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 27-MAR-2024, entry version 191. 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. 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. 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). RN [13] RP FUNCTION. RX PubMed=31548394; DOI=10.1073/pnas.1904774116; RA Padi S.K.R., Singh N., Bearss J.J., Olive V., Song J.H., Cardo-Vila M., RA Kraft A.S., Okumura K.; RT "Phosphorylation of DEPDC5, a component of the GATOR1 complex, releases RT inhibition of mTORC1 and promotes tumor growth."; RL Proc. Natl. Acad. Sci. U.S.A. 116:20505-20510(2019). 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 (PubMed:15199164, PubMed:1825810). Exerts CC its oncogenic activity through: the regulation of MYC transcriptional CC activity, the regulation of cell cycle progression and by CC phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, CC FOXO3) (By similarity). Phosphorylation of MYC leads to an increase of CC MYC protein stability and thereby an increase of transcriptional CC activity (PubMed:18438430). The stabilization of MYC exerted by PIM1 CC might explain partly the strong synergism between these two oncogenes CC in tumorigenesis (PubMed:18438430). Mediates survival signaling through CC phosphorylation of BAD, which induces release of the anti-apoptotic CC protein Bcl-X(L)/BCL2L1 (PubMed:15280015). Phosphorylation of MAP3K5, CC another proapoptotic protein, by PIM1, significantly decreases MAP3K5 CC kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and CC JNK/p38MAPK subsequently reducing caspase-3 activation and cell CC apoptosis (By similarity). Stimulates cell cycle progression at the G1- CC S and G2-M transitions by phosphorylation of CDC25A and CDC25C (By CC similarity). 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 (By similarity). Promotes cell CC cycle progression and tumorigenesis by down-regulating expression of a CC regulator of cell cycle progression, CDKN1B, at both transcriptional CC and post-translational levels (By similarity). Phosphorylation of CC CDKN1B, induces 14-3-3 proteins binding, nuclear export and proteasome- CC dependent degradation (By similarity). May affect the structure or CC silencing of chromatin by phosphorylating HP1 gamma/CBX3 (By CC similarity). Acts also as a regulator of homing and migration of bone CC marrow cells involving functional interaction with the CXCL12-CXCR4 CC signaling axis (PubMed:19687226). Acts as a positive regulator of CC mTORC1 signaling by mediating phosphorylation and inhibition of DEPDC5 CC component of the GATOR1 complex (PubMed:31548394). Acts as a negative CC regulator of innate immunity by mediating phosphorylation and CC inactivation of GBP1 in absence of infection: phosphorylation of GBP1 CC induces interaction with 14-3-3 protein sigma (SFN) and retention in CC the cytosol (By similarity). Also phosphorylates and activates the ATP- CC 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, ECO:0000269|PubMed:31548394}. 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; CC Evidence={ECO:0000250|UniProtKB:P11309}; CC -!- SUBUNIT: Interacts with RP9 (PubMed:10931201). Interacts with HSP90AA1, CC this interaction stabilizes PIM1 protein levels. Interacts CC (ubiquitinated form) with HSP70 and promotes its proteasomal CC degradation (By similarity). {ECO:0000250|UniProtKB:P11309, CC ECO:0000269|PubMed:10931201}. CC -!- SUBUNIT: [Isoform 1]: Isoform 1 is isolated as a monomer whereas CC isoform 2 complexes with other proteins. {ECO:0000269|PubMed:1825810}. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 10090-ENSMUSP00000024811; -. DR ProteomicsDB; 289897; -. [P06803-1] DR ProteomicsDB; 289898; -. [P06803-2] DR ProteomicsDB; 331150; -. DR Antibodypedia; 1207; 831 antibodies from 38 providers. DR DNASU; 18712; -. DR Ensembl; ENSMUST00000024811.9; ENSMUSP00000024811.8; ENSMUSG00000024014.9. [P06803-1] DR GeneID; 18712; -. DR KEGG; mmu:18712; -. DR UCSC; uc008bsz.1; mouse. DR UCSC; uc008bta.1; mouse. [P06803-1] DR AGR; MGI:97584; -. 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; GHRPCAD; -. DR OrthoDB; 4292089at2759; -. DR PhylomeDB; P06803; -. DR TreeFam; TF320810; -. DR BRENDA; 2.7.11.1; 3474. DR BioGRID-ORCS; 18712; 9 hits in 75 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 211 other cell types or 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:0071346; P:cellular response to type II interferon; ISS:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB. DR GO; GO:0045824; P:negative regulation of innate immune response; ISS:UniProtKB. 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:0045893; P:positive regulation of DNA-templated transcription; IMP:UniProtKB. DR GO; GO:1904263; P:positive regulation of TORC1 signaling; ISS:UniProtKB. 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 Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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 PANTHER; PTHR22984; SERINE/THREONINE-PROTEIN KINASE PIM; 1. DR PANTHER; PTHR22984:SF29; SERINE_THREONINE-PROTEIN KINASE PIM-1; 1. DR Pfam; PF00069; Pkinase; 1. DR PIRSF; PIRSF037993; STPK_Pim-1; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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 //