Adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1), or DCC-interacting protein 13-alpha (DIP13alpha), is a protein that in humans is encoded by the APPL1 gene.^[5][6][7] APPL1 contains several key interactory domains: pleckstrin homology (PH) domain, phosphotyrosine-binding (PTB) domain and Bin–Amphiphysin–Rvs (BAR) domain.^[8]

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APPL1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2EJ8, 2ELA, 2ELB, 2Q12, 2Q13, 2Z0N, 2Z0O, 5C5B
Identifiers
Aliases	APPL1, APPL, DIP13alpha, MODY14, adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1
External IDs	OMIM: 604299; MGI: 1920243; HomoloGene: 32143; GeneCards: APPL1; OMA:APPL1 - orthologs
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3p14.3 Start 57,227,726 bp[1] End 57,278,105 bp[1]
Gene location (Mouse) Chr. Chromosome 14 (mouse)[2] Band 14|14 A3 Start 26,640,945 bp[2] End 26,693,189 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Achilles tendon biceps brachii germinal epithelium body of pancreas vastus lateralis muscle human penis gastrocnemius muscle Skeletal muscle tissue of biceps brachii muscle of thigh Skeletal muscle tissue of rectus abdominis Top expressed in aortic valve ascending aorta secondary oocyte substantia nigra primitive streak conjunctival fornix iris supraoptic nucleus sciatic nerve Region I of hippocampus proper More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein kinase B binding protein binding identical protein binding phosphatidylserine binding phosphatidylinositol binding protein homodimerization activity protein-containing complex binding beta-tubulin binding Cellular component cytoplasm NuRD complex cytosol endosome early endosome membrane membrane vesicle membrane endosome membrane extracellular exosome nucleus early endosome ruffle plasma membrane cytoplasmic vesicle early phagosome macropinosome intracellular vesicle cell projection phagocytic vesicle Biological process regulation of glucose import extrinsic apoptotic signaling pathway in absence of ligand cell cycle cell population proliferation signal transduction insulin receptor signaling pathway regulation of protein localization to plasma membrane transforming growth factor beta receptor signaling pathway regulation of fibroblast migration signaling adiponectin-activated signaling pathway regulation of toll-like receptor 4 signaling pathway cellular response to hepatocyte growth factor stimulus regulation of innate immune response positive regulation of glucose import positive regulation of melanin biosynthetic process positive regulation of cytokine production involved in inflammatory response positive regulation of macropinocytosis negative regulation of Fc-gamma receptor signaling pathway involved in phagocytosis protein import into nucleus Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 26060 72993 Ensembl ENSG00000157500 ENSMUSG00000040760 UniProt Q9UKG1 Q8K3H0 RefSeq (mRNA) NM_012096 NM_145221 RefSeq (protein) NP_036228 NP_660256 Location (UCSC) Chr 3: 57.23 – 57.28 Mb Chr 14: 26.64 – 26.69 Mb PubMed search [3] [4]
Wikidata
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APPL1 is an adaptor protein localized to a subset of Rab5-positive ("early") endosomes, where it recruits other binding partners and regulates vesicle trafficking and endosomal signalling. APPL1 is enriched at very early endosomes which are negative for EEA1, indicating that APPL1 affects the earliest stages of endosomal traffic before EEA1 takes over. This is in line with observations that APPL1 and EEA1 compete for Rab5 binding. APPL1 affects the speed of internalization of key endosomal cargo (eg. EGF receptor) which is dependent on Rab5 activation.^[8]

PTB domain of APPL1 regulates many cell signalling events in specific endosomal compartments - sometimes termed the "signalling endosomes". This includes lysophosphatidic acid (LPA)-induced signaling (together with interacting protein GIPC1). Additional roles for APPL1 were pinpointed to the nucleus where APPL1 can localize once dissociated from endosomes.^[8]

APPL1 has been shown to interact with Deleted in Colorectal Cancer,^[9] AKT2,^[5] but also Rab5, Rab21, OCRL and almost 30 other proteins.^[8]