PIM3_MOUSE
ID PIM3_MOUSE Reviewed; 326 AA.
AC P58750;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 27-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Serine/threonine-protein kinase pim-3;
DE EC=2.7.11.1;
GN Name=Pim3;
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 [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon, and Salivary 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 [2]
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 [3]
RP TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, INTERACTION WITH SOCS6,
RP INDUCTION, MUTAGENESIS OF LYS-38, AND FUNCTION.
RX PubMed=21099329; DOI=10.4161/isl.2.5.13058;
RA Vlacich G., Nawijn M.C., Webb G.C., Steiner D.F.;
RT "Pim3 negatively regulates glucose-stimulated insulin secretion.";
RL Islets 2:308-317(2010).
RN [4]
RP FUNCTION.
RX PubMed=21187426; DOI=10.1073/pnas.1013214108;
RA Beharry Z., Mahajan S., Zemskova M., Lin Y.W., Tholanikunnel B.G., Xia Z.,
RA Smith C.D., Kraft A.S.;
RT "The Pim protein kinases regulate energy metabolism and cell growth.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:528-533(2011).
CC -!- FUNCTION: Proto-oncogene with serine/threonine kinase activity that can
CC prevent apoptosis and promote cell survival and protein translation.
CC May contribute to tumorigenesis through: the delivery of survival
CC signaling through phosphorylation of BAD which induces release of the
CC anti-apoptotic protein Bcl-X(L), the regulation of cell cycle
CC progression and protein synthesis and by regulation of MYC
CC transcriptional activity. Additionally to this role on tumorigenesis,
CC can also negatively regulate insulin secretion by inhibiting the
CC activation of MAPK1/3 (ERK1/2), through SOCS6. Involved also in the
CC control of energy metabolism and regulation of AMPK activity in
CC modulating MYC and PPARGC1A protein levels and cell growth.
CC {ECO:0000269|PubMed:15199164, ECO:0000269|PubMed:21099329,
CC ECO:0000269|PubMed:21187426}.
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 BAD (By similarity). Interacts with PPP2CA;
CC this interaction promotes dephosphorylation of PIM3, ubiquitination and
CC proteasomal degradation (By similarity). Interacts with SOCS6.
CC {ECO:0000250, ECO:0000269|PubMed:21099329}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Detected in pancreas but exclusively in beta-cells.
CC {ECO:0000269|PubMed:21099329}.
CC -!- INDUCTION: By glucose in pancreatic-beta-cells.
CC {ECO:0000269|PubMed:21099329}.
CC -!- PTM: Ubiquitinated, leading to proteasomal degradation. {ECO:0000250}.
CC -!- PTM: Phosphorylated. Interaction with PPP2CA promotes dephosphorylation
CC (By similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable and fertile, with a profound
CC reduction in body size at birth and throughout postnatal life due to a
CC reduction in the number of cells rather than cell size. Deficient mice
CC have also an increased glucose tolerance. {ECO:0000269|PubMed:15199164,
CC ECO:0000269|PubMed:21099329}.
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; BC017621; AAH17621.1; -; mRNA.
DR EMBL; BC026639; AAH26639.1; -; mRNA.
DR CCDS; CCDS27734.1; -.
DR RefSeq; NP_663453.1; NM_145478.2.
DR AlphaFoldDB; P58750; -.
DR SMR; P58750; -.
DR BioGRID; 230194; 1.
DR STRING; 10090.ENSMUSP00000044603; -.
DR iPTMnet; P58750; -.
DR PhosphoSitePlus; P58750; -.
DR PaxDb; P58750; -.
DR PRIDE; P58750; -.
DR ProteomicsDB; 288163; -.
DR Antibodypedia; 28269; 163 antibodies from 24 providers.
DR DNASU; 223775; -.
DR Ensembl; ENSMUST00000042818; ENSMUSP00000044603; ENSMUSG00000035828.
DR GeneID; 223775; -.
DR KEGG; mmu:223775; -.
DR UCSC; uc007xeq.1; mouse.
DR CTD; 415116; -.
DR MGI; MGI:1355297; Pim3.
DR VEuPathDB; HostDB:ENSMUSG00000035828; -.
DR eggNOG; KOG0583; Eukaryota.
DR GeneTree; ENSGT00940000153394; -.
DR HOGENOM; CLU_000288_63_0_1; -.
DR InParanoid; P58750; -.
DR OMA; WGTINGT; -.
DR OrthoDB; 930292at2759; -.
DR PhylomeDB; P58750; -.
DR TreeFam; TF320810; -.
DR BioGRID-ORCS; 223775; 3 hits in 75 CRISPR screens.
DR ChiTaRS; Pim3; mouse.
DR PRO; PR:P58750; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; P58750; protein.
DR Bgee; ENSMUSG00000035828; Expressed in paneth cell and 250 other tissues.
DR ExpressionAtlas; P58750; baseline and differential.
DR Genevisible; P58750; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0016572; P:histone phosphorylation; ISO:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0061179; P:negative regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; ISS:UniProtKB.
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 Apoptosis; ATP-binding; Cell cycle; Cytoplasm; Kinase; Nucleotide-binding;
KW Phosphoprotein; Proto-oncogene; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT CHAIN 1..326
FT /note="Serine/threonine-protein kinase pim-3"
FT /id="PRO_0000086534"
FT DOMAIN 40..293
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 170
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 46..54
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 69
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MUTAGEN 38
FT /note="K->R: Enhances insulin secretion after glucose
FT stimulation."
FT /evidence="ECO:0000269|PubMed:21099329"
SQ SEQUENCE 326 AA; 35970 MW; DD68CBF46354851E CRC64;
MLLSKFGSLA HLCGPGGVDH LPVKILQPAK ADKESFEKVY QVGAVLGSGG FGTVYAGSRI
ADGLPVAVKH VVKERVTEWG SLGGVAVPLE VVLLRKVGAA GGARGVIRLL DWFERPDGFL
LVLERPEPAQ DLFDFITERG ALDEPLARRF FAQVLAAVRH CHNCGVVHRD IKDENLLVDL
RSGELKLIDF GSGAVLKDTV YTDFDGTRVY SPPEWIRYHR YHGRSATVWS LGVLLYDMVC
GDIPFEQDEE ILRGRLFFRR RVSPECQQLI EWCLSLRPSE RPSLDQIAAH PWMLGTEGSV
PENCDLRLCA LDTDDGASTT SSSESL
