Details for: PIM2

Gene ID: 11040

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: PIM2

Ensembl ID: ENSG00000102096

Description: Pim-2 proto-oncogene, serine/threonine kinase

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • plasmablast CL0000980
    CSI 54.08
    rCSI 42.55%
    PRS 83.61
  • IgA plasma cell CL0000987
    CSI 36.89
    rCSI 37.76%
    PRS 86.43
  • IgG plasma cell CL0000985
    CSI 30.31
    rCSI 36.3%
    PRS 88.53
  • plasma cell CL0000786
    CSI 30
    rCSI 39.32%
    PRS 91.55
  • CD8-positive, alpha-beta cytotoxic T cell CL0000794
    CSI 22.06
    rCSI 26.34%
    PRS 92.53
  • CD4-positive, CD25-positive, alpha-beta regulatory T cell CL0000792
    CSI 19.08
    rCSI 18.73%
    PRS 90.97
  • effector memory CD8-positive, alpha-beta T cell CL0000913
    CSI 12.59
    rCSI 11.47%
    PRS 89.98
  • IgM plasma cell CL0000986
    CSI 11.22
    rCSI 50.49%
    PRS 94
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 10.95
    rCSI 13.22%
    PRS 85.95
  • regulatory T cell CL0000815
    CSI 9.12
    rCSI 10.57%
    PRS 79.87
  • naive thymus-derived CD4-positive, alpha-beta T cell CL0000895
    CSI 8.46
    rCSI 10.63%
    PRS 93.14
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 7.64
    rCSI 5.15%
    PRS 90.5
  • mature alpha-beta T cell CL0000791
    CSI 7.52
    rCSI 27.23%
    PRS 92.78
  • CD16-negative, CD56-bright natural killer cell, human CL0000938
    CSI 6.44
    rCSI 4.83%
    PRS 94.5
  • naive thymus-derived CD8-positive, alpha-beta T cell CL0000900
    CSI 6.33
    rCSI 4.45%
    PRS 91.8
  • activated CD4-positive, alpha-beta T cell CL0000896
    CSI 6.15
    rCSI 5.69%
    PRS 92.28
  • common dendritic progenitor CL0001029
    CSI 6.1
    rCSI 7.65%
    PRS 87.01
  • alpha-beta T cell CL0000789
    CSI 5.99
    rCSI 7.02%
    PRS 91.29
  • activated type II NK T cell CL0000931
    CSI 5.86
    rCSI 6.59%
    PRS 90.8
  • fraction A pre-pro B cell CL0002045
    CSI 5.85
    rCSI 6.69%
    PRS 89.02
  • effector memory CD4-positive, alpha-beta T cell CL0000905
    CSI 5.54
    rCSI 7.54%
    PRS 94.26
  • CD4-positive helper T cell CL0000492
    CSI 5.28
    rCSI 3.99%
    PRS 89.95
  • group 3 innate lymphoid cell CL0001071
    CSI 5.23
    rCSI 3.93%
    PRS 83.96
  • memory B cell CL0000787
    CSI 5.16
    rCSI 5.1%
    PRS 91.03
  • myeloid leukocyte CL0000766
    CSI 5.05
    rCSI 4.66%
    PRS 79.64
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 4.86
    rCSI 3.49%
    PRS 90.46
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 4.82
    rCSI 4.91%
    PRS 88.03
  • central memory CD4-positive, alpha-beta T cell CL0000904
    CSI 4.4
    rCSI 2.6%
    PRS 92.85
  • T follicular helper cell CL0002038
    CSI 4.31
    rCSI 3.22%
    PRS 90.35
  • naive T cell CL0000898
    CSI 4.24
    rCSI 2.95%
    PRS 91.61
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 4.15
    rCSI 5.44%
    PRS 88.61
  • CD4-positive, alpha-beta thymocyte CL0000810
    CSI 4.14
    rCSI 3.32%
    PRS 91.49
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 3.91
    rCSI 2.98%
    PRS 90.19
  • dendritic cell, human CL0001056
    CSI 3.82
    rCSI 5.87%
    PRS 86.63
  • double negative thymocyte CL0002489
    CSI 3.82
    rCSI 2.65%
    PRS 89.18
  • erythrocyte CL0000232
    CSI 3.64
    rCSI 8.25%
    PRS 79.11
  • mature T cell CL0002419
    CSI 3.61
    rCSI 2.81%
    PRS 91.74
  • unswitched memory B cell CL0000970
    CSI 3.52
    rCSI 2.96%
    PRS 90.68
  • class switched memory B cell CL0000972
    CSI 3.28
    rCSI 2.45%
    PRS 90.35
  • hematopoietic stem cell CL0000037
    CSI 3.23
