fra frazzled [Drosophila melanogaster (fruit fly)] - Gene

Summary

Official Symbol: fraprovided by FlyBase
Official Full Name: frazzledprovided by FlyBase
Primary source: FLYBASE:FBgn0011592
Locus tag: Dmel_CG8581
See related: AllianceGenome:FB:FBgn0011592
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: CG8581; CT24981; Dcc; DCC; Dmel\CG8581; Fra; fra/DCC
Summary: Enables protein domain specific binding activity. Involved in several processes, including neuron projection morphogenesis; regulation of neuron projection development; and salivary gland boundary specification. Located in axonal growth cone; dendrite; and neuronal cell body. Is expressed in several structures, including embryonic/larval midgut primordium; epidermis; head epidermis primordium; neuron projection bundle; and rhabdomere of eye photoreceptor cell. Human ortholog(s) of this gene implicated in colorectal cancer; congenital mirror movement disorder; and esophagus squamous cell carcinoma. Orthologous to human DCC (DCC netrin 1 receptor) and NEO1 (neogenin 1). [provided by Alliance of Genome Resources, Dec 2024]
Orthologs: all
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Genomic context

Location:: 49A10-49B3; 2-67 cM

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
Release 6.54	current	Release 6 plus ISO1 MT (GCF_000001215.4)	2R	NT_033778.4 (12529053..12564184)
Release 5.57	previous assembly	Release 5 (GCF_000001215.2)	2R	NT_033778.3 (8416558..8451689)

Chromosome 2R - NT_033778.4 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?

Frazzled/Dcc acts independently of Netrin to promote germline survival during Drosophila oogenesis.
Title: Frazzled/Dcc acts independently of Netrin to promote germline survival during Drosophila oogenesis.
In disc-proper epithelial cells, Fra can affect localization of adherens junction components and columnar cell shape. 3 conserved cytoplasmic P-motifs are required. Protrusion formation required the P3 motif. Apico-basal cell shape change needed the P1 motif and was promoted by RhoGef2 but inhibited by Rac1. The loss of AJ proteins from basolateral regions of epithelial cells required all 3 P-motifs and depended on par6.
Title: Frazzled can act through distinct molecular pathways in epithelial cells to regulate motility, apical constriction, and localisation of E-Cadherin.
Based on findings in other systems, we propose that adhesion to substrate-bound Net underlies both long- and short-range Net-Fra-dependent guidance in vivo, thereby eroding the distinction between them.
Title: Frazzled promotes growth cone attachment at the source of a Netrin gradient in the Drosophila visual system.
Frazzled expression is induced by the transcription factor Glide/Gcm in a dose-dependent manner.
Title: The Glide/Gcm fate determinant controls initiation of collective cell migration by regulating Frazzled.
Frazzled was found to have a role as a transcription factor whose activity regulates the responsiveness of commissural axons at the midline.
Title: The Intracellular Domain of the Frazzled/DCC Receptor Is a Transcription Factor Required for Commissural Axon Guidance.
Contact-mediated cell adhesion via Fmi acts in addition to the Net/Fra guidance system during axon pathfinding across the midline, underlining the importance of PCP molecules during vertebrates and invertebrates midline development.
Title: Flamingo, a seven-pass transmembrane cadherin, cooperates with Netrin/Frazzled in Drosophila midline guidance.
In peripodial cells Frazzled is endocytosed, and undergoes NetA-dependent degradation, which is required for eversion.
Title: Netrin-dependent downregulation of Frazzled/DCC is required for the dissociation of the peripodial epithelium in Drosophila.
Loss of frazzled function results in loss of comm2 expression.
Title: Requirement for commissureless2 function during dipteran insect nerve cord development.
show that Fra accumulates at dorsal and ventral leading edges of paired cardioblasts
Title: Frazzled/DCC facilitates cardiac cell outgrowth and attachment during Drosophila dorsal vessel formation.
Dscam1 functions to counter Drosophila sensory neuron dendritic targeting signals provided by secreted Netrin-B and Frazzled, a netrin receptor. Loss of Dscam1 function resulted in aberrant dendrite accumulation at a Netrin-B-expressing target.
Title: Dscam1-mediated self-avoidance counters netrin-dependent targeting of dendrites in Drosophila.

Submit: New GeneRIF Correction See all GeneRIFs (20)

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

Gene Ontology Provided by FlyBase

Function	Evidence Code	Pubs
enables netrin receptor activity	TAS Traceable Author Statement more info	PubMed
enables protein domain specific binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in axon guidance	IBA Inferred from Biological aspect of Ancestor more info
involved_in axon guidance	IGI Inferred from Genetic Interaction more info	PubMed
involved_in axon guidance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in axon guidance	TAS Traceable Author Statement more info	PubMed
involved_in axon midline choice point recognition	IGI Inferred from Genetic Interaction more info	PubMed
involved_in axon midline choice point recognition	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell-cell adhesion	IBA Inferred from Biological aspect of Ancestor more info
involved_in compound eye development	IGI Inferred from Genetic Interaction more info	PubMed
involved_in compound eye development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in dendrite guidance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in dendrite morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in dendrite morphogenesis	TAS Traceable Author Statement more info	PubMed
involved_in glial cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in motor neuron axon guidance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neuron migration	IBA Inferred from Biological aspect of Ancestor more info
involved_in peripheral nervous system neuron axonogenesis	IGI Inferred from Genetic Interaction more info	PubMed
involved_in peripheral nervous system neuron axonogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of axonogenesis	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of axonogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of dendrite development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in salivary gland boundary specification	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in axon	IDA Inferred from Direct Assay more info	PubMed
is_active_in axonal growth cone	IBA Inferred from Biological aspect of Ancestor more info
located_in axonal growth cone	IGI Inferred from Genetic Interaction more info	PubMed
located_in axonal growth cone	IMP Inferred from Mutant Phenotype more info	PubMed
located_in dendrite	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in neuronal cell body	IDA Inferred from Direct Assay more info	PubMed
located_in perivitelline space	HDA more info	PubMed
located_in plasma membrane	HDA more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info	PubMed

General protein information

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Preferred Names: frazzled

Names: CG8581-PA; CG8581-PB; CG8581-PC; DCC/Frazzled; Netrin-receptor; deleted in colorectal cancer; deleted in colorectal carcinoma; fra-PA; fra-PB; fra-PC

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

NT_033778.4 Reference assembly

Range

12529053..12564184

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_078992.3 → NP_523716.2 frazzled, isoform A [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_523716.2

Status: REVIEWED

UniProtKB/TrEMBL

A1Z920, Q94538

Related

FBpp0086935

Conserved Domains (6) summary

smart00408
Location:264 → 327

IGc2; Immunoglobulin C-2 Type

smart00410
Location:257 → 340

IG_like; Immunoglobulin like

cd00063
Location:611 → 703

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

pfam07679
Location:344 → 430

I-set; Immunoglobulin I-set domain

pfam06583
Location:1273 → 1521

Neogenin_C; Neogenin C-terminus

cl11960
Location:363 → 428

Ig; Immunoglobulin domain
NM_001299424.1 → NP_001286353.1 frazzled, isoform C [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_001286353.1

Status: REVIEWED

UniProtKB/TrEMBL

A0A0B4LEX6, Q94538

Conserved Domains (6) summary

smart00408
Location:264 → 327

IGc2; Immunoglobulin C-2 Type

smart00410
Location:257 → 340

IG_like; Immunoglobulin like

cd00063
Location:602 → 694

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

pfam07679
Location:344 → 430

I-set; Immunoglobulin I-set domain

pfam06583
Location:1264 → 1512

Neogenin_C; Neogenin C-terminus

cl11960
Location:363 → 428

Ig; Immunoglobulin domain
NM_165913.2 → NP_725185.1 frazzled, isoform B [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_725185.1

Status: REVIEWED

UniProtKB/TrEMBL

A1Z921, Q94537

Related

FBpp0086934

Conserved Domains (6) summary

smart00408
Location:264 → 327

IGc2; Immunoglobulin C-2 Type

smart00410
Location:257 → 340

IG_like; Immunoglobulin like

cd00063
Location:460 → 552

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

pfam07679
Location:344 → 430

I-set; Immunoglobulin I-set domain

pfam06583
Location:1122 → 1370

Neogenin_C; Neogenin C-terminus

cl11960
Location:363 → 428

Ig; Immunoglobulin domain