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Aliases for APPL2 Gene

Aliases for APPL2 Gene

  • Adaptor Protein, Phosphotyrosine Interacting With PH Domain And Leucine Zipper 2 2 3
  • Adaptor Protein, Phosphotyrosine Interaction, PH Domain And Leucine Zipper Containing 2 2 3 5
  • Adapter Protein Containing PH Domain, PTB Domain And Leucine Zipper Motif 2 3 4
  • DIP13B 3 4
  • DCC-Interacting Protein 13-Beta 2
  • DIP13 Beta 3
  • Dip13-Beta 4

External Ids for APPL2 Gene

Previous GeneCards Identifiers for APPL2 Gene

  • GC12M104091
  • GC12M105568
  • GC12M102626

Summaries for APPL2 Gene

Entrez Gene Summary for APPL2 Gene

  • 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. [provided by RefSeq, Oct 2011]

GeneCards Summary for APPL2 Gene

APPL2 (Adaptor Protein, Phosphotyrosine Interacting With PH Domain And Leucine Zipper 2) is a Protein Coding gene. Diseases associated with APPL2 include Phelan-Mcdermid Syndrome. Among its related pathways are EGFR1 Signaling Pathway. An important paralog of this gene is APPL1.

UniProtKB/Swiss-Prot for APPL2 Gene

  • Required for the regulation of cell proliferation in response to extracellular signals mediated by an early endosomal compartment. Links Rab5 to nuclear signal transduction.

Gene Wiki entry for APPL2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for APPL2 Gene

Genomics for APPL2 Gene

Regulatory Elements for APPL2 Gene

Enhancers for APPL2 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around APPL2 on UCSC Golden Path with GeneCards custom track

Promoters for APPL2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around APPL2 on UCSC Golden Path with GeneCards custom track

Genomic Location for APPL2 Gene

105,173,296 bp from pter
105,236,238 bp from pter
62,943 bases
Minus strand

Genomic View for APPL2 Gene

Genes around APPL2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
APPL2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for APPL2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for APPL2 Gene

Proteins for APPL2 Gene

  • Protein details for APPL2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    DCC-interacting protein 13-beta
    Protein Accession:
    Secondary Accessions:
    • B7Z411
    • B7Z4B0
    • F5GZG0
    • F8W1P5
    • Q8N4R7
    • Q9NVL2

    Protein attributes for APPL2 Gene

    664 amino acids
    Molecular mass:
    74493 Da
    Quaternary structure:
    • Binds RAB5A/Rab5 through an N-terminal domain. This interaction is essential for its recruitment to endosomal membranes as well as its role in cell proliferation. Binds subunits of the NuRD/MeCP1 complex.

    Three dimensional structures from OCA and Proteopedia for APPL2 Gene

    Alternative splice isoforms for APPL2 Gene


neXtProt entry for APPL2 Gene

Proteomics data for APPL2 Gene at MOPED

Post-translational modifications for APPL2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for APPL2 Gene

Domains & Families for APPL2 Gene

Gene Families for APPL2 Gene

Protein Domains for APPL2 Gene

Suggested Antigen Peptide Sequences for APPL2 Gene

Graphical View of Domain Structure for InterPro Entry



  • Contains 1 PH domain.
  • Contains 1 PH domain.
  • Contains 1 PID domain.
genes like me logo Genes that share domains with APPL2: view

Function for APPL2 Gene

Molecular function for APPL2 Gene

UniProtKB/Swiss-Prot Function:
Required for the regulation of cell proliferation in response to extracellular signals mediated by an early endosomal compartment. Links Rab5 to nuclear signal transduction.
genes like me logo Genes that share phenotypes with APPL2: view

Animal Model Products

miRNA for APPL2 Gene

miRTarBase miRNAs that target APPL2

No data available for Enzyme Numbers (IUBMB) , Gene Ontology (GO) - Molecular Function , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for APPL2 Gene

Localization for APPL2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for APPL2 Gene

Early endosome membrane; Peripheral membrane protein. Nucleus. Note=Early endosomal membrane-bound and nuclear. Translocated into the nucleus upon release from endosomal membranes following internalization of EGF.

Subcellular locations from

Jensen Localization Image for APPL2 Gene COMPARTMENTS Subcellular localization image for APPL2 gene
Compartment Confidence
endosome 5
extracellular 5
nucleus 5
cytosol 2

Gene Ontology (GO) - Cellular Components for APPL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IC 15016378
GO:0010008 endosome membrane IDA 15016378
GO:0016581 colocalizes_with NuRD complex IDA 15016378
GO:0070062 extracellular exosome IDA 19056867
genes like me logo Genes that share ontologies with APPL2: view

Pathways & Interactions for APPL2 Gene

SuperPathways for APPL2 Gene

Superpath Contained pathways
1 EGFR1 Signaling Pathway
genes like me logo Genes that share pathways with APPL2: view

Pathways by source for APPL2 Gene

1 BioSystems pathway for APPL2 Gene

Gene Ontology (GO) - Biological Process for APPL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0008283 cell proliferation IDA 15016378
genes like me logo Genes that share ontologies with APPL2: view

No data available for SIGNOR curated interactions for APPL2 Gene

Drugs & Compounds for APPL2 Gene

No Compound Related Data Available

Transcripts for APPL2 Gene

Unigene Clusters for APPL2 Gene

Adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 2:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for APPL2 Gene

