Property Summary

NCBI Gene PubMed Count 71
PubMed Score 491.62
PubTator Score 67.05

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (4)

Disease log2 FC p
Waldenstrons macroglobulinemia -1.284 9.7e-03
osteosarcoma 3.176 1.8e-07
aldosterone-producing adenoma -1.282 1.4e-02
ovarian cancer -1.900 6.4e-06

Protein-protein Interaction (1)

Gene RIF (50)

PMID Text
26731990 article provides evidence that GG genotype and G carrier (CG+GG) genotypes of the rs4640525 polymorphism in the APPL1 gene may be suitable susceptibility biomarkers for NAFLD
26583432 Data show that signal transducing adaptor proteins APPL1 and APPL2 are required for TGFbeta-induced nuclear translocation of TGFbeta type I receptor (TbetaRI)-ICD and for cancer cell invasiveness of prostate and breast cancer cell lines.
26473288 Low expression of APPL1 is associated with metastasis in prostate cancer.
26459602 APPL1 endosomes represent a distinct population of Rab5-positive sorting endosomes.
26073777 Two loss-of-function mutations in APPL1, identified by means of whole-exome sequencing, found in two large families with a high prevalence of Familial Diabetes Mellitus.
25780039 A role for APPL1 in TLR3/4-dependent TBK1 and IKKepsilon activation in macrophages.
25622892 APPL1 is a positive regulator of Dvl2-dependent transcriptional activity of AP-1.
24813896 APPL1 sensitizes insulin signaling by acting at a site downstream of the IR. Study uncovers a mechanism regulating insulin signaling and crosstalk between the insulin and adiponectin pathways.
24763056 ATM is the central modulator of APPL-mediated effects on radiosensitivity and DNA repair.
23986476 The activated EGF receptor enters distinct sub-populations of SNX15- and APPL1-labelled peripheral endocytic vesicles.
23977033 C-APPL1/A-APPL2 allele combination is associated with non-alcoholic fatty liver disease occurrence, with a more severe hepatic steatosis grade and with a reduced adiponectin cytoprotective effect on liver.
23909487 TRAF6-mediated ubiquitination of APPL1 is a vital step for the hepatic actions of insulin through modulation of membrane trafficking and activity of Akt.
23891720 It concludes that APPL1(PH) binding to BAR domain and Reptin is mutually exclusive which regulates the nucleocytoplasmic shuttling of Reptin.
23291133 Rab5a and APPL1 are overexpressed in breast cancer, and are positively correlated with the HER-2 expression.
23246927 neurons with APPL1-positive granules were restricted to the CA1 area and subiculum, areas associated with hippocampal vulnerability, suggesting a possible link between the perisomatic accumulation of APPL1 and Alzheimer's disease.
23055524 analysis of APPL1 and APPL2 proteins and their interaction with Rab
22685329 APPL1 regulates basal NF-kappaB activity by modulating the stability of NIK, which affects the activation of p65.
22685300 APPL1 is a novel target in endoplasmic reticulum (ER) stress-induced insulin resistance and PKCalpha is the kinase mediating ER stress-induced phosphorylation of APPL1 at Ser(430).
22379109 results demonstrate an important new function for APPL1 in regulating cell migration and adhesion turnover through a mechanism that depends on Src and Akt
22340213 Genetic variation(s) in APPL1/2 may be associated with CAD risk in T2DM in Chinese population.
22037462 These findings suggest that APPL1 is required for EGFR signaling by regulation of EGFR stabilities through inhibition of Rab5.
21926268 APPL1 plays a key role in coordinating the vasodilator and vasoconstrictor effects of insulin by modulating Akt-dependent NO production and ERK1/2-mediated ET-1 secretion in the endothelium.
21835890 Treating C2C12 myotubes with adiponectin promoted APPL1 interaction with protein phosphatase 2A (PP2A) and protein kinase Czeta (PKCzeta), leading to the activation of PP2A and subsequent dephosphorylation and inactivation of PKCzeta.
21645192 Data suggest that although annexin A2 is not an exclusive marker of APPL1/2 endosomes, it has an important function in membrane recruitment of APPL proteins, acting in parallel to Rab5.
21562756 APPL1 abundance is significantly higher in type 2 diabetic muscle; Improvements in hyperglycaemia and hypoadiponectinaemia are associated with reduced skeletal muscle APPL1, and increased plasma adiponectin levels and muscle AMPK phosphorylation.
21320486 Results show that APPL1 is recruited to aggresomes induced by proteasomal stress, and suggest that proteasome inhibitors in clinical use affect the localization, ubiquitination and solubility of APPL1.
21291857 interactions between TRP1-GIPC and GIPC-APPL-AKT provide a potential link between melanogenesis and PI3 kinase signaling
21285318 The adapter protein APPL1 links FSH receptor to inositol 1,4,5-trisphosphate production and is implicated in intracellular Ca(2+) mobilization.
20978232 Data indicate APPL1 functions as a scaffolding protein to facilitate adiponectin-stimulated p38 MAPK activation in myotubes.
20875820 Studies indicate that APPL1 has been recently identified as an AdipoR1 and AdipoR2 binding protein.
20814572 significant fluorescence resonance energy transfer between APPL minimal BAR domain FRET pairs
20600589 [REVIEW] Emerging roles for AppL1. APPL1 has been shown to interact with a variety of membrane receptors. Recent subcellular localizations of APPL1 place it in dynamic and varied venues in the cell: the cell membrane, the nucleus and the early endosomes
20484574 The promyogenic function of Cdo involves a coordinated activation of p38MAPK and Akt via association with scaffold proteins, JLP and Bnip-2 for p38MAPK and APPL1 for Akt.
20412119 Rab5a promoted proliferation of ovarian cancer cells, which may be associated with the APPL1-related epidermal growth factor signaling pathway.
20095645 Used mass spectrometry (MS) to identify 13 phosphorylated residues within APPL1.
19686092 APPL1 overexpression affects the composition of the HDAC1-containing NuRD complex and the expression of HDAC1 target p21WAF1/CIP1
19520843 Adiponectin activates AMP-activated protein kinase in muscle cells via APPL1/LKB1-dependent and phospholipase C/Ca2+/Ca2+/calmodulin-dependent protein kinase kinase-dependent pathways
19433865 APPL proteins exert their stimulatory effects on beta-catenin/TCF-dependent transcription by decreasing the activity of a Reptin-containing repressive complex
18632660 Adiponectin blocks interleukin-18-mediated endothelial cell death via APPL1-dependent AMP-activated protein kinase (AMPK) activation and IKK/NF-kappaB/PTEN suppression.
18581887 Observational study of gene-disease association. (HuGE Navigator)
18307981 Thus, binding to APPL1 helps localize OCRL at specific cellular sites, and disruption of this interaction may play a role in disease.
18034774 The findings suggest a role for APPL1 and APPL2 protein as dynamic scaffolds that modulate RAB5-associated signaling endosomal membranes by their ability to undergo domain-mediated oligomerization, membrane targeting and phosphoinositide binding.
17848569 These data suggest that APPL1 plays an important role in insulin-stimulated Glut4 translocation in muscle and adipose tissues and that its N-terminal portion may be critical for APPL1 function.
17581628 The crystal structures of human APPL1 N-terminal BAR-PH domain motif, is reported.
17502098 The ability of APPL1 to interact with multiple signaling molecules and phospholipids supports an important role for this adaptor in cell signaling.
17490420 Observational study of gene-disease association. (HuGE Navigator)
17287464 APPL1 acts as a common downstream effector of Adiponectin receptors R1 and -R2, mediating adiponectin-evoked endothelial nitric oxide production and endothelium-dependent vasodilation.
16622416 APPL1 interacts with adiponectin receptors in mammalian cells and the interaction is stimulated by adiponectin.
15070827 APPL1 is a potential interactor with FSHR
15016378 identification of a pathway directly linking the small GTPase Rab5, a key regulator of endocytosis, to signal transduction and mitogenesis via APPL1 and APPL2, two Rab5 effectors

