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APPL1 Gene(Protein Coding)

Adaptor Protein, Phosphotyrosine Interacting With PH Domain And Leucine Zipper 1

GCID:
GC03P057227
GIFtS:
63
Genes Participants
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Aliases for APPL1 Gene

Aliases for APPL1 Gene

  • Adaptor Protein, Phosphotyrosine Interacting With PH Domain And Leucine Zipper 1 2 3 5
  • 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
  • DCC-Interacting Protein 13-Alpha 2 3
  • 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 Dimerization of procaspase-8. 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 for APPL1 Gene

  • Adapter protein that interacts with proteins involved in different cellular signaling pathways. Required for the regulation of cell proliferation in response to extracellular signals from an early endosomal compartment. Links Rab5 to nuclear signal transduction. Involved in the regulation of the insulin receptor signaling pathway.

Gene Wiki entry for APPL1 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for APPL1 Gene

Genomics for APPL1 Gene

Products:

  1. Regulatory Element

Regulatory Elements for APPL1 Gene

Enhancers for APPL1 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH03G058172 1.9 FANTOM5 Ensembl ENCODE dbSUPER 11.6 +947.4 947421 4.6 HDGF FOXA2 PKNOX1 ARNT MLX CREB3L1 ARID4B DMAP1 YY1 SLC30A9 FLNB DNASE1L3 FLNB-AS1 RPP14 APPL1 HTD2 DENND6A ABHD6 KCTD6 ENSG00000283148
GH03G057947 1.9 FANTOM5 Ensembl ENCODE dbSUPER 10.8 +723.1 723066 6.6 HDGF FOXA2 PKNOX1 ZFP64 ARID4B SIN3A ZNF766 FOS SP5 ZNF592 FLNB-AS1 FLNB DENND6A KCTD6 APPL1 ABHD6 DNASE1L3 SLMAP PXK GC03P057941
GH03G058073 1.6 Ensembl ENCODE dbSUPER 10.8 +846.5 846455 2.4 HNRNPUL1 FOXA2 PKNOX1 MLX ARID4B SIN3A DMAP1 FEZF1 YY1 SLC30A9 DENND6A APPL1 FLNB-AS1 PXK GC03P058010
GH03G058160 1.3 ENCODE dbSUPER 11.6 +935.9 935881 5.5 HDGF PKNOX1 ATF1 FOXA2 CREB3L1 ARNT SIN3A YY1 ZNF766 GATA2 FLNB-AS1 FLNB DNASE1L3 APPL1 DENND6A ABHD6 RPP14 GC03P058010
GH03G057127 1.4 Ensembl ENCODE dbSUPER 10.6 -97.6 -97629 5.4 ARNT ZSCAN4 ARID4B SIN3A RAD21 ETS1 ZEB1 GLIS2 SCRT2 ZNF263 IL17RD ARHGEF3 APPL1 HESX1 ASB14 DNAH12 SLMAP RPL19P2 PIR43010
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around APPL1 on UCSC Golden Path with GeneCards custom track

Promoters for APPL1 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000153074 463 2001 PKNOX1 FOXA2 ARID4B SIN3A DMAP1 YY1 SLC30A9 ZNF143 FOS SP3

Transcription factor binding sites by QIAGEN in the APPL1 gene promoter:

Genomic Location for APPL1 Gene

Chromosome:
3
Start:
57,227,737 bp from pter
End:
57,273,471 bp from pter
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 Structure • Gene Density

RefSeq DNA sequence for APPL1 Gene

Proteins for APPL1 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • 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:
    • 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 DCC and the catalytic domain of the inactive form of AKT2 through its PID domain. Binds PIK3CA and subunits of the NuRD/MeCP1 complex. Interacts with OCRL and INPP5B. Interacts with NTRK2 (By similarity).

    Three dimensional structures from OCA and Proteopedia for APPL1 Gene

neXtProt entry for APPL1 Gene

Protein Expression for APPL1 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

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

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for APPL1 (APPL)
  • Cloud-Clone Corp. Antibodies for APPL1

No data available for DME Specific Peptides for APPL1 Gene

Domains & Families for APPL1 Gene

Gene Families for APPL1 Gene

HGNC:

Protein Domains for APPL1 Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for APPL1 Gene

GenScript: Design optimal peptide antigens:

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

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line
  7. Flow Cytometry

Molecular function for APPL1 Gene

GENATLAS Biochemistry:
amyloid beta (A4) precursor protein-like 1
UniProtKB/Swiss-Prot Function:
Adapter protein that interacts with proteins involved in different cellular signaling pathways. Required for the regulation of cell proliferation in response to extracellular signals from an early endosomal compartment. Links Rab5 to nuclear signal transduction. Involved in the regulation of the insulin receptor signaling pathway.

