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P06803 (PIM1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein kinase pim-1

EC=2.7.11.1
Gene names
Name:Pim1
Synonyms:Pim-1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length397 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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 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 By similarity. Ref.2 Ref.6 Ref.7 Ref.8 Ref.9

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium By similarity.

Subunit structure

Binds to RP9. Interacts with CDKN1B and FOXO3 By similarity. Isoform 2 is isolated as a monomer whereas isoform 1 complexes with other proteins. Isoform 2 is isolated as a monomer whereas isoform 1 complexes with other proteins. Isoform 1, but not isoform 2, binds BMX. Interacts with BAD. Interacts with PPP2CA; this interaction promotes dephosphorylation of PIM1, ubiquitination and proteasomal degradation By similarity. Interacts with HSP90, this interaction stabilizes PIM1 protein levels. Interacts (ubiquitinated form) with HSP70 and promotes its proteosomal degradation By similarity. Interacts with CDKN1A By similarity. Interacts with CDC25C By similarity. Interacts (via N-terminal 96 residues) with CDC25A By similarity. Interacts with MAP3K5 By similarity. Interacts with MYC By similarity. Ref.5 Ref.6 Ref.8

Subcellular location

Cytoplasm. Nucleus. Cell membrane. Note: Mainly located in the cytoplasm. Ref.2

Post-translational modification

Autophosphorylated on both serine/threonine and tyrosine residues. Phosphorylated. Interaction with PPP2CA promotes dephosphorylation By similarity. Ref.2

Ubiquitinated, leading to proteasomal degradation By similarity.

Involvement in disease

Frequently activated by provirus insertion in murine leukemia virus-induced T-cell lymphomas.

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. Ref.3 Ref.4 Ref.7

Sequence similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PIM subfamily.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processApoptosis
Cell cycle
   Cellular componentCell membrane
Cytoplasm
Membrane
Nucleus
   Coding sequence diversityAlternative initiation
   DiseaseProto-oncogene
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

cell cycle

Inferred from electronic annotation. Source: UniProtKB-KW

cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from mutant phenotype Ref.8. Source: UniProtKB

protein phosphorylation

Inferred from direct assay Ref.2. Source: UniProtKB

protein stabilization

Inferred from direct assay Ref.8. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from direct assay Ref.2. Source: UniProtKB

manganese ion binding

Inferred from direct assay Ref.2. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.8. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from direct assay Ref.2Ref.8. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative initiation. [Align] [Select]
Isoform 1 (identifier: 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.
Note: Initiates from CTG codon.
Isoform 2 (identifier: P06803-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-84: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 397397Serine/threonine-protein kinase pim-1
PRO_0000043351

Regions

Domain122 – 374253Protein kinase
Nucleotide binding128 – 1369ATP By similarity

Sites

Active site2511Proton acceptor By similarity
Binding site1511ATP
Binding site2051ATP; via carbonyl oxygen By similarity
Binding site2121ATP By similarity

Amino acid modifications

Modified residue921Phosphoserine By similarity
Modified residue1071Phosphothreonine By similarity
Modified residue1821Phosphoserine By similarity
Modified residue3451Phosphoserine By similarity

Natural variations

Alternative sequence1 – 8484Missing in isoform 2.
VSP_018853

Experimental info

Mutagenesis1511K → M: Loss of autophosphorylation and kinase activity. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 6, 2005. Version 2.
Checksum: 2511AD77FD3DC837

FASTA39744,542
        10         20         30         40         50         60 
MGPAAPLALP PPALPDPAGE PARGQPRQRP QSSSDSPSAL RASRSQSRNA TRSLSPGRRL 

        70         80         90        100        110        120 
SPSSLRRRCC SSRHRRRTDT LEVGMLLSKI NSLAHLRARP CNDLHATKLA PGKEKEPLES 

       130        140        150        160        170        180 
QYQVGPLLGS GGFGSVYSGI RVADNLPVAI KHVEKDRISD WGELPNGTRV PMEVVLLKKV 

       190        200        210        220        230        240 
SSDFSGVIRL LDWFERPDSF VLILERPEPV QDLFDFITER GALQEDLARG FFWQVLEAVR 

       250        260        270        280        290        300 
HCHNCGVLHR DIKDENILID LSRGEIKLID FGSGALLKDT VYTDFDGTRV YSPPEWIRYH 

       310        320        330        340        350        360 
RYHGRSAAVW SLGILLYDMV CGDIPFEHDE EIIKGQVFFR QTVSSECQHL IKWCLSLRPS 

       370        380        390 
DRPSFEEIRN HPWMQGDLLP QAASEIHLHS LSPGSSK 

« Hide

Isoform 2 [UniParc].

