The protein encoded by this gene has been shown to be involved in the regulation of cell proliferation, and in the crosstalk between the adiponectin signalling and insulin signalling pathways. The encoded protein binds many other proteins, including RAB5A, DCC, AKT2, PIK3CA, adiponectin receptors, and proteins of the NuRD/MeCP1 complex. This protein is found associated with end... See more...

Aliases for APPL1 Gene

Aliases for APPL1 Gene

  • Adaptor Protein, Phosphotyrosine Interacting With PH Domain And Leucine Zipper 1 2 3 5
  • DCC-Interacting Protein 13-Alpha 2 3 4
  • Adaptor Protein, Phosphotyrosine Interaction, PH Domain And Leucine Zipper Containing 1 2 3
  • Adapter Protein Containing PH Domain, PTB Domain And Leucine Zipper Motif 1 3 4
  • Dip13-Alpha 3 4
  • APPL 3 4
  • Adaptor Protein Containing PH Domain, PTB Domain And Leucine Zipper Motif 1 3
  • Signaling Adaptor Protein DIP13alpha 3
  • AKT2 Interactor 3
  • DIP13alpha 3
  • KIAA1428 4
  • MODY14 3
  • DIP13A 4

External Ids for APPL1 Gene

Previous GeneCards Identifiers for APPL1 Gene

  • GC09U990006
  • GC03P057237

Summaries for APPL1 Gene

Entrez Gene Summary for APPL1 Gene

  • The protein encoded by this gene has been shown to be involved in the regulation of cell proliferation, and in the crosstalk between the adiponectin signalling and insulin signalling pathways. The encoded protein binds many other proteins, including RAB5A, DCC, AKT2, PIK3CA, adiponectin receptors, and proteins of the NuRD/MeCP1 complex. This protein is found associated with endosomal membranes, but can be released by EGF and translocated to the nucleus. [provided by RefSeq, Jul 2008]

GeneCards Summary for APPL1 Gene

APPL1 (Adaptor Protein, Phosphotyrosine Interacting With PH Domain And Leucine Zipper 1) is a Protein Coding gene. Diseases associated with APPL1 include Maturity-Onset Diabetes Of The Young, Type 14 and Maturity-Onset Diabetes Of The Young. Among its related pathways are A-beta Signaling Pathways and Regulation by c-FLIP. Gene Ontology (GO) annotations related to this gene include identical protein binding and protein kinase B binding. An important paralog of this gene is APPL2.

UniProtKB/Swiss-Prot Summary for APPL1 Gene

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

Gene Wiki entry for APPL1 Gene

Additional gene information for APPL1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for APPL1 Gene

Genomics for APPL1 Gene

GeneHancer (GH) Regulatory Elements for APPL1 Gene

Promoters and enhancers for APPL1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around APPL1 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the APPL1 gene promoter:
  • AP-1
  • ATF-2
  • c-Jun
  • CUTL1
  • FOXO1
  • FOXO1a

Genomic Locations for APPL1 Gene

Genomic Locations for APPL1 Gene
chr3:57,227,726-57,278,105
(GRCh38/hg38)
Size:
50,380 bases
Orientation:
Plus strand
chr3:57,261,765-57,307,499
(GRCh37/hg19)
Size:
45,735 bases
Orientation:
Plus strand

Genomic View for APPL1 Gene

Genes around APPL1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
APPL1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for APPL1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for APPL1 Gene

Proteins for APPL1 Gene

  • Protein details for APPL1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UKG1-DP13A_HUMAN
    Recommended name:
    DCC-interacting protein 13-alpha
    Protein Accession:
    Q9UKG1
    Secondary Accessions:
    • Q9P2B9