AA Sequence

MPGIDKLPIEETLEDSPQTRSLLGVFEEDATAISNYMNQLYQAMHRIYDAQNELSAATHLTSKLLKEYEK      1 - 70
QRFPLGGDDEVMSSTLQQFSKVIDELSSCHAVLSTQLADAMMFPITQFKERDLKEILTLKEVFQIASNDH     71 - 140
DAAINRYSRLSKKRENDKVKYEVTEDVYTSRKKQHQTMMHYFCALNTLQYKKKIALLEPLLGYMQAQISF    141 - 210
FKMGSENLNEQLEEFLANIGTSVQNVRREMDSDIETMQQTIEDLEVASDPLYVPDPDPTKFPVNRNLTRK    211 - 280
AGYLNARNKTGLVSSTWDRQFYFTQGGNLMSQARGDVAGGLAMDIDNCSVMAVDCEDRRYCFQITSFDGK    281 - 350
KSSILQAESKKDHEEWICTINNISKQIYLSENPEETAARVNQSALEAVTPSPSFQQRHESLRPAAGQSRP    351 - 420
PTARTSSSGSLGSESTNLAALSLDSLVAPDTPIQFDIISPVCEDQPGQAKAFGQGGRRTNPFGESGGSTK    421 - 490
SETEDSILHQLFIVRFLGSMEVKSDDHPDVVYETMRQILAARAIHNIFRMTESHLLVTCDCLKLIDPQTQ    491 - 560
VTRLTFPLPCVVLYATHQENKRLFGFVLRTSSGRSESNLSSVCYIFESNNEGEKICDSVGLAKQIALHAE    561 - 630
LDRRASEKQKEIERVKEKQQKELNKQKQIEKDLEEQSRLIAASSRPNQASSEGQFVVLSSSQSEESDLGE    631 - 700
GGKKRESEA                                                                 701 - 709
//

