Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

P06803

- PIM1_MOUSE

UniProt

P06803 - PIM1_MOUSE

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

Serine/threonine-protein kinase pim-1

Gene

Pim1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei151 – 1511ATP
Binding sitei205 – 2051ATP; via carbonyl oxygenPROSITE-ProRule annotation
Binding sitei212 – 2121ATPPROSITE-ProRule annotation
Active sitei251 – 2511Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi128 – 1369ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB
  2. manganese ion binding Source: UniProtKB
  3. protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  1. apoptotic process Source: UniProtKB-KW
  2. cell cycle Source: UniProtKB-KW
  3. cell proliferation Source: UniProtKB
  4. negative regulation of apoptotic process Source: UniProtKB
  5. positive regulation of transcription, DNA-templated Source: UniProtKB
  6. protein phosphorylation Source: UniProtKB
  7. protein stabilization Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Cell cycle

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase pim-1 (EC:2.7.11.1)
Gene namesi
Name:Pim1
Synonyms:Pim-1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Unplaced

Organism-specific databases

MGIiMGI:97584. Pim1.

Subcellular locationi

Cytoplasm 1 Publication. Nucleus 1 Publication. Cell membrane 1 Publication
Note: Mainly located in the cytoplasm.

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-KW
  2. nucleus Source: UniProtKB-KW
  3. plasma membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

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

Disruption phenotypei

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.3 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi151 – 1511K → M: Loss of autophosphorylation and kinase activity. 1 Publication

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 397397Serine/threonine-protein kinase pim-1PRO_0000043351Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei92 – 921PhosphoserineBy similarity
Modified residuei107 – 1071PhosphothreonineBy similarity
Modified residuei182 – 1821PhosphoserineBy similarity
Modified residuei345 – 3451PhosphoserineBy similarity

Post-translational modificationi

Autophosphorylated on both serine/threonine and tyrosine residues. Phosphorylated. Interaction with PPP2CA promotes dephosphorylation (By similarity).By similarity
Ubiquitinated, leading to proteasomal degradation.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PRIDEiP06803.

PTM databases

PhosphoSiteiP06803.

Expressioni

Gene expression databases

CleanExiMM_PIM1.
GenevestigatoriP06803.

Interactioni

Subunit structurei

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).By similarity

Structurei

3D structure databases

ProteinModelPortaliP06803.
SMRiP06803. Positions 92-392.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini122 – 374253Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000231357.
HOVERGENiHBG106681.
InParanoidiP06803.
PhylomeDBiP06803.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
IPR017348. Ser/Thr_kinase_Pim-1.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFiPIRSF037993. STPK_Pim-1. 1 hit.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative initiation. Align

Isoform 1 (identifier: P06803-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MGPAAPLALP PPALPDPAGE PARGQPRQRP QSSSDSPSAL RASRSQSRNA
60 70 80 90 100
TRSLSPGRRL SPSSLRRRCC SSRHRRRTDT LEVGMLLSKI NSLAHLRARP
110 120 130 140 150
CNDLHATKLA PGKEKEPLES QYQVGPLLGS GGFGSVYSGI RVADNLPVAI
160 170 180 190 200
KHVEKDRISD WGELPNGTRV PMEVVLLKKV SSDFSGVIRL LDWFERPDSF
210 220 230 240 250
VLILERPEPV QDLFDFITER GALQEDLARG FFWQVLEAVR HCHNCGVLHR
260 270 280 290 300
DIKDENILID LSRGEIKLID FGSGALLKDT VYTDFDGTRV YSPPEWIRYH
310 320 330 340 350
RYHGRSAAVW SLGILLYDMV CGDIPFEHDE EIIKGQVFFR QTVSSECQHL
360 370 380 390
IKWCLSLRPS DRPSFEEIRN HPWMQGDLLP QAASEIHLHS LSPGSSK

Note: Initiates from CTG codon.

Length:397
Mass (Da):44,542
Last modified:December 6, 2005 - v2
Checksum:i2511AD77FD3DC837
GO
Isoform 2 (identifier: P06803-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:313
Mass (Da):35,537
Checksum:i79F4779E9DCBDC16
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 8484Missing in isoform 2. CuratedVSP_018853Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M13945 Genomic DNA. Translation: AAA39930.1.
PIRiA24169. TVMSP1.
UniGeneiMm.405293.
Mm.485038.

Genome annotation databases

UCSCiuc008bta.1. mouse. [P06803-1]

Keywords - Coding sequence diversityi

Alternative initiation

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M13945 Genomic DNA. Translation: AAA39930.1 .
PIRi A24169. TVMSP1.
UniGenei Mm.405293.
Mm.485038.

3D structure databases

ProteinModelPortali P06803.
SMRi P06803. Positions 92-392.
ModBasei Search...
MobiDBi Search...

PTM databases

PhosphoSitei P06803.

Proteomic databases

PRIDEi P06803.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

UCSCi uc008bta.1. mouse. [P06803-1 ]

Organism-specific databases

MGIi MGI:97584. Pim1.

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000231357.
HOVERGENi HBG106681.
InParanoidi P06803.
PhylomeDBi P06803.

Miscellaneous databases

PROi P06803.
SOURCEi Search...

Gene expression databases

CleanExi MM_PIM1.
Genevestigatori P06803.

Family and domain databases

InterProi IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
IPR017348. Ser/Thr_kinase_Pim-1.
[Graphical view ]
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
PIRSFi PIRSF037993. STPK_Pim-1. 1 hit.
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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. 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.

Entry informationi

Entry nameiPIM1_MOUSE
AccessioniPrimary (citable) accession number: P06803
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: December 6, 2005
Last modified: November 26, 2014
This is version 135 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3