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protein

DCC-interacting protein 13-alpha

aka Dip13-alpha

APPL1
protein:Q9UKG1disease:adad:direction:ambiguous

Gene

APPL1

Organism

Homo sapiens(9606)

Length

709 aa

Mass

79,663 Da

AI summarysource-grounded · cited inline
claude-haiku-4-5-20251001

APPL1 (DCC-interacting protein 13-alpha) is a multifunctional adapter protein that regulates cell proliferation, immune response, endosomal trafficking, and metabolic processes through interactions with membrane receptors, signaling proteins, and nuclear factors (UniProt: Q9UKG1). It modulates RAB5A-dependent signaling, controls TLR4 and PI3K/Akt pathways in immune cells, and regulates TGFBR1 nuclear trafficking. The protein also plays roles in adiponectin and insulin signaling, fibroblast migration, and Wnt/beta-catenin transcription.

APPL1 is associated with maturity-onset diabetes of the young 14 (MODY14), an autosomal dominant form of early-onset diabetes marked by defective insulin secretion (UniProt: Q9UKG1, MIM 616511). The protein's involvement in insulin and adiponectin signaling pathways reflects its broader role in metabolic regulation.

In Alzheimer's disease, APPL1 shows an ambiguous direction of regulation across subcellular fractions in post-mortem AD brain compared to age-matched controls (Chaparral AD proteomics). The mean log2 fold-change is −0.0841, indicating minimal net change, though this masks potential redistribution across the two measured fractions.

Generated from the curated entity record below. May contain errors — verify against source links.

Proteomics Evidence · AD

⚠ Ambiguous — detected in AD samples, direction unclear across fractions

P3

+0.674

P2

not detected

S2

-0.842

S3

not detected

Mean log₂FC across detected fractions: -0.0841 (2 of 4 fractions detected)

Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.

Related Publications

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Function

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:10490823, PubMed:15016378, PubMed:19661063, PubMed:26073777, PubMed:26583432). 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:19661063, PubMed:24879834, PubMed:26073777). 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)

Disease associations

  • Maturity-onset diabetes of the young 14MODY14

    A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.

Sources

Last updated 5/8/2026, 6:30:57 AM