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General Information
Symbol
Dmel\Appl
Species
D. melanogaster
Name
β amyloid protein precursor-like
Annotation Symbol
CG7727
Feature Type
FlyBase ID
FBgn0000108
Gene Model Status
Stock Availability
Gene Snapshot
In progress.Contributions welcome.
Also Known As
APP-like, APP, dAβ, EG:65F1.5 , Amyloid Precursor Protein-like
Key Links
Genomic Location
Cytogenetic map
Sequence location
X:530,501..579,044 [+]
Recombination map
1-0
Sequence
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
GO Summary Ribbons
Protein Family (UniProt)
Belongs to the APP family. (P14599)
Molecular Function (GO)
[Detailed GO annotations]
Experimental Evidence
Predictions / Assertions
Summaries
Protein Function (UniProtKB)
During development, plays a role in the regulation of the neddylation pathway. Appl and APP-BP1 interact antagonistically during development.
(UniProt, P14599)
Summary (Interactive Fly)
Gene Model and Products
Number of Transcripts
6
Number of Unique Polypeptides
6

Please see the GBrowse view of Dmel\Appl or the JBrowse view of Dmel\Appl for information on other features

To submit a correction to a gene model please use the Contact FlyBase form

Protein Domains (via Pfam)
Isoform displayed:
Pfam protein domains
InterPro name
classification
start
end
Protein Domains (via SMART)
Isoform displayed:
SMART protein domains
InterPro name
classification
start
end
Comments on Gene Model
Transposon inserted in intron
Low-frequency RNA-Seq exon junction(s) not annotated.
Gene model reviewed during 5.46
Gene model reviewed during 5.55
Sequence Ontology: Class of Gene
Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0070109
5422
887
FBtr0307291
6331
890
FBtr0307292
5251
830
FBtr0307293
5425
888
FBtr0307294
6324
883
FBtr0307295
5425
888
Additional Transcript Data and Comments
Reported size (kB)
6.5 (unknown)
Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
RefSeq ID
GenBank
FBpp0070104
98.3
887
5.31
FBpp0298292
98.6
890
5.31
FBpp0298293
91.8
830
5.29
FBpp0298294
98.5
888
5.21
FBpp0298295
97.9
883
5.25
FBpp0298296
98.5
888
5.17
Polypeptides with Identical Sequences

None of the polypeptides share 100% sequence identity.

Additional Polypeptide Data and Comments
Reported size (kDa)
886 (aa); 145, 130 (kD)
886 (aa); 98 (kD)
Comments
The 145kD and 130kD forms of the protein are made from the same gene as shown by the presence of both forms in S2 cells transfected with a heat shock Appl gene construct. The 145kD form was shown to be a precursor which is rapidly converted to the 130kD form.
The 130kD Appl protein is a secreted form which lacks the cytoplasmic domain and the membrane-spanning domain. It was shown to accumulate in the culture medium of cultured embryonic cells.
External Data
Subunit Structure (UniProtKB)
Interacts (via the intracellular domain, ICD) with APP-BP1.
(UniProt, P14599)
Domain
The clathrin-binding site is essential for its association with X11-alpha, -beta, and -gamma. The sequence specific recognition extends to peptide residues that are C-terminal to the NPXY motif. This interaction appears to be independent of phosphorylation (By similarity).
(UniProt, P14599)
Linkouts
Sequences Consistent with the Gene Model
Nucleotide / Polypeptide Records
 
Mapped Features

Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\Appl using the Feature Mapper tool.

External Data
Crossreferences
Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
Linkouts
Gene Ontology (16 terms)
Molecular Function (3 terms)
Terms Based on Experimental Evidence (1 term)
CV Term
Evidence
References
inferred from physical interaction with FLYBASE:APP-BP1; FB:FBgn0261112
inferred from physical interaction with FLYBASE:Aplip1; FB:FBgn0040281
inferred from physical interaction with FLYBASE:Fas2; FB:FBgn0000635
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
inferred from electronic annotation with InterPro:IPR015849
(assigned by InterPro )
inferred from electronic annotation with InterPro:IPR011178
(assigned by InterPro )
Biological Process (10 terms)
Terms Based on Experimental Evidence (10 terms)
CV Term
Evidence
References
inferred from mutant phenotype
inferred from direct assay
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
Terms Based on Predictions or Assertions (0 terms)
Cellular Component (3 terms)
Terms Based on Experimental Evidence (2 terms)
CV Term
Evidence
References
inferred from direct assay
inferred from direct assay
Terms Based on Predictions or Assertions (1 term)
CV Term
Evidence
References
inferred from electronic annotation with InterPro:IPR008155
(assigned by InterPro )
Expression Data
Expression Summary Ribbons
Colored tiles in ribbon indicate that expression data has been curated by FlyBase for that anatomical location. Colorless tiles indicate that there is no curated data for that location.
For complete stage-specific expression data, view the modENCODE Development RNA-Seq section under High-Throughput Expression below.
Transcript Expression
Polypeptide Expression
No Assay Recorded
Stage
Tissue/Position (including subcellular localization)
Reference
immunolocalization
Stage
Tissue/Position (including subcellular localization)
Reference
mass spectroscopy
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data
The 145kD precursor form of the Appl protein is membrane-associated.
Appl protein is expressed in many neurons in the brain, co-localising with the expression of Bace protein.
Appl protein is observed in a punctate pattern in the cytoplasm of neuronal cell bodies in larvae. This pattern is present in the ventral ganglion, the brain lobes and the photoreceptors. In the neuropil, the staining is not as homogenous. Strong uniform staining is observed in the neuropil of the three thoracic and eighth abdominal neuromeres. Staining is also observed in the neuropil of the brain lobes. Appl protein is observed in certain axons e.g. in the photoreceptor axons in the eye stalk. The membrane form appears to be enriched in regions where Appl protein is associated with neuronal processes (optic stalk and optic lobe). The pattern of Appl protein staining in the neuropil undergoes dynamic changes during metamorphosis. In the adult, the highest levels are found in the neuropil of the mushroom bodies. Staining is also observed in the brain, thoracic ganglion, lamina, and medulla.
Appl protein is observed in a punctate pattern in the cytoplasm of neuronal cell bodies in larvae. This pattern is present in the ventral ganglion, the brain lobes and the photoreceptors. In the neuropil, the staining is not as homogenous. Strong uniform staining is observed in the neuropil of the three thoracic and eighth abdominal neuromeres. Staining is also observed in the neuropil of the brain lobes. Appl protein is observed in certain axons e.g. in the photoreceptor axons in the eye stalk. The secreted form appears to be enriched in regions where Appl protein is not associated with neuronal processes (thoracic neuromeres). The pattern of Appl protein staining in the neuropil undergoes dynamic changes during metamorphosis. In the adult, the highest levels are found in the neuropil of the mushroom bodies. Staining is also observed in the brain, thoracic ganglion, lamina, and medulla.
The 130kD form of Appl protein is secreted into the culture medium of primary embryonic cells and S2 cells.
Appl protein is nervous system specific. In embryos, it is abundant in the axon tracts of commissures in the brain and ventral cord. In larvae, it is present in the brain and ventral cord. In the eye disc, it is localized behind the morphogenetic furrow. There is a gap of several columns between the morphogenetic furrow and cells containing Appl protein.
Marker for
 
Subcellular Localization
CV Term
Evidence
References
inferred from direct assay
inferred from direct assay
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

GBrowse - Visual display of RNA-Seq signals

View Dmel\Appl in GBrowse 2
RNA-Seq by Region - Search RNA-Seq expression levels by exon or genomic region
Reference
See Gelbart and Emmert, 2013 for analysis details and data files for all genes.
Developmental Proteome: Life Cycle
Developmental Proteome: Embryogenesis
External Data and Images
Linkouts
BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
FLIGHT - Cell culture data for RNAi and other high-throughput technologies
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Flygut - An atlas of the Drosophila adult midgut
Images
FlyExpress - Embryonic expression images (BDGP data)
  • Stages(s) 13-16
Alleles, Insertions, and Transgenic Constructs
Classical and Insertion Alleles ( 12 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 27 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of Appl
Transgenic constructs containing regulatory region of Appl
Deletions and Duplications ( 7 )
Phenotypes
For more details about a specific phenotype click on the relevant allele symbol.
Lethality
Allele
Sterility
Allele
Other Phenotypes
Allele
Phenotype manifest in
Allele
ventral adult lateral neuron & dendritic tree, with Scer\GAL4P2.4.Pdf
Orthologs
Human Orthologs (via DIOPT v7.1)
Homo sapiens (Human) (10)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
13 of 15
Yes
Yes
 
11 of 15
No
Yes
 
9 of 15
No
Yes
 
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
 
1 of 15
No
No
1 of 15
No
Yes
1 of 15
No
Yes
1 of 15
No
Yes
Model Organism Orthologs (via DIOPT v7.1)
Mus musculus (laboratory mouse) (11)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
12 of 15
Yes
Yes
11 of 15
No
Yes
10 of 15
No
Yes
1 of 15
No
No
1 of 15
No
No
 
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
Yes
1 of 15
No
Yes
1 of 15
No
Yes
Rattus norvegicus (Norway rat) (10)
11 of 13
Yes
Yes
8 of 13
No
Yes
3 of 13
No
Yes
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
Yes
1 of 13
No
Yes
1 of 13
No
Yes
1 of 13
No
No
Xenopus tropicalis (Western clawed frog) (3)
8 of 12
Yes
Yes
6 of 12
No
Yes
5 of 12
No
Yes
Danio rerio (Zebrafish) (5)
11 of 15
Yes
Yes
10 of 15
No
Yes
6 of 15
No
Yes
6 of 15
No
Yes
1 of 15
No
No
Caenorhabditis elegans (Nematode, roundworm) (3)
10 of 15
Yes
Yes
1 of 15
No
No
1 of 15
No
No
Arabidopsis thaliana (thale-cress) (0)
No records found.
Saccharomyces cerevisiae (Brewer's yeast) (0)
No records found.
Schizosaccharomyces pombe (Fission yeast) (0)
No records found.
Orthologs in Drosophila Species (via OrthoDB v9.1) ( EOG091903KP )
Organism
Common Name
Gene
AAA Syntenic Ortholog
Multiple Dmel Genes in this Orthologous Group
Drosophila melanogaster
fruit fly
Drosophila suzukii
Spotted wing Drosophila
Drosophila simulans
Drosophila sechellia
Drosophila erecta
Drosophila yakuba
Drosophila ananassae
Drosophila pseudoobscura pseudoobscura
Drosophila persimilis
Drosophila willistoni
Drosophila virilis
Drosophila mojavensis
Drosophila grimshawi
Orthologs in non-Drosophila Dipterans (via OrthoDB v9.1) ( EOG091504PW )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Musca domestica
House fly
Glossina morsitans
Tsetse fly
Lucilia cuprina
Australian sheep blowfly
Mayetiola destructor
Hessian fly
Mayetiola destructor
Hessian fly
Aedes aegypti
Yellow fever mosquito
Anopheles darlingi
American malaria mosquito
Anopheles gambiae
Malaria mosquito
Culex quinquefasciatus
Southern house mosquito
Orthologs in non-Dipteran Insects (via OrthoDB v9.1) ( EOG090W0505 )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Bombyx mori
Silkmoth
Danaus plexippus
Monarch butterfly
Heliconius melpomene
Postman butterfly
Apis florea
Little honeybee
Apis florea
Little honeybee
Apis mellifera
Western honey bee
Bombus impatiens
Common eastern bumble bee
Bombus terrestris
Buff-tailed bumblebee
Linepithema humile
Argentine ant
Megachile rotundata
Alfalfa leafcutting bee
Nasonia vitripennis
Parasitic wasp
Tribolium castaneum
Red flour beetle
Pediculus humanus
Human body louse
Pediculus humanus
Human body louse
Rhodnius prolixus
Kissing bug
Cimex lectularius
Bed bug
Acyrthosiphon pisum
Pea aphid
Zootermopsis nevadensis
Nevada dampwood termite
Orthologs in non-Insect Arthropods (via OrthoDB v9.1) ( EOG090X04WG )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Strigamia maritima
European centipede
Ixodes scapularis
Black-legged tick
Ixodes scapularis
Black-legged tick
Stegodyphus mimosarum
African social velvet spider
Tetranychus urticae
Two-spotted spider mite
Daphnia pulex
Water flea
Orthologs in non-Arthropod Metazoa (via OrthoDB v9.1) ( EOG091G0UW4 )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Strongylocentrotus purpuratus
Purple sea urchin
Strongylocentrotus purpuratus
Purple sea urchin
Strongylocentrotus purpuratus
Purple sea urchin
Ciona intestinalis
Vase tunicate
Gallus gallus
Domestic chicken
Gallus gallus
Domestic chicken
Paralogs
Paralogs (via DIOPT v7.1)
Drosophila melanogaster (Fruit fly) (2)
2 of 10
2 of 10
Human Disease Associations
FlyBase Human Disease Model Reports
Disease Model Summary Ribbon
Disease Ontology (DO) Annotations
Models Based on Experimental Evidence ( 5 )
Potential Models Based on Orthology ( 2 )
Modifiers Based on Experimental Evidence ( 2 )
Allele
Disease
Interaction
References
Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
 
