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Protein

Serine/threonine-protein kinase pim-1

Gene

PIM1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Phosphorylation of MAP3K5, an other proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis. Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C. Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability. Promote cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels. Phosphorylation of CDKN1B,induces 14-3-3-proteins binding, nuclear export and proteasome-dependent degradation. May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3. Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis.7 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.3 Publications

Cofactori

Mg2+3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei158ATP1
Binding sitei212ATP; via carbonyl oxygen1
Binding sitei219ATP1
Active sitei258Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi135 – 143ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • manganese ion binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB
  • ribosomal small subunit binding Source: UniProtKB
  • transcription factor binding Source: UniProtKB

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • cell cycle Source: UniProtKB-KW
  • cell proliferation Source: UniProtKB
  • cytokine-mediated signaling pathway Source: Reactome
  • hyaluronan metabolic process Source: Ensembl
  • multicellular organism development Source: ProtInc
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of DNA binding transcription factor activity Source: UniProtKB
  • positive regulation of cardiac muscle cell proliferation Source: BHF-UCL
  • positive regulation of cardioblast proliferation Source: BHF-UCL
  • positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle Source: UniProtKB
  • protein autophosphorylation Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • regulation of mitotic cell cycle Source: GO_Central
  • vitamin D receptor signaling pathway Source: CACAO

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processApoptosis, Cell cycle
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-6785807 Interleukin-4 and 13 signaling
SignaLinkiP11309
SIGNORiP11309

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase pim-1 (EC:2.7.11.1)
Gene namesi
Name:PIM1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000137193.13
HGNCiHGNC:8986 PIM1
MIMi164960 gene
neXtProtiNX_P11309

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi159H → Y: Increased kinase activity. 1 Publication1
Mutagenesisi172P → S: Decreased kinase activity. 1 Publication1
Mutagenesisi173N → K: Decreased kinase activity. 1 Publication1
Mutagenesisi284L → F: Decreased kinase activity. 1 Publication1

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi5292
OpenTargetsiENSG00000137193
PharmGKBiPA33318

Chemistry databases

ChEMBLiCHEMBL2147
DrugBankiDB03650 (3e)-3-[(4-Hydroxyphenyl)Imino]-1h-Indol-2(3h)-One
DB02656 2-(4-Morpholinyl)-8-Phenyl-4h-1-Benzopyran-4-One
DB07151 4-(4-hydroxy-3-methylphenyl)-6-phenylpyrimidin-2(5H)-one
DB00131 Adenosine monophosphate
DB04715 IMIDAZOPYRIDAZIN 1
DB04395 Phosphoaminophosphonic Acid-Adenylate Ester
DB04522 Phosphonoserine
DB04216 Quercetin
DB03777 Rbt205 Inhibitor
DB02010 Staurosporine
GuidetoPHARMACOLOGYi2158

Polymorphism and mutation databases

BioMutaiPIM1
DMDMi83305339

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000433491 – 404Serine/threonine-protein kinase pim-1Add BLAST404

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei99PhosphoserineCombined sources1 Publication1
Modified residuei114Phosphothreonine1 Publication1
Modified residuei189Phosphoserine1 Publication1
Modified residuei352Phosphoserine1 Publication1

Post-translational modificationi

Autophosphorylated on both serine/threonine and tyrosine residues. Phosphorylated. Interaction with PPP2CA promotes dephosphorylation.3 Publications
Ubiquitinated, leading to proteasomal degradation.2 Publications

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP11309
MaxQBiP11309
PaxDbiP11309
PeptideAtlasiP11309
PRIDEiP11309
ProteomicsDBi52741
52742 [P11309-2]

PTM databases

iPTMnetiP11309
PhosphoSitePlusiP11309

Expressioni

Tissue specificityi

Expressed primarily in cells of the hematopoietic and germline lineages. Isoform 1 and isoform 2 are both expressed in prostate cancer cell lines.1 Publication

Inductioni

Strongly induced in leukocytes by the JAK/STAT pathway in response to cytokines. Induced by different cellular stresses, heat shock and cytotoxic agents.3 Publications

Gene expression databases

BgeeiENSG00000137193
CleanExiHS_PIM1
ExpressionAtlasiP11309 baseline and differential
GenevisibleiP11309 HS

Organism-specific databases

HPAiCAB017040
HPA003941

Interactioni

Subunit structurei

Isoform 2 is isolated as a monomer whereas isoform 1 complexes with other proteins (By similarity). Binds to RP9 (By similarity). Isoform 1, but not isoform 2, binds BMX. Isoform 2 interacts with CDKN1B and FOXO3. Interacts with BAD. Interacts with PPP2CA; this interaction promotes dephosphorylation of PIM1, ubiquitination and proteasomal degradation (By similarity). Interacts with HSP90, this interaction stabilizes PIM1 protein levels. Interacts (ubiquitinated form) with HSP70 and promotes its proteosomal degradation. Interacts with CDKN1A. Interacts with CDC25C. Interacts (via N-terminal 96 residues) with CDC25A (By similarity). Interacts with MAP3K5. Interacts with MYC (By similarity).By similarity

Binary interactionsi

Show more details

GO - Molecular functioni

  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111310, 41 interactors
IntActiP11309, 19 interactors
MINTiP11309
STRINGi9606.ENSP00000362608

