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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

PIM1 Gene

protein-coding GIFtS: 70
GCID: GC06P037137

pim-1 oncogene

(Previous symbol: PIM)

Explore 48 diseases affiliated with
PIM1 via

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Pim-1 Oncogene¹ ²		Pim-1 Kinase 44 KDa Isoform²
PIM¹ ²		Pim-1 Oncogene (Proviral Integration Site 1)²
EC 2.7.11.1³ ⁸		Proto-Oncogene Serine/Threonine-Protein Kinase Pim-1²
Oncogene PIM1²		Serine/Threonine-Protein Kinase Pim-1²

External Ids:	HGNC: 8986¹	Entrez Gene: 5292²	Ensembl: ENSG00000137193⁷	OMIM: 164960⁵	UniProtKB: P11309³

Export aliases for PIM1 gene to outside databases

Previous GC identifers: GC06P037140 GC06P037184 GC06P037245 GC06P036856

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for PIM1:

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)

UniProtKB/Swiss-Prot: PIM1_HUMAN, P11309

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 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

summary for PIM1:

Pim kinases are constitutively active serine/threonine kinases that promote growth factor-independent

proliferation by phosphorylating, and thus inhibiting, a range of cellular proteins. Both Pim-1 and Pim-2

kinase are serine/threonine kinases that are involved in the control of cell growth, differentiation and

apoptosis. Pim-1 kinase is a serine/threonine kinase that is involved in the control of cell growth,

differentiation and apoptosis. It is expressed at high levels in the testes, prostate, oral epithelia,

hippocampus and hematopoietic tissues, and is expressed at low or undetectable levels in other tissues. In

the fetal liver and spleen, expression of Pim-1 kinase is high, but the protein is undetectable here in the

adult. Due to their constitutive activity, expression of Pim kinases is regulated at the level of

transcription, translation and degradation. Pim-1 kinase expression can be induced by a variety of

cytokines, mitogens and hormones, such as GM-CSF, interleukins, erythropoietin, IFN-? and prolactin. At the

transcriptional level, IL-2 can release the transcriptional attenuation of the Pim-1 kinase gene leading to

increased protein expression. Pim-2 kinase levels are linked to IL-3 availability. Eukaryotic translation

initiation factor 4E (eIF-4E) enhances Pim-1 kinase expression at the translational level and PP2A decreases

Pim-1 kinase levels. Pim-1 kinase autophoshorylation is thought to occur and the enzyme is stabilized by

interactions with Hsp90? and ?. In addition, the PI 3-K signaling pathway is involved in Pim-1 kinase

regulation and the JAK2/STAT5 pathway plays an important role in mediating cytokine and growth

factor-stimulated Pim-1 kinase expression. Both Pim-1 and Pim-2 kinase have been found to be overexpressed

or mutated in a variety of human tumors including B cell lymphomas, leukemias, prostate cancer and oral

cancer. Synergism between Pim kinases and the oncogenic Myc genes has been shown to contribute to

transformation by inhibiting apoptosis, and upregulation of Pim-1 and Pim-2 kinase is associated with cell

survival. Furthermore, dysregulation of the Pim-1 kinase gene alters differentiation and proliferation, and

enhances the transforming potential of its substrates such as Cdc25A. Pim-1 and Pim-3 also help maintain the

embryonic stem cell identity by supporting ESC self-renewal, and inhibiting differentiation and apoptosis.

Gene Wiki entry for PIM1

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000006.11 NC_018917.1 NT_007592.15

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the PIM1 gene promoter:
SRF Max1 C/EBPbeta MAZR AP-1 SRF (504 AA) ATF-2 Lmo2 E47 c-Jun
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: PIM1 promoter sequence

Search SABiosciences Chromatin IP Primers for PIM1

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat PIM1

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 6p21.2 Ensembl cytogenetic band: 6p21.2 HGNC cytogenetic band: 6p21

PIM1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
PIM1 gene location

GeneLoc information about chromosome 6 GeneLoc Exon Structure

GeneLoc location for GC06P037137: view genomic region (about GC identifiers)

Start:	37,137,922 bp from pter	End:	37,143,204 bp from pter
Size:	5,283 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: PIM1_HUMAN, P11309 (See protein sequence)

Recommended Name: Serine/threonine-protein kinase pim-1

Size: 404 amino acids; 45412 Da

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)

Subcellular location: Isoform 2: Cytoplasm. Nucleus

Subcellular location: Isoform 1: Cell membrane

6/73 PDB 3D structures from and Proteopedia for PIM1 (see all 73):

1XQZ (3D)

1XR1 (3D)

1XWS (3D)

1YHS (3D)

1YI3 (3D)

1YI4 (3D)

Secondary accessions: Q38RT9 Q5T7H7 Q96RG3

Alternative initiation: 2 isoforms: P11309-1 P11309-2 (Initiates from CTG codon)

Explore the universe of human proteins at neXtProt for PIM1: NX_P11309

Post-translational modifications:

Autophosphorylated on both serine/threonine and tyrosine residues. Phosphorylated. Interaction with PPP2CA promotes

dephosphorylation¹

Ubiquitinated, leading to proteasomal degradation¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P11309

4/10 DME Specific Peptides for PIM1 (P11309) (see all 10)

GQVFFRQ

GGFGSVY

HRDIKDEN

DLFDFITE

PIM1 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (2 alternative transcripts):

NP_001230115.1 NP_002639.1

ENSEMBL proteins:

ENSP00000362608

Human Recombinant Protein Products:

	EMD Millipore Purified and/or Recombinant PIM1 Protein
	R&D Systems Recombinant & Natural Proteins for PIM1
	Enzo Life Sciences proteins for PIM1
	OriGene Purified Protein: PIM1 OriGene Protein Over-expression Lysate: PIM1 OriGene Custom Protein Services for PIM1
	GenScript Purified and Recombinant Proteins for PIM1
	Novus Biologicals PIM1 Proteins Novus Biologicals PIM1 Lysate
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for PIM1

Gene Ontology (GO): 3 cellular component terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005634	nucleus	IEA	--
GO:0005737	cytoplasm	IDA	1825810
GO:0005886	plasma membrane	IEA	--

PIM1 for ontologies About GeneDecksing

PIM1 Antibody Products:

	Browse EMD Millipore's Extensive Line of Mono- and Polyclonal Antibodies
	Browse R&D Systems for Antibodies
	Cell Signaling Technology (CST) Antibodies for PIM1
	OriGene Antibodies (see all 2): PIM1 OriGene Custom Antibody Services for PIM1
	GenScript Custom Superior Antibodies Services for PIM1
	Novus Biologicals PIM1 Antibodies
	Abcam antibodies for PIM1
	Uscn Antibodies for PIM1
	ThermoFisher Antibodies for PIM1

Assay Products for PIM1:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	Browse R&D Systems for biochemical assays
	GenScript PIM1-Activity-based Kinase Assay for Compound Screening
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for PIM1

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

PIM1 for domains About GeneDecksing

5/6 InterPro domains/families (see all 6):

IPR017441 Protein_kinase_ATP_BS

IPR002290 Ser/Thr_dual-sp_kinase_dom

IPR011009 Kinase-like_dom

IPR008271 Ser/Thr_kinase_AS

IPR000719 Prot_kinase_cat_dom

Graphical View of Domain Structure for InterPro Entry P11309

ProtoNet protein and cluster: P11309

UniProtKB/Swiss-Prot: PIM1_HUMAN, P11309

Similarity: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PIM subfamily

Similarity: Contains 1 protein kinase domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary: