Appl1 adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Appl1provided by RGD
Official Full Name: adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1provided by RGD
Primary source: RGD:1309388
See related: EnsemblRapid:ENSRNOG00000013574 AllianceGenome:RGD:1309388
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: RGD1309388
Summary: Predicted to enable several functions, including beta-tubulin binding activity; phospholipid binding activity; and protein homodimerization activity. Predicted to be involved in several processes, including cell surface receptor signaling pathway; positive regulation of biosynthetic process; and regulation of endocytosis. Is active in postsynapse and presynapse. Human ortholog(s) of this gene implicated in maturity-onset diabetes of the young type 14. Orthologous to human APPL1 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Biased expression in Brain (RPKM 237.3), Thymus (RPKM 154.1) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 16p16

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	16	NC_086034.1 (2125234..2173457, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	16	NC_051351.1 (2118503..2166741, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	16	NC_005115.4 (2560103..2602035, complement)

Chromosome 16 - NC_086034.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

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.
LncRNA CEBPA-AS1 alleviates cerebral ischemia-reperfusion injury by sponging miR-340-5p regulating APPL1/LKB1/AMPK pathway.
Title: LncRNA CEBPA-AS1 alleviates cerebral ischemia-reperfusion injury by sponging miR-340-5p regulating APPL1/LKB1/AMPK pathway.
PTB domain and leucine zipper motif 1 (APPL1) inhibits myocardial ischemia/hypoxia-reperfusion injury via inactivation of apoptotic protease activating factor-1 (APAF-1)/Caspase9 signaling pathway.
Title: PTB domain and leucine zipper motif 1 (APPL1) inhibits myocardial ischemia/hypoxia-reperfusion injury via inactivation of apoptotic protease activating factor-1 (APAF-1)/Caspase9 signaling pathway.
APPL1 may be a key regulator of insulin resistance in skeletal muscle, and Resistance training may be an important physiological treatment increasing APPL1 expression, which is attenuated in T2 Diabetes.
Title: Resistance training recovers attenuated APPL1 expression and improves insulin-induced Akt signal activation in skeletal muscle of type 2 diabetic rats.
APPL1 gates PI3K activation at the plasma membrane upon long-term potentiation induction.
Title: APPL1 gates long-term potentiation through its plekstrin homology domain.
AdipoR1 and the adaptor protein APPL1 mediated the protective effects of gAcrp. In addition, the function of adiponectin and phosphorylation of AMPK were prominently diminished by inhibition of PI3K.
Title: AdipoR1/APPL1 potentiates the protective effects of globular adiponectin on angiotensin II-induced cardiac hypertrophy and fibrosis in neonatal rat atrial myocytes and fibroblasts.
Adiponectin increased colocalization of actin and APPL1.
Title: Adiponectin stimulates Rho-mediated actin cytoskeleton remodeling and glucose uptake via APPL1 in primary cardiomyocytes.
a role of adiponectin-stimulated APPL1-AMPK signaling in cell migration in cardiac fibroblasts
Title: Adiponectin mediated APPL1-AMPK signaling induces cell migration, MMP activation, and collagen remodeling in cardiac fibroblasts.
In mesenteric resistance arteries downregulation of APPL1 is inhibited following antidiabetic treatment of diabetic fatty rats.
Title: Antidiabetic treatment restores adiponectin serum levels and APPL1 expression, but does not improve adiponectin-induced vasodilation and endothelial dysfunction in Zucker diabetic fatty rats.
Hypoadiponectinemia induces APPL1 downregulation in the resistance vessels, contributing to the development of vascular insulin resistance in vascular endothelium in normotensive spontaneously hypertensive rats.
Title: A novel mechanism for vascular insulin resistance in normotensive young SHRs: hypoadiponectinemia and resultant APPL1 downregulation.

Submit: New GeneRIF Correction See all GeneRIFs (14)

General gene information

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Markers

RH129512 (e-PCR)
- UniSTS:212815

RH139821 (e-PCR)
- UniSTS:221905

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables beta-tubulin binding	ISO Inferred from Sequence Orthology more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables phosphatidylinositol binding	ISO Inferred from Sequence Orthology more info
enables phosphatidylserine binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables protein kinase B binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein kinase B binding	ISO Inferred from Sequence Orthology more info
enables protein-containing complex binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in adiponectin-activated signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in cellular response to hepatocyte growth factor stimulus	ISO Inferred from Sequence Orthology more info
involved_in insulin receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in insulin receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in maintenance of synapse structure	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of Fc-gamma receptor signaling pathway involved in phagocytosis	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of D-glucose import	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cytokine production involved in inflammatory response	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of macropinocytosis	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of melanin biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in protein import into nucleus	ISO Inferred from Sequence Orthology more info
involved_in regulation of D-glucose import	ISO Inferred from Sequence Orthology more info
involved_in regulation of G1/S transition of mitotic cell cycle	ISO Inferred from Sequence Orthology more info
involved_in regulation of fibroblast migration	ISO Inferred from Sequence Orthology more info
involved_in regulation of innate immune response	ISO Inferred from Sequence Orthology more info
involved_in regulation of protein localization to plasma membrane	ISO Inferred from Sequence Orthology more info
involved_in regulation of toll-like receptor 4 signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in transforming growth factor beta receptor signaling pathway	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytoplasmic vesicle	ISO Inferred from Sequence Orthology more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in early endosome	ISO Inferred from Sequence Orthology more info
located_in early endosome membrane	IEA Inferred from Electronic Annotation more info
located_in early phagosome	ISO Inferred from Sequence Orthology more info
located_in endosome	ISO Inferred from Sequence Orthology more info
is_active_in endosome membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in endosome membrane	ISO Inferred from Sequence Orthology more info
is_active_in glutamatergic synapse	ISO Inferred from Sequence Orthology more info
located_in intracellular vesicle	ISO Inferred from Sequence Orthology more info
located_in macropinosome	ISO Inferred from Sequence Orthology more info
located_in membrane	ISO Inferred from Sequence Orthology more info
located_in nucleus	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
is_active_in postsynapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in presynapse	IDA Inferred from Direct Assay more info	PubMed
located_in ruffle	ISO Inferred from Sequence Orthology more info
located_in vesicle membrane	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: DCC-interacting protein 13-alpha

Names: adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 1

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.

mRNA and Protein(s)

NM_001399084.1 → NP_001386013.1 DCC-interacting protein 13-alpha

Status: VALIDATED

Source sequence(s)

JAXUCZ010000016

UniProtKB/TrEMBL

A6KMK1, D3ZWA8

Related

ENSRNOP00000084269.1, ENSRNOT00000094750.2

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:489 → 624

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_036323735.1-RS_2024_02

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

Reference GRCr8

Genomic

NC_086034.1 Reference GRCr8

Range

2125234..2173457 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_039095136.2 → XP_038951064.1 DCC-interacting protein 13-alpha isoform X1

UniProtKB/TrEMBL

A6KMK1

Related

ENSRNOP00000112063.1, ENSRNOT00000147099.1

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:506 → 637

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