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Protein

Serine/threonine-protein kinase pim-2

Gene

Pim2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression, the regulation of cap-dependent protein translation and through survival signaling by phosphorylation of a pro-apoptotic protein, BAD. Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM2 might explain partly the strong synergism between these 2 oncogenes in tumorigenesis. Regulates cap-dependent protein translation in a mammalian target of rapamycin complex 1 (mTORC1)-independent manner and in parallel to the PI3K-Akt pathway. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Promotes cell survival in response to a variety of proliferative signals via positive regulation of the I-kappa-B kinase/NF-kappa-B cascade; this process requires phosphorylation of MAP3K8/COT. Promotes growth factor-independent proliferation by phosphorylation of cell cycle factors such as CDKN1A and CDKN1B. Involved in the positive regulation of chondrocyte survival and autophagy in the epiphyseal growth plate.8 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei120ATPPROSITE-ProRule annotation1
Active sitei222Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi97 – 105ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • protein kinase activity Source: MGI
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • apoptotic mitochondrial changes Source: MGI
  • G1/S transition of mitotic cell cycle Source: UniProtKB
  • negative regulation of apoptotic process Source: MGI
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of protein binding Source: MGI
  • positive regulation of autophagy Source: UniProtKB
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • positive regulation of macroautophagy Source: MGI
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • protein autophosphorylation Source: GO_Central
  • protein phosphorylation Source: UniProtKB
  • protein stabilization Source: UniProtKB
  • regulation of mitotic cell cycle Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Cell cycle

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase pim-2 (EC:2.7.11.1)
Gene namesi
Name:Pim2
Synonyms:Pim-2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:97587. Pim2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Disruption phenotypei

Mice are viable and fertile. Deficient mice shown reduced T-cell activation and expansion in the presence of the serine/threonine protein kinase mTOR inhibitor rapamycin. Triple knockout mice PIM1/PIM2/PIM3 shown a profound reduction in body size at birth and throughout postnatal life due to a reduction in the number of cells rather than cell size.2 Publications

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000243661 – 370Serine/threonine-protein kinase pim-2Add BLAST370

Post-translational modificationi

Autophosphorylated.3 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ62070.
PRIDEiQ62070.

PTM databases

iPTMnetiQ62070.
PhosphoSitePlusiQ62070.

Expressioni

Tissue specificityi

Widely expressed, with highest expression in spleen, thymus and brain. Expressed in epiphyseal chondrocytes.2 Publications

Inductioni

Induced by a wide range of growth factors and mitogens; IL2, IL3, IL4, IL7,IL9 and by interferon-gamma (IFNG).3 Publications

Gene expression databases

CleanExiMM_PIM2.

Interactioni

Subunit structurei

Interacts with MYC.1 Publication

Protein-protein interaction databases

BioGridi202167. 1 interactor.
MINTiMINT-232729.
STRINGi10090.ENSMUSP00000033495.

Structurei

3D structure databases

ProteinModelPortaliQ62070.
SMRiQ62070.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini91 – 345Protein kinasePROSITE-ProRule annotationAdd BLAST255

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0583. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000231357.
HOVERGENiHBG106681.
InParanoidiQ62070.
KOiK08806.
PhylomeDBiQ62070.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
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 (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative initiation. AlignAdd to basket

Isoform 1 (identifier: Q62070-1) [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
MARATNLNAA PSAGASGPPD SLPSTLAPPS PGSPAALPRA STPCGLSGFS
60 70 80 90 100
GLNIRSTSSM LTKPLQGHPS PPVTPTQPPG GKDRAAFEAE YRLGPLLGKG
110 120 130 140 150
GFGTVFAGHR VTDRRQVAIK VISRNRVLGW STVSDSVTCP LEVALLWKVG
160 170 180 190 200
EGNGHPGVIR LLDWFETPEG FMLVLERPMP AQDLFDYITE KGPLGESCSR
210 220 230 240 250
SFFTQVVAAV QHCHARGVVH RDIKDENILI DLCRGSIKLI DFGSGALLHD
260 270 280 290 300
EPYTDFDGTR VYSPPEWISR HQYHALPATV WSLGVLLYDM VCGDIPFERD
310 320 330 340 350
QEILEAELHF PAHVSPDCCA LIRRCLAPKP CSRPSLEEIL LDPWMQSPAE
360 370
EKPINSSKGS PTPLPWSLLP
Note: Initiates from CTG codon.
Length:370
Mass (Da):40,060
Last modified:November 1, 1996 - v1
Checksum:i12BB70BFD04DBE8A
GO
Isoform 2 (identifier: Q62070-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-25: Missing.
     26-26: L → M

Note: Initiates from CTG codon.
Show »
Length:345
Mass (Da):37,741
Checksum:iEA5EA9E7718C74E3
GO
Isoform 3 (identifier: Q62070-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-59: Missing.

Note: Mutagen in position: 61:K->A (loss of kinase activity).
Show »
Length:311
Mass (Da):34,487
Checksum:iF7B770908D23A710
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0188561 – 59Missing in isoform 3. 2 PublicationsAdd BLAST59
Alternative sequenceiVSP_0188541 – 25Missing in isoform 2. 1 PublicationAdd BLAST25
Alternative sequenceiVSP_01885526L → M in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L41495 mRNA. Translation: AAA98922.1.
L41495 mRNA. Translation: AAA98923.1.
L41495 mRNA. Translation: AAA98924.1.
AL671978 Genomic DNA. Translation: CAM24546.1.
BC027376 mRNA. Translation: AAH27376.1.
CCDSiCCDS29976.1. [Q62070-1]
PIRiS55333.
RefSeqiNP_613072.1. NM_138606.2. [Q62070-1]
UniGeneiMm.347478.

Genome annotation databases

GeneIDi18715.
KEGGimmu:18715.
UCSCiuc009smz.2. mouse. [Q62070-1]

Keywords - Coding sequence diversityi

Alternative initiation

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L41495 mRNA. Translation: AAA98922.1.
L41495 mRNA. Translation: AAA98923.1.
L41495 mRNA. Translation: AAA98924.1.
AL671978 Genomic DNA. Translation: CAM24546.1.
BC027376 mRNA. Translation: AAH27376.1.
CCDSiCCDS29976.1. [Q62070-1]
PIRiS55333.
RefSeqiNP_613072.1. NM_138606.2. [Q62070-1]
UniGeneiMm.347478.

3D structure databases

ProteinModelPortaliQ62070.
SMRiQ62070.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202167. 1 interactor.
MINTiMINT-232729.
STRINGi10090.ENSMUSP00000033495.

PTM databases

iPTMnetiQ62070.
PhosphoSitePlusiQ62070.

Proteomic databases

PaxDbiQ62070.
PRIDEiQ62070.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi18715.
KEGGimmu:18715.
UCSCiuc009smz.2. mouse. [Q62070-1]

Organism-specific databases

CTDi11040.
MGIiMGI:97587. Pim2.

Phylogenomic databases

eggNOGiKOG0583. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000231357.
HOVERGENiHBG106681.
InParanoidiQ62070.
KOiK08806.
PhylomeDBiQ62070.

Miscellaneous databases

PROiQ62070.
SOURCEiSearch...

Gene expression databases

CleanExiMM_PIM2.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
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]
ProtoNetiSearch...

Entry informationi

Entry nameiPIM2_MOUSE
AccessioniPrimary (citable) accession number: Q62070
Secondary accession number(s): A2AER1
, Q62071, Q62072, Q8R2P0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: November 1, 1996
Last modified: November 2, 2016
This is version 128 of the entry and version 1 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.