Disease Associations of Human Orthologs (via DIOPT v7.1 and OMIM)
Note that ortholog calls supported by only 1 or 2 algorithms (DIOPT score < 3) are not shown.
Functional Complementation Data
Functional complementation data is computed by FlyBase using a combination of the orthology data obtained from DIOPT and OrthoDB and the allele-level genetic interaction data curated from the literature.
Interactions
Summary of Physical Interactions
Summary of Genetic Interactions
esyN Network Diagram
esyN Network Key:
Suppression
Enhancement

Please look at the allele data for full details of the genetic interactions
Starting gene(s)
Interaction type
Interacting gene(s)
Reference
Starting gene(s)
Interaction type
Interacting gene(s)
Reference
External Data
Subunit Structure (UniProtKB)
Interacts (via the intracellular domain, ICD) with APP-BP1.
(UniProt, P14599 )
Linkouts
BioGRID - A database of protein and genetic interactions.
DroID - A comprehensive database of gene and protein interactions.
InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.
MIST (genetic) - An integrated Molecular Interaction Database
MIST (protein-protein) - An integrated Molecular Interaction Database
Pathways
Genomic Location and Detailed Mapping Data
Chromosome (arm)
X
Recombination map
1-0
Cytogenetic map
Sequence location
X:530,501..579,044 [+]
FlyBase Computed Cytological Location
Cytogenetic map
Evidence for location
1B9-1B10
Limits computationally determined from genome sequence between P{EP}svrEP356&P{EP}argEP452 and P{EP}DreddEP1412&P{EP}Suv4-20EP1216a
Experimentally Determined Cytological Location
Cytogenetic map
Notes
References
1B5-1B8
(determined by in situ hybridisation)
Experimentally Determined Recombination Data
Left of (cM)
Right of (cM)
Notes
Stocks and Reagents
Stocks (25)
Genomic Clones (27)
cDNA Clones (178)
 

Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.

cDNA clones, fully sequences
BDGP DGC clones
Other clones
Drosophila Genomics Resource Center cDNA clones

For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.

cDNA Clones, End Sequenced (ESTs)
RNAi and Array Information
Linkouts
DRSC - Results frm RNAi screens
GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
Antibody Information
Laboratory Generated Antibodies
Commercially Available Antibodies
 
Other Information
Relationship to Other Genes
Source for database identify of
Source for database merge of
Additional comments
Other Comments
Appl is not required for learning but is specifically involved in long-term memory.
Appl exerts it effects downstream of Fas2 during synaptic bouton growth.
Neuronal overexpression of Appl gene product disrupts axonal transport. The proposed cellular function of Appl in vesicle transport could provide membrane trafficking as a common connection between APP and Presenilins.
The Appl cytoplasmic domain is required to promote synapse formation, being essential for both the satellite bouton-promoting activity and the formation of extra parent boutons caused when Appl is overexpressed. The satellite bouton-promoting activity depends on the presence of the internalization signal, the formation of extra parent boutons depends on the presence of an intact extracellular domain. The distribution of Appl is altered in hyperexcitable mutants.
Appl promotes synapse differentiation at the neuromuscular junction.
In vivo regulation of Appl processing and trafficking in neurons is studied using an immunocytochemical approach. Results suggest that the transmembrane and secreted forms of Appl have their respective roles and reinforce previous studies that Appl is essential for optimal nervous system function.
Flies deleted for Appl are viable, fertile and morphologically normal, but show subtle behavioural defects in fast phototaxis assay. These defects can be rescued in transgenes for wild type Drosophila or human Appl gene.
Identification, secretion and neural expression of Appl provides further evidence that the β amyloid protein precursor associated with Alzheimer's disease and Appl might be functionally homologous in their respective organisms and suggest an ancestral nervous system function.
Appl defines a locus in the position 1B that has previously been shown to be important for neural development.
The Appl gene is important for neural development.
The Appl gene is known to be homologous to the human protein associated with Alzheimer disease.
The APPL-encoding gene initially suggested (FBrf0050824) to correspond to vnd, but this has been disproved, since a terminal deletion which retains vnd+ function removes most of the Appl coding sequences (FBrf0051559).
Origin and Etymology
Discoverer
Etymology
Identification
External Crossreferences and Linkouts ( 81 )
Sequence Crossreferences
NCBI Gene - Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
GenBank Nucleotide - A collection of sequences from several sources, including GenBank, RefSeq, TPA, and PDB.
GenBank Protein - A collection of sequences from several sources, including translations from annotated coding regions in GenBank, RefSeq and TPA, as well as records from SwissProt, PIR, PRF, and PDB.
RefSeq - A comprehensive, integrated, non-redundant, well-annotated set of reference sequences including genomic, transcript, and protein.
UniProt/Swiss-Prot - Manually annotated and reviewed records of protein sequence and functional information
UniProt/TrEMBL - Automatically annotated and unreviewed records of protein sequence and functional information
Other crossreferences
BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones
Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Flygut - An atlas of the Drosophila adult midgut
GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)
KEGG Genes - Molecular building blocks of life in the genomic space.
modMine - A data warehouse for the modENCODE project
Linkouts
BioGRID - A database of protein and genetic interactions.
DPiM - Drosophila Protein interaction map
DroID - A comprehensive database of gene and protein interactions.
DRSC - Results frm RNAi screens
FLIGHT - Cell culture data for RNAi and other high-throughput technologies
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
FlyMine - An integrated database for Drosophila genomics
Interactive Fly - A cyberspace guide to Drosophila development and metazoan evolution
InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.
MIST (genetic) - An integrated Molecular Interaction Database
MIST (protein-protein) - An integrated Molecular Interaction Database
Synonyms and Secondary IDs (22)
Reported As
Symbol Synonym
BcDNA:GH04413
Name Synonyms
Amyloid Precursor Protein-like
Amyloid Precursor-Like Protein
Amyloid precursor protein Like
Beta amyloid protein precursor-like
amyloid precursor protein
amyloid precursor protein-like
beta amyloid protein precursor-like
β amyloid protein precursor-like
β-amyloid-protein-precursor-like
Secondary FlyBase IDs
  • FBgn0028498
Datasets (0)
Study focus (0)
Experimental Role
Project
Project Type
Title
References (185)