Q62070 (PIM2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase pim-2
EC=2.7.11.1

Gene names

Name:	Pim2
Synonyms:	Pim-2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	370 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.11 Ref.12
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	Interacts with MYC. Ref.12
Tissue specificity	Widely expressed, with highest expression in spleen, thymus and brain. Expressed in epiphyseal chondrocytes. Ref.4 Ref.11
Induction	Induced by a wide range of growth factors and mitogens; IL2, IL3, IL4, IL7,IL9 and by interferon-gamma (IFNG). Ref.4 Ref.6 Ref.10
Post-translational modification	Autophosphorylated. Ref.5 Ref.6 Ref.7
Disruption phenotype	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. Ref.8 Ref.10
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PIM subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Apoptosis Cell cycle
Coding sequence diversity	Alternative initiation
Disease	Proto-oncogene
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G1/S transition of mitotic cell cycle Inferred from sequence or structural similarity. Source: UniProtKB apoptotic mitochondrial changes Inferred from direct assay Ref.5. Source: MGI negative regulation of apoptotic process Inferred from direct assay Ref.5. Source: MGI negative regulation of cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from direct assay Ref.7. Source: UniProtKB positive regulation of autophagy Inferred from mutant phenotype Ref.11. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from mutant phenotype Ref.12. Source: UniProtKB protein stabilization Inferred from direct assay Ref.12. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from direct assay Ref.12. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative initiation. [Align] [Select]

Isoform 1 (identifier: Q62070-1)

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: Q62070-2)

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

Note: Initiates from CTG codon.

Isoform 3 (identifier: Q62070-3)

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).

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 370	370	Serine/threonine-protein kinase pim-2		PRO_0000024366
Regions
	Domain	91 – 345	255	Protein kinase
	Nucleotide binding	97 – 105	9	ATP By similarity
Sites
	Active site	222	1	Proton acceptor By similarity
	Binding site	120	1	ATP By similarity
Natural variations
	Alternative sequence	1 – 59	59	Missing in isoform 3.		VSP_018856
	Alternative sequence	1 – 25	25	Missing in isoform 2.		VSP_018854
	Alternative sequence	26	1	L → M in isoform 2.		VSP_018855

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 12BB70BFD04DBE8A	FASTA	370	40,060
	10 20 30 40 50 60 MARATNLNAA PSAGASGPPD SLPSTLAPPS PGSPAALPRA STPCGLSGFS GLNIRSTSSM 70 80 90 100 110 120 LTKPLQGHPS PPVTPTQPPG GKDRAAFEAE YRLGPLLGKG GFGTVFAGHR VTDRRQVAIK 130 140 150 160 170 180 VISRNRVLGW STVSDSVTCP LEVALLWKVG EGNGHPGVIR LLDWFETPEG FMLVLERPMP 190 200 210 220 230 240 AQDLFDYITE KGPLGESCSR SFFTQVVAAV QHCHARGVVH RDIKDENILI DLCRGSIKLI 250 260 270 280 290 300 DFGSGALLHD EPYTDFDGTR VYSPPEWISR HQYHALPATV WSLGVLLYDM VCGDIPFERD 310 320 330 340 350 360 QEILEAELHF PAHVSPDCCA LIRRCLAPKP CSRPSLEEIL LDPWMQSPAE EKPINSSKGS 370 PTPLPWSLLP
	Isoform 2 [UniParc]. Checksum: EA5EA9E7718C74E3	FASTA	345	37,741
	10 20 30 40 50 60 MAPPSPGSPA ALPRASTPCG LSGFSGLNIR STSSMLTKPL QGHPSPPVTP TQPPGGKDRA 70 80 90 100 110 120 AFEAEYRLGP LLGKGGFGTV FAGHRVTDRR QVAIKVISRN RVLGWSTVSD SVTCPLEVAL 130 140 150 160 170 180 LWKVGEGNGH PGVIRLLDWF ETPEGFMLVL ERPMPAQDLF DYITEKGPLG ESCSRSFFTQ 190 200 210 220 230 240 VVAAVQHCHA RGVVHRDIKD ENILIDLCRG SIKLIDFGSG ALLHDEPYTD FDGTRVYSPP 250 260 270 280 290 300 EWISRHQYHA LPATVWSLGV LLYDMVCGDI PFERDQEILE AELHFPAHVS PDCCALIRRC 310 320 330 340 LAPKPCSRPS LEEILLDPWM QSPAEEKPIN SSKGSPTPLP WSLLP
	Isoform 3 [UniParc]. Checksum: F7B770908D23A710	FASTA	311	34,487
	10 20 30 40 50 60 MLTKPLQGHP SPPVTPTQPP GGKDRAAFEA EYRLGPLLGK GGFGTVFAGH RVTDRRQVAI 70 80 90 100 110 120 KVISRNRVLG WSTVSDSVTC PLEVALLWKV GEGNGHPGVI RLLDWFETPE GFMLVLERPM 130 140 150 160 170 180 PAQDLFDYIT EKGPLGESCS RSFFTQVVAA VQHCHARGVV HRDIKDENIL IDLCRGSIKL 190 200 210 220 230 240 IDFGSGALLH DEPYTDFDGT RVYSPPEWIS RHQYHALPAT VWSLGVLLYD MVCGDIPFER 250 260 270 280 290 300 DQEILEAELH FPAHVSPDCC ALIRRCLAPK PCSRPSLEEI LLDPWMQSPA EEKPINSSKG 310 SPTPLPWSLL P

