Tchem PIM1 Serine/threonine-protein kinase pim-1

Protein Summary

Description

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. The protein encoded by this gene belongs to the Ser/Thr protein kinase family, and PIM subfamily. This gene is expressed primarily in B-lymphoid and myeloid cell lines, and is overexpressed in hematopoietic malignancies and in prostate cancer. It plays a role in signal transduction in blood cells, contributing to both cell proliferation and survival, and thus provides a selective advantage in tumorigenesis. Both the human and orthologous mouse genes have been reported to encode two isoforms (with preferential cellular localization) resulting from the use of alternative in-frame translation initiation codons, the upstream non-AUG (CUG) and downstream AUG codons (PMIDs:16186805, 1825810).[provided by RefSeq, Aug 2011]

Uniprot Accession IDs

• P11309
• Q38RT9
• Q5T7H7
• Q96RG3

Gene Name

• PIM1

Ensembl ID

• ENST00000373509
• ENSP00000362608
• ENSG00000137193

Symbol

• PIM

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
disease perturbation	1
PubMedID	1
molecular function	0.98
virus perturbation	0.98
transcription factor binding site profile	0.96

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Camk Group / Pim Family / Serine/threonine-protein Kinase Pim-1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 207.3   (req: < 5)

Gene RIFs: 176   (req: <= 3)

Antibodies: 649   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 207.3   (req: >= 5)

Gene RIFs: 176   (req: > 3)

Antibodies: 649   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 18

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 2684

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 3

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (5)

ProKinO

The ProKinO is a protein kinase-specific ontology, which provides a controlled vocabulary of terms, their hierarchy, and relationships unifying sequence, structure, function, mutation and pathway information on kinases.

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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (3)

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1 – 3 of 3

quercetin

PIM1Tchem Kinase

pKd : 7.6

abemaciclib

PIM1Tchem Kinase

INHIBITOR pKi : 9.22

ruboxistaurin

PIM1Tchem Kinase

pKd : 7.92

Active Ligands (2684)

Explore Active Ligands

1 – 10 of 2684

staurosporine

PIM1Tchem Kinase

pKd : 7.89

SID103904479

PIM1Tchem Kinase

pKi : 9

SID103904480

PIM1Tchem Kinase

pKi : 8.4

OTS-167

PIM1Tchem Kinase

pKd : 7.55

SID103904484

PIM1Tchem Kinase

pKi : 8.2

SID103904463

PIM1Tchem Kinase

pKi : 8.3

voruciclib

PIM1Tchem Kinase

pIC50 : 7.92

silmitasertib

PIM1Tchem Kinase

pKd : 7.58

SID103904470

PIM1Tchem Kinase

pKi : 8.1

Bisindolylmaleimide I

PIM1Tchem Kinase

pKd : 8

Protein-Protein Interactions (94)

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1 – 10 of 94

• See Interactions on String-DB

MARK3

Tchem

Family:  Kinase

Novelty:  0.01304552

p_int:  0.999988439

p_ni:  0.000011561

Score:  0.636

Data Source:  BioPlex,STRINGDB

DCP1B

Tdark

Novelty:  0.36605365

p_int:  0.999978026

p_ni:  0.000021974

Score:  0.875

Data Source:  BioPlex,STRINGDB

EDC3

Tbio

Novelty:  0.02077346

p_int:  0.999778636

p_ni:  0.000221364

Score:  0.871

Data Source:  BioPlex,STRINGDB

DCAF4

Tbio

Novelty:  0.24190895

p_int:  0.999157732

p_ni:  0.000842267

p_wrong:  1e-9

Score:  0.211

Data Source:  BioPlex,STRINGDB

DCP1A

Tbio

Novelty:  0.02038933

p_int:  0.970527453

p_ni:  0.029472547

Score:  0.869

Data Source:  BioPlex,STRINGDB

DDX6

Tbio

Family:  Enzyme

Novelty:  0.01032357

p_int:  0.936654222

p_ni:  0.063345778

Score:  0.873

Data Source:  BioPlex,STRINGDB

MYC

Tchem

Family:  TF

Novelty:  0.00005734

Score:  0.98

Data Source:  STRINGDB

NFATC1

Tchem

Family:  TF

Novelty:  0.00130337

Score:  0.966

Data Source:  STRINGDB

STAT3

Tchem

Family:  TF

Novelty:  0.00011808

Score:  0.952

Data Source:  STRINGDB

SND1

Tbio

Family:  Epigenetic

Novelty:  0.00949997

Score:  0.935

Data Source:  STRINGDB

Nearest Tclin Targets (2)

