Biomarker: S18-2

Histology type: endometrial carcinoma

Country: Sweden

Region: Stockholm

Followed up time :

Subgroup 1 name : EC

Subgroup 1 number: 42

Subgroup 2 name: normal endometrium (NE)

Subgroup 2 number: 84

Conclusion: We conclude that high expression of S18-2 and free E2F1, and low pan-keratin, beta-catenin, and E-cadherin signals might be a good set of prognostic markers for EC.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : combination of high S18-2 and free E2F1 expression

Funtion description: The EC cell line HEC-1-A, which overexpresses S18-2 constitutively, showed an increased proliferation capacity in vitro and in vivo (in SCID mice). Moreover, pan-keratin, beta-catenin and E-cadherin signals are diminished in these cells, compared to the parental HEC-1-A line, in contrast to vimentin signal that is increased. This may be associated with epithelial-mesenchymal cell transition (EMT).

Funtion Uniprot: Catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:15274632, PubMed:10545183, PubMed:10593990, PubMed:10206644, PubMed:10899933, PubMed:10811883, PubMed:12679784, PubMed:12740439, PubMed:25043039, PubMed:26280335, PubMed:30598546, PubMed:30630874, PubMed:28269784, PubMed:20460383). Requires the presence of the other members of the gamma-secretase complex for protease activity (PubMed:15274632, PubMed:25043039, PubMed:26280335, PubMed:30598546, PubMed:30630874). Plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels (PubMed:9738936, PubMed:10593990, PubMed:10899933, PubMed:10811883). Stimulates cell-cell adhesion via its interaction with CDH1; this stabilizes the complexes between CDH1 (E-cadherin) and its interaction partners CTNNB1 (beta-catenin), CTNND1 and JUP (gamma-catenin) (PubMed:11953314). Under conditions of apoptosis or calcium influx, cleaves CDH1 (PubMed:11953314). This promotes the disassembly of the complexes between CDH1 and CTNND1, JUP and CTNNB1, increases the pool of cytoplasmic CTNNB1, and thereby negatively regulates Wnt signaling (PubMed:9738936, PubMed:11953314). Required for normal embryonic brain and skeleton development, and for normal angiogenesis (By similarity). Mediates the proteolytic cleavage of EphB2/CTF1 into EphB2/CTF2 (PubMed:17428795, PubMed:28269784). The holoprotein functions as a calcium-leak channel that allows the passive movement of calcium from endoplasmic reticulum to cytosol and is therefore involved in calcium homeostasis (PubMed:25394380, PubMed:16959576). Involved in the regulation of neurite outgrowth (PubMed:15004326, PubMed:20460383). Is a regulator of presynaptic facilitation, spike transmission and synaptic vesicles replenishment in a process that depends on gamma-secretase activity. It acts through the control of SYT7 presynaptic expression (By similarity).

UniProt ID: P49768

UniProt Link: https://www.uniprot.org/uniprotkb/P49768/entry

Biological function from UniProt: #Apoptosis #Cell adhesion #Notch signaling pathway

Molecular function from UniProt:

Tissue specificity from UniProt: Detected in azurophile granules in neutrophils and in platelet cytoplasmic granules (at protein level) (PubMed:11987239). Expressed in a wide range of tissues including various regions of the brain, liver, spleen and lymph nodes (PubMed:7596406, PubMed:8641442, PubMed:8574969).

Subcellular UniProt: #Cell membrane #Cell projection #Endoplasmic reticulum #Endosome #Golgi apparatus

Alternative name from UniProt:

Recommended name: Presenilin-1

Gene name from HGNC: PSEN1 (AD3, FAD, PS1, S182)

HPA class: Cancer-related genes Disease related genes Enzymes Human disease related genes Potential drug targets Transporters

AlphaFold DB: P49768

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/P49768

HPA link: https://www.proteinatlas.org/ENSG00000080815-PSEN1

Tissue specificity RNA from HPA: Low tissue specificity

Tissue expression from HPA: Granular cytoplasmic expression in most tissues.

Single cell type specificity Cell type enriched (Oligodendrocytes)

Immune cell specificity: Low immune cell specificity

Subcellular summary HPA Located in Nucleoplasm, Golgi apparatus, Cell Junctions (Single cell variability, CCD Protein)

Cancer prognostic summary HPA Prognostic marker in renal cancer (favorable) and liver cancer (unfavorable)

Pathology link: https://www.proteinatlas.org/ENSG00000080815-PSEN1/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000080815-PSEN1/pathology/endometrial+cancer

Expression figure legend: S18-2 protein expression in cancerous and normal cells

Expression figure link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008351/figure/F1/

Phenotype ID: 607822;600274;613694;613737;

Disease: Alzheimer disease 3 (AD3);Frontotemporal dementia (FTD);Cardiomyopathy, dilated 1U (CMD1U);Acne inversa, familial, 3 (ACNINV3);Pick disease of the brain (PIDB);

Note1: The disease is caused by variants affecting the gene represented in this entry;The disease is caused by variants affecting the gene represented in this entry;The disease is caused by variants affecting the gene represented in this entry;The disease is caused by variants affecting the gene represented in this entry;The gene represented in this entry may be involved in disease pathogenesis;

OMIM: 606473

OMIM link1: https://www.omim.org/entry/607822;https://www.omim.org/entry/600274;https://www.omim.org/entry/613694;https://www.omim.org/entry/613737;https://www.omim.org/entry/172700;

OMIM link2: https://www.omim.org/entry/606473

HGNC ID: HGNC:19801

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:19801