Appl beta amyloid protein precursor-like [Drosophila melanogaster (fruit fly)] - Gene

Summary

Official Symbol: Applprovided by FlyBase
Official Full Name: beta amyloid protein precursor-likeprovided by FlyBase
Primary source: FLYBASE:FBgn0000108
Locus tag: Dmel_CG7727
See related: AllianceGenome:FB:FBgn0000108
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Drosophila melanogaster
Lineage: Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea; Drosophilidae; Drosophila; Sophophora
Also known as: Abeta; APP; APP-like; appl; APPL; BcDNA:GH04413; CG7727; dAbeta; dAPPl; dAPPL; Dmel\CG7727; EG:65F1.5
Summary: Predicted to enable heparin binding activity and transition metal ion binding activity. Involved in several processes, including memory; nervous system development; and response to axon injury. Located in several cellular components, including axon; extracellular region; and neuronal cell body. Is expressed in several structures, including anterior-posterior subdivision of organism; ganglia; neuron projection bundle; photoreceptor neurons; and synaptic neuropil domain. Used to study Alzheimer's disease and Alzheimer's disease 1. Human ortholog(s) of this gene implicated in APP-related cerebral amyloid angiopathy; Alzheimer's disease (multiple); cognitive disorder; traumatic brain injury; and visual epilepsy. Orthologous to several human genes including APLP2 (amyloid beta precursor like protein 2). [provided by Alliance of Genome Resources, Dec 2024]
Orthologs: all
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Genomic context

Location:: 1B9-1B10; 1-0 cM

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
Release 6.54	current	Release 6 plus ISO1 MT (GCF_000001215.4)	X	NC_004354.4 (530501..579044)
Release 5.57	previous assembly	Release 5 (GCF_000001215.2)	X	NC_004354.3 (424534..473077)

Chromosome X - NC_004354.4 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

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

N-Acetyltransferase 9 ameliorates Abeta42-mediated neurodegeneration in the Drosophila eye.
Title: N-Acetyltransferase 9 ameliorates Aβ42-mediated neurodegeneration in the Drosophila eye.
Nutraceutical and Probiotic Approaches to Examine Molecular Interactions of the Amyloid Precursor Protein APP in Drosophila Models of Alzheimer's Disease.
Title: Nutraceutical and Probiotic Approaches to Examine Molecular Interactions of the Amyloid Precursor Protein APP in Drosophila Models of Alzheimer's Disease.
Interactions between amyloid precursor protein-like (APPL) and MAGUK scaffolding proteins contribute to appetitive long-term memory in Drosophila melanogaster.
Title: Interactions between amyloid precursor protein-like (APPL) and MAGUK scaffolding proteins contribute to appetitive long-term memory in Drosophila melanogaster.
APPL is essential for visual working memory. Interestingly, this short-term memory declines rapidly with age, and this is accompanied by enhanced processing of APPL in aged flies. Furthermore, reducing secretase-mediated proteolytic processing of APPL can prevent the age-related memory loss, whereas overexpression of the secretases aggravates the aging effect.
Title: Drosophila Full-Length Amyloid Precursor Protein Is Required for Visual Working Memory and Prevents Age-Related Memory Impairment.
Results show that Drosophila APPL-RNAi largely mimics transgenic amyloid beta in various phenotypes which include eye degeneration, reduced longevity and motor neuron deficit functions. This is the first report showing comparable phenotypes between APPL and amyloid beta in Alzheimer's disease model of Drosophila.
Title: Knockdown of APPL mimics transgenic Aβ induced neurodegenerative phenotypes in Drosophila.
Appl siRNA inhibition in cortex glia resulted in longer sleep and reduced expression of genes involved in glutamate recycling.
Title: Amyloid Precursor Protein in Drosophila Glia Regulates Sleep and Genes Involved in Glutamate Recycling.
memory is altered by two connected mechanisms-APPL loss-of-function and amyloid peptide toxicity-revealing in Drosophila a functional interaction between APPL and amyloid peptide.
Title: Amyloid-β Peptide Exacerbates the Memory Deficit Caused by Amyloid Precursor Protein Loss-of-Function in Drosophila.
The results of this study showed that increased production of the endogenous Drosophila Amyloid Intracellular Domain (dAICD) caused disruption of circadian rest-activity rhythms during aging.
Title: Manipulations of amyloid precursor protein cleavage disrupt the circadian clock in aging Drosophila.
Our data demonstrate that, in addition to secreted APPL, the noncleaved form is involved in memory, raising the possibility that secreted and full-length APPL act together in memory processes.
Title: The full-length form of the Drosophila amyloid precursor protein is involved in memory formation.
findings suggest that a normal function of presenilin (PS)is to repress kinesin-1 and dynein motor activity during axonal transport of amyloid precursor protein (APP) vesicles; perturbations of APP/PS transport could contribute to early neuropathology observed in Alzheimer's Disease
Title: Presenilin controls kinesin-1 and dynein function during APP-vesicle transport in vivo.