Text Mined References (83)

PMID Year Title
26731990 2015 Association of APPL1 Gene Polymorphism with Non-Alcoholic Fatty Liver Disease Susceptibility in a Chinese Han Population.
26583432 2016 APPL proteins promote TGF?-induced nuclear transport of the TGF? type I receptor intracellular domain.
26473288 2015 Endosomal gene expression: a new indicator for prostate cancer patient prognosis?
26459602 2015 APPL endosomes are not obligatory endocytic intermediates but act as stable cargo-sorting compartments.
26073777 2015 Loss-of-Function Mutations in APPL1 in Familial Diabetes Mellitus.
25814554 2015 Phospho-tyrosine dependent protein-protein interaction network.
25780039 2015 A role for APPL1 in TLR3/4-dependent TBK1 and IKK? activation in macrophages.
25622892 2015 APPL1 endocytic adaptor as a fine tuner of Dvl2-induced transcription.
25416956 2014 A proteome-scale map of the human interactome network.
25241761 2014 Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network.
24813896 2014 APPL1 potentiates insulin sensitivity by facilitating the binding of IRS1/2 to the insulin receptor.
24763056 2014 APPL proteins modulate DNA repair and radiation survival of pancreatic carcinoma cells by regulating ATM.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
23986476 2013 SNX15 links clathrin endocytosis to the PtdIns3P early endosome independently of the APPL1 endosome.
23977033 2013 Association of genetic variation in adaptor protein APPL1/APPL2 loci with non-alcoholic fatty liver disease.
23909487 2013 TRAF6-mediated ubiquitination of APPL1 enhances hepatic actions of insulin by promoting the membrane translocation of Akt.
23891720 2013 Mutually exclusive binding of APPL(PH) to BAR domain and Reptin regulates ?-catenin dependent transcriptional events.
23752268 2013 The functional interactome landscape of the human histone deacetylase family.
23414517 2013 A human skeletal muscle interactome centered on proteins involved in muscular dystrophies: LGMD interactome.
23291133 2012 [Expression and significance of Rab5a and APPL1 in breast cancer].
23246927 2013 Characterization and distribution of adaptor protein containing a PH domain, PTB domain and leucine zipper motif (APPL1) in Alzheimer's disease hippocampus: an immunohistochemical study.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23055524 2012 Membrane curvature protein exhibits interdomain flexibility and binds a small GTPase.
22814378 2012 N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.
22685329 2012 APPL1 regulates basal NF-?B activity by stabilizing NIK.
22685300 2012 Phosphorylation of adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain, and leucine zipper motif 1 (APPL1) at Ser430 mediates endoplasmic reticulum (ER) stress-induced insulin resistance in hepatocytes.
22379109 2012 The endosomal adaptor protein APPL1 impairs the turnover of leading edge adhesions to regulate cell migration.
22340213 2011 Genetic variability in adapter proteins with APPL1/2 is associated with the risk of coronary artery disease in type 2 diabetes mellitus in Chinese Han population.
22037462 2011 Adaptor protein containing PH domain, PTB domain and leucine zipper (APPL1) regulates the protein level of EGFR by modulating its trafficking.
21926268 2011 APPL1 counteracts obesity-induced vascular insulin resistance and endothelial dysfunction by modulating the endothelial production of nitric oxide and endothelin-1 in mice.
21835890 2011 APPL1 mediates adiponectin-induced LKB1 cytosolic localization through the PP2A-PKCzeta signaling pathway.
21666675 2011 Recognition of the F&H motif by the Lowe syndrome protein OCRL.
21645192 2011 Biochemical characterization of APPL endosomes: the role of annexin A2 in APPL membrane recruitment.
21562756 2011 Increased abundance of the adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain and leucine zipper motif (APPL1) in patients with obesity and type 2 diabetes: evidence for altered adiponectin signalling.
21320486 2011 Recruitment of APPL1 to ubiquitin-rich aggresomes in response to proteasomal impairment.
21291857 2011 Interactions between GIPC-APPL and GIPC-TRP1 regulate melanosomal protein trafficking and melanogenesis in human melanocytes.
21285318 2011 The adapter protein APPL1 links FSH receptor to inositol 1,4,5-trisphosphate production and is implicated in intracellular Ca(2+) mobilization.
21269460 2011 Initial characterization of the human central proteome.
21233288 2011 The PH domain proteins IPIP27A and B link OCRL1 to receptor recycling in the endocytic pathway.
20978232 2011 APPL1 mediates adiponectin-stimulated p38 MAPK activation by scaffolding the TAK1-MKK3-p38 MAPK pathway.
