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
last maintenance update: 01 Sep, 2023
Cytoplasm Membrane; Peripheral membraneprotein Endosome membrane Earlyendosome Late endosome
Function (UniProt annotation)
Acts as component of the retromer cargo-selectivecomplex (CSC) The CSC is believed to be the core functionalcomponent of retromer or respective retromer complex variantsacting to prevent missorting of selected transmembrane cargoproteins into the lysosomal degradation pathway The recruitmentof the CSC to the endosomal membrane involves RAB7A and SNX3 TheSNX-BAR retromer mediates retrograde transport of cargo proteinsfrom endosomes to the trans-Golgi network (TGN) and is involved inendosome-to-plasma membrane transport for cargo protein recyclingThe SNX3-retromer mediates the retrograde endosome-to-TGNtransport of WLS distinct from the SNX-BAR retromer pathway TheSNX27-retromer is believed to be involved in endosome-to-plasmamembrane trafficking and recycling of a broad spectrum of cargoproteins The CSC seems to act as recruitment hub for otherproteins, such as the WASH complex and TBC1D5 Required toregulate transcytosis of the polymeric immunoglobulin receptor(pIgR-pIgA) (Probable) Involved in GLUT1 endosome-to-plasmamembrane trafficking; the function is dependent of associationwith ANKRD27 (PubMed:24856514) (Microbial infection) The heterotrimeric retromer cargo-selective complex (CSC) mediates the exit of human papillomavirusfrom the early endosome and the delivery to the Golgi apparatus
Endocytosis is a mechanism for cells to remove ligands, nutrients, and plasma membrane (PM) proteins, and lipids from the cell surface, bringing them into the cell interior. Transmembrane proteins entering through clathrin-dependent endocytosis (CDE) have sequences in their cytoplasmic domains that bind to the APs (adaptor-related protein complexes) and enable their rapid removal from the PM. In addition to APs and clathrin, there are numerous accessory proteins including dynamin. Depending on the various proteins that enter the endosome membrane, these cargoes are sorted to distinct destinations. Some cargoes, such as nutrient receptors, are recycled back to the PM. Ubiquitylated membrane proteins, such as activated growth-factor receptors, are sorted into intraluminal vesicles and eventually end up in the lysosome lumen via multivesicular endosomes (MVEs). There are distinct mechanisms of clathrin-independent endocytosis (CIE) depending upon the cargo and the cell type.
19 WNT proteins have been identified in human cells. The WNTs are members of a conserved metazoan family of secreted morphogens that activate several signaling pathways in the responding cell: the canonical (beta-catenin) WNT signaling cascade and several non-canonical pathways, including the planar cell polarity (PCP), the regulation of intracellular calcium signaling and activation of JNK kinases. WNT proteins exist in a gradient outside the secreting cell and are able to act over both short and long ranges to promote proliferation, changes in cell migration and polarity and tissue homeostasis, among others (reviewed in Saito-Diaz et al, 2012; Willert and Nusse, 2012). The WNTs are ~40kDa proteins with 23 conserved cysteine residues in the N-terminal that may form intramolecular disulphide bonds. They also contain an N-terminal signal sequence and a number of N-linked glycosylation sites (Janda et al, 2012). In addition to being glycosylated, WNTs are also lipid-modified in the endoplasmic reticulum by a WNT-specific O-acyl-transferase, Porcupine (PORCN), contributing to their characteristic hydrophobicity. PORCN-dependent palmitoylation is required for the secretion of WNT as well as its signaling activity, as either depletion of PORCN or mutation of the conserved serine acylation site results in the intracellular accumulation of WNT ligand (Takada et al, 2006; Barrott et al, 2011; Biechele et al, 2011; reviewed in Willert and Nusse, 2012).Secretion of WNT requires a number of other dedicated factors including the sorting receptor Wntless (WLS) (also knownas Evi, Sprinter, and GPR177), which binds WNT and escorts it to the cell surface (Banziger et al, 2006; Bartscherer et al, 2006; Goodman et al, 2006). A WNT-specific retromer containing SNX3 is subsequently required for the recycling of WLS back to the Golgi (reviewed in Herr et al, 2012; Johannes and Wunder, 2011). Once at the cell surface, WNT makes extensive contacts with components of the extracellular matrix such as heparan sulphate proteoglycans (HSPGs) and may be bound by any of a number of regulatory proteins, including WIFs and SFRPs. The diffusion of the WNT ligand may be aided by its packing either into WNT multimers, exosomes or onto lipoprotein particles to shield the hydrophobic lipid adducts from the aqueous extracellular environment (Gross et al, 2012; Luga et al, 2012, Korkut et al, 2009; reviewed in Willert and Nusse, 2012)
Affinity Capture-MS, Affinity Capture-Western, Co-fractionation, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, coimmunoprecipitation, molecular sieving, transmission electron microscopy
Affinity Capture-MS, Affinity Capture-Western, Co-fractionation, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, coimmunoprecipitation, molecular sieving, transmission electron microscopy
Affinity Capture-MS, Affinity Capture-Western, Co-fractionation, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, coimmunoprecipitation, molecular sieving, transmission electron microscopy
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