Human Gene PIM1 (uc003onk.3)
  Description: Homo sapiens pim-1 oncogene (PIM1), transcript variant 1, mRNA.
RefSeq Summary (NM_002648): The protein encoded by this gene belongs to the Ser/Thr protein kinase family, and PIM subfamily. This gene is expressed primarily in B-lymphoid and myeloid cell lines, and is overexpressed in hematopoietic malignancies and in prostate cancer. It plays a role in signal transduction in blood cells, contributing to both cell proliferation and survival, and thus provides a selective advantage in tumorigenesis. Both the human and orthologous mouse genes have been reported to encode two isoforms (with preferential cellular localization) resulting from the use of alternative in-frame translation initiation codons, the upstream non-AUG (CUG) and downstream AUG codons (PMIDs:16186805, 1825810).[provided by RefSeq, Aug 2011].
Transcript (Including UTRs)
   Position: hg19 chr6:37,137,922-37,143,204 Size: 5,283 Total Exon Count: 6 Strand: +
Coding Region
   Position: hg19 chr6:37,138,352-37,141,867 Size: 3,516 Coding Exon Count: 6 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr6:37,137,922-37,143,204)mRNA (may differ from genome)Protein (313 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMalacards
MGIneXtProtOMIMPubMedReactomeTreefam
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: PIM1_HUMAN
DESCRIPTION: RecName: Full=Serine/threonine-protein kinase pim-1; EC=2.7.11.1;
FUNCTION: 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 exerced 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.
CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
COFACTOR: Magnesium.
SUBUNIT: 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).
INTERACTION: Q9UNQ0:ABCG2; NbExp=9; IntAct=EBI-1018629, EBI-1569435; P51813:BMX; NbExp=8; IntAct=EBI-696621, EBI-696657;
SUBCELLULAR LOCATION: Isoform 2: Cytoplasm. Nucleus.
SUBCELLULAR LOCATION: Isoform 1: Cell membrane.
TISSUE SPECIFICITY: Expressed primarily in cells of the hematopoietic and germline lineages. Isoform 1 and isoform 2 are both expressed in prostate cancer cell lines.
INDUCTION: Strongly induced in leukocytes by the JAK/STAT pathway in response to cytokines. Induced by different cellular stresses, heat shock and cytotoxic agents.
PTM: Autophosphorylated on both serine/threonine and tyrosine residues. Phosphorylated. Interaction with PPP2CA promotes dephosphorylation.
PTM: Ubiquitinated, leading to proteasomal degradation.
SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PIM subfamily.
SIMILARITY: Contains 1 protein kinase domain.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/PIM1ID261.html";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): PIM1
CDC HuGE Published Literature: PIM1
Positive Disease Associations: E-Selectin
Related Studies:
  1. E-Selectin
    Andrew D Paterson et al. Arteriosclerosis, thrombosis, and vascular biology 2009, Genome-wide association identifies the ABO blood group as a major locus associated with serum levels of soluble E-selectin., Arteriosclerosis, thrombosis, and vascular biology. [PubMed 19729612]
    ABO is a major locus for serum soluble E-selectin levels. We excluded population stratification, fine-mapped the association to sub-A alleles, and also document association with additional variation in the ABO region.

-  MalaCards Disease Associations
  MalaCards Gene Search: PIM1
Diseases sorted by gene-association score: prostate cancer (5), retinitis pigmentosa (0)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • D014635 Valproic Acid
  • D000082 Acetaminophen
  • D001564 Benzo(a)pyrene
  • D013749 Tetrachlorodibenzodioxin
  • C061365 flusilazole
  • C012589 trichostatin A
  • C026486 1,2,5,6-dibenzanthracene
  • C028474 1,4-bis(2-(3,5-dichloropyridyloxy))benzene
  • C011269 2,5-hexanedione
  • C532162 2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine
          more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 101.74 RPKM in Esophagus - Mucosa
Total median expression: 1207.47 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -218.21430-0.507 Picture PostScript Text
3' UTR -454.091337-0.340 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011009 - Kinase-like_dom
IPR000719 - Prot_kinase_cat_dom
IPR017441 - Protein_kinase_ATP_BS
IPR002290 - Ser/Thr_dual-sp_kinase_dom
IPR008271 - Ser/Thr_kinase_AS
IPR017348 - Ser/Thr_kinase_Pim-1

Pfam Domains:
PF00069 - Protein kinase domain
PF06293 - Lipopolysaccharide kinase (Kdo/WaaP) family
PF07714 - Protein tyrosine kinase
PF14531 - Kinase-like

SCOP Domains:
56112 - Protein kinase-like (PK-like)

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1XQZ - X-ray MuPIT 1XR1 - X-ray MuPIT 1XWS - X-ray MuPIT 1YHS - X-ray MuPIT 1YI3 - X-ray MuPIT 1YI4 - X-ray MuPIT 1YWV - X-ray MuPIT 1YXS - X-ray MuPIT 1YXT - X-ray MuPIT 1YXU - X-ray MuPIT 1YXV - X-ray MuPIT 1YXX - X-ray MuPIT 2BIK - X-ray MuPIT 2BIL - X-ray MuPIT 2BZH - X-ray MuPIT 2BZI - X-ray MuPIT 2BZJ - X-ray MuPIT 2BZK - X-ray MuPIT 2C3I - X-ray MuPIT 2J2I - X-ray MuPIT 2O3P - X-ray MuPIT 2O63 - X-ray MuPIT 2O64 - X-ray MuPIT 2O65 - X-ray MuPIT 2OBJ - X-ray MuPIT 2OI4 - X-ray MuPIT 2XIX - X-ray MuPIT 2XIY - X-ray MuPIT 2XIZ - X-ray MuPIT 2XJ0 - X-ray MuPIT 2XJ1 - X-ray MuPIT 2XJ2 - X-ray MuPIT 3A99 - X-ray MuPIT 3BGP - X-ray MuPIT 3BGQ - X-ray MuPIT 3BGZ - X-ray MuPIT 3BWF - X-ray MuPIT 3C4E - X-ray MuPIT 3CXW - X-ray MuPIT 3CY2 - X-ray MuPIT 3CY3 - X-ray MuPIT 3DCV - X-ray MuPIT 3F2A - X-ray MuPIT 3JPV - X-ray MuPIT 3JXW - X-ray MuPIT 3JY0 - X-ray MuPIT 3JYA - X-ray MuPIT 3MA3 - X-ray MuPIT 3QF9 - X-ray MuPIT 3R00 - X-ray MuPIT 3R01 - X-ray MuPIT 3R02 - X-ray MuPIT 3R04 - X-ray MuPIT 3T9I - X-ray MuPIT 3UIX - X-ray MuPIT 3UMW - X-ray MuPIT 3UMX - X-ray MuPIT 3VBQ - X-ray MuPIT 3VBT - X-ray MuPIT 3VBV - X-ray MuPIT 3VBW - X-ray MuPIT 3VBX - X-ray MuPIT 3VBY - X-ray MuPIT 3VC4 - X-ray MuPIT 4A7C - X-ray MuPIT 4AS0 - X-ray MuPIT 4DTK - X-ray MuPIT 4ENX - X-ray MuPIT 4ENY - X-ray MuPIT 4GW8 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P11309
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGDEnsembl   
 Protein SequenceProtein Sequence   
 AlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0008134 transcription factor binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0030145 manganese ion binding
GO:0043024 ribosomal small subunit binding
GO:0046872 metal ion binding

Biological Process:
GO:0006468 protein phosphorylation
GO:0006915 apoptotic process
GO:0007049 cell cycle
GO:0007275 multicellular organism development
GO:0007346 regulation of mitotic cell cycle
GO:0008283 cell proliferation
GO:0016310 phosphorylation
GO:0019221 cytokine-mediated signaling pathway
GO:0030212 hyaluronan metabolic process
GO:0031659 positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle
GO:0043066 negative regulation of apoptotic process
GO:0043433 negative regulation of sequence-specific DNA binding transcription factor activity
GO:0046777 protein autophosphorylation
GO:0060045 positive regulation of cardiac muscle cell proliferation
GO:0070561 vitamin D receptor signaling pathway
GO:1905062 positive regulation of cardioblast proliferation