    rCSI 2.15%
    PRS 81.11
  • immature B cell CL0000816
    CSI 3.22
    rCSI 2.39%
    PRS 88.86
  • group 2 innate lymphoid cell CL0001069
    CSI 3.19
    rCSI 17.26%
    PRS 94.72
  • early lymphoid progenitor CL0000936
    CSI 3.18
    rCSI 2.79%
    PRS 83.24
  • precursor B cell CL0000817
    CSI 3.16
    rCSI 2.77%
    PRS 85.58
  • megakaryocyte CL0000556
    CSI 3.14
    rCSI 13.62%
    PRS 84.22
  • deuterosomal cell CL4033044
    CSI 3.09
    rCSI 10.43%
    PRS 76.61
  • natural T-regulatory cell CL0000903
    CSI 3.07
    rCSI 5.82%
    PRS 95.85
  • pro-B cell CL0000826
    CSI 3.04
    rCSI 2.52%
    PRS 80.78
  • activated CD8-positive, alpha-beta T cell CL0000906
    CSI 3.02
    rCSI 2.97%
    PRS 91.41
  • plasmacytoid dendritic cell, human CL0001058
    CSI 2.94
    rCSI 2.05%
    PRS 81.54
  • T-helper 17 cell CL0000899
    CSI 2.91
    rCSI 2.31%
    PRS 93.96
  • mononuclear phagocyte CL0000113
    CSI 2.77
    rCSI 6.1%
    PRS 81.89
  • ciliated epithelial cell CL0000067
    CSI 2.75
    rCSI 2.42%
    PRS 67.23
  • ependymal cell CL0000065
    CSI 2.56
    rCSI 5.19%
    PRS 56.66
  • T-helper 1 cell CL0000545
    CSI 2.36
    rCSI 4.25%
    PRS 93.21
  • lung ciliated cell CL1000271
    CSI 2.34
    rCSI 2.71%
    PRS 70.35
  • Langerhans cell CL0000453
    CSI 2.33
    rCSI 3.56%
    PRS 89.2
  • innate lymphoid cell CL0001065
    CSI 2.31
    rCSI 4.77%
    PRS 75.79
  • effector CD4-positive, alpha-beta T cell CL0001044
    CSI 2.19
    rCSI 6.29%
    PRS 93.78
  • CD8-positive, alpha-beta thymocyte CL0000811
    CSI 2.18
    rCSI 3.4%
    PRS 93.96
  • mature B cell CL0000785
    CSI 2.04
    rCSI 1.77%
    PRS 87.6
  • granulocyte CL0000094
    CSI 1.98
    rCSI 3.02%
    PRS 85.65
  • multi-ciliated epithelial cell CL0005012
    CSI 1.96
    rCSI 1.96%
    PRS 72.05
  • neutrophil CL0000775
    CSI 1.93
    rCSI 10.81%
    PRS 80.07
  • small pre-B-II cell CL0000954
    CSI 1.7
    rCSI 1.64%
    PRS 91.88
  • intraepithelial lymphocyte CL0002496
    CSI 1.66
    rCSI 4.53%
    PRS 94.43
  • common lymphoid progenitor CL0000051
    CSI 1.48
    rCSI 1.97%
    PRS 92.39
  • lung resident memory CD8-positive, alpha-beta T cell CL4033039
    CSI 1.41
    rCSI 3.66%
    PRS 93.79
  • CD4-positive, alpha-beta cytotoxic T cell CL0000934
    CSI 1.38
    rCSI 1.89%
    PRS 93.05
  • memory T cell CL0000813
    CSI 1.29
    rCSI 2.48%
    PRS 94.59
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 1.27
    rCSI 1.15%
    PRS 76.45
  • basophil CL0000767
    CSI 1.23
    rCSI 2.6%
    PRS 89.73
  • transitional stage B cell CL0000818
    CSI 1.21
    rCSI 3.96%
    PRS 93.44
  • myeloid dendritic cell CL0000782
    CSI 1.19
    rCSI 1.72%
    PRS 90.52
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 1.11
    rCSI 5.59%
    PRS 89.49
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.07
    rCSI 1.29%
    PRS 59.59
  • follicular B cell CL0000843
    CSI 0.98
    rCSI 3.57%
    PRS 92.51
  • large pre-B-II cell CL0000957
    CSI 0.95
    rCSI 2.7%
    PRS 84.27
  • germinal center B cell CL0000844
    CSI 0.93
    rCSI 2.77%
    PRS 88.33
  • antibody secreting cell CL0000946
    CSI 0.84
    rCSI 3.76%
    PRS 95.81
  • CD8-alpha-alpha-positive, alpha-beta intraepithelial T cell CL0000915
    CSI 0.71
    rCSI 3.23%
    PRS 94.04
  • helper T cell CL0000912
    CSI 0.69
    rCSI 0.98%
    PRS 77.87
  • CD34-positive, CD56-positive, CD117-positive common innate lymphoid precursor, human CL0001074
    CSI 0.3
    rCSI 3.53%
    PRS 93.2
  • erythroid progenitor cell CL0000038
    CSI 0.25
    rCSI 1.41%
    PRS 83.91

