APPL1
APPL1 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1, also known as APPL or DCC-interacting protein 13-alpha) is a multifunctional adapter protein. It binds membrane receptors, nuclear factors and signalling proteins to regulate proliferation, immune response, endosomal trafficking and metabolism. Browse Assay Genie's current range of APPL1 research reagents below, or read on for the biology behind the target.
APPL1 is a multifunctional adapter protein that binds to a wide range of membrane receptors, nuclear factors and signalling proteins. Through these interactions it regulates cell proliferation, immune response, endosomal trafficking and cell metabolism. It influences proliferation through interaction with RAB5A and subunits of the NuRD/MeCP1 complex, and it acts as a positive regulator of beta-catenin/TCF-dependent transcription by binding RUVBL2 (reptin), relieving RUVBL2-mediated repression of beta-catenin/TCF target genes.
In immune cells, APPL1 is a positive regulator of the innate immune response, activating AKT1 signalling through a complex with PIK3R1. It inhibits Fc-gamma receptor-mediated phagocytosis through PI3K/Akt signalling in macrophages and regulates TLR4 signalling in activated macrophages. It is also involved in trafficking of TGFBR1 from endosomes to the nucleus along microtubules in a TRAF6-dependent manner, and it is required for fibroblast migration in response to HGF signalling. In metabolism, it regulates adiponectin and insulin signalling, and the crosstalk between the two pathways.
The APPL1 gene encodes a protein that is a member of the BAR-PH domain containing gene group. It is found on endosomal membranes but can be released by EGF and translocated to the nucleus. Reported binding partners include RAB5A, DCC, AKT2, PIK3CA, adiponectin receptors and NuRD/MeCP1 complex proteins. The previous symbol APPL and the name DCC-interacting protein 13-alpha reflect its early identification. The mouse ortholog is Appl1.
APPL1 regulates adiponectin and insulin signalling and mediates crosstalk between the two pathways, making it a focus in metabolic research.
APPL1 activates AKT1 signalling, inhibits Fc-gamma receptor-mediated phagocytosis and regulates TLR4 signalling in activated macrophages.
APPL1 associates with early endosome membranes via RAB5A and takes part in TGFBR1 transport from endosomes to the nucleus.
APPL1 interacts with NuRD/MeCP1 subunits and RUVBL2 to modulate cell proliferation and beta-catenin/TCF-dependent transcription.
APPL1 is a multifunctional adapter protein that binds membrane receptors, nuclear factors and signalling proteins. It regulates cell proliferation, immune response, endosomal trafficking and cell metabolism, including adiponectin and insulin signalling, and supports fibroblast migration through HGF signalling.
APPL1 is the approved HGNC symbol; APPL is a previous symbol. UniProt lists the protein as DCC-interacting protein 13-alpha. The earlier gene name was adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 1.
APPL1 is found on early endosome membranes, and also in the cytoplasm, nucleus, membrane ruffles and phagosomes. EGF can release it from endosomes for translocation to the nucleus. A mouse ortholog, Appl1, exists; check the datasheet of any product for its validated reactivity.
Binding partners and pathway components of APPL1, including PI3K/Akt signalling, endosomal trafficking and Wnt-related targets.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q9UKG1; product specifications from Assay Genie datasheets.