Browse PIM1

Summary
SymbolPIM1
NamePim-1 proto-oncogene, serine/threonine kinase
Aliases PIM; pim-1 oncogene; Oncogene PIM1; pim-1 kinase 44 kDa isoform; pim-1 oncogene (proviral integration site 1 ......
Chromosomal Location6p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Isoform 2: Cytoplasm. Nucleus.; SUBCELLULAR LOCATION: Isoform 1: Cell membrane.
Domain PF00069 Protein kinase domain
Function

Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Phosphorylation of MAP3K5, an other proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis. Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C. Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability. Promote cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels. Phosphorylation of CDKN1B,induces 14-3-3-proteins binding, nuclear export and proteasome-dependent degradation. May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3. Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis.

> Gene Ontology
 
Biological Process GO:0006022 aminoglycan metabolic process
GO:0007584 response to nutrient
GO:0009991 response to extracellular stimulus
GO:0030203 glycosaminoglycan metabolic process
GO:0030212 hyaluronan metabolic process
GO:0030522 intracellular receptor signaling pathway
GO:0031667 response to nutrient levels
GO:0031668 cellular response to extracellular stimulus
GO:0031669 cellular response to nutrient levels
GO:0031670 cellular response to nutrient
GO:0033273 response to vitamin
GO:0033280 response to vitamin D
GO:0043433 negative regulation of sequence-specific DNA binding transcription factor activity
GO:0046777 protein autophosphorylation
GO:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0070561 vitamin D receptor signaling pathway
GO:0071295 cellular response to vitamin
GO:0071305 cellular response to vitamin D
GO:0071396 cellular response to lipid
GO:0071407 cellular response to organic cyclic compound
GO:0071496 cellular response to external stimulus
GO:1903510 mucopolysaccharide metabolic process
Molecular Function GO:0004674 protein serine/threonine kinase activity
GO:0008134 transcription factor binding
GO:0030145 manganese ion binding
GO:0043021 ribonucleoprotein complex binding
GO:0043024 ribosomal small subunit binding
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa04630 Jak-STAT signaling pathway
Reactome R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-168256: Immune System
R-HSA-6785807: Interleukin-4 and 13 signaling
R-HSA-449147: Signaling by Interleukins
Summary
SymbolPIM1
NamePim-1 proto-oncogene, serine/threonine kinase
Aliases PIM; pim-1 oncogene; Oncogene PIM1; pim-1 kinase 44 kDa isoform; pim-1 oncogene (proviral integration site 1 ......
Chromosomal Location6p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between PIM1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between PIM1 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
19147983Prostate CarcinomaInhibit immunityTreatment of human and mouse prostate cancer cell lines with the PIM-1-specific mAb resulted in disruption of PIM-1/Hsp90 complexes, decreased PIM-1 and Hsp90 levels, reduced Akt phosphorylation at Ser473, reduced phosphorylation of Bad at Ser112 and Ser136, and increased cleavage of caspase-9, an indicator of activation of the mitochondrial cell death pathway. The mAb induced cancer cell apoptosis and synergistically enhanced antitumor activity when used in combination with cisplatin and epirubicin. In tumor models, the PIM-1-specific mAb substantially inhibited growth of the human prostate cancer cell line DU145 in SCID mice and the mouse prostate cancer cell TRAMP-C1 in C57BL/6 mice.
28698206Hodgkin LymphomaInhibit immunityGenetic or chemical PIM inhibition with a newly developed pan-PIM inhibitor, SEL24-B489, induced RS cell apoptosis. PIM inhibition decreased cap-dependent protein translation, blocked JAK-STAT signaling, and markedly attenuated NFκB-dependent gene expression. Taken together, our data indicate that PIM kinases in cHL exhibit pleiotropic effects, orchestrating tumor immune escape and supporting RS cell survival.
Summary
SymbolPIM1
NamePim-1 proto-oncogene, serine/threonine kinase
Aliases PIM; pim-1 oncogene; Oncogene PIM1; pim-1 kinase 44 kDa isoform; pim-1 oncogene (proviral integration site 1 ......
Chromosomal Location6p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of PIM1 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolPIM1
NamePim-1 proto-oncogene, serine/threonine kinase
Aliases PIM; pim-1 oncogene; Oncogene PIM1; pim-1 kinase 44 kDa isoform; pim-1 oncogene (proviral integration site 1 ......
Chromosomal Location6p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of PIM1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.1050.791
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.3540.858
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.0920.941
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.0160.975
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.1420.951
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.1390.963
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.240.585
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.4610.739
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.0310.984
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.9160.531
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.0970.618
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.0590.628
> Mutation difference between responders and non-responders
 

There is no record.

