InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PIM1

Summary

InnateDB Protein

IDBP-85490.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PIM1

Protein Name

pim-1 oncogene

Synonyms

PIM;

Species

Homo sapiens

Ensembl Protein

ENSP00000362608

InnateDB Gene

IDBG-85488 (PIM1)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:10664448, ECO:0000269PubMed:12431783, ECO:0000269PubMed:15528381, ECO:0000269PubMed:16356754, ECO:0000269PubMed:1825810, ECO:0000269PubMed:18593906, ECO:0000269PubMed:19749799}.

Subcellular Localization

Isoform 2: Cytoplasm. Nucleus.Isoform 1: Cell membrane.

Disease Associations

Tissue Specificity

Expressed primarily in cells of the hematopoietic and germline lineages. Isoform 1 and isoform 2 are both expressed in prostate cancer cell lines. {ECO:0000269PubMed:16186805}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 44 experimentally validated interaction(s) in this database.
They are also associated with 2 interaction(s) predicted by orthology.

Experimentally validated
Total	44 [view]
Protein-Protein	43 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	2 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008134	transcription factor binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0016773	phosphotransferase activity, alcohol group as acceptor
GO:0030145	manganese ion binding
GO:0043024	ribosomal small subunit binding

Biological Process

GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0007049	cell cycle
GO:0007275	multicellular organismal development
GO:0008283	cell proliferation
GO:0009103	lipopolysaccharide biosynthetic process
GO:0030212	hyaluronan metabolic process
GO:0031659	positive regulation of cyclin-dependent protein kinase activity involved in G1/S
GO:0043066	negative regulation of apoptotic process
GO:0043433	negative regulation of sequence-specific DNA binding transcription factor activity
GO:0046777	protein autophosphorylation

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005886	plasma membrane
GO:0016020	membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR010440 Lipopolysaccharide kinase
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF06293

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt