PIM2_MOUSE
ID PIM2_MOUSE Reviewed; 370 AA.
AC Q62070; A2AER1; Q62071; Q62072; Q8R2P0;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Serine/threonine-protein kinase pim-2;
DE EC=2.7.11.1;
GN Name=Pim2; Synonyms=Pim-2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), AND ALTERNATIVE
RP INITIATION.
RX PubMed=7781606;
RA van der Lugt N.M., Domen J., Verhoeven E., Linders K., van der Gulden H.,
RA Allen J., Berns A.;
RT "Proviral tagging in E mu-myc transgenic mice lacking the Pim-1 proto-
RT oncogene leads to compensatory activation of Pim-2.";
RL EMBO J. 14:2536-2544(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC STRAIN=FVB/N; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP TISSUE SPECIFICITY, FUNCTION IN TUMORIGENESIS, AND INDUCTION BY IL2; IL3;
RP IL4; IL7; IL9 AND INTERFERON-GAMMA.
RX PubMed=9294606; DOI=10.1038/sj.onc.1201288;
RA Allen J.D., Verhoeven E., Domen J., van der Valk M., Berns A.;
RT "Pim-2 transgene induces lymphoid tumors, exhibiting potent synergy with c-
RT myc.";
RL Oncogene 15:1133-1141(1997).
RN [5]
RP FUNCTION AS APOPTOTIC INHIBITOR, AUTOPHOSPHORYLATION, PHOSPHORYLATION OF
RP BAD, AND ALTERNATIVE SPLICING (ISOFORMS 1; 2 AND 3).
RX PubMed=12869584; DOI=10.1101/gad.1105003;
RA Fox C.J., Hammerman P.S., Cinalli R.M., Master S.R., Chodosh L.A.,
RA Thompson C.B.;
RT "The serine/threonine kinase Pim-2 is a transcriptionally regulated
RT apoptotic inhibitor.";
RL Genes Dev. 17:1841-1854(2003).
RN [6]
RP INDUCTION BY IL3, FUNCTION AS APOPTOTIC INHIBITOR, PHOSPHORYLATION OF BAD,
RP AND MUTAGENESIS.
RX PubMed=12954615; DOI=10.1074/jbc.m307933200;
RA Yan B., Zemskova M., Holder S., Chin V., Kraft A., Koskinen P.J., Lilly M.;
RT "The PIM-2 kinase phosphorylates BAD on serine 112 and reverses BAD-induced
RT cell death.";
RL J. Biol. Chem. 278:45358-45367(2003).
RN [7]
RP FUNCTION AS A POSITIVE REGULATOR OF I-KAPPAB KINASE/NF-KAPPAB CASCADE, AND
RP PHOSPHORYLATION OF MAP3K8/COT.
RX PubMed=15548703; DOI=10.1158/0008-5472.can-04-2284;
RA Hammerman P.S., Fox C.J., Cinalli R.M., Xu A., Wagner J.D., Lindsten T.,
RA Thompson C.B.;
RT "Lymphocyte transformation by Pim-2 is dependent on nuclear factor-kappaB
RT activation.";
RL Cancer Res. 64:8341-8348(2004).
RN [8]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=15199164; DOI=10.1128/mcb.24.13.6104-6115.2004;
RA Mikkers H., Nawijn M., Allen J., Brouwers C., Verhoeven E., Jonkers J.,
RA Berns A.;
RT "Mice deficient for all PIM kinases display reduced body size and impaired
RT responses to hematopoietic growth factors.";
RL Mol. Cell. Biol. 24:6104-6115(2004).
RN [9]
RP FUNCTION IN THE REGULATION OF CAP-DEPENDENT PROTEIN TRANSLATION.
RX PubMed=15705789; DOI=10.1182/blood-2004-09-3706;
RA Hammerman P.S., Fox C.J., Birnbaum M.J., Thompson C.B.;
RT "Pim and Akt oncogenes are independent regulators of hematopoietic cell
RT growth and survival.";
RL Blood 105:4477-4483(2005).
RN [10]
RP DISRUPTION PHENOTYPE, AND INDUCTION BY IL4 AND IL7.
RX PubMed=15642745; DOI=10.1084/jem.20042020;
RA Fox C.J., Hammerman P.S., Thompson C.B.;
RT "The Pim kinases control rapamycin-resistant T cell survival and
RT activation.";
RL J. Exp. Med. 201:259-266(2005).
RN [11]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17476689; DOI=10.1002/jcp.21117;
RA Bohensky J., Shapiro I.M., Leshinsky S., Watanabe H., Srinivas V.;
RT "PIM-2 is an independent regulator of chondrocyte survival and autophagy in
RT the epiphyseal growth plate.";
RL J. Cell. Physiol. 213:246-251(2007).
RN [12]
RP FUNCTION IN PHOSPHORYLATION OF MYC, AND INTERACTION WITH MYC.
RX PubMed=18438430; DOI=10.1038/onc.2008.123;
RA Zhang Y., Wang Z., Li X., Magnuson N.S.;
RT "Pim kinase-dependent inhibition of c-Myc degradation.";
RL Oncogene 27:4809-4819(2008).
CC -!- FUNCTION: Proto-oncogene with serine/threonine kinase activity involved
CC in cell survival and cell proliferation. Exerts its oncogenic activity
CC through: the regulation of MYC transcriptional activity, the regulation
CC of cell cycle progression, the regulation of cap-dependent protein
CC translation and through survival signaling by phosphorylation of a pro-
CC apoptotic protein, BAD. Phosphorylation of MYC leads to an increase of
CC MYC protein stability and thereby an increase of transcriptional
CC activity. The stabilization of MYC exerted by PIM2 might explain partly
CC the strong synergism between these 2 oncogenes in tumorigenesis.
CC Regulates cap-dependent protein translation in a mammalian target of
CC rapamycin complex 1 (mTORC1)-independent manner and in parallel to the
CC PI3K-Akt pathway. Mediates survival signaling through phosphorylation
CC of BAD, which induces release of the anti-apoptotic protein Bcl-
CC X(L)/BCL2L1. Promotes cell survival in response to a variety of
CC proliferative signals via positive regulation of the I-kappa-B
CC kinase/NF-kappa-B cascade; this process requires phosphorylation of
CC MAP3K8/COT. Promotes growth factor-independent proliferation by
CC phosphorylation of cell cycle factors such as CDKN1A and CDKN1B.
CC Involved in the positive regulation of chondrocyte survival and
CC autophagy in the epiphyseal growth plate. {ECO:0000269|PubMed:12869584,
CC ECO:0000269|PubMed:12954615, ECO:0000269|PubMed:15199164,
CC ECO:0000269|PubMed:15548703, ECO:0000269|PubMed:15705789,
CC ECO:0000269|PubMed:17476689, ECO:0000269|PubMed:18438430,
CC ECO:0000269|PubMed:9294606}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- SUBUNIT: Interacts with MYC. {ECO:0000269|PubMed:18438430}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=3;
CC Name=1;
CC IsoId=Q62070-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q62070-2; Sequence=VSP_018854, VSP_018855;
CC Name=3;
CC IsoId=Q62070-3; Sequence=VSP_018856;
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest expression in
CC spleen, thymus and brain. Expressed in epiphyseal chondrocytes.
CC {ECO:0000269|PubMed:17476689, ECO:0000269|PubMed:9294606}.
CC -!- INDUCTION: Induced by a wide range of growth factors and mitogens; IL2,
CC IL3, IL4, IL7,IL9 and by interferon-gamma (IFNG).
CC {ECO:0000269|PubMed:12954615, ECO:0000269|PubMed:15642745,
CC ECO:0000269|PubMed:9294606}.
CC -!- PTM: Autophosphorylated. {ECO:0000269|PubMed:12869584,
CC ECO:0000269|PubMed:12954615, ECO:0000269|PubMed:15548703}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable and fertile. Deficient mice shown
CC reduced T-cell activation and expansion in the presence of the
CC serine/threonine protein kinase mTOR inhibitor rapamycin. Triple
CC knockout mice PIM1/PIM2/PIM3 shown a profound reduction in body size at
CC birth and throughout postnatal life due to a reduction in the number of
CC cells rather than cell size. {ECO:0000269|PubMed:15199164,
CC ECO:0000269|PubMed:15642745}.
CC -!- MISCELLANEOUS: [Isoform 1]: Initiates from CTG codon.
CC -!- MISCELLANEOUS: [Isoform 2]: Initiates from CTG codon. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: Mutagen in position: 61:K->A (loss of
CC kinase activity). {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. PIM subfamily. {ECO:0000305}.
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DR EMBL; L41495; AAA98922.1; -; mRNA.
DR EMBL; L41495; AAA98923.1; -; mRNA.
DR EMBL; L41495; AAA98924.1; -; mRNA.
DR EMBL; AL671978; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC027376; AAH27376.1; -; mRNA.
DR CCDS; CCDS29976.1; -. [Q62070-1]
DR PIR; S55333; S55333.
DR RefSeq; NP_613072.1; NM_138606.2. [Q62070-1]
DR AlphaFoldDB; Q62070; -.
DR SMR; Q62070; -.
DR BioGRID; 202167; 1.
DR STRING; 10090.ENSMUSP00000033495; -.
DR iPTMnet; Q62070; -.
DR PhosphoSitePlus; Q62070; -.
DR EPD; Q62070; -.
DR PaxDb; Q62070; -.
DR PRIDE; Q62070; -.
DR DNASU; 18715; -.
DR GeneID; 18715; -.
DR KEGG; mmu:18715; -.
DR UCSC; uc009smz.2; mouse. [Q62070-1]
DR CTD; 11040; -.
DR MGI; MGI:97587; Pim2.
DR eggNOG; KOG0583; Eukaryota.
DR InParanoid; Q62070; -.
DR PhylomeDB; Q62070; -.
DR BioGRID-ORCS; 18715; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Pim2; mouse.
DR PRO; PR:Q62070; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q62070; protein.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0008637; P:apoptotic mitochondrial changes; IDA:MGI.
DR GO; GO:0006915; P:apoptotic process; IMP:MGI.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0016236; P:macroautophagy; IMP:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0032091; P:negative regulation of protein binding; IMP:MGI.
DR GO; GO:0010508; P:positive regulation of autophagy; IMP:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IMP:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IDA:UniProtKB.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; IBA:GO_Central.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Alternative initiation; Apoptosis; ATP-binding; Cell cycle; Kinase;
KW Nucleotide-binding; Phosphoprotein; Proto-oncogene; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..370
FT /note="Serine/threonine-protein kinase pim-2"
FT /id="PRO_0000024366"
FT DOMAIN 91..345
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..42
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 61..83
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 349..370
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 22..36
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 222
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 97..105
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 120
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT VAR_SEQ 1..59
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:7781606"
FT /id="VSP_018856"
FT VAR_SEQ 1..25
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7781606"
FT /id="VSP_018854"
FT VAR_SEQ 26
FT /note="L -> M (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7781606"
FT /id="VSP_018855"
SQ SEQUENCE 370 AA; 40060 MW; 12BB70BFD04DBE8A CRC64;
MARATNLNAA PSAGASGPPD SLPSTLAPPS PGSPAALPRA STPCGLSGFS GLNIRSTSSM
LTKPLQGHPS PPVTPTQPPG GKDRAAFEAE YRLGPLLGKG GFGTVFAGHR VTDRRQVAIK
VISRNRVLGW STVSDSVTCP LEVALLWKVG EGNGHPGVIR LLDWFETPEG FMLVLERPMP
AQDLFDYITE KGPLGESCSR SFFTQVVAAV QHCHARGVVH RDIKDENILI DLCRGSIKLI
DFGSGALLHD EPYTDFDGTR VYSPPEWISR HQYHALPATV WSLGVLLYDM VCGDIPFERD
QEILEAELHF PAHVSPDCCA LIRRCLAPKP CSRPSLEEIL LDPWMQSPAE EKPINSSKGS
PTPLPWSLLP