No ASD Table

Relevant External Links for APPL2 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for APPL2 Gene

mRNA expression in normal human tissues for APPL2 Gene

Protein differential expression in normal tissues from HIPED for APPL2 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (22.0), Heart (12.0), and Platelet (9.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for APPL2 Gene

SOURCE GeneReport for Unigene cluster for APPL2 Gene Hs.506603

mRNA Expression by UniProt/SwissProt for APPL2 Gene

Tissue specificity: High levels in brain, heart, kidney and skeletal muscle.
genes like me logo Genes that share expression patterns with APPL2: view

Protein tissue co-expression partners for APPL2 Gene

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for APPL2 Gene

Orthologs for APPL2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for APPL2 Gene

Organism Taxonomy Gene Similarity Type Details
(Bos Taurus)
Mammalia APPL2 35
  • 91.34 (n)
  • 93.66 (a)
APPL2 36
  • 94 (a)
(Canis familiaris)
Mammalia APPL2 35
  • 89.68 (n)
  • 94.11 (a)
APPL2 36
  • 94 (a)
(Mus musculus)
Mammalia Appl2 35
  • 87.92 (n)
  • 92.75 (a)
Appl2 16
Appl2 36
  • 93 (a)
(Pan troglodytes)
Mammalia APPL2 35
  • 99.6 (n)
  • 99.7 (a)
APPL2 36
  • 100 (a)
(Rattus norvegicus)
Mammalia Appl2 35
  • 87.31 (n)
  • 92.45 (a)
(Monodelphis domestica)
Mammalia APPL2 36
  • 89 (a)
(Ornithorhynchus anatinus)
Mammalia APPL2 36
  • 89 (a)
(Gallus gallus)
Aves APPL2 35
  • 77.25 (n)
  • 84.35 (a)
-- 36
  • 86 (a)
-- 36
  • 79 (a)
(Anolis carolinensis)
Reptilia APPL2 36
  • 82 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia appl2 35
  • 72.21 (n)
  • 76.31 (a)
(Danio rerio)
Actinopterygii appl2 35
  • 66.72 (n)
  • 70.84 (a)
appl2 36
  • 69 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 39 (a)
Species with no ortholog for APPL2:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for APPL2 Gene

Gene Tree for APPL2 (if available)
Gene Tree for APPL2 (if available)

Paralogs for APPL2 Gene

Paralogs for APPL2 Gene

(1) SIMAP similar genes for APPL2 Gene using alignment to 7 proteins:

genes like me logo Genes that share paralogs with APPL2: view

Variants for APPL2 Gene

Sequence variations from dbSNP and Humsavar for APPL2 Gene

SNP ID Clin Chr 12 pos Sequence Context AA Info Type
rs2272495 - 105,190,099(-) CAAAG(C/T)AACAG reference, missense
rs1982308 -- 105,194,876(+) GGATA(C/T)ATAAA intron-variant
rs7133728 -- 105,218,948(+) CACAG(A/C)GGTTT intron-variant
rs8015 -- 105,173,353(-) CAACA(A/C/G)ACTAT utr-variant-3-prime
rs9143 -- 105,173,833(-) TCTCA(C/T)AATTG utr-variant-3-prime

Structural Variations from Database of Genomic Variants (DGV) for APPL2 Gene

Variant ID Type Subtype PubMed ID
nsv832506 CNV Gain 17160897
nsv899499 CNV Loss 21882294

Variation tolerance for APPL2 Gene

Residual Variation Intolerance Score: 84.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.51; 77.64% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for APPL2 Gene

Human Gene Mutation Database (HGMD)

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for APPL2 Gene

Disorders for APPL2 Gene

MalaCards: The human disease database

(1) MalaCards diseases for APPL2 Gene - From: GeneCards

Disorder Aliases PubMed IDs
phelan-mcdermid syndrome
  • 22q13.3 deletion syndrome
- elite association - COSMIC cancer census association via MalaCards
Search APPL2 in MalaCards View complete list of genes associated with diseases


  • 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 (PubMed:11431708). {ECO:0000269 PubMed:11431708}.

Relevant External Links for APPL2

Atlas of Genetics and Cytogenetics in Oncology and Haematology:
genes like me logo Genes that share disorders with APPL2: view

No data available for Genatlas for APPL2 Gene

Publications for APPL2 Gene

  1. Disruption of the ProSAP2 gene in a t(12;22)(q24.1;q13.3) is associated with the 22q13.3 deletion syndrome. (PMID: 11431708) Bonaglia M.C. … Zuffardi O. (Am. J. Hum. Genet. 2001) 2 3 4 23 67
  2. APPL1, APPL2, Akt2 and FOXO1a interact with FSHR in a potential signaling complex. (PMID: 17030088) Nechamen C.A. … Dias J.A. (Mol. Cell. Endocrinol. 2007) 2 3 23
  3. Endosomal adaptor proteins APPL1 and APPL2 are novel activators of beta-catenin/TCF-mediated transcription. (PMID: 19433865) Rashid S. … Miaczynska M. (J. Biol. Chem. 2009) 3 23
  4. Phospho-tyrosine dependent protein-protein interaction network. (PMID: 25814554) Grossmann A. … Stelzl U. (Mol. Syst. Biol. 2015) 3
  5. Temporal proteomics of NGF-TrkA signaling identifies an inhibitory role for the E3 ligase Cbl-b in neuroblastoma cell differentiation. (PMID: 25921289) Emdal K.B. … Olsen J.V. (Sci Signal 2015) 3

Products for APPL2 Gene

Sources for APPL2 Gene