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [PIM2](/details-gene/11040) (Pim-2 proto-oncogene, serine/threonine kinase) is a protein-coding gene located on the X chromosome that encodes a serine/threonine-protein kinase. This kinase plays a critical role in fundamental cellular processes including cell cycle progression, protein stabilization, and the negative regulation of apoptosis. Its function as a proto-oncogene is underscored by its involvement in promoting cell survival and proliferation. **Overall**, expression data reveals that [PIM2](/details-gene/11040) is a highly significant gene in the adaptive immune system, with particularly strong expression in terminally differentiated B-lymphocytes such as [plasmablasts](/details-cell/CL0000980) and various classes of [plasma cells](/details-cell/CL0000786). It is also significantly expressed in several T cell subsets, including [CD8-positive, alpha-beta cytotoxic T cells](/details-cell/CL0000794) and [regulatory T cells](/details-cell/CL0000815), suggesting a broad role in lymphocyte biology. Its clinical relevance is noted in its OMIM association ([300295](https://omim.org/entry/300295)). ## Cellular Roles and Expression Landscape The expression profile of [PIM2](/details-gene/11040) firmly establishes its importance within the hematopoietic system, particularly in mature, activated lymphocytes. The **Overall** analysis identifies [PIM2](/details-gene/11040) as a top marker for cells of the B cell lineage responsible for antibody production. It exhibits the highest significance in [plasmablasts](/details-cell/CL0000980) (CSI: 54.08), followed by [IgA plasma cells](/details-cell/CL0000987), [IgG plasma cells](/details-cell/CL0000985), and generic [plasma cells](/details-cell/CL0000786). This strong and specific expression pattern suggests that [PIM2](/details-gene/11040) is a crucial workhorse kinase required for the high metabolic and secretory activity, as well as the long-term survival, of these terminally differentiated cells. Beyond the B cell compartment, [PIM2](/details-gene/11040) also plays a significant role in the T cell lineage. It is highly expressed in [CD8-positive, alpha-beta cytotoxic T cells](/details-cell/CL0000794), [CD4-positive, CD25-positive, alpha-beta regulatory T cells](/details-cell/CL0000792), and their respective memory and naive subsets. This indicates a conserved function in supporting the proliferation, survival, and effector functions across different lymphocyte populations. Its moderate expression in [CD1c-positive myeloid dendritic cells](/details-cell/CL0002399) suggests it may also contribute to the function of some antigen-presenting cells. ## Pathways and Molecular Function The molecular functions of [PIM2](/details-gene/11040) are consistent with its role as a proto-oncogenic kinase driving cell survival and proliferation. As a protein serine/threonine kinase ([GO:0004674](https://www.ebi.ac.uk/QuickGO/term/GO:0004674)), its primary activity is protein phosphorylation ([GO:0006468](https://www.ebi.ac.uk/QuickGO/term/GO:0006468)), requiring ATP binding ([GO:0005524](https://www.ebi.ac.uk/QuickGO/term/GO:0005524)). This kinase activity is integral to several key biological processes: * **Cell Cycle Regulation:** [PIM2](/details-gene/11040) is involved in the [G1/S transition of the mitotic cell cycle](/details-cell/GO0000082) and its broader regulation ([GO:0007346](https://www.ebi.ac.uk/QuickGO/term/GO:0007346)). Research has shown that PIM kinases can promote cell cycle progression by phosphorylating and regulating cell cycle inhibitors like p27Kip1 and p21Cip1/WAF1 ([Link](https://doi.org/10.1158/0008-5472.can-08-0634), [Link](https://doi.org/10.1016/j.biocel.2010.03.012)). * **Survival and Apoptosis:** The gene is a potent [negative regulator of the apoptotic process](/details-cell/GO0043066), contributing to cell survival by influencing [apoptotic mitochondrial changes](/details-cell/GO0008637). This anti-apoptotic function is critical for the maintenance of long-lived cells like plasma cells and memory T cells, where it is highly expressed. Studies have directly implicated PIM2 in preventing apoptosis and promoting tumorigenesis in liver cells ([Link](https://doi.org/10.1016/j.jss.2008.03.033)). * **Autophagy and Signaling:** [PIM2](/details-gene/11040) positively regulates macroautophagy ([GO:0016239](https://www.ebi.ac.uk/QuickGO/term/GO:0016239)) and [canonical NF-kappaB signal transduction](/details-cell/GO0043123), two pathways essential for cellular homeostasis, stress response, and immune cell activation. These functions align perfectly with its expression in highly proliferative and long-lived lymphocyte populations, providing the molecular basis for its role in sustaining robust immune responses. ## Research Directions The specific and high-level expression of the proto-oncogene [PIM2](/details-gene/11040) in terminally differentiated lymphocytes, combined with its known anti-apoptotic and pro-proliferative functions, makes it a compelling subject for translational research, particularly in hematological malignancies. **Proposed Hypotheses:** 1. Given its exceptionally high expression in [plasmablasts](/details-cell/CL0000980) and [plasma cells](/details-cell/CL0000786), [PIM2](/details-gene/11040) kinase activity is a critical dependency for the survival of malignant plasma cells in multiple myeloma. Its inhibition would therefore represent a targeted therapeutic strategy to induce apoptosis in these cancer cells. 2. The significant expression of [PIM2](/details-gene/11040) in [regulatory T cells](/details-cell/CL0000815) suggests that its activity is necessary for their suppressive function and stability, potentially by regulating the expression of key transcription factors like FOXP3 through downstream signaling or by supporting their metabolic fitness in inflammatory environments. **Experimental Approach:** To test the first hypothesis regarding the role of [PIM2](/details-gene/11040) in multiple myeloma, a multi-pronged approach could be employed. Initially, CRISPR-Cas9 or shRNA could be used to silence [PIM2](/details-gene/11040) expression in a panel of human multiple myeloma cell lines. The impact on cell viability, proliferation, and apoptosis could be quantified using assays like CellTiter-Glo, BrdU incorporation, and Annexin V/PI flow cytometry. Subsequently, the efficacy of selective small-molecule inhibitors of PIM2 kinase could be evaluated in these cell lines and in patient-derived xenograft (PDX) mouse models of multiple myeloma to assess their potential for inducing tumor regression *in vivo*. **Therapeutic Potential:** As a serine/threonine kinase with a clear role in promoting cell survival and proliferation, [PIM2](/details-gene/11040) is an attractive therapeutic target. The strategy would focus on **inhibition**. Its high expression in lymphocyte malignancies, such as multiple myeloma and potentially certain lymphomas or leukemias, suggests that PIM2 inhibitors could offer a targeted therapy with a favorable therapeutic window. The availability of its crystal structure facilitates the rational design of potent and selective small-molecule inhibitors ([Link](https://doi.org/10.1371/journal.pone.0007112)), making it a highly druggable target for oncological applications.

