TISIDB

Summary
Symbol	PIM1
Name	Pim-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 Location	6p21
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 [ TOP ]
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 [ TOP ]
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 [ TOP ]
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
Symbol	PIM1
Name	Pim-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 Location	6p21
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

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Literatures describing the relation between PIM1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
19147983	Prostate Carcinoma	Inhibit immunity	Treatment 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.
28698206	Hodgkin Lymphoma	Inhibit immunity	Genetic 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
Symbol	PIM1
Name	Pim-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 Location	6p21
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

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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
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	PIM1
Name	Pim-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 Location	6p21
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

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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
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.105	0.791
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.354	0.858
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.092	0.941
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.016	0.975
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.142	0.951
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.139	0.963
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.24	0.585
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.461	0.739
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.031	0.984
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.916	0.531
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	1.097	0.618
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.059	0.628

> Mutation difference between responders and non-responders [ TOP ]
There is no record.

Summary
Symbol	PIM1
Name	Pim-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 Location	6p21
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 [ TOP ]

Summary
Symbol	PIM1
Name	Pim-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 Location	6p21
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 [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PIM1
Name	Pim-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 Location	6p21
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 [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	PIM1
Name	Pim-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 Location	6p21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PIM1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PIM1
Name	Pim-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 Location	6p21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PIM1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PIM1
Name	Pim-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 Location	6p21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PIM1 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting PIM1.

ID	Name	Drug Type	Targets	#Targets
DB00131	Adenosine monophosphate	Small Molecule	ACSL1, ACSS1, ACSS2, ADCY1, ADK, CREB1, FBP1, HINT1, PDE4B, PDE4D, ......	15
DB01754	3,4-Dihydroxy-1-Methylquinolin-2(1h)-One	Small Molecule	PIM1	1
DB02010	Staurosporine	Small Molecule	CDK2, CHRM1, CSK, GSK3B, ITK, LCK, MAPKAPK2, PDPK1, PIK3CG, PIM1, ......	13
DB02656	LY-294002	Small Molecule	PIK3CG, PIM1	2
DB03366	Imidazole	Small Molecule	AK2, CYCS, DMC1, GPHN, LTA4H, MB, MYO1E, NOS2, PIM1	9
DB03650	(3e)-3-[(4-Hydroxyphenyl)Imino]-1h-Indol-2(3h)-One	Small Molecule	PIM1	1
DB03777	Rbt205 Inhibitor	Small Molecule	PDPK1, PIM1, PRKCI	3
DB04216	Quercetin	Small Molecule	ACTB, AHR, ATP5A1, ATP5B, ATP5C1, CBR1, CEBPB, CSNK2A1, CSNK2B, CY ......	27
DB04395	Phosphoaminophosphonic Acid-Adenylate Ester	Small Molecule	ACTA1, CCT3, CFTR, CSNK2A1, DAPK1, DTYMK, EPHA2, EPHB2, GALK1, GSK ......	26
DB04522	Dexfosfoserine	Small Molecule	CFTR, KCNC4, PDPK1, PIM1, PRKACA, PRKCQ, PYGL, PYGM, REG1A, RHO, S ......	13
DB04530	S,S-(2-Hydroxyethyl)Thiocysteine	Small Molecule	ARG1, CYTH2, PDE1B, PDE4B, PIM1, PRKACA, SERPINB5, SNX3, TYMS	9
DB04715	IMIDAZOPYRIDAZIN 1	Small Molecule	PIM1	1
DB07151	4-(4-hydroxy-3-methylphenyl)-6-phenylpyrimidin-2(5H)-one	Small Molecule	PIM1	1
DB07242	(4R)-7,8-dichloro-1',9-dimethyl-1-oxo-1,2,4,9-tetrahydrospiro[beta-carboline-3,4'-piperidine]-4-carbonitrile	Small Molecule	DAPK3, PIM1	2
DB07524	N-phenyl-1H-pyrrolo[2,3-b]pyridin-3-amine	Small Molecule	PIM1	1
DB08022	(2S)-1,3-benzothiazol-2-yl{2-[(2-pyridin-3-ylethyl)amino]pyrimidin-4-yl}ethanenitrile	Small Molecule	PIM1	1
DB08166	(4R)-7-chloro-9-methyl-1-oxo-1,2,4,9-tetrahydrospiro[beta-carboline-3,4'-piperidine]-4-carbonitrile	Small Molecule	PIM1	1
DB08230	5,7-DIHYDROXY-2-(3,4,5-TRIHYDROXYPHENYL)-4H-CHROMEN-4-ONE	Small Molecule	PIM1	1
DB08705	6-(5-BROMO-2-HYDROXYPHENYL)-2-OXO-4-PHENYL-1,2-DIHYDROPYRIDINE-3-CARBONITRILE	Small Molecule	PIM1	1
DB08707	4-[3-(4-chlorophenyl)-2,1-benzisoxazol-5-yl]pyrimidin-2-amine	Small Molecule	PIM1	1
DB08708	N-cyclohexyl-3-[3-(trifluoromethyl)phenyl][1,2,4]triazolo[4,3-b]pyridazin-6-amine	Small Molecule	PIM1	1
DB08709	2,3-diphenyl-1H-indole-7-carboxylic acid	Small Molecule	PIM1	1

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