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Upstream (2)

1 – 2 of 2

FLT3

Tclin

Family:  Kinase

KEGG Distance:  2

Common Pathways:  2

1: Acute myeloid leukemia

2: Pathways in cancer

KIT

Tclin

Family:  Kinase

KEGG Distance:  2

Common Pathways:  2

1: Acute myeloid leukemia

2: Pathways in cancer

Pathways (19)

Reactome (4)

KEGG (5)

PathwayCommons (6)

WikiPathways (4)

Cytokine Signaling in Immune system (R-HSA-1280215)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Cytokine Signaling in Immune system	922 targets	R-HSA-1280215
Reactome	Immune System	2246 targets	R-HSA-168256
Reactome	Interleukin-4 and Interleukin-13 signaling	111 targets	R-HSA-6785807
Reactome	Signaling by Interleukins	619 targets	R-HSA-449147

Name	Explore in Pharos	Explore in Source
Cytokine Signaling in Immune system	922 targets	R-HSA-1280215
Immune System	2246 targets	R-HSA-168256
Interleukin-4 and Interleukin-13 signaling	111 targets	R-HSA-6785807
Signaling by Interleukins	619 targets	R-HSA-449147

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (24)

Functions (5)

Components (6)

Processes (13)

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GO Term	Evidence	Assigned by
ATP binding	Inferred from Direct Assay (IDA)	UniProtKB
manganese ion binding	Inferred from Direct Assay (IDA)	UniProtKB
protein serine/threonine kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
ribosomal small subunit binding	Inferred from Physical Interaction (IPI)	UniProtKB
transcription factor binding	Inferred from Physical Interaction (IPI)	UniProtKB

Disease Associations (null)

No disease associations found

GWAS Traits (9)

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5

1 – 5 of 9

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mean corpuscular volume	EFO_0004526	1	1	1		75.5
mean reticulocyte volume	EFO_0010701	1	2	2		69.2
red blood cell distribution width	EFO_0005192	2	1	2		60.5
platelet count	EFO_0004309	1	1	1		24.3
monocyte percentage of leukocytes	EFO_0007989	1	1	1		12.8

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5

1 – 5 of 9

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mean corpuscular volume	EFO_0004526	1		75.5
mean reticulocyte volume	EFO_0010701	2		69.2
red blood cell distribution width	EFO_0005192	2		60.5
platelet count	EFO_0004309	1		24.3
monocyte percentage of leukocytes	EFO_0007989	1		12.8

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative initiation
Apoptosis
ATP-binding
Cell cycle
Cell membrane
Complete proteome
Cytoplasm
Direct protein sequencing
Kinase

GWAS Trait Find Similar Targets

No Header	No Header
apolipoprotein B measurement
birth weight
low density lipoprotein cholesterol measurement
mean corpuscular volume
mean reticulocyte volume
monocyte percentage of leukocytes
platelet count
red blood cell distribution width
total cholesterol measurement

MGI Phenotype Find Similar Targets

No Header	No Header
endocrine/exocrine gland phenotype
hematopoietic system phenotype
immune system phenotype
neoplasm

IDG Resources

No IDG generated resources found

Orthologs (8)

1 – 5 of 8

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Mouse	proviral integration site 1	MGI:97584	18712
Rat	Pim-1 proto-oncogene, serine/threonine kinase	RGD:3330	24649
Horse	Pim-1 proto-oncogene, serine/threonine kinase	VGNC:21456	100053898
Cow	Pim-1 proto-oncogene, serine/threonine kinase	VGNC:32899	281402
Pig	Pim-1 proto-oncogene, serine/threonine kinase		100157844

Species	Name	OMA	EggNOG	Inparanoid
Mouse	proviral integration site 1
Rat	Pim-1 proto-oncogene, serine/threonine kinase
Horse	Pim-1 proto-oncogene, serine/threonine kinase
Cow	Pim-1 proto-oncogene, serine/threonine kinase
Pig	Pim-1 proto-oncogene, serine/threonine kinase

Publication Statistics

PubMed Score 207.30

PubMed score by year

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PubTator Score 589.62

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Related Publications

Text Mined References (212)

GeneRif Annotations (176)

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PMID	Year	Title