    Protein attributes for APPL1 Gene

    Size:
    709 amino acids
    Molecular mass:
    79663 Da
    Quaternary structure:
    • Homodimer (PubMed:18034774). 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 (PubMed:15016378). Binds DCC and the catalytic domain of the inactive form of AKT2 through its PID domain (PubMed:10490823, PubMed:12011067). Binds PIK3CA and subunits of the NuRD/MeCP1 complex (PubMed:10490823, PubMed:15016378). Interacts with OCRL and INPP5B (PubMed:21666675, PubMed:17765681, PubMed:20133602, PubMed:21233288). Interacts with NTRK2 (By similarity). Interacts with APPL2; interaction is independent of follicle stimulating hormone stimulation; interaction is decreased by adiponectin in a time-dependent manner (PubMed:17030088, PubMed:18034774, PubMed:19661063). Forms a complex with APPL2 and RUVBL2 (PubMed:19433865). Forms a complex comprising APPL2, RUVBL2, CTNNB1, HDAC1 and HDAC2; interaction reduces interaction between CTNNB1, HDAC1, HDAC2 and RUVBL2 leading to the decrease of deacetylase activity of this complex; affects the recruitment of repressive complexes to the Wnt target genes (PubMed:19433865). Interacts with ANXA2 (PubMed:21645192). Interacts with TGFBR1; interaction is TGF beta dependent; mediates trafficking of the TGFBR1 from the endosomes to the nucleus via microtubules in a TRAF6-dependent manner (PubMed:26583432). Interacts with PRKCZ (PubMed:26583432). Interacts with PIK3R1 and APPL2 (By similarity). Interacts with ADIPOR1; ADIPOQ enhances this interaction; inhibites adiponectin-stimulated binding of APPL2 to ADIPOR1 (By similarity).

    Three dimensional structures from OCA and Proteopedia for APPL1 Gene

neXtProt entry for APPL1 Gene

Post-translational modifications for APPL1 Gene

  • Phosphorylation at Ser-410 by PKA severely impairs binding to OCRL.
  • Ubiquitination at Lys63, Lys66, and Lys581
  • Modification sites at PhosphoSitePlus

Other Protein References for APPL1 Gene

Antibody Products

  • Abcam antibodies for APPL1
  • Boster Bio Antibodies for APPL1

No data available for DME Specific Peptides for APPL1 Gene

Domains & Families for APPL1 Gene

Gene Families for APPL1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins

Suggested Antigen Peptide Sequences for APPL1 Gene

GenScript: Design optimal peptide antigens:
  • Adapter protein containing PH domain, PTB domain and leucine zipper motif 1 (DP13A_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9UKG1

UniProtKB/Swiss-Prot:

DP13A_HUMAN :
  • Overexpression of an N-terminal domain (residues 1-319) or a C-terminal region (residues 273-709) has a proapoptotic effect.
Domain:
  • Overexpression of an N-terminal domain (residues 1-319) or a C-terminal region (residues 273-709) has a proapoptotic effect.
  • The F&H motif, an approximately 12-13 amino-acid sequence centered around Phe and His residues, is essential for binding to OCRL and INPP5B.
genes like me logo Genes that share domains with APPL1: view

Function for APPL1 Gene

Molecular function for APPL1 Gene

UniProtKB/Swiss-Prot 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:26583432, PubMed:15016378, PubMed:26073777, PubMed:19661063, PubMed:10490823). 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:26073777, PubMed:19661063, PubMed:24879834). 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).
GENATLAS Biochemistry:
amyloid beta (A4) precursor protein-like 1

Phenotypes From GWAS Catalog for APPL1 Gene

Gene Ontology (GO) - Molecular Function for APPL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001786 phosphatidylserine binding IDA 18034774
GO:0005515 protein binding IPI 10490823
GO:0035091 phosphatidylinositol binding IDA 18034774
GO:0042802 identical protein binding IPI 17502098
GO:0042803 protein homodimerization activity IDA 18034774
genes like me logo Genes that share ontologies with APPL1: view
genes like me logo Genes that share phenotypes with APPL1: view

Human Phenotype Ontology for APPL1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for APPL1 Gene

MGI Knock Outs for APPL1:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for APPL1

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for APPL1 Gene

Localization for APPL1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for APPL1 Gene

Early endosome membrane; Peripheral membrane protein. Nucleus. Cytoplasm. Endosome. Cell projection, ruffle. Cytoplasmic vesicle, phagosome. Note=Early endosomal membrane-bound and nuclear. Translocated into the nucleus upon release from endosomal membranes following internalization of EGF. {ECO:0000269 PubMed:15016378}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for APPL1 gene
Compartment Confidence
plasma membrane 5
nucleus 5
endosome 5
cytosol 4
extracellular 1
cytoskeleton 1
mitochondrion 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Centrosome (1)
  • Mitotic spindle (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for APPL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001726 ruffle ISS --
GO:0005634 nucleus IDA,IEA 15016378
GO:0005737 cytoplasm IEA,IDA 19433865
GO:0005768 endosome IEA,IDA 26583432
GO:0005769 early endosome IEA,ISS --
genes like me logo Genes that share ontologies with APPL1: view

Pathways & Interactions for APPL1 Gene

genes like me logo Genes that share pathways with APPL1: view

Pathways by source for APPL1 Gene

SIGNOR curated interactions for APPL1 Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for APPL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006606 protein import into nucleus IDA 26583432
GO:0007049 cell cycle IEA --
GO:0007165 signal transduction TAS 10490823
GO:0007179 transforming growth factor beta receptor signaling pathway IMP 26583432
GO:0008283 cell proliferation IDA 15016378
genes like me logo Genes that share ontologies with APPL1: view

Drugs & Compounds for APPL1 Gene

(1) Drugs for APPL1 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(3) Additional Compounds for APPL1 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with APPL1: view

Transcripts for APPL1 Gene

mRNA/cDNA for APPL1 Gene

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for APPL1

Alternative Splicing Database (ASD) splice patterns (SP) for APPL1 Gene

No ASD Table

Relevant External Links for APPL1 Gene

GeneLoc Exon Structure for
APPL1
ECgene alternative splicing isoforms for
APPL1

Expression for APPL1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for APPL1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for APPL1 Gene

This gene is overexpressed in Lymph node (15.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for APPL1 Gene



Protein tissue co-expression partners for APPL1 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of APPL1 Gene:

APPL1

SOURCE GeneReport for Unigene cluster for APPL1 Gene:

Hs.476415

mRNA Expression by UniProt/SwissProt for APPL1 Gene:

Q9UKG1-DP13A_HUMAN
Tissue specificity: High levels in heart, ovary, pancreas and skeletal muscle.

Evidence on tissue expression from TISSUES for APPL1 Gene

  • Liver(4.4)
  • Nervous system(3.7)
  • Muscle(2.5)
  • Blood(2.3)
  • Heart(2.3)
  • Kidney(2.1)
  • Pancreas(2)
  • Skin(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for APPL1 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • nervous
  • reproductive
  • urinary
Regions:
Head and neck:
  • brain
  • ear
  • eye
  • head
Thorax:
  • heart
Abdomen:
  • kidney
  • pancreas
Pelvis:
  • penis
  • placenta
  • uterus
General:
  • blood vessel
  • peripheral nerve
  • peripheral nervous system
genes like me logo Genes that share expression patterns with APPL1: view

No data available for mRNA differential expression in normal tissues for APPL1 Gene

Orthologs for APPL1 Gene

This gene was present in the common ancestor of chordates.

