ID:PKN2_HUMAN DESCRIPTION: RecName: Full=Serine/threonine-protein kinase N2; EC=2.7.11.13; AltName: Full=PKN gamma; AltName: Full=Protein kinase C-like 2; AltName: Full=Protein-kinase C-related kinase 2; FUNCTION: PKC-related serine/threonine-protein kinase and Rho/Rac effector protein that participates in specific signal transduction responses in the cell. Plays a role in the regulation of cell cycle progression, actin cytoskeleton assembly, cell migration, cell adhesion, tumor cell invasion and transcription activation signaling processes. Phosphorylates CTTN in hyaluronan-induced astrocytes and hence decreases CTTN ability to associate with filamentous actin. Phosphorylates HDAC5, therefore lead to impair HDAC5 import. Direct RhoA target required for the regulation of the maturation of primordial junctions into apical junction formation in bronchial epithelial cells. Required for G2/M phases of the cell cycle progression and abscission during cytokinesis in a ECT2-dependent manner. Stimulates FYN kinase activity that is required for establishment of skin cell-cell adhesion during keratinocytes differentiation. Regulates epithelial bladder cells speed and direction of movement during cell migration and tumor cell invasion. Inhibits Akt pro-survival-induced kinase activity. Mediates Rho protein-induced transcriptional activation via the c- fos serum response factor (SRF). Phosphorylates HCV NS5B leading to stimulation of HCV RNA replication. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. ENZYME REGULATION: Kinase activity is activated upon binding to GTP-bound Rhoa/Rac1 GTPases. Activated by caspase-3 (CASP3) cleavage during apoptosis. Activated by lipids, particularly cardiolipin and to a lesser extent by other acidic phospholipids and unsaturated fatty acids. Two specific sites, Thr-816 (activation loop of the kinase domain) and Thr-958 (turn motif), need to be phosphorylated for its full activation. BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=15.83 uM for HDAC5; SUBUNIT: Interacts (via the REM repeats) with RHOA (GTP-bound form preferentially). Interacts (via the REM repeats) with RAC1 (GTP- bound form preferentially). Interacts with NCK1 (via SH3 domains). Interacts with CD44 (By similarity). Interacts with RHOA (GTP- bound form preferentially) and RAC1 (GTP-bound form preferentially); the interactions induce its autophosphorylation. Interacts (via C-terminal kinase domain) with PDPK1; the interaction stimulates PDPK1 kinase activity. Interacts with MAP3K2; the interaction activates PRK2 kinase activity in a MAP3K2-independent kinase activity. Interacts (via C-terminus domain) with AKT1; the interaction occurs with the C-terminus cleavage product of PRK2 in apoptotic cells. Interacts (via C- terminus) with PTPN13 (via PDZ 3 domain). Interacts with HCV NS5B (via N-terminus finger domain). Interacts with NCK1, NCK2 and RHOC. SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Membrane (By similarity). Cell projection, lamellipodium. Cytoplasm, cytoskeleton. Cleavage furrow. Midbody. Cell junction. Note=Colocalizes with PTPN13 in lamellipodia-like structures, regions of large actin turnover. Accumulates during telophase at the cleavage furrow and concentrates finally around the midbody in cytokinesis. Recruited to nascent cell-cell contacts at the apical surface of cells. In the course of viral infection, colocalizes with HCV NS5B at perinuclear region in the cytoplasm. TISSUE SPECIFICITY: Ubiquitous. Expressed in numerous tumor cell lines, especially in bladder tumor cells. INDUCTION: Up-regulated during keratinocyte differentiation. DOMAIN: The N-terminus region interferes with the interaction between AKT1 and the C-terminus region of PKN2. DOMAIN: The C1 domain does not bind the diacylglycerol (DAG). DOMAIN: The apoptotic C-terminus cleavage product inhibits EGF- induced kinase activity of AKT1 phosphorylation at 'Thr-308' and 'Ser-473' sites, PDPK1 autophosphorylation and kinases PRKCD and PRKCZ phosphorylations. PTM: Autophosphorylated. Phosphorylated during mitosis. PTM: Activated by limited proteolysis with trypsin (By similarity). Proteolytically cleaved by caspase-3 during the induction of apoptotic cell death. SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily. SIMILARITY: Contains 1 AGC-kinase C-terminal domain. SIMILARITY: Contains 1 C2 domain. SIMILARITY: Contains 1 protein kinase domain. SIMILARITY: Contains 3 REM (Hr1) repeats.
Glomerular Filtration Rate Shih-Jen Hwang et al. BMC medical genetics 2007, A genome-wide association for kidney function and endocrine-related traits in the NHLBI's Framingham Heart Study., BMC medical genetics.
[PubMed 17903292]
Kidney function traits and TSH are associated with SNPs on the Affymetrix GeneChip Human Mapping 100K SNP set. These data will serve as a valuable resource for replication as more SNPs associated with kidney function and endocrine traits are identified.
Hip Douglas P Kiel et al. BMC medical genetics 2007, Genome-wide association with bone mass and geometry in the Framingham Heart Study., BMC medical genetics.
[PubMed 17903296]
The FHS 100K SNP project offers an unbiased genome-wide strategy to identify new candidate loci and to replicate previously suggested candidate genes for osteoporosis.
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.
ModBase Predicted Comparative 3D Structure on Q16513
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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.
US Server