Summary
SymbolPIM1
NamePim-1 proto-oncogene, serine/threonine kinase
Aliases PIM; pim-1 oncogene; Oncogene PIM1; pim-1 kinase 44 kDa isoform; pim-1 oncogene (proviral integration site 1 ......
Chromosomal Location6p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PIM1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolPIM1
NamePim-1 proto-oncogene, serine/threonine kinase
Aliases PIM; pim-1 oncogene; Oncogene PIM1; pim-1 kinase 44 kDa isoform; pim-1 oncogene (proviral integration site 1 ......
Chromosomal Location6p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PIM1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PIM1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolPIM1
NamePim-1 proto-oncogene, serine/threonine kinase
Aliases PIM; pim-1 oncogene; Oncogene PIM1; pim-1 kinase 44 kDa isoform; pim-1 oncogene (proviral integration site 1 ......
Chromosomal Location6p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PIM1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolPIM1
NamePim-1 proto-oncogene, serine/threonine kinase
Aliases PIM; pim-1 oncogene; Oncogene PIM1; pim-1 kinase 44 kDa isoform; pim-1 oncogene (proviral integration site 1 ......
Chromosomal Location6p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of PIM1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolPIM1
NamePim-1 proto-oncogene, serine/threonine kinase
Aliases PIM; pim-1 oncogene; Oncogene PIM1; pim-1 kinase 44 kDa isoform; pim-1 oncogene (proviral integration site 1 ......
Chromosomal Location6p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between PIM1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolPIM1
NamePim-1 proto-oncogene, serine/threonine kinase
Aliases PIM; pim-1 oncogene; Oncogene PIM1; pim-1 kinase 44 kDa isoform; pim-1 oncogene (proviral integration site 1 ......
Chromosomal Location6p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting PIM1 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting PIM1.
ID Name Drug Type Targets #Targets
DB00131Adenosine monophosphateSmall MoleculeACSL1, ACSS1, ACSS2, ADCY1, ADK, CREB1, FBP1, HINT1, PDE4B, PDE4D, ......15
DB017543,4-Dihydroxy-1-Methylquinolin-2(1h)-OneSmall MoleculePIM11
DB02010StaurosporineSmall MoleculeCDK2, CHRM1, CSK, GSK3B, ITK, LCK, MAPKAPK2, PDPK1, PIK3CG, PIM1, ......13
DB02656LY-294002Small MoleculePIK3CG, PIM12
DB03366ImidazoleSmall MoleculeAK2, CYCS, DMC1, GPHN, LTA4H, MB, MYO1E, NOS2, PIM19
DB03650(3e)-3-[(4-Hydroxyphenyl)Imino]-1h-Indol-2(3h)-OneSmall MoleculePIM11
DB03777Rbt205 InhibitorSmall MoleculePDPK1, PIM1, PRKCI3
DB04216QuercetinSmall MoleculeACTB, AHR, ATP5A1, ATP5B, ATP5C1, CBR1, CEBPB, CSNK2A1, CSNK2B, CY ......27
DB04395Phosphoaminophosphonic Acid-Adenylate EsterSmall MoleculeACTA1, CCT3, CFTR, CSNK2A1, DAPK1, DTYMK, EPHA2, EPHB2, GALK1, GSK ......26
DB04522DexfosfoserineSmall MoleculeCFTR, KCNC4, PDPK1, PIM1, PRKACA, PRKCQ, PYGL, PYGM, REG1A, RHO, S ......13
DB04530S,S-(2-Hydroxyethyl)ThiocysteineSmall MoleculeARG1, CYTH2, PDE1B, PDE4B, PIM1, PRKACA, SERPINB5, SNX3, TYMS9
DB04715IMIDAZOPYRIDAZIN 1Small MoleculePIM11
DB071514-(4-hydroxy-3-methylphenyl)-6-phenylpyrimidin-2(5H)-oneSmall MoleculePIM11
DB07242(4R)-7,8-dichloro-1',9-dimethyl-1-oxo-1,2,4,9-tetrahydrospiro[beta-carboline-3,4'-piperidine]-4-carbonitrileSmall MoleculeDAPK3, PIM12
DB07524N-phenyl-1H-pyrrolo[2,3-b]pyridin-3-amineSmall MoleculePIM11
DB08022(2S)-1,3-benzothiazol-2-yl{2-[(2-pyridin-3-ylethyl)amino]pyrimidin-4-yl}ethanenitrileSmall MoleculePIM11
DB08166(4R)-7-chloro-9-methyl-1-oxo-1,2,4,9-tetrahydrospiro[beta-carboline-3,4'-piperidine]-4-carbonitrileSmall MoleculePIM11
DB082305,7-DIHYDROXY-2-(3,4,5-TRIHYDROXYPHENYL)-4H-CHROMEN-4-ONESmall MoleculePIM11
DB087056-(5-BROMO-2-HYDROXYPHENYL)-2-OXO-4-PHENYL-1,2-DIHYDROPYRIDINE-3-CARBONITRILESmall MoleculePIM11
DB087074-[3-(4-chlorophenyl)-2,1-benzisoxazol-5-yl]pyrimidin-2-amineSmall MoleculePIM11
DB08708N-cyclohexyl-3-[3-(trifluoromethyl)phenyl][1,2,4]triazolo[4,3-b]pyridazin-6-amineSmall MoleculePIM11
DB087092,3-diphenyl-1H-indole-7-carboxylic acidSmall MoleculePIM11