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Protein

Serine/threonine-protein kinase pim-1

Gene

Pim1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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 similarity5 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei67ATP1
Binding sitei121ATP; via carbonyl oxygenPROSITE-ProRule annotation1
Binding sitei128ATPPROSITE-ProRule annotation1
Active sitei167Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi44 – 52ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processApoptosis, Cell cycle
LigandATP-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:97584 Pim1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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)DescriptionActionsGraphical viewLength
Mutagenesisi67K → M: Loss of autophosphorylation and kinase activity. 1 Publication1

Keywords - Diseasei

Proto-oncogene

Chemistry databases

ChEMBLiCHEMBL3297640

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000433511 – 313Serine/threonine-protein kinase pim-1Add BLAST313

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei8PhosphoserineBy similarity1
Modified residuei23PhosphothreonineBy similarity1
Modified residuei98PhosphoserineBy similarity1
Modified residuei261PhosphoserineBy similarity1

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

PaxDbiP06803
PRIDEiP06803

PTM databases

iPTMnetiP06803
PhosphoSitePlusiP06803

Expressioni

Gene expression databases

BgeeiENSMUSG00000024014 Expressed in 232 organ(s), highest expression level in blood
CleanExiMM_PIM1

Interactioni

Subunit structurei

Isoform 1 is isolated as a monomer whereas isoform 2 complexes with other proteins (PubMed:1825810). Isoform 2, but not isoform 1, binds BMX (By similarity). Binds to RP9 (PubMed:10931201). Interacts with CDKN1B and FOXO3 (By similarity). Interacts with BAD (PubMed:15280015). Interacts with PPP2CA; this interaction promotes dephosphorylation of PIM1, ubiquitination and proteasomal degradation (By similarity). Interacts with HSP90AA1, this interaction stabilizes PIM1 protein levels (By similarity). 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 (PubMed:18438430). Interacts with CBX3 (By similarity).By similarity4 Publications

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000024811

Chemistry databases

BindingDBiP06803

Structurei

3D structure databases

ProteinModelPortaliP06803
SMRiP06803
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini38 – 290Protein kinasePROSITE-ProRule annotationAdd BLAST253

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0583 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000119045
HOGENOMiHOG000231357
HOVERGENiHBG106681
InParanoidiP06803
KOiK04702
OMAiCQHLIKW
OrthoDBiEOG091G0IMW
PhylomeDBiP06803
TreeFamiTF320810

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR017348 PIM1/2/3
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PIRSFiPIRSF037993 STPK_Pim-1, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative initiation. AlignAdd to basket
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
MLLSKINSLA HLRAAPCNDL HATKLAPGKE KEPLESQYQV GPLLGSGGFG
60 70 80 90 100
SVYSGIRVAD NLPVAIKHVE KDRISDWGEL PNGTRVPMEV VLLKKVSSDF
110 120 130 140 150
SGVIRLLDWF ERPDSFVLIL ERPEPVQDLF DFITERGALQ EDLARGFFWQ
160 170 180 190 200
VLEAVRHCHN CGVLHRDIKD ENILIDLSRG EIKLIDFGSG ALLKDTVYTD
210 220 230 240 250
FDGTRVYSPP EWIRYHRYHG RSAAVWSLGI LLYDMVCGDI PFEHDEEIIK
260 270 280 290 300
GQVFFRQTVS SECQHLIKWC LSLRPSDRPS FEEIRNHPWM QGDLLPQAAS
310
EIHLHSLSPG SSK
Length:313
Mass (Da):35,451
Last modified:October 10, 2018 - v3
Checksum:i1294F16A03B7C7D7
GO
Isoform 2 (identifier: P06803-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MGPAAPLALP...RRTDTLEVGM

Note: Initiates from CTG codon.1 Publication
Show »
Length:397
Mass (Da):44,457
Checksum:i4E712B836341D3F6
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti15A → R in AAA39930 (PubMed:3015420).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0598301M → MGPAAPLALPPPALPDPAGE PARGQPRQRPQSSSDSPSAL RASRSQSRNATRSLSPGRRL SPSSLRRRCCSSRHRRRTDT LEVGM in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M13945 Genomic DNA Translation: AAA39930.1
AC163629 Genomic DNA No translation available.
BC042885 mRNA Translation: AAH42885.1
BC053019 mRNA Translation: AAH53019.1
BC055316 mRNA Translation: AAH55316.1
CCDSiCCDS79520.1 [P06803-2]
PIRiA24169 TVMSP1
RefSeqiNP_032868.2, NM_008842.3
UniGeneiMm.328931
Mm.405293
Mm.485038

Genome annotation databases

EnsembliENSMUST00000024811; ENSMUSP00000024811; ENSMUSG00000024014 [P06803-1]
GeneIDi18712
KEGGimmu:18712
UCSCiuc008bta.1 mouse [P06803-1]

Keywords - Coding sequence diversityi

Alternative initiation

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M13945 Genomic DNA Translation: AAA39930.1
AC163629 Genomic DNA No translation available.
BC042885 mRNA Translation: AAH42885.1
BC053019 mRNA Translation: AAH53019.1
BC055316 mRNA Translation: AAH55316.1
CCDSiCCDS79520.1 [P06803-2]
PIRiA24169 TVMSP1
RefSeqiNP_032868.2, NM_008842.3
UniGeneiMm.328931
Mm.405293
Mm.485038

3D structure databases

ProteinModelPortaliP06803
SMRiP06803
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000024811

Chemistry databases

BindingDBiP06803
ChEMBLiCHEMBL3297640

PTM databases

iPTMnetiP06803
PhosphoSitePlusiP06803

Proteomic databases

PaxDbiP06803
PRIDEiP06803

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000024811; ENSMUSP00000024811; ENSMUSG00000024014 [P06803-1]
GeneIDi18712
KEGGimmu:18712
UCSCiuc008bta.1 mouse [P06803-1]

Organism-specific databases

CTDi5292
MGIiMGI:97584 Pim1

Phylogenomic databases

eggNOGiKOG0583 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000119045
HOGENOMiHOG000231357
HOVERGENiHBG106681
InParanoidiP06803
KOiK04702
OMAiCQHLIKW
OrthoDBiEOG091G0IMW
PhylomeDBiP06803
TreeFamiTF320810

Miscellaneous databases

PROiPR:P06803
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000024014 Expressed in 232 organ(s), highest expression level in blood
CleanExiMM_PIM1

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR017348 PIM1/2/3
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PIRSFiPIRSF037993 STPK_Pim-1, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPIM1_MOUSE
AccessioniPrimary (citable) accession number: P06803
Secondary accession number(s): F6XDQ5, Q8CFN8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: October 10, 2018
Last modified: November 7, 2018
This is version 161 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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