PIM1

1XQZ, 1XR1, 1XWS, 1YHS, 1YI3, 1YI4, 1YWV, 1YXS, 1YXT, 1YXU, 1YXV, 1YXX, 2BIK, 2BIL, 2BZH, 2BZI, 2BZJ, 2BZK, 2C3I, 2J2I, 2O3P, 2O63, 2O64, 2O65, 2OBJ, 2OI4, 2XIX, 2XIY, 2XIZ, 2XJ0, 2XJ1, 2XJ2, 3A99, 3BGP, 3BGQ, 3BGZ, 3BWF, 3C4E, 3CXW, 3CY2, 3CY3, 3DCV, 3F2A, 3JPV, 3JXW, 3JY0, 3JYA, 3MA3, 3QF9, 3R00, 3R01, 3R02, 3R04, 3T9I, 3UIX, 3UMW, 3UMX, 3VBQ, 3VBT, 3VBV, 3VBW, 3VBX, 3VBY, 3VC4, 3WE8, 4A7C, 4ALU, 4ALV, 4ALW, 4AS0, 4BZN, 4BZO, 4DTK, 4ENX, 4ENY, 4GW8, 4I41, 4IAA, 4JX3, 4JX7, 4K0Y, 4K18, 4K1B, 4LL5, 4LM5, 4MBI, 4MBL, 4MED, 4MTA, 4N6Y, 4N6Z, 4N70, 4RBL, 4RC2, 4RC3, 4RC4, 4RPV, 4TY1, 4WRS, 4WSY, 4WT6, 4XHK, 4XH6, 5C1Q, 5DWR, 5DIA, 5DHJ, 5DGZ, 5EOL, 5IPJ, 5IIS529218712ENSG00000137193ENSMUSG00000024014P11309P06803Q8CFN8NM_002648NM_001243186NM_008842NM_001364913NP_001230115NP_002639NP_032868NP_001351842Proto-oncogene serine/threonine-protein kinase Pim-1 is an enzyme that in humans is encoded by the PIM1 gene.1xqz: Crystal Structure of hPim-1 kinase at 2.1 A resolution1xr1: Crystal structure of hPim-1 kinase in complex with AMP-PNP at 2.1 A Resolution1xws: Crystal Structure of the human PIM1 kinase domain1yhs: Crystal structure of Pim-1 bound to staurosporine1yi3: Crystal Structure of Pim-1 bound to LY2940021yi4: Structure of Pim-1 bound to adenosine1ywv: Crystal Structures of Proto-Oncogene Kinase Pim1: a Target of Aberrant Somatic Hypermutations in Diffuse Large Cell Lymphoma1yxs: Crystal Structure of Kinase Pim1 with P123M mutation1yxt: Crystal Structure of Kinase Pim1 in complex with AMPPNP1yxu: Crystal Structure of Kinase Pim1 in Complex with AMP1yxv: Crystal Structure of Kinase Pim1 in complex with 3,4-Dihydroxy-1-methylquinolin-2(1H)-one1yxx: Crystal Structure of Kinase Pim1 in complex with (3E)-3--1H-INDOL-2(3H)-ONE2bik: HUMAN PIM1 PHOSPHORYLATED ON SER2612bil: THE HUMAN PROTEIN KINASE PIM1 IN COMPLEX WITH ITS CONSENSUS PEPTIDE PIMTIDE2bzh: CRYSTAL STRUCTURE OF THE HUMAN PIM1 IN COMPLEX WITH A RUTHENIUM ORGANOMETALLIC LIGAND RU12bzi: CRYSTAL STRUCTURE OF THE HUMAN PIM1 IN COMPLEX WITH A RUTHENIUM ORGANOMETALLIC LIGAND RU22bzj: CRYSTAL STRUCTURE OF THE HUMAN PIM1 IN COMPLEX WITH A RUTHENIUM ORGANOMETALLIC LIGAND RU32bzk: CRYSTAL STRUCTURE OF THE HUMAN PIM1 IN COMPLEX WITH AMPPNP AND PIMTIDE2c3i: CRYSTAL STRUCTURE OF HUMAN PIM1 IN COMPLEX WITH IMIDAZOPYRIDAZIN I2j2i: CRYSTAL STRUCTURE OF THE HUMAB PIM1 IN COMPLEX WITH LY3335312o3p: Crystal structure of Pim1 with Quercetin2o63: Crystal structure of Pim1 with Myricetin2o64: Crystal structure of Pim1 with Quercetagetin2o65: Crystal structure of Pim1 with Pentahydroxyflavone2obj: Crystal structure of human PIM-1 Kinase in complex with inhibitor2oi4: Crystal structure of human PIM1 in complex with fluorinated ruthenium pyridocarbazole Proto-oncogene serine/threonine-protein kinase Pim-1 is an enzyme that in humans is encoded by the PIM1 gene. Pim-1 is a proto-oncogene which encodes for the serine/threonine kinase of the same name. The pim-1 oncogene was first described in relation to murine T-cell lymphomas, as it was the locus most frequently activated by the Moloney