Submit: New GeneRIF Correction See all GeneRIFs (26)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

NCBI Orthologs

Orthologs from OrthoDB

mobile_element

Loc: 551477-558981 mobile_element_type = transposon:412{}5

Gene Ontology Provided by FlyBase

Function	Evidence Code	Pubs
enables heparin binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables transition metal ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in axonogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in central nervous system development	IBA Inferred from Biological aspect of Ancestor more info
involved_in learning or memory	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in long-term memory	IDA Inferred from Direct Assay more info	PubMed
involved_in long-term memory	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mushroom body development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neuron projection morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in peripheral nervous system development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to axon injury	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to electrical stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in short-term memory	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in synapse organization	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in axon	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	IEA Inferred from Electronic Annotation more info
is_active_in neuron projection	IBA Inferred from Biological aspect of Ancestor more info
is_active_in neuronal cell body	IBA Inferred from Biological aspect of Ancestor more info
located_in neuronal cell body	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: beta amyloid protein precursor-like

Names: APP-like; Appl-PA; Appl-PB; Appl-PC; Appl-PD; Appl-PE; Appl-PF; CG7727-PA; CG7727-PB; CG7727-PC; CG7727-PD; CG7727-PE; CG7727-PF; amyloid Precursor-Like protein; amyloid precursor protein; amyloid precursor protein like; amyloid precursor protein-like; beta-amyloid-protein-precursor-like

NCBI Reference Sequences (RefSeq)

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Genome Annotation

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

Reference assembly

Genomic

NC_004354.4 Reference assembly

Range

530501..579044

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001258522.2 → NP_001245451.1 beta amyloid protein precursor-like, isoform E [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_001245451.1

Status: REVIEWED

UniProtKB/TrEMBL

M9NDH5

Conserved Domains (6) summary

smart00006
Location:26 → 198

A4_EXTRA; amyloid A4

pfam02177
Location:33 → 141

APP_N; Amyloid A4 N-terminal heparin-binding

pfam10515
Location:831 → 880

APP_amyloid; beta-amyloid precursor protein C-terminus

pfam12924
Location:143 → 198

APP_Cu_bd; Copper-binding of amyloid precursor, CuBD

pfam12925
Location:387 → 576

APP_E2; E2 domain of amyloid precursor protein

cl20817
Location:625 → 678

GBP_C; Guanylate-binding protein, C-terminal domain
NM_001258521.2 → NP_001245450.1 beta amyloid protein precursor-like, isoform D [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_001245450.1

Status: REVIEWED

UniProtKB/TrEMBL

M9NGF6

Conserved Domains (6) summary

smart00006
Location:26 → 199

A4_EXTRA; amyloid A4

pfam02177
Location:33 → 142

APP_N; Amyloid A4 N-terminal heparin-binding

pfam10515
Location:836 → 885

APP_amyloid; beta-amyloid precursor protein C-terminus

pfam12924
Location:144 → 199

APP_Cu_bd; Copper-binding of amyloid precursor, CuBD

pfam12925
Location:388 → 581

APP_E2; E2 domain of amyloid precursor protein

cl20817
Location:630 → 683

GBP_C; Guanylate-binding protein, C-terminal domain
NM_001258523.2 → NP_001245452.1 beta amyloid protein precursor-like, isoform F [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_001245452.1

Status: REVIEWED

UniProtKB/TrEMBL

M9NFQ0

Conserved Domains (6) summary

smart00006
Location:26 → 199

A4_EXTRA; amyloid A4

pfam02177
Location:33 → 142

APP_N; Amyloid A4 N-terminal heparin-binding

pfam10515
Location:836 → 885

APP_amyloid; beta-amyloid precursor protein C-terminus

pfam12924
Location:144 → 199

APP_Cu_bd; Copper-binding of amyloid precursor, CuBD

pfam12925
Location:388 → 581

APP_E2; E2 domain of amyloid precursor protein

cl20817
Location:630 → 683

GBP_C; Guanylate-binding protein, C-terminal domain
NM_057278.5 → NP_476626.2 beta amyloid protein precursor-like, isoform A [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_476626.2

Status: REVIEWED

UniProtKB/Swiss-Prot

P14599, Q9TVV0, Q9U4H3, Q9W5F1

Related

FBpp0070104

Conserved Domains (6) summary

smart00006
Location:26 → 198

A4_EXTRA; amyloid A4

pfam02177
Location:33 → 141

APP_N; Amyloid A4 N-terminal heparin-binding

pfam10515
Location:835 → 884

APP_amyloid; beta-amyloid precursor protein C-terminus

pfam12924
Location:143 → 198

APP_Cu_bd; Copper-binding of amyloid precursor, CuBD

pfam12925
Location:387 → 580

APP_E2; E2 domain of amyloid precursor protein

cl20817
Location:629 → 682

GBP_C; Guanylate-binding protein, C-terminal domain
NM_001258520.2 → NP_001245449.1 beta amyloid protein precursor-like, isoform C [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_001245449.1

Status: REVIEWED

UniProtKB/TrEMBL

M9NEM2

Conserved Domains (5) summary

pfam02177
Location:26 → 84

APP_N; Amyloid A4 N-terminal heparin-binding

pfam10515
Location:778 → 827

APP_amyloid; beta-amyloid precursor protein C-terminus

pfam12924
Location:86 → 141

APP_Cu_bd; Copper-binding of amyloid precursor, CuBD

pfam12925
Location:330 → 523

APP_E2; E2 domain of amyloid precursor protein

cl20817
Location:572 → 625

GBP_C; Guanylate-binding protein, C-terminal domain
NM_001258519.1 → NP_001245448.1 beta amyloid protein precursor-like, isoform B [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_001245448.1

Status: REVIEWED

UniProtKB/TrEMBL

M9NE22

Conserved Domains (6) summary

smart00006
Location:26 → 198

A4_EXTRA; amyloid A4

pfam02177
Location:33 → 141

APP_N; Amyloid A4 N-terminal heparin-binding

pfam10515
Location:834 → 887

APP_amyloid; beta-amyloid precursor protein C-terminus

pfam12924
Location:143 → 198

APP_Cu_bd; Copper-binding of amyloid precursor, CuBD

pfam12925
Location:387 → 580

APP_E2; E2 domain of amyloid precursor protein

cl20817
Location:629 → 682

GBP_C; Guanylate-binding protein, C-terminal domain