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APPL1 adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 [ Homo sapiens (human) ]

Gene ID: 26060, updated on 3-Nov-2024

Summary

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Official Symbol
APPL1provided by HGNC
Official Full Name
adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1provided by HGNC
Primary source
HGNC:HGNC:24035
See related
Ensembl:ENSG00000157500 MIM:604299; AllianceGenome:HGNC:24035
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
APPL; MODY14; DIP13alpha
Summary
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]
Expression
Ubiquitous expression in thyroid (RPKM 14.2), ovary (RPKM 12.3) and 25 other tissues See more
Orthologs
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Genomic context

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See APPL1 in Genome Data Viewer
Location:
3p14.3
Exon count:
23
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (57227729..57273471)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (57267997..57313740)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (57261757..57307499)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene interleukin 17 receptor D Neighboring gene uncharacterized LOC105377101 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:57192947-57193632 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:57193633-57194316 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14478 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14479 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:57218732-57218927 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr3:57233699-57234296 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14480 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19986 Neighboring gene HESX homeobox 1 Neighboring gene uncharacterized LOC105377102 Neighboring gene MPRA-validated peak4664 silencer Neighboring gene uncharacterized LOC124909384 Neighboring gene MPRA-validated peak4666 silencer Neighboring gene ankyrin repeat and SOCS box containing 14 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:57358479-57359002 Neighboring gene dynein axonemal heavy chain 12 Neighboring gene NANOG hESC enhancer GRCh37_chr3:57372950-57373478 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:57402873-57403048 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:57434949-57435862 Neighboring gene small nucleolar RNA U13

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Dysfunctional APPL1-Mediated Epigenetic Regulation in Diabetic Vascular Injury.
    Title: Dysfunctional APPL1-Mediated Epigenetic Regulation in Diabetic Vascular Injury.
  2. Reduced APPL1 impairs osteogenic differentiation of mesenchymal stem cells by facilitating MGP expression to disrupt the BMP2 pathway in osteoporosis.
    Title: Reduced APPL1 impairs osteogenic differentiation of mesenchymal stem cells by facilitating MGP expression to disrupt the BMP2 pathway in osteoporosis.
  3. APPL1 Is a Prognostic Biomarker and Correlated with Treg Cell Infiltration via Oxygen-Consuming Metabolism in Renal Clear Cell Carcinoma.
    Title: APPL1 Is a Prognostic Biomarker and Correlated with Treg Cell Infiltration via Oxygen-Consuming Metabolism in Renal Clear Cell Carcinoma.
  4. Aberrant protein expression of Appl1, Sortilin and Syndecan-1 during the biological progression of prostate cancer.
    Title: Aberrant protein expression of Appl1, Sortilin and Syndecan-1 during the biological progression of prostate cancer.
  5. Impairment of APPL1/Myoferlin facilitates adipogenic differentiation of mesenchymal stem cells by blocking autophagy flux in osteoporosis.
    Title: Impairment of APPL1/Myoferlin facilitates adipogenic differentiation of mesenchymal stem cells by blocking autophagy flux in osteoporosis.
  6. Rapid whole cell imaging reveals a calcium-APPL1-dynein nexus that regulates cohort trafficking of stimulated EGF receptors.
    Title: Rapid whole cell imaging reveals a calcium-APPL1-dynein nexus that regulates cohort trafficking of stimulated EGF receptors.
  7. APPL1 as an important regulator of insulin and adiponectin-signaling pathways in the PCOS: A narrative review.
    Title: APPL1 as an important regulator of insulin and adiponectin-signaling pathways in the PCOS: A narrative review.
  8. we demonstrate a novel role for the interaction between APPL1 and Rab5 in governing crosstalk between signaling and trafficking pathways on endosomes to affect cancer cell migration
    Title: α5β1 integrin trafficking and Rac activation are regulated by APPL1 in a Rab5-dependent manner to inhibit cell migration.
  9. Present study demonstrated that expression of APPL1 protein and mRNA was upregulated in gastric carcinoma (GC) tissues and cell lines. The expression of APPL1 in GC was statistically associated with metastasis stage. Overexpression of APPL1 promotes invasion and metastasis of gastric cancer cells and the underlying molecular mechanism may facilitate EMT via Akt2 phosphorylation.
    Title: APPL1 promotes the migration of gastric cancer cells by regulating Akt2 phosphorylation.
  10. Decreased expression of APPL1 is associated with polycystic ovary syndrome.
    Title: Evidence for decreased expression of APPL1 associated with reduced insulin and adiponectin receptors expression in PCOS patients.
Submit: New GeneRIF Correction See all GeneRIFs (60)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See Variation Viewer (GRCh37.p13)

