1. Gene Aliases

PIM3, Pim-3 Proto-Oncogene, Serine/Threonine Kinase, Serine/Threonine-Protein Kinase Pim-3, Pim-3 Oncogene, EC 2.7.11.1, Serine/Threonine Kinase Pim-3, Pim-3

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=PIM3&keywords=pim3]

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

GO terms:

apoptotic process [A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died. GO:0006915]

cellular response to forskolin [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a forskolin stimulus. GO:1904322]

negative regulation of apoptotic process [Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process.|This term should only be used when it is not possible to determine which phase or subtype of the apoptotic process is negatively regulated by a gene product. Whenever detailed information is available, the more granular children terms should be used. GO:0043066]

negative regulation of insulin secretion involved in cellular response to glucose stimulus [Any process that decreases the frequency, rate or extent of the regulated release of insulin that contributes to the response of a cell to glucose. GO:0061179]

phosphorylation [The process of introducing a phosphate group into a molecule, usually with the formation of a phosphoric ester, a phosphoric anhydride or a phosphoric amide. GO:0016310]

protein autophosphorylation [The phosphorylation by a protein of one or more of its own amino acid residues (cis-autophosphorylation), or residues on an identical protein (trans-autophosphorylation). GO:0046777]

regulation of mitotic cell cycle [Any process that modulates the rate or extent of progress through the mitotic cell cycle. GO:0007346]

MSigDB Signatures:

ZWANG_CLASS_1_TRANSIENTLY_INDUCED_BY_EGF: Class I of genes transiently induced by EGF [GeneID =1950] in 184A1 cells (mammary epithelium).[https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/ZWANG_CLASS_1_TRANSIENTLY_INDUCED_BY_EGF.html]

7. Gene Descriptions

NCBI Gene Summary: The protein encoded by this gene belongs to the Ser/Thr protein kinase family, and PIM subfamily. This gene is overexpressed in hematological and epithelial tumors and is associated with MYC coexpression. It plays a role in the regulation of signal transduction cascades, contributing to both cell proliferation and survival, and provides a selective advantage in tumorigenesis. [provided by RefSeq, Jun 2012]

GeneCards Summary: PIM3 (Pim-3 Proto-Oncogene, Serine/Threonine Kinase) is a Protein Coding gene. Diseases associated with PIM3 include Hepatic Flexure Cancer and Spinocerebellar Ataxia, X-Linked 5. Among its related pathways are Apoptosis and Autophagy and NF-kappaB Signaling. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is PIM1.

UniProtKB/Swiss-Prot Summary: Proto-oncogene with serine/threonine kinase activity that can prevent apoptosis, promote cell survival and protein translation. May contribute to tumorigenesis through: the delivery of survival signaling through phosphorylation of BAD which induces release of the anti-apoptotic protein Bcl-X(L), the regulation of cell cycle progression, protein synthesis and by regulation of MYC transcriptional activity. Additionally to this role on tumorigenesis, can also negatively regulate insulin secretion by inhibiting the activation of MAPK1/3 (ERK1/2), through SOCS6. Involved also in the control of energy metabolism and regulation of AMPK activity in modulating MYC and PPARGC1A protein levels and cell growth.

8. Cellular Location of Gene Product

Localized to the cytosol. Predicted location: Intracellular [https://www.proteinatlas.org/ENSG00000198355/subcellular]

9. Mechanistic Information

Summary

Pim3, a proto-oncogene with serine/threonine kinase activity, is implicated in promoting cell survival and protein translation [CS: 8]. In the context of skin diseases or toxicities, the dysregulation of Pim3 can be mechanistically linked to its role in cell survival pathways [CS: 7]. When skin cells encounter stress or toxicity, such as in psoriasis, there's an increased demand for mechanisms that prevent apoptosis and promote cell repair and survival [CS: 8]. The role of Pim3 in phosphorylating BAD and inducing the release of the anti-apoptotic protein Bcl-X(L) directly responds to this demand [CS: 7]. This phosphorylation impedes apoptosis, allowing damaged or stressed skin cells to survive longer, which might be a response to ensure the maintenance of skin integrity during periods of stress or disease [CS: 7].

Additionally, the involvement of Pim3 in regulating MYC transcriptional activity and influencing the control of energy metabolism further elucidates its role in response to skin stress [CS: 7]. The upregulation of Pim3 in skin-related diseases can be seen as a cellular response to enhance energy metabolism and protein synthesis, critical for cell survival and repair under toxic conditions [CS: 8]. This upregulation effectively counters the initial stress by bolstering cellular resources and energy, necessary for the maintenance and repair of skin tissue under adverse conditions [CS: 8].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: low tissue specificity [https://www.proteinatlas.org/ENSG00000198355/tissue]

Cell type enchanced: extravillous trophoblasts, langerhans cells, syncytiotrophoblasts (cell type enhanced) [https://www.proteinatlas.org/ENSG00000198355/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest

Most relevant biomarkers with lower score or lower probability of association with disease or organ of interest: