Gene Information
Gene Symbol
APPL, DIP13alpha, MODY14
Entrez Gene ID
Gene Name
Adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1
Chromosomal Location
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. [provided by RefSeq, Jul 2008]
RefSeq DNA
RefSeq mRNA

Gene Ontology (GO)

GO ID Ontology Function Evidence Reference
GO:0006606 Biological process Protein import into nucleus IDA 26583432
GO:0007165 Biological process Signal transduction TAS 10490823
GO:0007179 Biological process Transforming growth factor beta receptor signaling pathway IMP 26583432
GO:0008283 Biological process Cell proliferation IDA 15016378
GO:0008286 Biological process Insulin receptor signaling pathway IBA 21873635
Protein Information
Protein Name
DCC-interacting protein 13-alpha, AKT2 interactor, adapter protein containing PH domain, PTB domain and leucine zipper motif 1, adaptor protein containing pH domain, PTB domain and leucine zipper motif 1, adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 1, dip13-alpha, signaling adaptor protein DIP13alpha
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).
Refseq Proteins
Pfam Accession Pfam ID
PF00169 PH
PF00640 PID

Longevity regulating pathway
Pathways in cancer
Colorectal cancer


Caspase activation via Dependence Receptors in the absence of ligand

ENSP00000306459 Q9UBX8
    View interactions

Associated Diseases

Disease groupDisease NameReferences
Endocrine System Diseases
PubMed ID Associated gene/s Associated condition Genetic Mutation Diagnostic Criteria Association with PCOS Ethnicity Conclusion
hyperandrogenism, reduction or lack of ovulation and polycystic ovaries 
Rotterdam criteria 
44 infertile women aged 1840 years who underwent oocyte recovery: 22 PCOS patients and 22 women with normal ovulatory function as control group. 
Reduction of APPL1, insulin receptor and adiponectin system genes in GCs could be involved in the development of PCOS 

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