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APPL1

The protein encoded by this gene has been shown to be involved in the regulation of cell proliferation, and in the crosstalk between the adiponectin signalling and insulin signalling pathways. The encoded protein binds many other proteins, including RAB5A, DCC, AKT2, PIK3CA, adiponectin receptors, and proteins of the NuRD/MeCP1 complex. This protein is found associated with endosomal membranes, but can be released by EGF and translocated to the nucleus.
Protein class

Disease related genes, Human disease related genes

Predicted location

Intracellular

Single cell type specificity

Low cell type specificity

Immune cell specificity

Immune cell enhanced (naive B-cell)

Cell line specificity

Low cell line specificity

Interaction

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).

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