Rabbit anti-Human APPL2 Polyclonal Antibody

Uniprot Id

Q8NEU8

Target Species

Human

Target Name

APPL2

Target Full Name

DCC-interacting protein 13-beta

Target 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. Regulates signaling pathway leading to cell proliferation through interaction with RAB5A and subunits of the NuRD/MeCP1 complex. Plays a role in immune response by modulating phagocytosis, inflammatory and innate immune responses. In macrophages, enhances Fc-gamma receptor-mediated phagocytosis through interaction with RAB31 leading to activation of PI3K/Akt signaling. In response to LPS, modulates inflammatory responses by playing a key role on the regulation of TLR4 signaling and in the nuclear translocation of RELA/NF-kappa-B p65 and the secretion of pro- and anti-inflammatory cytokines. Also functions as a negative regulator of innate immune response via inhibition of AKT1 signaling pathway by forming a complex with APPL1 and PIK3R1. Plays a role in endosomal trafficking of TGFBR1 from the endosomes to the nucleus. Plays a role in cell metabolism by regulating adiponecting ans insulin signaling pathways and adaptative thermogenesis. In muscle, negatively regulates adiponectin-simulated glucose uptake and fatty acid oxidation by inhibiting adiponectin signaling pathway through APPL1 sequestration thereby antagonizing APPL1 action. In muscles, negativeliy regulates insulin-induced plasma membrane recruitment of GLUT4 and glucose uptake through interaction with TBC1D1. Plays a role in cold and diet-induced adaptive thermogenesis by activating ventromedial hypothalamus (VMH) neurons throught AMPK inhibition which enhances sympathetic outflow to subcutaneous white adipose tissue (sWAT), sWAT beiging and cold tolerance. Also plays a role in other signaling pathways namely Wnt/beta-catenin, HGF and glucocorticoid receptor signaling. 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. May affect adult neurogenesis in hippocampus and olfactory system via regulating the sensitivity of glucocorticoid receptor. Required for fibroblast migration through HGF cell signaling.

Target Involvement

A chromosomal aberration involving APPL2/DIP13B is found in patients with chromosome 22q13.3 deletion syndrome. Translocation t(12;22)(q24.1;q13.3) with SHANK3/PSAP2 (PubMed:11431708).

Target Subcellular Location

Early endosome membrane; Peripheral membrane protein. Nucleus. Cell membrane. Endosome membrane. Cytoplasm. Cytoplasmic vesicle, phagosome. Cell projection, ruffle. Cell projection, ruffle membrane. Cell membrane. Cytoplasmic vesicle, phagosome membrane.

Target Tissue Specificity

High levels in brain, heart, kidney and skeletal muscle.

Target Synonyms

Adapter protein containing PH domain; Adapter protein containing PH domain PTB domain and leucine zipper motif 2 ; adaptor protein; phosphotyrosine interaction; PH domain and leucine zipper containing 2; APLP2; Appl2; DCC interacting protein 13 beta; DCC-interacting protein 13-beta; Dip13 beta ; Dip13-beta; DP13B_HUMAN; PTB domain and leucine zipper motif 2

Target Background

The protein encoded by this gene is one of two effectors of the small GTPase RAB5A/Rab5, which are involved in a signal transduction pathway. Both effectors contain an N-terminal Bin/Amphiphysin/Rvs (BAR) domain, a central pleckstrin homology (PH) domain, and a C-terminal phosphotyrosine binding (PTB) domain, and they bind the Rab5 through the BAR domain. They are associated with endosomal membranes and can be translocated to the nucleus in response to the EGF stimulus. They interact with the NuRD/MeCP1 complex (nucleosome remodeling and deacetylase /methyl-CpG-binding protein 1 complex) and are required for efficient cell proliferation. A chromosomal aberration t(12;22)(q24.1;q13.3) involving this gene and the PSAP2 gene results in 22q13.3 deletion syndrome, also known as Phelan-McDermid syndrome.