Checksum: 79F4779E9DCBDC16
Show »

FASTA31335,537

References

[1]"The primary structure of the putative oncogene pim-1 shows extensive homology with protein kinases."
Selten G., Cuypers H.T., Boelens W., Robanus-Maandag E., Verbeek J., Domen J., van Beveren C., Berns A.
Cell 46:603-611(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2).
[2]"The pim-1 oncogene encodes two related protein-serine/threonine kinases by alternative initiation at AUG and CUG."
Saris C.J., Domen J., Berns A.
EMBO J. 10:655-664(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE INITIATION, FUNCTION, COMPLEX FORMATION, AUTOPHOSPHORYLATION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-151.
[3]"Impaired interleukin-3 response in Pim-1-deficient bone marrow-derived mast cells."
Domen J., van der Lugt N.M., Laird P.W., Saris C.J., Clarke A.R., Hooper M.L., Berns A.
Blood 82:1445-1452(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[4]"Pim-1 levels determine the size of early B lymphoid compartments in bone marrow."
Domen J., van der Lugt N.M., Acton D., Laird P.W., Linders K., Berns A.
J. Exp. Med. 178:1665-1673(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[5]"PAP-1, a novel target protein of phosphorylation by Pim-1 kinase."
Maita H., Harada Y., Nagakubo D., Kitaura H., Ikeda M., Tamai K., Takahashi K., Ariga H., Iguchi-Ariga S.M.M.
Eur. J. Biochem. 267:5168-5178(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RP9.
[6]"Pim-1 kinase promotes inactivation of the pro-apoptotic Bad protein by phosphorylating it on the Ser112 gatekeeper site."
Aho T.L., Sandholm J., Peltola K.J., Mankonen H.P., Lilly M., Koskinen P.J.
FEBS Lett. 571:43-49(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF BAD, INTERACTION WITH BAD.
[7]"Mice deficient for all PIM kinases display reduced body size and impaired responses to hematopoietic growth factors."
Mikkers H., Nawijn M., Allen J., Brouwers C., Verhoeven E., Jonkers J., Berns A.
Mol. Cell. Biol. 24:6104-6115(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[8]"Pim kinase-dependent inhibition of c-Myc degradation."
Zhang Y., Wang Z., Li X., Magnuson N.S.
Oncogene 27:4809-4819(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF MYC, INTERACTION WITH MYC.
[9]"Dissection of PIM serine/threonine kinases in FLT3-ITD-induced leukemogenesis reveals PIM1 as regulator of CXCL12-CXCR4-mediated homing and migration."
Grundler R., Brault L., Gasser C., Bullock A.N., Dechow T., Woetzel S., Pogacic V., Villa A., Ehret S., Berridge G., Spoo A., Dierks C., Biondi A., Knapp S., Duyster J., Schwaller J.
J. Exp. Med. 206:1957-1970(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CXCR4, FUNCTION IN CELL MIGRATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M13945 Genomic DNA. Translation: AAA39930.1.
PIRTVMSP1. A24169.
UniGeneMm.405293.
Mm.485038.

3D structure databases

ProteinModelPortalP06803.
SMRP06803. Positions 92-392.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteP06803.

Proteomic databases

PRIDEP06803.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

UCSCuc008bta.1. mouse. [P06803-1]

Organism-specific databases

MGIMGI:97584. Pim1.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000231357.
HOVERGENHBG106681.
InParanoidP06803.
PhylomeDBP06803.

Gene expression databases

CleanExMM_PIM1.
GenevestigatorP06803.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR017348. Ser/Thr_kinase_Pim-1.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFPIRSF037993. STPK_Pim-1. 1 hit.
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

PROP06803.
SOURCESearch...

Entry information

Entry namePIM1_MOUSE
AccessionPrimary (citable) accession number: P06803
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: December 6, 2005
Last modified: June 11, 2014
This is version 132 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot