PIM1_MOUSE
ID PIM1_MOUSE Reviewed; 313 AA.
AC P06803; F6XDQ5; Q8CFN8;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 10-OCT-2018, sequence version 3.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Serine/threonine-protein kinase pim-1;
DE EC=2.7.11.1;
GN Name=Pim1; Synonyms=Pim-1;
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 [GENOMIC DNA] (ISOFORM 1).
RX PubMed=3015420; DOI=10.1016/0092-8674(86)90886-x;
RA Selten G., Cuypers H.T., Boelens W., Robanus-Maandag E., Verbeek J.,
RA Domen J., van Beveren C., Berns A.;
RT "The primary structure of the putative oncogene pim-1 shows extensive
RT homology with protein kinases.";
RL Cell 46:603-611(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE INITIATION, FUNCTION,
RP SUBUNIT, AUTOPHOSPHORYLATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP LYS-67.
RX PubMed=1825810; DOI=10.1002/j.1460-2075.1991.tb07994.x;
RA Saris C.J., Domen J., Berns A.;
RT "The pim-1 oncogene encodes two related protein-serine/threonine kinases by
RT alternative initiation at AUG and CUG.";
RL EMBO J. 10:655-664(1991).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Brain, and Eye;
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 [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=7689870;
RA Domen J., van der Lugt N.M., Laird P.W., Saris C.J., Clarke A.R.,
RA Hooper M.L., Berns A.;
RT "Impaired interleukin-3 response in Pim-1-deficient bone marrow-derived
RT mast cells.";
RL Blood 82:1445-1452(1993).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=8228813; DOI=10.1084/jem.178.5.1665;
RA Domen J., van der Lugt N.M., Acton D., Laird P.W., Linders K., Berns A.;
RT "Pim-1 levels determine the size of early B lymphoid compartments in bone
RT marrow.";
RL J. Exp. Med. 178:1665-1673(1993).
RN [7]
RP INTERACTION WITH RP9.
RX PubMed=10931201; DOI=10.1046/j.1432-1327.2000.01585.x;
RA Maita H., Harada Y., Nagakubo D., Kitaura H., Ikeda M., Tamai K.,
RA Takahashi K., Ariga H., Iguchi-Ariga S.M.M.;
RT "PAP-1, a novel target protein of phosphorylation by Pim-1 kinase.";
RL Eur. J. Biochem. 267:5168-5178(2000).
RN [8]
RP FUNCTION IN PHOSPHORYLATION OF BAD, AND INTERACTION WITH BAD.
RX PubMed=15280015; DOI=10.1016/j.febslet.2004.06.050;
RA Aho T.L., Sandholm J., Peltola K.J., Mankonen H.P., Lilly M.,
RA Koskinen P.J.;
RT "Pim-1 kinase promotes inactivation of the pro-apoptotic Bad protein by
RT phosphorylating it on the Ser112 gatekeeper site.";
RL FEBS Lett. 571:43-49(2004).
RN [9]
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 [10]
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).
RN [11]
RP FUNCTION IN PHOSPHORYLATION OF CXCR4, AND FUNCTION IN CELL MIGRATION.
RX PubMed=19687226; DOI=10.1084/jem.20082074;
RA Grundler R., Brault L., Gasser C., Bullock A.N., Dechow T., Woetzel S.,
RA Pogacic V., Villa A., Ehret S., Berridge G., Spoo A., Dierks C., Biondi A.,
RA Knapp S., Duyster J., Schwaller J.;
RT "Dissection of PIM serine/threonine kinases in FLT3-ITD-induced
RT leukemogenesis reveals PIM1 as regulator of CXCL12-CXCR4-mediated homing
RT and migration.";
RL J. Exp. Med. 206:1957-1970(2009).
RN [12]
RP FUNCTION.
RX PubMed=27923061; DOI=10.1371/journal.pgen.1006474;
RA Brunmeir R., Wu J., Peng X., Kim S.Y., Julien S.G., Zhang Q., Xie W.,
RA Xu F.;
RT "Comparative Transcriptomic and Epigenomic Analyses Reveal New Regulators
RT of Murine Brown Adipogenesis.";
RL PLoS Genet. 12:E1006474-E1006474(2016).
CC -!- FUNCTION: Proto-oncogene with serine/threonine kinase activity involved
CC in cell survival and cell proliferation and thus providing a selective
CC advantage in tumorigenesis. Exerts its oncogenic activity through: the
CC regulation of MYC transcriptional activity, the regulation of cell
CC cycle progression and by phosphorylation and inhibition of proapoptotic
CC proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an
CC increase of MYC protein stability and thereby an increase of
CC transcriptional activity. The stabilization of MYC exerted by PIM1
CC might explain partly the strong synergism between these two oncogenes
CC in tumorigenesis. Mediates survival signaling through phosphorylation
CC of BAD, which induces release of the anti-apoptotic protein Bcl-
CC X(L)/BCL2L1. Phosphorylation of MAP3K5, another proapoptotic protein,
CC by PIM1, significantly decreases MAP3K5 kinase activity and inhibits
CC MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently
CC reducing caspase-3 activation and cell apoptosis. Stimulates cell cycle
CC progression at the G1-S and G2-M transitions by phosphorylation of
CC CDC25A and CDC25C. Phosphorylation of CDKN1A, a regulator of cell cycle
CC progression at G1, results in the relocation of CDKN1A to the cytoplasm
CC and enhanced CDKN1A protein stability. Promotes cell cycle progression
CC and tumorigenesis by down-regulating expression of a regulator of cell
CC cycle progression, CDKN1B, at both transcriptional and post-
CC translational levels. Phosphorylation of CDKN1B, induces 14-3-3
CC binding, nuclear export and proteasome-dependent degradation. May
CC affect the structure or silencing of chromatin by phosphorylating HP1
CC gamma/CBX3. Acts also as a regulator of homing and migration of bone
CC marrow cells involving functional interaction with the CXCL12-CXCR4
CC signaling axis (By similarity). Also phosphorylates and activates the
CC ATP-binding cassette transporter ABCG2, allowing resistance to drugs
CC through their excretion from cells (By similarity). Promotes brown
CC adipocyte differentiation (PubMed:27923061).
CC {ECO:0000250|UniProtKB:P11309, ECO:0000269|PubMed:15199164,
CC ECO:0000269|PubMed:15280015, ECO:0000269|PubMed:1825810,
CC ECO:0000269|PubMed:18438430, ECO:0000269|PubMed:19687226,
CC ECO:0000269|PubMed:27923061}.
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 -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- SUBUNIT: Isoform 1 is isolated as a monomer whereas isoform 2 complexes
CC with other proteins (PubMed:1825810). Isoform 2, but not isoform 1,
CC binds BMX (By similarity). Binds to RP9 (PubMed:10931201). Interacts
CC with CDKN1B and FOXO3 (By similarity). Interacts with BAD
CC (PubMed:15280015). Interacts with PPP2CA; this interaction promotes
CC dephosphorylation of PIM1, ubiquitination and proteasomal degradation
CC (By similarity). Interacts with HSP90AA1, this interaction stabilizes
CC PIM1 protein levels (By similarity). Interacts (ubiquitinated form)
CC with HSP70 and promotes its proteosomal degradation (By similarity).
CC Interacts with CDKN1A (By similarity). Interacts with CDC25C (By
CC similarity). Interacts (via N-terminal 96 residues) with CDC25A (By
CC similarity). Interacts with MAP3K5 (By similarity). Interacts with MYC
CC (PubMed:18438430). Interacts with CBX3 (By similarity).
CC {ECO:0000250|UniProtKB:P11309, ECO:0000269|PubMed:10931201,
CC ECO:0000269|PubMed:15280015, ECO:0000269|PubMed:1825810,
CC ECO:0000269|PubMed:18438430}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:1825810}. Nucleus
CC {ECO:0000269|PubMed:1825810}. Cell membrane
CC {ECO:0000269|PubMed:1825810}. Note=Mainly located in the cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=1;
CC IsoId=P06803-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P06803-2; Sequence=VSP_059830;
CC -!- PTM: Autophosphorylated on both serine/threonine and tyrosine residues.
CC Phosphorylated. Interaction with PPP2CA promotes dephosphorylation (By
CC similarity). {ECO:0000250|UniProtKB:P11309}.
CC -!- PTM: Ubiquitinated, leading to proteasomal degradation.
CC {ECO:0000250|UniProtKB:P11309}.
CC -!- DISEASE: Note=Frequently activated by provirus insertion in murine
CC leukemia virus-induced T-cell lymphomas.
CC -!- DISRUPTION PHENOTYPE: Deficient mice are viable and fertile however
CC they have a specific defect in interleukin-7 (IL7)-driven growth of
CC pre-B cells, as well as IL3-dependent growth of bone marrow-derived
CC mast cells. Triple knockout mice PIM1/PIM2/PIM3 are viable and fertile
CC too, but their body size is reduced at birth and throughout postnatal
CC life due to a reduction in the number of cells rather than cell size.
CC {ECO:0000269|PubMed:15199164, ECO:0000269|PubMed:7689870,
CC ECO:0000269|PubMed:8228813}.
CC -!- MISCELLANEOUS: [Isoform 2]: Initiates from CTG codon.
CC {ECO:0000269|PubMed:1825810}.
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; M13945; AAA39930.1; -; Genomic_DNA.
DR EMBL; AC163629; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC042885; AAH42885.1; -; mRNA.
DR EMBL; BC053019; AAH53019.1; -; mRNA.
DR EMBL; BC055316; AAH55316.1; -; mRNA.
DR CCDS; CCDS79520.1; -. [P06803-1]
DR PIR; A24169; TVMSP1.
DR RefSeq; NP_032868.2; NM_008842.3. [P06803-1]
DR AlphaFoldDB; P06803; -.
DR SMR; P06803; -.
DR STRING; 10090.ENSMUSP00000024811; -.
DR BindingDB; P06803; -.
DR ChEMBL; CHEMBL3297640; -.
DR iPTMnet; P06803; -.
DR PhosphoSitePlus; P06803; -.
DR EPD; P06803; -.
DR PaxDb; P06803; -.
DR PRIDE; P06803; -.
DR ProteomicsDB; 289897; -. [P06803-1]
DR ProteomicsDB; 289898; -. [P06803-2]
DR ProteomicsDB; 331150; -.
DR Antibodypedia; 1207; 727 antibodies from 38 providers.
DR DNASU; 18712; -.
DR Ensembl; ENSMUST00000024811; ENSMUSP00000024811; ENSMUSG00000024014. [P06803-1]
DR GeneID; 18712; -.
DR KEGG; mmu:18712; -.
DR UCSC; uc008bsz.1; mouse.
DR UCSC; uc008bta.1; mouse. [P06803-1]
DR CTD; 5292; -.
DR MGI; MGI:97584; Pim1.
DR VEuPathDB; HostDB:ENSMUSG00000024014; -.
DR eggNOG; KOG0583; Eukaryota.
DR GeneTree; ENSGT00940000153394; -.
DR HOGENOM; CLU_000288_63_0_1; -.
DR InParanoid; P06803; -.
DR OMA; QDIHLEP; -.
DR OrthoDB; 930292at2759; -.
DR PhylomeDB; P06803; -.
DR TreeFam; TF320810; -.
DR BRENDA; 2.7.11.1; 3474.
DR BioGRID-ORCS; 18712; 8 hits in 70 CRISPR screens.
DR ChiTaRS; Pim1; mouse.
DR PRO; PR:P06803; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; P06803; protein.
DR Bgee; ENSMUSG00000024014; Expressed in granulocyte and 208 other tissues.
DR ExpressionAtlas; P06803; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; ISO:MGI.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0043024; F:ribosomal small subunit binding; ISO:MGI.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:1990748; P:cellular detoxification; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0090336; P:positive regulation of brown fat cell differentiation; IMP:UniProtKB.
DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; ISO:MGI.
DR GO; GO:1905062; P:positive regulation of cardioblast proliferation; ISO:MGI.
DR GO; GO:0045737; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IDA:UniProtKB.
DR GO; GO:1902033; P:regulation of hematopoietic stem cell proliferation; IDA:CACAO.
DR GO; GO:0022898; P:regulation of transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0070561; P:vitamin D receptor signaling pathway; ISO:MGI.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR017348; PIM1/2/3.
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 PIRSF; PIRSF037993; STPK_Pim-1; 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; Cell membrane;
KW Cytoplasm; Kinase; Magnesium; Membrane; Metal-binding; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Proto-oncogene; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT CHAIN 1..313
FT /note="Serine/threonine-protein kinase pim-1"
FT /id="PRO_0000043351"
FT DOMAIN 38..290
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 167
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 44..52
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 67
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 121
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 128
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 8
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11309"
FT MOD_RES 23
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P11309"
FT MOD_RES 98
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11309"
FT MOD_RES 261
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11309"
FT VAR_SEQ 1
FT /note="M -> MGPAAPLALPPPALPDPAGEPARGQPRQRPQSSSDSPSALRASRSQS
FT RNATRSLSPGRRLSPSSLRRRCCSSRHRRRTDTLEVGM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:1825810"
FT /id="VSP_059830"
FT MUTAGEN 67
FT /note="K->M: Loss of autophosphorylation and kinase
FT activity."
FT /evidence="ECO:0000269|PubMed:1825810"
FT CONFLICT 15
FT /note="A -> R (in Ref. 1; AAA39930)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 313 AA; 35451 MW; 1294F16A03B7C7D7 CRC64;
MLLSKINSLA HLRAAPCNDL HATKLAPGKE KEPLESQYQV GPLLGSGGFG SVYSGIRVAD
NLPVAIKHVE KDRISDWGEL PNGTRVPMEV VLLKKVSSDF SGVIRLLDWF ERPDSFVLIL
ERPEPVQDLF DFITERGALQ EDLARGFFWQ VLEAVRHCHN CGVLHRDIKD ENILIDLSRG
EIKLIDFGSG ALLKDTVYTD FDGTRVYSPP EWIRYHRYHG RSAAVWSLGI LLYDMVCGDI
PFEHDEEIIK GQVFFRQTVS SECQHLIKWC LSLRPSDRPS FEEIRNHPWM QGDLLPQAAS
EIHLHSLSPG SSK
