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

Summary

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: mouse all
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Genomic context

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_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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?

Dysfunctional APPL1-Mediated Epigenetic Regulation in Diabetic Vascular Injury.
Title: Dysfunctional APPL1-Mediated Epigenetic Regulation in Diabetic Vascular Injury.
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.
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.
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.
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.
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.
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.
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.
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.
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

Associated conditions

Description	Tests
Maturity-onset diabetes of the young type 14 MedGen: C4225299 OMIM: 616511 GeneReviews: Maturity-Onset Diabetes of the Young Overview	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S2921 (e-PCR)
- UniSTS:152074

D8S2278 (e-PCR)
- UniSTS:473906

D8S2279 (e-PCR)
- UniSTS:473907

D3S2814E (e-PCR)
- UniSTS:150850

D11S3114 (e-PCR)
- UniSTS:152207

SHGC-77071 (e-PCR)
- UniSTS:4301

RH99000 (e-PCR)
- UniSTS:83920

G38326 (e-PCR)
- UniSTS:6873

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 more info	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

NG_047003.1 RefSeqGene

Range

4993..50735

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

NC_000003.12 Reference GRCh38.p14 Primary Assembly

Range

57227729..57273471

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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