murine leukemia virus. Subsequently, the oncogene has been implicated in multiple human cancers, including prostate cancer, acute myeloid leukemia and other hematopoietic malignancies. Primarily expressed in spleen, thymus, bone marrow, prostate, oral epithelial, hippocampus and fetal liver cells, Pim-1 has also been found to be highly expressed in cell cultures isolated from human tumors. Pim-1 is mainly involved in cell cycle progression, apoptosis and transcriptional activation, as well as more general signal transduction pathways. Located on chromosome 6 (6p21.2), the gene encompasses 5Kb of DNA, including 6 exons and 5 introns. Expression of Pim-1 has been shown to be regulated by the JAK/STAT pathway. Direct binding of transcription factors STAT3 and STAT5 to the Pim-1 promoter results in the transcription of Pim-1. The Pim-1 gene has been found to be conserved in dogs, cows, mice, rats, zebrafish and C. elegans. Pim-1 deficient mice have been shown to be phenotypically normal, indicating that there is redundancy in the function of this kinase. In fact, sequence homology searches have shown that two other Pim-1-like kinases, Pim-2 and Pim-3, are structurally and functionally similar. The Pim-1 gene encodes has multiple translation initiation sites, resulting in two proteins of 34 and 44kD. Human, murine and rat Pim-1 contain 313 amino acids, and have a 94 – 97% amino acid identity. The active site of the protein, ranging from amino acids 38-290, is composed of several conserved motifs, including a glycine loop motif, a phosphate binding site and a proton acceptor site. Modification of the protein at amino acid 67 (lysine to methionine) results in the inactivation of the kinase. Pim-1 is primarily involved in cytokine signaling, and has been implicated in many signal transduction pathways. Because Pim-1 transcription is initiated by STAT3 and STAT5, its production is regulated by the cytokines that regulate the STAT pathway, or STAT factors. These include interleukins (IL-2, IL-3,IL-5, IL-6, IL-7, IL12, IL-15), prolactin, TNFα, EGF and IFNγ, among others. Pim-1 itself can bind to negative regulators of the JAK/STAT pathway, resulting in a negative feedback loop. Although little is known about the post-transcriptional modifications of Pim-1, it has been hypothesized that Hsp90 is responsible for the folding and stabilization of Pim-1, although the exact mechanism has yet to be discovered. Furthermore, the serine/threonine phosphatase PP2 has been shown to degrade Pim-1. PIM1 has been shown to interact with: Other known substrates/binding partners of Pim-1 include proteins involved in transcription regulation (nuclear adaptor protein p100, HP-1, PAP-1 and TRAF2 / SNX6), and regulation of the JAK/STAT pathway (SOCS1 and SOCS3). Furthermore, Pim-1 has been shown to be a cofactor for c-Myc, a transcription factor believed to regulate 15% of all genes, and their synergy has been in prostate tumorigenesis. Pim-1 is able to phosphorylate many targets, including itself. Many of its targets are involved in cell cycle regulation.