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005730 nucleolus
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0016020 membrane


-  Descriptions from all associated GenBank mRNAs
  DQ022562 - Homo sapiens pim-1 kinase 44 kDa isoform mRNA, complete cds.
M54915 - Human h-pim-1 protein (h-pim-1) mRNA, complete cds.
BC020224 - Homo sapiens pim-1 oncogene, mRNA (cDNA clone MGC:31919 IMAGE:4591723), complete cds.
JD408057 - Sequence 389081 from Patent EP1572962.
JD370400 - Sequence 351424 from Patent EP1572962.
M24779 - Homo sapiens protein kinase-related oncogene (PIM1) mRNA, complete cds.
JD389881 - Sequence 370905 from Patent EP1572962.
JD405919 - Sequence 386943 from Patent EP1572962.
JD186989 - Sequence 168013 from Patent EP1572962.
JD405097 - Sequence 386121 from Patent EP1572962.
JD114988 - Sequence 96012 from Patent EP1572962.
JD317397 - Sequence 298421 from Patent EP1572962.
JD164372 - Sequence 145396 from Patent EP1572962.
M16750 - Human pim-1 oncogene mRNA, complete cds.
KJ891809 - Synthetic construct Homo sapiens clone ccsbBroadEn_01203 PIM1 gene, encodes complete protein.
KJ905265 - Synthetic construct Homo sapiens clone ccsbBroadEn_14761 PIM1 gene, encodes complete protein.
CU676514 - Synthetic construct Homo sapiens gateway clone IMAGE:100023380 5' read PIM1 mRNA.
AB528988 - Synthetic construct DNA, clone: pF1KE0920, Homo sapiens PIM1 gene for pim-1 oncogene, without stop codon, in Flexi system.
AK301158 - Homo sapiens cDNA FLJ61426 complete cds, highly similar to Proto-oncogene serine/threonine-protein kinase Pim-1 (EC 2.7.11.1).
CS074015 - Sequence 29 from Patent WO2005033310.
CS074016 - Sequence 30 from Patent WO2005033310.
CS074017 - Sequence 31 from Patent WO2005033310.
AK301314 - Homo sapiens cDNA FLJ50255 complete cds.
AK309347 - Homo sapiens cDNA, FLJ99388.
CS074018 - Sequence 32 from Patent WO2005033310.
JD071504 - Sequence 52528 from Patent EP1572962.
JD143416 - Sequence 124440 from Patent EP1572962.
JD158161 - Sequence 139185 from Patent EP1572962.
JD489959 - Sequence 470983 from Patent EP1572962.
JD402813 - Sequence 383837 from Patent EP1572962.
JD162549 - Sequence 143573 from Patent EP1572962.
JD430589 - Sequence 411613 from Patent EP1572962.
JD431699 - Sequence 412723 from Patent EP1572962.
JD350069 - Sequence 331093 from Patent EP1572962.
JD130951 - Sequence 111975 from Patent EP1572962.
JD082064 - Sequence 63088 from Patent EP1572962.
JD554099 - Sequence 535123 from Patent EP1572962.
JD506360 - Sequence 487384 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04630 - Jak-STAT signaling pathway
hsa05221 - Acute myeloid leukemia

Reactome (by CSHL, EBI, and GO)

Protein P11309 (Reactome details) participates in the following event(s):

R-HSA-6785807 Interleukin-4 and 13 signaling
R-HSA-449147 Signaling by Interleukins
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-168256 Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: NM_002648, NP_002639, P11309, PIM1_HUMAN, Q38RT9, Q5T7H7, Q96RG3
UCSC ID: uc003onk.3
RefSeq Accession: NM_002648
Protein: P11309 (aka PIM1_HUMAN)
CCDS: CCDS4830.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_002648.3
exon count: 6CDS single in 3' UTR: no RNA size: 2751
ORF size: 942CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2084.00frame shift in genome: no % Coverage: 98.47
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.