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Proviral tagging in E mu-myc transgenic mice lacking the Pim-1 proto-oncogene leads to compensatory activation of Pim-2." van der Lugt N.M., Domen J., Verhoeven E., Linders K., van der Gulden H., Allen J., Berns A. EMBO J. 14:2536-2544(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), ALTERNATIVE INITIATION.
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Strain: FVB/N. Tissue: Mammary gland.
[4]	"Pim-2 transgene induces lymphoid tumors, exhibiting potent synergy with c-myc." Allen J.D., Verhoeven E., Domen J., van der Valk M., Berns A. Oncogene 15:1133-1141(1997) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, FUNCTION IN TUMORIGENESIS, INDUCTION BY IL2; IL3; IL4; IL7; IL9 AND INTERFERON-GAMMA.
[5]	"The serine/threonine kinase Pim-2 is a transcriptionally regulated apoptotic inhibitor." Fox C.J., Hammerman P.S., Cinalli R.M., Master S.R., Chodosh L.A., Thompson C.B. Genes Dev. 17:1841-1854(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS APOPTOTIC INHIBITOR, AUTOPHOSPHORYLATION, PHOSPHORYLATION OF BAD, ALTERNATIVE SPLICING (ISOFORMS 1; 2 AND 3).
[6]	"The PIM-2 kinase phosphorylates BAD on serine 112 and reverses BAD-induced cell death." Yan B., Zemskova M., Holder S., Chin V., Kraft A., Koskinen P.J., Lilly M. J. Biol. Chem. 278:45358-45367(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION BY IL3, FUNCTION AS APOPTOTIC INHIBITOR, PHOSPHORYLATION OF BAD, MUTAGENESIS.
[7]	"Lymphocyte transformation by Pim-2 is dependent on nuclear factor-kappaB activation." Hammerman P.S., Fox C.J., Cinalli R.M., Xu A., Wagner J.D., Lindsten T., Thompson C.B. Cancer Res. 64:8341-8348(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS A POSITIVE REGULATOR OF I-KAPPAB KINASE/NF-KAPPAB CASCADE, PHOSPHORYLATION OF MAP3K8/COT.
[8]	"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.
[9]	"Pim and Akt oncogenes are independent regulators of hematopoietic cell growth and survival." Hammerman P.S., Fox C.J., Birnbaum M.J., Thompson C.B. Blood 105:4477-4483(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN THE REGULATION OF CAP-DEPENDENT PROTEIN TRANSLATION.
[10]	"The Pim kinases control rapamycin-resistant T cell survival and activation." Fox C.J., Hammerman P.S., Thompson C.B. J. Exp. Med. 201:259-266(2005) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE, INDUCTION BY IL4 AND IL7.
[11]	"PIM-2 is an independent regulator of chondrocyte survival and autophagy in the epiphyseal growth plate." Bohensky J., Shapiro I.M., Leshinsky S., Watanabe H., Srinivas V. J. Cell. Physiol. 213:246-251(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[12]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00121075. IPI00162793. IPI00377846.
PIR	S55333.
RefSeq	NP_613072.1. NM_138606.2.
UniGene	Mm.347478.
3D structure databases
ProteinModelPortal	Q62070.
SMR	Q62070. Positions 49-364.
ModBase	Search...
PTM databases
PhosphoSite	Q62070.
Proteomic databases
PRIDE	Q62070.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	18715.
KEGG	mmu:18715.
UCSC	uc009smz.1. mouse.
Organism-specific databases
CTD	11040.
MGI	MGI:97587. Pim2.
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000231357.
HOVERGEN	HBG106681.
InParanoid	A2AER1.
KO	K08806.
OrthoDB	EOG4CC41R.
Gene expression databases
CleanEx	MM_PIM2.
Genevestigator	Q62070.
GermOnline	ENSMUSG00000031155. Mus musculus.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	294801.
SOURCE	Search...

Entry information

Entry name

PIM2_MOUSE

Accession

Primary (citable) accession number: Q62070
Secondary accession number(s): A2AER1 , Q62071, Q62072, Q8R2P0

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 27, 2002
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 100 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program