Names & Taxonomy
- Uniprot ID:
- P11309
- Entry Name:
- PIM1_HUMAN
- Status:
- reviewed
- Protein Names:
- Serine/threonine-protein kinase pim-1 (EC 2.7.11.1)
- Gene Names:
- PIM1
- Gene Names Primary:
- PIM1
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 404
- Sequence:
- MPHEPHEPLTPPFSALPDPAGAPSRRQSRQRPQLSSDSPSAFRASRSHSRNATRSHSHSHSPRHSLRHSPGSGSCGSSSGHRPCADILEVGMLLSKINSLAHLRAAPCNDLHATKLAPGKEKEPLESQYQVGPLLGSGGFGSVYSGIRVSDNLPVAIKHVEKDRISDWGELPNGTRVPMEVVLLKKVSSGFSGVIRLLDWFERPDSFVLILERPEPVQDLFDFITERGALQEELARSFFWQVLEAVRHCHNCGVLHRDIKDENILIDLNRGELKLIDFGSGALLKDTVYTDFDGTRVYSPPEWIRYHRYHGRSAAVWSLGILLYDMVCGDIPFEHDEEIIRGQVFFRQRVSSECQHLIRWCLALRPSDRPTFEEIQNHPWMQDVLLPQETAEIHLHSLSPGPSK
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Isoform 2: Cytoplasm. Nucleus.; Isoform 1: Cell membrane.
Function
- 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.
- Catalytic Activity:
- ATP + a protein = ADP + a phosphoprotein.
- Cofactor:
- COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
- Active Site:
- ACT_SITE 258 258 Proton acceptor.
- Cross Reference Drug Bank:
- DB00131
- Gene Ontology Go:
- cytoplasm
nucleus
plasma membrane
ATP binding
manganese ion binding
protein serine/threonine kinase activity
ribosomal small subunit binding
transcription factor binding
apoptotic process
cell cycle
cell proliferation
hyaluronan metabolic process
multicellular organism development
negative regulation of apoptotic process
negative regulation of sequence-specific DNA binding transcription factor activity
positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle
protein autophosphorylation
protein phosphorylation
vitamin D receptor signaling pathway - Gene Ontology Biological Process:
- apoptotic process
cell cycle
cell proliferation
hyaluronan metabolic process
multicellular organism development
negative regulation of apoptotic process
negative regulation of sequence-specific DNA binding transcription factor activity
positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle
protein autophosphorylation
protein phosphorylation
vitamin D receptor signaling pathway - Gene Ontology Molecular Function:
- ATP binding
manganese ion binding
protein serine/threonine kinase activity
ribosomal small subunit binding
transcription factor binding - Gene Ontology Cellular Component:
- cytoplasm
nucleus
plasma membrane - Keywords:
- 3D-structure
ATP-binding
Alternative initiation
Apoptosis
Cell cycle
Cell membrane
Complete proteome
Cytoplasm
Direct protein sequencing
Kinase
Magnesium
Membrane
Metal-binding
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Proto-oncogene
Reference proteome
Serine/threonine-protein kinase
Transferase
Ubl conjugation - Interacts With:
- Q9UNQ0; Q8N9N5; Q8N7W2-2; P51813; P46527; P07954; O43524; Q9BZS1-1; P51116; Q96MH2; Q5T203; P39019; G5E9B5; Q9Y2K1