Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

PIM1 (P11309) - Overview - Molecular Target Synopsis

Protein


PIM1, Serine/threonine-protein kinase pim-1
Enzyme Classification 2.7.11.1
UniProt P11309

Also Known as PIM1_HUMAN, PIM1

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. Isoform 1 is isolated as a monomer whereas isoform 2 complexes with other proteins (By similarity). Binds to RP9 (By similarity). Isoform 2, but not isoform 1, binds BMX (PubMed:16186805). Isoform 1 interacts with CDKN1B and FOXO3 (PubMed:18593906). Interacts with BAD (By similarity). Interacts with PPP2CA; this interaction promotes dephosphorylation of PIM1, ubiquitination and proteasomal degradation (PubMed:12473674). Interacts with HSP90AA1, this interaction stabilizes PIM1 protein levels. Interacts (ubiquitinated form) with HSP70 and promotes its proteosomal degradation (PubMed:15798097). Interacts with CDKN1A (PubMed:12431783). Interacts with CDC25C (PubMed:16356754). Interacts (via N-terminal 96 residues) with CDC25A (By similarity). Interacts with MAP3K5 (PubMed:19749799). Interacts with MYC (By similarity). Interacts with CBX3 (PubMed:10664448).

6QXK
HUMAN PIM1 BOUND TO OX0999
RCSB/PDB
Inspect Structure
See all 3D Structures for PIM1

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
404P11309-1
313ENSG00000137193ENST00000373509ENSP00000362608P11309-2

Sub-cellular localization


UniProt: PIM1 is active in the following subcellular-locations: cell membrane, cytoplasm, nucleus.
GO terms: PIM1 is active in the following subcellular-locations: cytoplasm, cytosol, nucleolus, nucleoplasm, nucleus, plasma membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PIM1 has gain in 4 cell-lines, loss in 0 cell-lines and no signal in 1001 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: K_562, RPMI_8226, MDA_MB_231

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: K-562, KU812, MOLM-16

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, K562, A549

(see details)

RNA Interference


PIM1 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: RMGI, BT474. (see details)

3D Structures


For PIM1 there are:
151 structures (157 chains) solved
147 are solved in complex with at least one small molecule ligand
3 are solved with an approved drug

PIM1 is solved in complex with the approved drug(s):

MIX/MITOXANTRONE (4I41_A),
ADN/ADENOSINE (1YI4_A),
AMP/ADENOSINE PHOSPHATE (1YXU_A, 1YXU_B, 1YXU_C, 1YXU_D).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PIM1 has been screened with 3826 compounds (5342 bioactivities), 2025 compounds have bioactivities that show binding affinity of <= 500nM (2404 bioactivities). (see details)