Gene Ontology (GO) - Molecular Function for APPL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 10490823
GO:0042802 identical protein binding IPI 17581628
GO:0043422 protein kinase B binding IPI 17848569
genes like me logo Genes that share ontologies with APPL1: view
genes like me logo Genes that share phenotypes with APPL1: view

Animal Models for APPL1 Gene

MGI Knock Outs for APPL1:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for APPL1

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , 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. 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
extracellular 5
nucleus 5
cytosol 5
endosome 5
plasma membrane 1
cytoskeleton 1
mitochondrion 1

Gene Ontology (GO) - Cellular Components for APPL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA,IDA 15016378
GO:0005737 cytoplasm IC 10490823
GO:0005768 endosome IEA --
GO:0005769 early endosome IEA,ISS --
GO:0005829 cytosol IDA 17848569
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

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:0007049 cell cycle IEA --
GO:0007165 signal transduction TAS 10490823
GO:0008283 cell proliferation IDA 15016378
GO:0008286 insulin receptor signaling pathway IMP,TAS 17848569
GO:0046324 regulation of glucose import IMP 17848569
genes like me logo Genes that share ontologies with APPL1: view

Drugs & Compounds for APPL1 Gene

Products:

  1. Drug

(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

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone
  5. Flow Cytometry

mRNA/cDNA for APPL1 Gene

(2) REFSEQ mRNAs :
(7) Additional mRNA sequences :
(216) Selected AceView cDNA sequences:
(8) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for APPL1 Gene

Adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 1:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for APPL1

Flow Cytometry Products

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

Products:

  1. Primer

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

mRNA expression in normal human tissues for APPL1 Gene
mRNA expression by BioGPS for APPL1 GenemRNA expression by GTEx 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, PaxDb, 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)
  • 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
Organs:
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

Primer Products

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 35 34
  • 99.91 (n)
 OneToOne
cow
(Bos Taurus)
 Mammalia APPL1 34 35
  • 94.44 (n)
dog
(Canis familiaris)
 Mammalia APPL1 34 35
  • 94.26 (n)
oppossum
(Monodelphis domestica)
 Mammalia APPL1 35
  • 94 (a)
 OneToOne
mouse
(Mus musculus)
 Mammalia Appl1 16 35 34
  • 92.36 (n)
rat
(Rattus norvegicus)
 Mammalia Appl1 34
  • 91.98 (n)
platypus
(Ornithorhynchus anatinus)
 Mammalia -- 35
  • 89 (a)
 OneToMany
-- 35
  • 85 (a)
 OneToMany
chicken
(Gallus gallus)
 Aves APPL1 34 35
  • 81.92 (n)
lizard
(Anolis carolinensis)
 Reptilia APPL1 35
  • 89 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia appl1 34
  • 73.39 (n)
African clawed frog
(Xenopus laevis)
 Amphibia MGC68986 34
zebrafish
(Danio rerio)
 Actinopterygii appl1 34 35
  • 71.95 (n)
sea squirt
(Ciona savignyi)
 Ascidiacea -- 35
  • 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)

Paralogs for APPL1 Gene

Paralogs for APPL1 Gene

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

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 Sequence Context AA Info Type
rs796065047 Pathogenic, Maturity-onset diabetes of the young 14 (MODY14) [MIM:616511] 57,238,111(+) TTATA(A/G)ATGAG reference, missense
VAR_035909 A breast cancer sample
rs869320673 Pathogenic 57,260,016(+) CTGTT(A/T)AAAGT reference, stop-gained
rs1000005961 -- 57,267,476(+) TTCCT(C/T)GTAGG intron-variant
rs1000009301 -- 57,265,736(+) ATGCC(-/T)TTTTT 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)

Relevant External Links for APPL1 Gene

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

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

Disorders for APPL1 Gene

MalaCards: The human disease database

(26) MalaCards diseases for APPL1 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
maturity-onset diabetes of the young, type 14
  • maturity-onset diabetes of the young type 14
maturity-onset diabetes of the young
  • mason-type diabetes
myopathy of extraocular muscle
  • myopathy of extraocular muscles
skin lipoma
  • cutaneous lipoma
deafness, autosomal recessive 65
  • autosomal recessive nonsyndromic deafness 65
- 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.

Relevant External Links for APPL1

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

No data available for Genatlas for APPL1 Gene

Publications for APPL1 Gene

  1. 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 J.R. (Oncogene 1999) 2 3 4 22 64
  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 22 64
  3. Genetic variation within the APPL locus is not associated with metabolic or inflammatory traits in a healthy White population. (PMID: 17490420) Staiger H. … HAoring H.U. (Diabet. Med. 2007) 3 22 46 64
  4. APPL proteins link Rab5 to nuclear signal transduction via an endosomal compartment. (PMID: 15016378) Miaczynska M. … Zerial M. (Cell 2004) 3 4 22 64
  5. Loss-of-Function Mutations in APPL1 in Familial Diabetes Mellitus. (PMID: 26073777) Prudente S. … Doria A. (Am. J. Hum. Genet. 2015) 3 4 64

Products for APPL1 Gene

  • Addgene plasmids for APPL1

Sources for APPL1 Gene

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