20875820 2010 Adiponectin receptor binding proteins--recent advances in elucidating adiponectin signalling pathways.
20814572 2010 APPL proteins FRET at the BAR: direct observation of APPL1 and APPL2 BAR domain-mediated interactions on cell membranes using FRET microscopy.
20600589 2010 Emerging roles for the FSH receptor adapter protein APPL1 and overlap of a putative 14-3-3? interaction domain with a canonical G-protein interaction site.
20484574 2010 Cdo interacts with APPL1 and activates Akt in myoblast differentiation.
20412119 2010 Rab5a overexpression promoting ovarian cancer cell proliferation may be associated with APPL1-related epidermal growth factor signaling pathway.
20133602 2010 Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1.
20095645 2010 Identification of phosphorylation sites within the signaling adaptor APPL1 by mass spectrometry.
20068231 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
19686092 2009 Functional characterization of the interactions between endosomal adaptor protein APPL1 and the NuRD co-repressor complex.
19520843 2009 Adiponectin activates AMP-activated protein kinase in muscle cells via APPL1/LKB1-dependent and phospholipase C/Ca2+/Ca2+/calmodulin-dependent protein kinase kinase-dependent pathways.
19433865 2009 Endosomal adaptor proteins APPL1 and APPL2 are novel activators of beta-catenin/TCF-mediated transcription.
19413330 2009 Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.
19056867 2009 Large-scale proteomics and phosphoproteomics of urinary exosomes.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18632660 2008 Adiponectin blocks interleukin-18-mediated endothelial cell death via APPL1-dependent AMP-activated protein kinase (AMPK) activation and IKK/NF-kappaB/PTEN suppression.
18581887 2008 [Association of variants in APPL1 gene with body fat and its distribution in Chinese patients with type 2 diabetic mellitus].
18570454 2008 Proteomic analysis of exosomes from human neural stem cells by flow field-flow fractionation and nanoflow liquid chromatography-tandem mass spectrometry.
18307981 2008 All known patient mutations in the ASH-RhoGAP domains of OCRL affect targeting and APPL1 binding.
18034774 2008 Membrane targeting by APPL1 and APPL2: dynamic scaffolds that oligomerize and bind phosphoinositides.
17848569 2007 The interaction of Akt with APPL1 is required for insulin-stimulated Glut4 translocation.
17765681 2007 A role of the Lowe syndrome protein OCRL in early steps of the endocytic pathway.
17581628 2007 Structure of the APPL1 BAR-PH domain and characterization of its interaction with Rab5.
17525332 2007 ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.
17502098 2007 Crystal structures of the BAR-PH and PTB domains of human APPL1.
17490420 2007 Genetic variation within the APPL locus is not associated with metabolic or inflammatory traits in a healthy White population.
17287464 2007 Adiponectin-induced endothelial nitric oxide synthase activation and nitric oxide production are mediated by APPL1 in endothelial cells.
17030088 2007 APPL1, APPL2, Akt2 and FOXO1a interact with FSHR in a potential signaling complex.
16959974 2006 The consensus coding sequences of human breast and colorectal cancers.
16751776 2006 A germline-specific class of small RNAs binds mammalian Piwi proteins.
16622416 2006 APPL1 binds to adiponectin receptors and mediates adiponectin signalling and function.
16273093 2006 A quantitative protein interaction network for the ErbB receptors using protein microarrays.
16189514 2005 Towards a proteome-scale map of the human protein-protein interaction network.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15345747 2004 Phosphoproteomic analysis of the developing mouse brain.
15302935 2004 Large-scale characterization of HeLa cell nuclear phosphoproteins.
15070827 2004 Human follicle-stimulating hormone (FSH) receptor interacts with the adaptor protein APPL1 in HEK 293 cells: potential involvement of the PI3K pathway in FSH signaling.
15016378 2004 APPL proteins link Rab5 to nuclear signal transduction via an endosomal compartment.
12621049 2003 APPL suppresses androgen receptor transactivation via potentiating Akt activity.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12168954 2002 Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones.
12011067 2002 Mediation of the DCC apoptotic signal by DIP13 alpha.
10718198 2000 Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro.
10490823 1999 Identification of a chromosome 3p14.3-21.1 gene, APPL, encoding an adaptor molecule that interacts with the oncoprotein-serine/threonine kinase AKT2.