P06803 · PIM1_MOUSE
- ProteinSerine/threonine-protein kinase pim-1
- GenePim1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids313 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis (PubMed:15199164, PubMed:1825810).
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) (By similarity).
Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity (PubMed:18438430).
The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis (PubMed:18438430).
Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1 (PubMed:15280015).
Phosphorylation of MAP3K5, another 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 (By similarity).
Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C (By similarity).
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 (By similarity).
Promotes cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels (By similarity).
Phosphorylation of CDKN1B, induces 14-3-3 proteins binding, nuclear export and proteasome-dependent degradation (By similarity).
May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3 (By similarity).
Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis (PubMed:19687226).
Acts as a positive regulator of mTORC1 signaling by mediating phosphorylation and inhibition of DEPDC5 component of the GATOR1 complex (PubMed:31548394).
Acts as a negative regulator of innate immunity by mediating phosphorylation and inactivation of GBP1 in absence of infection: phosphorylation of GBP1 induces interaction with 14-3-3 protein sigma (SFN) and retention in the cytosol (By similarity).
Also phosphorylates and activates the ATP-binding cassette transporter ABCG2, allowing resistance to drugs through their excretion from cells (By similarity).
Promotes brown adipocyte differentiation (PubMed:27923061).
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) (By similarity).
Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity (PubMed:18438430).
The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis (PubMed:18438430).
Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1 (PubMed:15280015).
Phosphorylation of MAP3K5, another 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 (By similarity).
Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C (By similarity).
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 (By similarity).
Promotes cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels (By similarity).
Phosphorylation of CDKN1B, induces 14-3-3 proteins binding, nuclear export and proteasome-dependent degradation (By similarity).
May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3 (By similarity).
Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis (PubMed:19687226).
Acts as a positive regulator of mTORC1 signaling by mediating phosphorylation and inhibition of DEPDC5 component of the GATOR1 complex (PubMed:31548394).
Acts as a negative regulator of innate immunity by mediating phosphorylation and inactivation of GBP1 in absence of infection: phosphorylation of GBP1 induces interaction with 14-3-3 protein sigma (SFN) and retention in the cytosol (By similarity).
Also phosphorylates and activates the ATP-binding cassette transporter ABCG2, allowing resistance to drugs through their excretion from cells (By similarity).
Promotes brown adipocyte differentiation (PubMed:27923061).
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]
Cofactor
Features
Showing features for binding site, active site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSerine/threonine-protein kinase pim-1
- EC number
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP06803
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Mainly located in the cytoplasm.
Keywords
- Cellular component
Phenotypes & Variants
Involvement in disease
Disruption phenotype
Deficient mice are viable and fertile however they have a specific defect in interleukin-7 (IL7)-driven growth of pre-B cells, as well as IL3-dependent growth of bone marrow-derived mast cells. Triple knockout mice PIM1/PIM2/PIM3 are viable and fertile too, but their body size is reduced at birth and throughout postnatal life due to a reduction in the number of cells rather than cell size.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 67 | Loss of autophosphorylation and kinase activity. | ||||
Sequence: K → M |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 7 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Chemistry
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000043351 | 1-313 | Serine/threonine-protein kinase pim-1 | |||
Sequence: MLLSKINSLAHLRAAPCNDLHATKLAPGKEKEPLESQYQVGPLLGSGGFGSVYSGIRVADNLPVAIKHVEKDRISDWGELPNGTRVPMEVVLLKKVSSDFSGVIRLLDWFERPDSFVLILERPEPVQDLFDFITERGALQEDLARGFFWQVLEAVRHCHNCGVLHRDIKDENILIDLSRGEIKLIDFGSGALLKDTVYTDFDGTRVYSPPEWIRYHRYHGRSAAVWSLGILLYDMVCGDIPFEHDEEIIKGQVFFRQTVSSECQHLIKWCLSLRPSDRPSFEEIRNHPWMQGDLLPQAASEIHLHSLSPGSSK | ||||||
Modified residue | 8 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 23 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 98 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 261 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Autophosphorylated on both serine/threonine and tyrosine residues. Phosphorylated. Interaction with PPP2CA promotes dephosphorylation (By similarity).
Ubiquitinated, leading to proteasomal degradation.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 38-290 | Protein kinase | ||||
Sequence: YQVGPLLGSGGFGSVYSGIRVADNLPVAIKHVEKDRISDWGELPNGTRVPMEVVLLKKVSSDFSGVIRLLDWFERPDSFVLILERPEPVQDLFDFITERGALQEDLARGFFWQVLEAVRHCHNCGVLHRDIKDENILIDLSRGEIKLIDFGSGALLKDTVYTDFDGTRVYSPPEWIRYHRYHGRSAAVWSLGILLYDMVCGDIPFEHDEEIIKGQVFFRQTVSSECQHLIKWCLSLRPSDRPSFEEIRNHPWM |
Sequence similarities
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative initiation.
P06803-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length313
- Mass (Da)35,451
- Last updated2018-10-10 v3
- Checksum1294F16A03B7C7D7
P06803-2
- Name2
- NoteInitiates from CTG codon.
- Differences from canonical
- 1-1: M → MGPAAPLALPPPALPDPAGEPARGQPRQRPQSSSDSPSALRASRSQSRNATRSLSPGRRLSPSSLRRRCCSSRHRRRTDTLEVGM
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A3Q4EGX3 | A0A3Q4EGX3_MOUSE | Pim1 | 79 | ||
A0A3Q4EGB5 | A0A3Q4EGB5_MOUSE | Pim1 | 195 |
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_059830 | 1 | in isoform 2 | |||
Sequence: M → MGPAAPLALPPPALPDPAGEPARGQPRQRPQSSSDSPSALRASRSQSRNATRSLSPGRRLSPSSLRRRCCSSRHRRRTDTLEVGM | ||||||
Sequence conflict | 15 | in Ref. 1; AAA39930 | ||||
Sequence: A → R |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M13945 EMBL· GenBank· DDBJ | AAA39930.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AC163629 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC042885 EMBL· GenBank· DDBJ | AAH42885.1 EMBL· GenBank· DDBJ | mRNA | ||
BC053019 EMBL· GenBank· DDBJ | AAH53019.1 EMBL· GenBank· DDBJ | mRNA | ||
BC055316 EMBL· GenBank· DDBJ | AAH55316.1 EMBL· GenBank· DDBJ | mRNA |