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AIP1 (ASK-interacting protein 1), also known as DAB2IP (DAB2 interacting protein), is a 1,189 amino acid protein that localizes to both the membrane and the cytoplasm and contains one Ras-GAP domain, one PH domain and one C2 domain. Expressed at low levels in prostate tissue, AIP1 functions as a Ras GTPase-activating protein that interacts with ASK 1 and, via this interaction, disrupts the association of ASK 1 with an inhibitory 14-3-3 complex, thereby allowing free ASK 1 to function within the cell. AIP1 exists as multiple alternatively spliced isoforms and is down-regulated in prostate cancer tissue, suggesting a role in tumor suppression. Chromosomal aberrations in the gene encoding AIP1 are associated with acute myeloid leukemia (AML), implicating a role for AIP1 fusion proteins in tumorigenesis.Function : Seems to act as scaffold molecule at synaptic junctions by assembling neurotransmitter receptors and cell adhesion proteins. May play a role in regulating activin-mediated signaling in neuronal cells. Enhances the ability of PTEN to suppress AKT1 activation.Subunit : Interacts (via its WW domains) with DRPLA. Interacts (via its second PDZ domain) with PTEN (via unphosphorylated C-terminus); this interaction diminishes the degradation rate of PTEN (By similarity). Interacts (via guanylate kinase domain) with DLGAP1 (By similarity). Interacts (via the PDZ domains) with GRIN2A, GRID2 and NLGN1 (By similarity). Interacts with CTNND2, CTNNB1, MAGUIN-1, ACVR2A, SMAD2 and SMAD3 (By similarity). Part of a complex consisting of AIP1, ACVR2A, ACVR1B and SMAD3 (By similarity). May interact with HTR2A (By similarity). Interacts with IGSF9, RAPGEF2 and HTR4 (By similarity). Identified in a complex with ACTN4, CASK, IQGAP1, NPHS1, SPTAN1 and SPTBN1 (By similarity). Interacts with DDN. Subcellular Location : Cell junction, synapse, synaptosome (By similarity). Cell membrane; Peripheral membrane protein (By similarity). Note=Membrane-associated in synaptosomes (By similarity). Tissue Specificity : Specifically expressed in brain.Similarity : Belongs to the MAGUK family.Contains 1 guanylate kinase-like domain.Contains 6 PDZ (DHR) domains.Contains 2 WW domains.Database links : UniProtKB/Swiss-Prot: Q86UL8.3
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