241 human active and 13 inactive phosphatases in total;
194 phosphatases have substrate data;
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336 protein substrates;
83 non-protein substrates;
1215 dephosphorylation interactions;
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299 KEGG pathways;
876 Reactome pathways;
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last scientific update: 11 Mar, 2019
Nucleus Cytoplasm Cytoplasm, cytoskeleton,spindle Cytoplasmic vesicle, secretory vesicle, acrosomeCleavage furrow Midbody, Midbody ring Cell membrane; Peripheral membraneprotein; Cytoplasmic side Note=Colocalizes with RND2 in Golgi-derived proacrosomal vesicles and the acrosome (By similarity)During interphase, localized to the nucleus and cytoplasm alongwith microtubules, in anaphase, is redistributed to the centralspindle and, in telophase and cytokinesis, to the midbody ring,also called Flemming body Colocalizes with RHOA at the myosincontractile ring during cytokinesis Colocalizes with ECT2 to themitotic spindles during anaphase/metaphase, the cleavage furrowduring telophase and at the midbody at the end of cytokinesisColocalizes with Cdc42 to spindle microtubules from prometaphaseto telophase
Function (UniProt annotation)
Component of the centralspindlin complex that serves asa microtubule-dependent and Rho-mediated signaling required forthe myosin contractile ring formation during the cell cyclecytokinesis Required for proper attachment of the midbody to thecell membrane during cytokinesis Plays key roles in controllingcell growth and differentiation of hematopoietic cells throughmechanisms other than regulating Rac GTPase activity Alsoinvolved in the regulation of growth-related processes inadipocytes and myoblasts May be involved in regulatingspermatogenesis and in the RACGAP1 pathway in neuronalproliferation Shows strong GAP (GTPase activation) activitytowards CDC42 and RAC1 and less towards RHOA Essential for theearly stages of embryogenesis May play a role in regulatingcortical activity through RHOA during cytokinesis May participatein the regulation of sulfate transport in male germ cells
The cycling of Rho GTPases is tightly controlled by three classes of protein. These are (1) guanine nucleotide dissociation inhibitors or GDIs, which maintain Rho proteins in an inactive state in the cytoplasm, (2) guanine nucleotide exchange factors or GEFs, which destabilize the interaction between Rho proteins and their bound nucleotide, the net result of which is the exchange of bound GDP for the more abundant GTP, and (3) GTPase Activating Proteins or GAPs, which stimulate the low intrinsic GTP hydrolysis activity of Rho family members, thus promoting their inactivation. GDIs, GEFs, and GAPs are themselves subject to tight regulation, and the overall level of Rho activity reflects the balance of their activities.
In their active GTP-bound state, Rho family members have the ability to interact with a large variety of so-called effector proteins. By changing the subcellular localization of effectors, by altering their enzymatic properties, or by directing the formation of specific effector complexes, members of the Rho family mediate their various effects.
This Rho GTPase cycle is diagrammed in the figure below. External or internal cues promote the release of Rho GTPases from the inhibitory complex (1) which allows them to associate with the plasma membrane (2) where they are activated by GEFs (3) and can signal to effector proteins. Then, GAPs inactivate the GTPases by accelerating the intrinsic GTPase activity, leading to the GDP bound form (4). Once again, the GDI molecules stabilize the inactive GDP bound form in the cytoplasm, waiting for further instructions (5). (Figure and text from Tcherkezian and Lamarche Vane, 2007)
Antigen presenting cells (APCs) such as B cells, dendritic cells (DCs) and monocytes/macrophages express major histocompatibility complex class II molecules (MHC II) at their surface and present exogenous antigenic peptides to CD4+ T helper cells. CD4+ T cells play a central role in immune protection. On their activation they stimulate differentiation of B cells into antibody-producing B-cell blasts and initiate adaptive immune responses. MHC class II molecules are transmembrane glycoprotein heterodimers of alpha and beta subunits. Newly synthesized MHC II molecules present in the endoplasmic reticulum bind to a chaperone protein called invariant (Ii) chain. The binding of Ii prevents the premature binding of self antigens to the nascent MHC molecules in the ER and also guides MHC molecules to endocytic compartments. In the acidic endosomal environment, Ii is degraded in a stepwise manner, ultimately to free the class II peptide-binding groove for loading of antigenic peptides. Exogenous antigens are internalized by the APC by receptor mediated endocytosis, phagocytosis or pinocytosis into endocytic compartments of MHC class II positive cells, where engulfed antigens are degraded in a low pH environment by multiple acidic proteases, generating MHC class II epitopes. Antigenic peptides are then loaded into the class II ligand-binding groove. The resulting class II peptide complexes then move to the cell surface, where they are scanned by CD4+ T cells for specific recognition (Berger & Roche 2009, Zhou & Blum 2004, Watts 2004, Landsverk et al. 2009)
Retrograde traffic from the cis-Golgi to the ERGIC or the ER is mediated in part by microtubule-directed COPI-coated vesicles (Letourneur et al, 1994; Shima et al, 1999; Spang et al, 1998; reviewed in Lord et al, 2013; Spang et al, 2013). These assemble at the cis side of the Golgi in a GBF-dependent fashion and are tethered at the ER by the ER-specific SNAREs and by the conserved NRZ multisubunit tethering complex, known as DSL in yeast (reviewed in Tagaya et al, 2014; Hong and Lev, 2014). Typical cargo of these retrograde vesicles includes 'escaped' ER chaperone proteins, which are recycled back to the ER for reuse by virtue of their interaction with the Golgi localized KDEL receptors (reviewed in Capitani and Sallese, 2009; Cancino et al, 2013)
Kinesins are a superfamily of microtubule-based motor proteins that have diverse functions in transport of vesicles, organelles and chromosomes, and regulate microtubule dynamics. There are 14 families of kinesins, all reprsented in humans. A standardized nomenclature was published in 2004 (Lawrence et al.)
Affinity Capture-MS, Co-fractionation, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, cosedimentation through density gradient, fluorescence microscopy, pull down, two hybrid
association, colocalization, physical, physical association
Affinity Capture-MS, Co-fractionation, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, cosedimentation through density gradient, fluorescence microscopy, pull down, two hybrid
association, colocalization, physical, physical association
Affinity Capture-MS, Co-fractionation, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, cosedimentation through density gradient, fluorescence microscopy, pull down, two hybrid
association, colocalization, physical, physical association
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