PIM1_BOVIN
ID PIM1_BOVIN Reviewed; 313 AA.
AC Q9N0P9;
DT 21-FEB-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Serine/threonine-protein kinase pim-1;
DE EC=2.7.11.1;
GN Name=PIM1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11182156; DOI=10.1016/s0165-2427(00)00259-2;
RA Wang Z., Petersen K., Weaver M.S., Magnuson N.S.;
RT "cDNA cloning, sequencing and characterization of bovine pim-1.";
RL Vet. Immunol. Immunopathol. 78:177-195(2001).
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. Interacts with CDKN1B and FOXO3. Interacts with
CC BAD. Interacts with PPP2CA; this interaction promotes dephosphorylation
CC of PIM1, ubiquitination and proteasomal degradation. Interacts with
CC HSP90, this interaction stabilizes PIM1 protein levels. Interacts
CC (ubiquitinated form) with HSP70 and promotes its proteosomal
CC degradation. Interacts with CDKN1A. Interacts with CDC25C. Interacts
CC (via N-terminal 96 residues) with CDC25A. Interacts with MAP3K5.
CC Interacts with MYC. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC -!- PTM: Autophosphorylated (By similarity). Phosphorylated. Interaction
CC with PPP2CA promotes 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; AF259078; AAF67200.1; -; mRNA.
DR RefSeq; NP_776569.1; NM_174144.2.
DR AlphaFoldDB; Q9N0P9; -.
DR SMR; Q9N0P9; -.
DR STRING; 9913.ENSBTAP00000000511; -.
DR PaxDb; Q9N0P9; -.
DR PRIDE; Q9N0P9; -.
DR Ensembl; ENSBTAT00000000511; ENSBTAP00000000511; ENSBTAG00000000396.
DR GeneID; 281402; -.
DR KEGG; bta:281402; -.
DR CTD; 5292; -.
DR VEuPathDB; HostDB:ENSBTAG00000000396; -.
DR VGNC; VGNC:32899; PIM1.
DR eggNOG; KOG0583; Eukaryota.
DR GeneTree; ENSGT00940000153394; -.
DR HOGENOM; CLU_000288_63_0_1; -.
DR InParanoid; Q9N0P9; -.
DR OMA; QDIHLEP; -.
DR OrthoDB; 930292at2759; -.
DR TreeFam; TF320810; -.
DR Proteomes; UP000009136; Chromosome 23.
DR Bgee; ENSBTAG00000000396; Expressed in esophagus and 106 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
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:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0030145; F:manganese ion binding; IEA:Ensembl.
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; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:1905062; P:positive regulation of cardioblast proliferation; IEA:Ensembl.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IEA:Ensembl.
DR GO; GO:0046777; P:protein autophosphorylation; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IEA:Ensembl.
DR GO; GO:1902033; P:regulation of hematopoietic stem cell proliferation; IEA:Ensembl.
DR GO; GO:0022898; P:regulation of transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0070561; P:vitamin D receptor signaling pathway; IEA:Ensembl.
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 2: Evidence at transcript level;
KW Apoptosis; ATP-binding; Cell cycle; Cytoplasm; Kinase; Magnesium;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Proto-oncogene;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Ubl conjugation.
FT CHAIN 1..313
FT /note="Serine/threonine-protein kinase pim-1"
FT /id="PRO_0000086528"
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 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"
SQ SEQUENCE 313 AA; 35630 MW; 9EF40229A847AD47 CRC64;
MLLSKINSLA HLRAAPCSDL HATKLAPGKE KEPLESQYQV GPLLGSGGFG SVYSGIRVAD
NLPVAIKHVE KDRISDWGEL PNGTRVPMEV VLLKKVSSGF SGVIRLLDWF ERPDSFVLIL
ERPEPVQDLF DFITERGALQ EELARSFFWQ VLEAVRHCHD CGVLHRDIKD ENILIDLNRG
ELKLIDFGSG ALLKDTVYTD FDGTRVYSPP EWIRYHRYHG RSAAVWSLGI LLYDMVCGDI
PFEHDEEIVR GQVFFRQRVS SECQHLIRWC LALRPSDRPT FEEIQNHPWM QDVLLPQETA
EIHLHSLSPG PSK