Orthologs for APPL1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia APPL1 33 32
  • 99.91 (n)
OneToOne
cow
(Bos Taurus)
Mammalia APPL1 33 32
  • 94.44 (n)
OneToOne
dog
(Canis familiaris)
Mammalia APPL1 33 32
  • 94.26 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia APPL1 33
  • 94 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Appl1 17 33 32
  • 92.36 (n)
rat
(Rattus norvegicus)
Mammalia Appl1 32
  • 91.98 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia -- 33
  • 89 (a)
OneToMany
-- 33
  • 85 (a)
OneToMany
chicken
(Gallus gallus)
Aves APPL1 33 32
  • 81.92 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia APPL1 33
  • 89 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia appl1 32
  • 73.39 (n)
African clawed frog
(Xenopus laevis)
Amphibia MGC68986 32
zebrafish
(Danio rerio)
Actinopterygii appl1 33 32
  • 71.95 (n)
OneToOne
sea squirt
(Ciona savignyi)
Ascidiacea -- 33
  • 43 (a)
OneToMany
Species where no ortholog for APPL1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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 APPL1 Gene

ENSEMBL:
Gene Tree for APPL1 (if available)
TreeFam:
Gene Tree for APPL1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for APPL1: view image

Paralogs for APPL1 Gene

(1) SIMAP similar genes for APPL1 Gene using alignment to 3 proteins:

  • DP13A_HUMAN
  • C9JAB0_HUMAN
  • C9K0C4_HUMAN
genes like me logo Genes that share paralogs with APPL1: view

Variants for APPL1 Gene

Sequence variations from dbSNP and Humsavar for APPL1 Gene

SNP ID Clin Chr 03 pos Variation AA Info Type
rs796065047 pathogenic, Maturity-onset diabetes of the young, type 14, Maturity-onset diabetes of the young 14 (MODY14) [MIM:616511] 57,238,111(+) G/A coding_sequence_variant, missense_variant
rs869320673 pathogenic, Maturity-onset diabetes of the young, type 14 57,260,016(+) T/A coding_sequence_variant, stop_gained
VAR_035909 A breast cancer sample p.Glu643Gln
rs1000005961 -- 57,267,476(+) C/G/T intron_variant
rs1000009301 -- 57,265,737(+) TTTTTT/TTTTTTT intron_variant

Structural Variations from Database of Genomic Variants (DGV) for APPL1 Gene

Variant ID Type Subtype PubMed ID
esv3575575 CNV gain 25503493

Variation tolerance for APPL1 Gene

Residual Variation Intolerance Score: 24.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.18; 69.63% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for APPL1 Gene

Human Gene Mutation Database (HGMD)
APPL1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
APPL1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for APPL1 Gene

Disorders for APPL1 Gene

MalaCards: The human disease database

(29) MalaCards diseases for APPL1 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search APPL1 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

DP13A_HUMAN
  • Maturity-onset diabetes of the young 14 (MODY14) [MIM:616511]: 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. {ECO:0000269 PubMed:26073777}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for APPL1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with APPL1: view

No data available for Genatlas for APPL1 Gene

Publications for APPL1 Gene

  1. APPL1, APPL2, Akt2 and FOXO1a interact with FSHR in a potential signaling complex. (PMID: 17030088) Nechamen CA … Dias JA (Molecular and cellular endocrinology 2007) 2 3 4 23 56
  2. Identification of a chromosome 3p14.3-21.1 gene, APPL, encoding an adaptor molecule that interacts with the oncoprotein-serine/threonine kinase AKT2. (PMID: 10490823) Mitsuuchi Y … Testa JR (Oncogene 1999) 2 3 4 23 56
  3. Yin-Yang regulation of adiponectin signaling by APPL isoforms in muscle cells. (PMID: 19661063) Wang C … Dong LQ (The Journal of biological chemistry 2009) 3 4 23 56
  4. Endosomal adaptor proteins APPL1 and APPL2 are novel activators of beta-catenin/TCF-mediated transcription. (PMID: 19433865) Rashid S … Miaczynska M (The Journal of biological chemistry 2009) 3 4 23 56
  5. Membrane targeting by APPL1 and APPL2: dynamic scaffolds that oligomerize and bind phosphoinositides. (PMID: 18034774) Chial HJ … Chen YQ (Traffic (Copenhagen, Denmark) 2008) 3 4 23 56

Products for APPL1 Gene

Sources for APPL1 Gene