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables beta-tubulin binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables phosphatidylinositol binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables phosphatidylserine binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein homodimerization activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein kinase B binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables protein kinase B binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein-containing complex binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in adiponectin-activated signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cellular response to hepatocyte growth factor stimulus ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in insulin receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in insulin receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in insulin receptor signaling pathway TAS
Traceable Author Statement
more info
 PubMed 
involved_in maintenance of synapse structure IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in maintenance of synapse structure IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of Fc-gamma receptor signaling pathway involved in phagocytosis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of D-glucose import IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of cytokine production involved in inflammatory response ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of macropinocytosis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of melanin biosynthetic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein import into nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of D-glucose import IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of G1/S transition of mitotic cell cycle IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of fibroblast migration ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of innate immune response ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of protein localization to plasma membrane IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of toll-like receptor 4 signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in signal transduction TAS
Traceable Author Statement
more info
 PubMed 
involved_in signaling IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in transforming growth factor beta receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoplasmic vesicle IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol IDA
Inferred from Direct Assay
more info
 PubMed 
located_in early endosome IDA
Inferred from Direct Assay
more info
 PubMed 
located_in early endosome ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in early endosome membrane IEA
Inferred from Electronic Annotation
more info
  
located_in early phagosome ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in endosome IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in endosome membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in endosome membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in endosome membrane TAS
Traceable Author Statement
more info
  
located_in extracellular exosome HDA PubMed 
is_active_in glutamatergic synapse IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in glutamatergic synapse IMP
Inferred from Mutant Phenotype
more info
 PubMed 
located_in intracellular vesicle IDA
Inferred from Direct Assay
more info
 PubMed 
located_in macropinosome ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in postsynapse IEA
Inferred from Electronic Annotation
more info
  
located_in presynapse IEA
Inferred from Electronic Annotation
more info
  
located_in ruffle ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in vesicle membrane IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
DCC-interacting protein 13-alpha
Names
AKT2 interactor
adapter protein containing PH domain, PTB domain and leucine zipper motif 1
adaptor protein containing pH domain, PTB domain and leucine zipper motif 1
adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 1
dip13-alpha
signaling adaptor protein DIP13alpha

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_047003.1 RefSeqGene

    Range
    4993..50735
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_012096.3 → NP_036228.1  DCC-interacting protein 13-alpha

    See identical proteins and their annotated locations for NP_036228.1

    Status: REVIEWED

    Source sequence(s)
    AC093928, AF169797, BC028599
    Consensus CDS
    CCDS2882.1
    UniProtKB/Swiss-Prot
    Q9P2B9, Q9UKG1
    UniProtKB/TrEMBL
    B4DQX8
    Related
    ENSP00000288266.3, ENST00000288266.8
    Conserved Domains (3) summary
    cd07631
    Location:20 → 234
    BAR_APPL1; The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing 1
    cd13158
    Location:490 → 625
    PTB_APPL; Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif (APPL; also called DCC-interacting protein (DIP)-13alpha) Phosphotyrosine-binding (PTB) domain
    cd13247
    Location:252 → 376
    BAR-PH_APPL; Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif Bin1/amphiphysin/Rvs167 (BAR)-Pleckstrin homology (PH) domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    57227729..57273471
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011533583.4 → XP_011531885.1  DCC-interacting protein 13-alpha isoform X1

    UniProtKB/TrEMBL
    B4DQX8
    Conserved Domains (3) summary
    cd07631
    Location:3 → 217
    BAR_APPL1; The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing 1
    cd13158
    Location:473 → 608
    PTB_APPL; Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif (APPL; also called DCC-interacting protein (DIP)-13alpha) Phosphotyrosine-binding (PTB) domain
    cd13247
    Location:235 → 359
    BAR-PH_APPL; Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif Bin1/amphiphysin/Rvs167 (BAR)-Pleckstrin homology (PH) domain

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060927.1 Alternate T2T-CHM13v2.0

    Range
    57267997..57313740
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054346145.1 → XP_054202120.1  DCC-interacting protein 13-alpha isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9UKG1.1 GenPept UniProtKB/Swiss-Prot:Q9UKG1

Gene LinkOut

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