PIM1_RAT
ID PIM1_RAT Reviewed; 313 AA.
AC P26794;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Serine/threonine-protein kinase pim-1;
DE EC=2.7.11.1;
GN Name=Pim1; Synonyms=Pim-1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Testis;
RX PubMed=1620615; DOI=10.1093/nar/20.12.3183;
RA Wingett D., Reeves R., Magnuson N.S.;
RT "Characterization of the testes-specific pim-1 transcript in rat.";
RL Nucleic Acids Res. 20:3183-3189(1992).
RN [2]
RP FUNCTION IN PHOSPHORYLATION OF CDC25A, AND INTERACTION WITH CDC25A.
RX PubMed=10373478; DOI=10.1074/jbc.274.26.18659;
RA Mochizuki T., Kitanaka C., Noguchi K., Muramatsu T., Asai A., Kuchino Y.;
RT "Physical and functional interactions between Pim-1 kinase and Cdc25A
RT phosphatase. Implications for the Pim-1-mediated activation of the c-Myc
RT signaling pathway.";
RL J. Biol. Chem. 274:18659-18666(1999).
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). 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 PIM1 might explain partly
CC the strong synergism between these two oncogenes in tumorigenesis.
CC Mediates survival signaling through phosphorylation of BAD, which
CC induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1.
CC Phosphorylation of MAP3K5, another proapoptotic protein, by PIM1,
CC significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-
CC mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing
CC 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 protein
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. Also phosphorylates and activates the ATP-binding
CC cassette transporter ABCG2, allowing resistance to drugs through their
CC excretion from cells. Promotes brown adipocyte differentiation (By
CC similarity). {ECO:0000250|UniProtKB:P06803,
CC ECO:0000250|UniProtKB:P11309}.
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: Binds to RP9 (By similarity). Interacts with CDKN1B and FOXO3
CC (By similarity). Interacts (via N-terminal 96 residues) with CDC25A.
CC Interacts with BAD (By similarity). Interacts with PPP2CA; this
CC interaction promotes dephosphorylation of PIM1, ubiquitination and
CC proteasomal degradation (By similarity). Interacts with HSP90, this
CC interaction stabilizes PIM1 protein levels. Interacts (ubiquitinated
CC form) with HSP70 and promotes its proteosomal degradation (By
CC similarity). Interacts with CDKN1A (By similarity). Interacts with
CC CDC25C (By similarity). Interacts (via N-terminal 96 residues) with
CC CDC25A. Interacts with MAP3K5 (By similarity). Interacts with MYC (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Cell membrane {ECO:0000250}.
CC -!- PTM: Autophosphorylated on both serine/threonine and tyrosine residues
CC (By similarity). Phosphorylated. Interaction with PPP2CA promotes
CC dephosphorylation (By similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated, leading to proteasomal degradation. {ECO:0000250}.
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; X63675; CAA45214.1; -; mRNA.
DR PIR; S26298; S26298.
DR RefSeq; NP_058730.1; NM_017034.1.
DR AlphaFoldDB; P26794; -.
DR SMR; P26794; -.
DR STRING; 10116.ENSRNOP00000000637; -.
DR PhosphoSitePlus; P26794; -.
DR PaxDb; P26794; -.
DR Ensembl; ENSRNOT00000000637; ENSRNOP00000000637; ENSRNOG00000000529.
DR GeneID; 24649; -.
DR KEGG; rno:24649; -.
DR UCSC; RGD:3330; rat.
DR CTD; 5292; -.
DR RGD; 3330; Pim1.
DR eggNOG; KOG0583; Eukaryota.
DR GeneTree; ENSGT00940000153394; -.
DR HOGENOM; CLU_000288_63_0_1; -.
DR InParanoid; P26794; -.
DR OMA; QDIHLEP; -.
DR OrthoDB; 930292at2759; -.
DR PhylomeDB; P26794; -.
DR PRO; PR:P26794; -.
DR Proteomes; UP000002494; Chromosome 20.
DR Bgee; ENSRNOG00000000529; Expressed in testis and 19 other tissues.
DR Genevisible; P26794; RN.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005730; C:nucleolus; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0030145; F:manganese ion binding; ISS:UniProtKB.
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:0043024; F:ribosomal small subunit binding; ISO:RGD.
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:RGD.
DR GO; GO:0090336; P:positive regulation of brown fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; ISO:RGD.
DR GO; GO:1905062; P:positive regulation of cardioblast proliferation; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0046777; P:protein autophosphorylation; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISO:RGD.
DR GO; GO:1902033; P:regulation of hematopoietic stem cell proliferation; ISO:RGD.
DR GO; GO:0022898; P:regulation of transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0070561; P:vitamin D receptor signaling pathway; ISO:RGD.
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; Cell membrane; Cytoplasm; Kinase;
KW Magnesium; Membrane; Metal-binding; Nucleotide-binding; Nucleus;
KW 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_0000086530"
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 /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
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 98
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11309"
FT MOD_RES 261
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11309"
SQ SEQUENCE 313 AA; 35631 MW; D5757DA9F1821BF9 CRC64;
MLLSKINSLA HLRAAPCNDL HANKLAPGKE KEPLESQYQV GPLLGSGGFG SVYSGIRVAD
NLPVAIKHVE KDRISDWGEL PNGTRVPMEV VLLKKVSSGF SGVIRLLDWF ERPDSFVLIL
ERPEPVQDLF DFITERGALQ EELARSFFWQ VLEAVRHCHN CGVLHRDIKD ENILIDLNRG
ELKLIDFGSG ALLKDTVYTD FDGTRVYSPP EWIRYHRYHG RSAAVWSLGI LLYDMVCGDI
PFEHDEEIVK GQVYFRQRVS SECQHLIRWC LSLRPSDRPS FEEIQNHPWM QDVLLPQATA
EIHLHSLSPS PSK