Chemistry databases

BindingDBiP11309

Structurei

Secondary structure

1404
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni126 – 128Combined sources3
Beta strandi129 – 134Combined sources6
Beta strandi136 – 140Combined sources5
Beta strandi142 – 148Combined sources7
Turni149 – 151Combined sources3
Beta strandi154 – 161Combined sources8
Helixi162 – 164Combined sources3
Beta strandi168 – 170Combined sources3
Turni172 – 174Combined sources3
Beta strandi176 – 178Combined sources3
Helixi179 – 187Combined sources9
Beta strandi189 – 191Combined sources3
Beta strandi192 – 194Combined sources3
Beta strandi197 – 202Combined sources6
Beta strandi204 – 212Combined sources9
Beta strandi215 – 219Combined sources5
Helixi220 – 227Combined sources8
Helixi232 – 251Combined sources20
Helixi261 – 263Combined sources3
Beta strandi264 – 267Combined sources4
Turni268 – 271Combined sources4
Beta strandi272 – 275Combined sources4
Helixi278 – 280Combined sources3
Helixi296 – 298Combined sources3
Helixi301 – 306Combined sources6
Helixi311 – 328Combined sources18
Helixi336 – 341Combined sources6
Helixi352 – 361Combined sources10
Helixi366 – 368Combined sources3
Helixi372 – 376Combined sources5
Helixi379 – 381Combined sources3
Helixi387 – 394Combined sources8
Turni395 – 398Combined sources4

3D structure databases

DisProtiDP00322
ProteinModelPortaliP11309
SMRiP11309
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP11309

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini129 – 381Protein kinasePROSITE-ProRule annotationAdd BLAST253

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0583 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000119045
HOGENOMiHOG000231357
HOVERGENiHBG106681
InParanoidiP11309
KOiK04702
OMAiCQHLIKW
OrthoDBiEOG091G0IMW
PhylomeDBiP11309
TreeFamiTF320810

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR017348 PIM1/2/3
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PIRSFiPIRSF037993 STPK_Pim-1, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative initiation. AlignAdd to basket

Isoform 1 (identifier: P11309-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPHEPHEPLT PPFSALPDPA GAPSRRQSRQ RPQLSSDSPS AFRASRSHSR
60 70 80 90 100
NATRSHSHSH SPRHSLRHSP GSGSCGSSSG HRPCADILEV GMLLSKINSL
110 120 130 140 150
AHLRAAPCND LHATKLAPGK EKEPLESQYQ VGPLLGSGGF GSVYSGIRVS
160 170 180 190 200
DNLPVAIKHV EKDRISDWGE LPNGTRVPME VVLLKKVSSG FSGVIRLLDW
210 220 230 240 250
FERPDSFVLI LERPEPVQDL FDFITERGAL QEELARSFFW QVLEAVRHCH
260 270 280 290 300
NCGVLHRDIK DENILIDLNR GELKLIDFGS GALLKDTVYT DFDGTRVYSP
310 320 330 340 350
PEWIRYHRYH GRSAAVWSLG ILLYDMVCGD IPFEHDEEII RGQVFFRQRV
360 370 380 390 400
SSECQHLIRW CLALRPSDRP TFEEIQNHPW MQDVLLPQET AEIHLHSLSP

GPSK
Note: Initiates from CTG codon.
Length:404
Mass (Da):45,412
Last modified:December 6, 2005 - v3
Checksum:i18C421B7CFF87818
GO
Isoform 2 (identifier: P11309-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-91: Missing.

Show »
Length:313
Mass (Da):35,686
Checksum:i35BA76D3668E69A3
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti106 – 107AP → RA in AAA60089 (PubMed:3475233).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041004144Y → H in a colorectal adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_041005215E → Q1 Publication1
Natural variantiVAR_041006226E → K1 Publication1
Natural variantiVAR_041007233E → D1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0165301 – 91Missing in isoform 2. 4 PublicationsAdd BLAST91

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M27903 Genomic DNA Translation: AAA60090.1
M16750 mRNA Translation: AAA60089.1
M54915 mRNA Translation: AAA36447.1
M24779 mRNA Translation: AAA81553.1
DQ022562 mRNA Translation: AAY87461.1
AL353579 Genomic DNA No translation available.
CH471081 Genomic DNA Translation: EAX03934.1
BC020224 mRNA Translation: AAH20224.1
AF386792 Genomic DNA Translation: AAK70871.1
CCDSiCCDS4830.1 [P11309-2]
PIRiJU0327 TVHUP1
RefSeqiNP_001230115.1, NM_001243186.1 [P11309-1]
NP_002639.1, NM_002648.3 [P11309-2]
UniGeneiHs.81170

Genome annotation databases

EnsembliENST00000373509; ENSP00000362608; ENSG00000137193 [P11309-2]
GeneIDi5292
KEGGihsa:5292
UCSCiuc003onk.4 human [P11309-1]

Keywords - Coding sequence diversityi

Alternative initiation, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPIM1_HUMAN
AccessioniPrimary (citable) accession number: P11309
Secondary accession number(s): Q38RT9, Q5T7H7, Q96RG3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: December 6, 2005
Last modified: July 18, 2018
This is version 218 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

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