Multifunctional adapter protein that binds to various membrane receptors, nuclear factors and signaling proteins to regulate many processes, such as cell proliferation, immune response, endosomal trafficking and cell metabolism (PubMed:26583432, PubMed:15016378, PubMed:26073777, PubMed:19661063, PubMed:10490823). Regulates signaling pathway leading to cell proliferation through interaction with RAB5A and subunits of the NuRD/MeCP1 complex (PubMed:15016378). Functions as a positive regulator of innate immune response via activation of AKT1 signaling pathway by forming a complex with APPL1 and PIK3R1 (By similarity). Inhibits Fc-gamma receptor-mediated phagocytosis through PI3K/Akt signaling in macrophages (By similarity). Regulates TLR4 signaling in activated macrophages (By similarity). Involved in trafficking of the TGFBR1 from the endosomes to the nucleus via microtubules in a TRAF6-dependent manner (PubMed:26583432). Plays a role in cell metabolism by regulating adiponecting and insulin signaling pathways (PubMed:26073777, PubMed:19661063, PubMed:24879834). Required for fibroblast migration through HGF cell signaling (By similarity). Positive regulator of beta-catenin/TCF-dependent transcription through direct interaction with RUVBL2/reptin resulting in the relief of RUVBL2-mediated repression of beta-catenin/TCF target genes by modulating the interactions within the beta-catenin-reptin-HDAC complex (PubMed:19433865). Homodimer (PubMed:18034774). Binds RAB5A/Rab5 through an N-terminal domain. This interaction is essential for its recruitment to endosomal membranes as well as its role in cell proliferation (PubMed:15016378). Binds DCC and the catalytic domain of the inactive form of AKT2 through its PID domain (PubMed:10490823, PubMed:12011067). Binds PIK3CA and subunits of the NuRD/MeCP1 complex (PubMed:10490823, PubMed:15016378). Interacts with OCRL and INPP5B (PubMed:21666675, PubMed:17765681, PubMed:20133602, PubMed:21233288). Interacts with NTRK2 (By similarity). Interacts with APPL2; interaction is independent of follicle stimulating hormone stimulation; interaction is decreased by adiponectin in a time-dependent manner (PubMed:17030088, PubMed:18034774, PubMed:19661063). Forms a complex with APPL2 and RUVBL2 (PubMed:19433865). Forms a complex comprising APPL2, RUVBL2, CTNNB1, HDAC1 and HDAC2; interaction reduces interaction between CTNNB1, HDAC1, HDAC2 and RUVBL2 leading to the decrease of deacetylase activity of this complex; affects the recruitment of repressive complexes to the Wnt target genes (PubMed:19433865). Interacts with ANXA2 (PubMed:21645192). Interacts with TGFBR1; interaction is TGF beta dependent; mediates trafficking of the TGFBR1 from the endosomes to the nucleus via microtubules in a TRAF6-dependent manner (PubMed:26583432). Interacts with PRKCZ (PubMed:26583432). Interacts with PIK3R1 and APPL2 (By similarity). Interacts with ADIPOR1; ADIPOQ enhances this interaction; inhibites adiponectin-stimulated binding of APPL2 to ADIPOR1 (By similarity). Early endosomal membrane-bound and nuclear. Translocated into the nucleus upon release from endosomal membranes following internalization of EGF. High levels in heart, ovary, pancreas and skeletal muscle. Overexpression of an N-terminal domain (residues 1-319) or a C-terminal region (residues 273-709) has a proapoptotic effect. The F&H motif, an approximately 12-13 amino-acid sequence centered around Phe and His residues, is essential for binding to OCRL and INPP5B. Phosphorylation at Ser-410 by PKA severely impairs binding to OCRL. The disease is caused by variants affecting the gene represented in this entry.