Genular Protein ID: 1610401288

Symbol: PIM2_HUMAN

Name: Serine/threonine-protein kinase pim-2

UniProtKB Accession Codes:

Q9P1W9 A8K4G6 Q99739

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 12 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugCentral 1 EC 3 EMBL 5 Ensembl 2 EvolutionaryTrace 1 ExpressionAtlas 1 GO 17 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GuidetoPHARMACOLOGY 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PIRSF 1 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 1 Rhea 6 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 9804974

Title: The human Pim-2 proto-oncogene and its testicular expression.

PubMed ID: 9804974

DOI: 10.1016/s0167-4781(98)00185-7

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 16548883

Title: Transcriptomic and proteomic analyses of rhabdomyosarcoma cells reveal differential cellular gene expression in response to enterovirus 71 infection.

PubMed ID: 16548883

DOI: 10.1111/j.1462-5822.2005.00644.x

PubMed ID: 18593906

Title: Pim kinases promote cell cycle progression by phosphorylating and down-regulating p27Kip1 at the transcriptional and posttranscriptional levels.

PubMed ID: 18593906

DOI: 10.1158/0008-5472.can-08-0634

PubMed ID: 18675992

Title: Serine/threonine kinase Pim-2 promotes liver tumorigenesis induction through mediating survival and preventing apoptosis of liver cell.

PubMed ID: 18675992

DOI: 10.1016/j.jss.2008.03.033

PubMed ID: 20307683

Title: Pim-2 phosphorylation of p21(Cip1/WAF1) enhances its stability and inhibits cell proliferation in HCT116 cells.

PubMed ID: 20307683

DOI: 10.1016/j.biocel.2010.03.012

PubMed ID: 19841674

Title: Crystal structure of the PIM2 kinase in complex with an organoruthenium inhibitor.

PubMed ID: 19841674

DOI: 10.1371/journal.pone.0007112

PubMed ID: 17344846

Title: Patterns of somatic mutation in human cancer genomes.

PubMed ID: 17344846

DOI: 10.1038/nature05610

Sequence Information:

  • Length: 311
  • Mass: 34190
  • Checksum: 160E56C368C67A69
  • Sequence:
    • MLTKPLQGPP APPGTPTPPP GGKDREAFEA EYRLGPLLGK GGFGTVFAGH RLTDRLQVAI 
KVIPRNRVLG WSPLSDSVTC PLEVALLWKV GAGGGHPGVI RLLDWFETQE GFMLVLERPL 
PAQDLFDYIT EKGPLGEGPS RCFFGQVVAA IQHCHSRGVV HRDIKDENIL IDLRRGCAKL 
IDFGSGALLH DEPYTDFDGT RVYSPPEWIS RHQYHALPAT VWSLGILLYD MVCGDIPFER 
DQEILEAELH FPAHVSPDCC ALIRRCLAPK PSSRPSLEEI LLDPWMQTPA EDVPLNPSKG 
GPAPLAWSLL P