007	RAGE activation by S100P in colon cancer stimulates growth, migration, and cell signaling pathways.	Fuentes MK et al
10639564	2000	S100P calcium-binding protein overexpression is associated with immortalization of human breast epithelial cells in vitro and early stages of breast cancer development in vivo.	Guerreiro Da Silva ID et al
11943709	2002	Discovery of novel tumor markers of pancreatic cancer using global gene expression technology.	Iacobuzio-Donahue CA et al
14672411	2003	Characterization of the tissue-specific expression of the s100P gene which encodes an EF-hand Ca2+-binding protein.	Jin G et al
12808036	2003	Ca2+-dependent binding and activation of dormant ezrin by dimeric S100P.	Koltzscher M et al
18162774	2008	Diagnostic utility of S100P and von Hippel-Lindau gene product (pVHL) in pancreatic adenocarcinoma-with implication of their roles in early tumorigenesis.	Lin F et al
12750293	2003	Molecular profiling of pancreatic adenocarcinoma and chronic pancreatitis identifies multiple genes differentially regulated in pancreatic cancer.	Logsdon CD et al
11888886	2002	Clinical validation of candidate genes associated with prostate cancer progression in the CWR22 model system using tissue microarrays.	Mousses S et al
14767473	2004	Genome-wide cDNA microarray analysis of gene expression profiles in pancreatic cancers using populations of tumor cells and normal ductal epithelial cells selected for purity by laser microdissection.	Nakamura T et al
12746458	2003	Calcium-regulated interaction of Sgt1 with S100A6 (calcyclin) and other S100 proteins.	Nowotny M et al
17000674	2006	S100P is an early developmental marker of pancreatic carcinogenesis.	Ohuchida K et al
18282279	2008	The calcium-binding protein S100P in normal and malignant human tissues.	Parkkila S et al
14716296	2004	Identification of maspin and S100P as novel hypomethylation targets in pancreatic cancer using global gene expression profiling.	Sato N et al
16424059	2006	Induction of metastasis by S100P in a rat mammary model and its association with poor survival of breast cancer patients.	Wang G et al
17875703	2007	The role of S100P in the invasion of pancreatic cancer cells is mediated through cytoskeletal changes and regulation of cathepsin D.	Whiteman HJ et al
12507480	2003	The crystal structure at 2A resolution of the Ca2+ -binding protein S100P.	Zhang H et al
16901338	2006	Identification of 491 proteins in the tear fluid proteome reveals a large number of proteases and protease inhibitors.	de Souza GA et al

Other Information

Locus ID:

NCBI: 6286
MIM: 600614
HGNC: 10504
Ensembl: ENSG00000163993

Variants:

dbSNP: 6286
ClinVar: 6286
TCGA: ENSG00000163993
COSMIC: S100P

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000163993	ENST00000296370	P25815

Expression (GTEx)

100

150

200

250

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

Pathways

Pathway	Source	External ID
Immune System	REACTOME	R-HSA-168256
Innate Immune System	REACTOME	R-HSA-168249
Neutrophil degranulation	REACTOME	R-HSA-6798695

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
38342601	2024	RBMS1 Coordinates with the m(6)A Reader YTHDF1 to Promote NSCLC Metastasis through Stimulating S100P Translation.	1
38640980	2024	S100P facilitates LUAD progression via PKA/c-Jun-mediated tumor-associated macrophage recruitment and polarization.	0
38342601	2024	RBMS1 Coordinates with the m(6)A Reader YTHDF1 to Promote NSCLC Metastasis through Stimulating S100P Translation.	1
38640980	2024	S100P facilitates LUAD progression via PKA/c-Jun-mediated tumor-associated macrophage recruitment and polarization.	0
37433400	2023	Novel cell subtypes of SPP1 + S100P+, MS4A1-SPP1 + S100P+ were key subpopulations in intrahepatic cholangiocarcinoma.	1
37627296	2023	An Extracellular/Membrane-Bound S100P Pool Regulates Motility and Invasion of Human Extravillous Trophoblast Lines and Primary Cells.	0
37853345	2023	S100P as a potential biomarker for immunosuppressive microenvironment in pancreatic cancer: a bioinformatics analysis and in vitro study.	2
37433400	2023	Novel cell subtypes of SPP1 + S100P+, MS4A1-SPP1 + S100P+ were key subpopulations in intrahepatic cholangiocarcinoma.	1
37627296	2023	An Extracellular/Membrane-Bound S100P Pool Regulates Motility and Invasion of Human Extravillous Trophoblast Lines and Primary Cells.	0
37853345	2023	S100P as a potential biomarker for immunosuppressive microenvironment in pancreatic cancer: a bioinformatics analysis and in vitro study.	2
35597866	2022	Calcium-binding protein S100P is a new target gene of MACC1, drives colorectal cancer metastasis and serves as a prognostic biomarker.	9
36187124	2022	S100P promotes trophoblast syncytialization during early placenta development by regulating YAP1.	2
36233301	2022	Calcium-Bound S100P Protein Is a Promiscuous Binding Partner of the Four-Helical Cytokines.	4
35597866	2022	Calcium-binding protein S100P is a new target gene of MACC1, drives colorectal cancer metastasis and serves as a prognostic biomarker.	9
36187124	2022	S100P promotes trophoblast syncytialization during early placenta development by regulating YAP1.	2

Citation

Sayka Barry ; Tatjana Crnogorac-Jurcevic

S100P (S100 calcium binding protein P)

Atlas Genet Cytogenet Oncol Haematol. 2008-07-01

Online version: http://atlasgeneticsoncology.org/gene/42196/gene-explorer/css/gene-fusions-explorer/