APPL2
entrez
55198
canonical
uniprot
Q8NEU8
canonical
ensembl
ENSG00000136044
resolver
ensp
ENSP00000258530
resolver
ensp
ENSP00000444472
resolver
ensp
ENSP00000446917
resolver
ensp
ENSP00000532338
resolver
ensp
ENSP00000643956
resolver
ensp
ENSP00000781577
resolver
genesymbol
APPL2
resolver
genesymbol_syn
DIP13B
resolver
hgnc
HGNC:18242
resolver
uniprot
B7Z411
resolver
uniprot
B7Z4B0
resolver
uniprot
F5GZG0
resolver
uniprot
F8W1P5
resolver
uniprot
Q8N4R7
resolver
uniprot
Q9NVL2
resolver
uniprot_entry
DP13B_HUMAN
resolver
uniprot_sec
B7Z411
resolver
uniprot_sec
B7Z4B0
resolver
uniprot_sec
F5GZG0
resolver
uniprot_sec
F8W1P5
resolver
uniprot_sec
Q8N4R7
resolver
uniprot_sec
Q9NVL2
resolver
amino_acid_sequence
MPAVDKLLLEEALQDSPQTRSLLSVFEEDAGTLTDYTNQLLQAMQRVYGAQNEMCLATQQLSKQLLAYEKQNFALGKGDEEVISTLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKDLTEVSTLKDLFGLASNEHDLSMAKYSRLPKKKENEKVKTEVGKEVAAARRKQHLSSLQYYCALNALQYRKQMAMMEPMIGFAHGQINFFKKGAEMFSKRMDSFLSSVADMVQSIQVELEAEAEKMRVSQQELLSVDESVYTPDSDVAAPQINRNLIQKAGYLNLRNKTGLVTTTWERLYFFTQGGNLMCQPRGAVAGGLIQDLDNCSVMAVDCEDRRYCFQITTPNGKSGIILQAESRKENEEWICAINNISRQIYLTDNPEAVAIKLNQTALQAVTPITSFGKKQESSCPSQNLKNSEMENENDKIVPKATASLPEAEELIAPGTPIQFDIVLPATEFLDQNRGSRRTNPFGETEDESFPEAEDSLLQQMFIVRFLGSMAVKTDSTTEVIYEAMRQVLAARAIHNIFRMTESHLMVTSQSLRLIDPQTQVSRANFELTSVTQFAAHQENKRLVGFVIRVPESTGEESLSTYIFESNSEGEKICYAINLGKEIIEVQKDPEALAQLMLSIPLTNDGKYVLLNDQPDDDDGNPNEHRGAESEA
uniprot
proteins
disease_involvement
DISEASE: Note=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. {ECO:0000269|PubMed:11431708}.
uniprot
proteins
function
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:15016378, PubMed:24879834, PubMed:26583432). Regulates signaling pathway leading to cell proliferation through interaction with RAB5A and subunits of the NuRD/MeCP1 complex (PubMed:15016378). 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 (By similarity). Plays a role in endosomal trafficking of TGFBR1 from the endosomes to the nucleus (PubMed:26583432). Plays a role in cell metabolism by regulating adiponecting and insulin signaling pathways and adaptative thermogenesis (By similarity) (PubMed:24879834). In muscle, negatively regulates adiponectin-simulated glucose uptake and fatty acid oxidation by inhibiting adiponectin signaling pathway through APPL1 sequestration thereby antagonizing APPL1 action (By similarity). In muscles, negatively regulates insulin-induced plasma membrane recruitment of GLUT4 and glucose uptake through interaction with TBC1D1 (PubMed:24879834). 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 (By similarity). Also plays a role in other signaling pathways namely Wnt/beta-catenin, HGF and glucocorticoid receptor signaling (By similarity) (PubMed:19433865). 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). May affect adult neurogenesis in hippocampus and olfactory system via regulating the sensitivity of glucocorticoid receptor. Required for fibroblast migration through HGF cell signaling (By similarity). {ECO:0000250|UniProtKB:Q8K3G9, ECO:0000269|PubMed:15016378, ECO:0000269|PubMed:19433865, ECO:0000269|PubMed:24879834, ECO:0000269|PubMed:26583432}.
uniprot
proteins
mass_dalton
74493
uniprot
proteins
pubmed
11431708
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15016378
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16541075
uniprot
proteins
pubmed
17030088
uniprot
proteins
pubmed
18034774
uniprot
proteins
pubmed
19433865
uniprot
proteins
pubmed
21645192
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23055524
uniprot
proteins
pubmed
24879834
uniprot
proteins
pubmed
26583432
uniprot
proteins
sequence_length
664
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Early endosome membrane {ECO:0000269|PubMed:15016378}; Peripheral membrane protein {ECO:0000269|PubMed:15016378}. Nucleus {ECO:0000269|PubMed:15016378, ECO:0000269|PubMed:18034774}. Cell membrane {ECO:0000269|PubMed:18034774}. Endosome membrane {ECO:0000269|PubMed:21645192}. Cytoplasm {ECO:0000250|UniProtKB:Q8K3G9}. Cytoplasmic vesicle, phagosome {ECO:0000250|UniProtKB:Q8K3G9}. Cell projection, ruffle {ECO:0000250|UniProtKB:Q8K3G9}. Cell projection, ruffle membrane {ECO:0000250|UniProtKB:Q8K3G9}. Cell membrane {ECO:0000250|UniProtKB:Q8K3G9}. Cytoplasmic vesicle, phagosome membrane {ECO:0000250|UniProtKB:Q8K3G9}. Note=Early endosomal membrane-bound and nuclear (PubMed:15016378). Translocated into the nucleus upon release from endosomal membranes following internalization of EGF (PubMed:15016378). Associates dynamically with cytoplasmic membrane structures that undergo changes in shape, movement, fusion and fission events (PubMed:18034774). PI(4,5)P2 levels are important for membrane association of APPL2 (PubMed:18034774). Absent of endosome in macrophage. Colocalized with RAB31 at early-stage phagosome (By similarity). Localized on macropinosomes in LPS-activated macrophages. Associated with membrane domains in contact with pathogens and pathogen-derived ligands like LPS. First recruited to the ruffles, and accumulates on macropinosomes (By similarity). {ECO:0000250|UniProtKB:Q8K3G9, ECO:0000269|PubMed:15016378, ECO:0000269|PubMed:18034774}.
uniprot
proteins