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Details on Person UniProt:P11309 PIM1

Class:Id	ReferenceGeneProduct:61734
_chainChangeLog	chain:1-404 added on Fri February 6 2015
_displayName	UniProt:P11309 PIM1
_timestamp	2025-05-21 21:44:55
chain	chain:1-313
checksum	35BA76D3668E69A3
comment	FUNCTION Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis (PubMed:15528381, PubMed:1825810, PubMed:31548394). 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) (PubMed:18593906). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity (By similarity). The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis (By similarity). Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1 (By similarity). Phosphorylation of MAP3K5, another 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 (PubMed:19749799). Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C (PubMed:16356754). 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 (PubMed:12431783). Promotes cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels (PubMed:18593906). Phosphorylation of CDKN1B, induces 14-3-3 proteins binding, nuclear export and proteasome-dependent degradation (PubMed:18593906). May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3 (PubMed:10664448). Also acts as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis (By similarity). Acts as a positive regulator of mTORC1 signaling by mediating phosphorylation and inhibition of DEPDC5 component of the GATOR1 complex (PubMed:31548394). Acts as a negative regulator of innate immunity by mediating phosphorylation and inactivation of GBP1 in absence of infection: phosphorylation of GBP1 induces interaction with 14-3-3 protein sigma (SFN) and retention in the cytosol (PubMed:37797010). Also phosphorylates and activates the ATP-binding cassette transporter ABCG2, allowing resistance to drugs through their excretion from cells (PubMed:18056989). Promotes brown adipocyte differentiation (By similarity).CATALYTIC ACTIVITY L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)COFACTOR Interacts with RP9 (By similarity). Interacts with HSP90AA1, this interaction stabilizes PIM1 protein levels (PubMed:15798097). Interacts (ubiquitinated form) with HSP70 and promotes its proteasomal degradation (PubMed:15798097).SUBUNIT Isoform 1 is isolated as a monomer whereas isoform 2 complexes with other proteins.SUBUNIT Isoform 2, but not isoform 1, binds BMX.SUBUNIT (Microbial infection) Interacts with Epstein-Barr virus EBNA6; this interaction upregulates and stabilizes PIM1 and induces cell proliferation by inhibiting the growth suppressive properties of p21.INTERACTION Expressed primarily in cells of the hematopoietic and germline lineages. Isoform 1 and isoform 2 are both expressed in prostate cancer cell lines.INDUCTION By interferon-gamma (IFNG) (PubMed:37797010). Strongly induced in leukocytes by the JAK/STAT pathway in response to cytokines. Induced by different cellular stresses, heat shock and cytotoxic agents (PubMed:15528381, PubMed:15798097, PubMed:16186805).PTM Autophosphorylated on both serine/threonine and tyrosine residues. Phosphorylated. Interaction with PPP2CA promotes dephosphorylation.PTM Ubiquitinated, leading to proteasomal degradation.MISCELLANEOUS Initiates from CTG codon.SIMILARITY Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PIM subfamily.
description	recommendedName: Serine/threonine-protein kinase pim-1 ecNumber evidence="7 9 11 20"2.7.11.1
geneName	PIM1
identifier	P11309
isSequenceChanged	FALSE
keyword	3D-structure Alternative initiation Apoptosis ATP-binding Cell cycle Cell membrane Cytoplasm Direct protein sequencing Host-virus interaction Kinase Magnesium Membrane Metal-binding Nucleotide-binding Nucleus Phosphoprotein Proteomics identification Proto-oncogene Reference proteome Serine/threonine-protein kinase Transferase Ubl conjugation
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9841277] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9909836] Weiser, Joel, 2024-05-14 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9948485] Weiser, Joel, 2025-05-21
name	PIM1
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8948430] ENSEMBL:ENSG00000137193 PIM1 [Homo sapiens]
secondaryIdentifier	PIM1_HUMAN Q38RT9 Q5T7H7 Q96RG3
sequenceLength	313
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:242856] UniProt:P11309-2 PIM1 [Homo sapiens] [ReferenceIsoform:402791] UniProt:P11309-1 PIM1 [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:3215094] PIM1 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:9954209] PIM1 [cytosol] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:P11309 PIM1 (61734)