241 human active and 13 inactive phosphatases in total;
194 phosphatases have substrate data;
336 protein substrates;
83 non-protein substrates;
1215 dephosphorylation interactions;
299 KEGG pathways;
876 Reactome pathways;
last scientific update: 11 Mar, 2019
last maintenance update: 01 Sep, 2023
Cytoplasm Cell membrane Golgi apparatus,trans-Golgi network Note=Translocation to the cell membrane is required for kinaseactivation
Function (UniProt annotation)
Serine/threonine-protein kinase that converts transientdiacylglycerol (DAG) signals into prolonged physiological effectsdownstream of PKC, and is involved in the regulation of MAPK8/JNK1and Ras signaling, Golgi membrane integrity and trafficking, cellsurvival through NF-kappa-B activation, cell migration, celldifferentiation by mediating HDAC7 nuclear export, cellproliferation via MAPK1/3 (ERK1/2) signaling, and plays a role incardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-inducedapoptosis and flagellin-stimulated inflammatory responsePhosphorylates the epidermal growth factor receptor (EGFR) on dualthreonine residues, which leads to the suppression of epidermalgrowth factor (EGF)-induced MAPK8/JNK1 activation and subsequentJUN phosphorylation Phosphorylates RIN1, inducing RIN1 binding to14-3-3 proteins YWHAB, YWHAE and YWHAZ and increased competitionwith RAF1 for binding to GTP-bound form of Ras proteins (NRAS,HRAS and KRAS) Acts downstream of the heterotrimeric G-proteinbeta/gamma-subunit complex to maintain the structural integrity ofthe Golgi membranes, and is required for protein transport alongthe secretory pathway In the trans-Golgi network (TGN), regulatesthe fission of transport vesicles that are on their way to theplasma membrane May act by activating the lipid kinasephosphatidylinositol 4-kinase beta (PI4KB) at the TGN for thelocal synthesis of phosphorylated inositol lipids, which induces asequential production of DAG, phosphatidic acid (PA) and lyso-PA(LPA) that are necessary for membrane fission and generation ofspecific transport carriers to the cell surface Under oxidativestress, is phosphorylated at Tyr-463 via SRC-ABL1 and contributesto cell survival by activating IKK complex and subsequent nucleartranslocation and activation of NFKB1 Involved in cell migrationby regulating integrin alpha-5/beta-3 recycling and promoting itsrecruitment in newly forming focal adhesion In osteoblastdifferentiation, mediates the bone morphogenetic protein 2 (BMP2)-induced nuclear export of HDAC7, which results in the inhibitionof HDAC7 transcriptional repression of RUNX2 In neurons, plays animportant role in neuronal polarity by regulating the biogenesisof TGN-derived dendritic vesicles, and is involved in themaintenance of dendritic arborization and Golgi structure inhippocampal cells May potentiate mitogenesis induced by theneuropeptide bombesin or vasopressin by mediating an increase inthe duration of MAPK1/3 (ERK1/2) signaling, which leads toaccumulation of immediate-early gene products including FOS thatstimulate cell cycle progression Plays an important role in theproliferative response induced by low calcium in keratinocytes,through sustained activation of MAPK1/3 (ERK1/2) pathwayDownstream of novel PKC signaling, plays a role in cardiachypertrophy by phosphorylating HDAC5, which in turn triggersXPO1/CRM1-dependent nuclear export of HDAC5, MEF2A transcriptionalactivation and induction of downstream target genes that promotemyocyte hypertrophy and pathological cardiac remodeling Mediatescardiac troponin I (TNNI3) phosphorylation at the PKA sites, whichresults in reduced myofilament calcium sensitivity, andaccelerated crossbridge cycling kinetics The PRKD1-HDAC5 pathwayis also involved in angiogenesis by mediating VEGFA-inducedspecific subset of gene expression, cell migration, and tubeformation In response to VEGFA, is necessary and required forHDAC7 phosphorylation which induces HDAC7 nuclear export andendothelial cell proliferation and migration During apoptosisinduced by cytarabine and other genotoxic agents, PRKD1 is cleavedby caspase-3 at Asp-378, resulting in activation of its kinasefunction and increased sensitivity of cells to the cytotoxiceffects of genotoxic agents In epithelial cells, is required fortransducing flagellin-stimulated inflammatory responses by bindingand phosphorylating TLR5, which contributes to MAPK14/p38activation and production of inflammatory cytokines May play arole in inflammatory response by mediating activation of NF-kappa-B May be involved in pain transmission by directly modulatingTRPV1 receptor Plays a role in activated KRAS-mediatedstabilization of ZNF304 in colorectal cancer (CRC) cells(PubMed:24623306) Regulates nuclear translocation oftranscription factor TFEB in macrophages upon live Sentericainfection (By similarity)
Rap1 is a small GTPase that controls diverse processes, such as cell adhesion, cell-cell junction formation and cell polarity. Like all G proteins, Rap1 cycles between an inactive GDP-bound and an active GTP-bound conformation. A variety of extracellular signals control this cycle through the regulation of several unique guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs). Rap1 plays a dominant role in the control of cell-cell and cell-matrix interactions by regulating the function of integrins and other adhesion molecules in various cell types. Rap1 also regulates MAP kinase (MAPK) activity in a manner highly dependent on the context of cell types.
Aldosterone is a steroid hormone synthesized in and secreted from the outer layer of the adrenal cortex, the zona glomerulosa. Aldosterone plays an important role in the regulation of systemic blood pressure through the absorption of sodium and water. Angiotensin II (Ang II), potassium (K+) and adrenocorticotropin (ACTH) are the main extracellular stimuli which regulate aldosterone secretion. These physiological agonists all converge on two major intracellular signaling pathways: calcium (Ca2+) mobilization and an increase in cAMP production. The increase in cytosolic calcium levels activates calcium/calmodulin- dependent protein kinases (CaMK), and the increased cAMP levels stimulate the activity of cAMP-dependent protein kinase, or protein kinase A (PKA). The activated CaMK, and possibly PKA, activates transcription factors (NURR1 and NGF1B, CREB) to induce StAR and CYP11B2 expression, the early and late rate- limiting steps in aldosterone biosynthesis, respectively, thereby stimulating aldosterone secretion.