ref(2)P refractory to sigma P [Drosophila melanogaster (fruit fly)] - Gene

Summary

Official Symbol: ref(2)Pprovided by FlyBase
Official Full Name: refractory to sigma Pprovided by FlyBase
Primary source: FLYBASE:FBgn0003231
Locus tag: Dmel_CG10360
See related: AllianceGenome:FB:FBgn0003231
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: CG10360; Dmel\CG10360; dP62; p62; P62; p62/Ref(2)P; p63; ref; ref(2)p; Ref(2)p; Ref(2)P; Ref(2)P/p62; ref(2)Pn; ref(2)Po2; Ref(2P); Ref2; Ref2(P); ref2p; Ref2p; Ref2P; SQSTM1
Summary: Predicted to enable K63-linked polyubiquitin modification-dependent protein binding activity and protein kinase C binding activity. Involved in selective autophagy and sperm mitochondrion organization. Located in autophagosome. Is expressed in several structures, including circulatory system; extended germ band embryo; gut section; larval medial midline neurons; and ovary. Human ortholog(s) of this gene implicated in GNE myopathy; Paget's disease of bone; and frontotemporal dementia and/or amyotrophic lateral sclerosis-3. Orthologous to human SQSTM1 (sequestosome 1). [provided by Alliance of Genome Resources, Apr 2022]
Orthologs: all
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Genomic context

Location:: 37F1-37F1; 2-54 cM

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
Release 6.54	current	Release 6 plus ISO1 MT (GCF_000001215.4)	2L	NT_033779.5 (19542468..19545548)
Release 5.57	previous assembly	Release 5 (GCF_000001215.2)	2L	NT_033779.4 (19542468..19545548)

Chromosome 2L - NT_033779.5 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Inhibition of Ref(2)P, the Drosophila homologue of the p62/SQSTM1 gene, increases lifespan and leads to a decline in motor function.
Title: Inhibition of Ref(2)P, the Drosophila homologue of the p62/SQSTM1 gene, increases lifespan and leads to a decline in motor function.
Homeostatic Regulation of ROS-Triggered Hippo-Yki Pathway via Autophagic Clearance of Ref(2)P/p62 in the Drosophila Intestine.
Title: Homeostatic Regulation of ROS-Triggered Hippo-Yki Pathway via Autophagic Clearance of Ref(2)P/p62 in the Drosophila Intestine.
Atg17-positive structures appear at aggregates of the selective cargo Ref(2)P/p62 near lysosomes
Title: Atg17/FIP200 localizes to perilysosomal Ref(2)P aggregates and promotes autophagy by activation of Atg1 in Drosophila.
Ref(2)P is a crucial downstream effector of a pathway involving Pink1 and Parkin.
Title: Drosophila ref(2)P is required for the parkin-mediated suppression of mitochondrial dysfunction in pink1 mutants.
p62, Ref(2)P and ubiquitinated proteins are conserved markers of neuronal aging, aggregate formation and progressive autophagic defects
Title: p62, Ref(2)P and ubiquitinated proteins are conserved markers of neuronal aging, aggregate formation and progressive autophagic defects.
Our findings reveal a major role for Ref(2)P in the formation of ubiquitin-positive protein aggregates both under physiological conditions and when normal protein turnover is inhibited.
Title: Ref(2)P, the Drosophila melanogaster homologue of mammalian p62, is required for the formation of protein aggregates in adult brain.
A single (albeit complex) mutation in the gene ref(2)P confers resistance against sigma and show that this mutation has increased in frequency under positive selection.
Title: The age and evolution of an antiviral resistance mutation in Drosophila melanogaster.
Alleles were generated to identify critical residues involved in the restrictive (inhibiting viral multiplication) or permissive (allowing viral multiplication) character of Ref(2)P.
Title: Control of sigma virus multiplication by the ref(2)P gene of Drosophila melanogaster: an in vivo study of the PB1 domain of Ref(2)P.
results demonstrate the conservation of the atypical protein kinase C-ref(2)p complex for the control of innate immunity signal transduction in Drosophila melanogaster
Title: The Drosophila atypical protein kinase C-ref(2)p complex constitutes a conserved module for signaling in the toll pathway.

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Pathways from PubChem

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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 K63-linked polyubiquitin modification-dependent protein binding	IBA Inferred from Biological aspect of Ancestor more info
enables polyubiquitin modification-dependent protein binding	IDA Inferred from Direct Assay more info	PubMed
enables protein kinase C binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein-membrane adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in aggrephagy	IBA Inferred from Biological aspect of Ancestor more info
involved_in endosome organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in macroautophagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitochondrion organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitophagy	IBA Inferred from Biological aspect of Ancestor more info
involved_in sperm mitochondrion organization	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in aggresome	IBA Inferred from Biological aspect of Ancestor more info
is_active_in amphisome	IBA Inferred from Biological aspect of Ancestor more info
located_in autophagosome	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: refractory to sigma P

Names: CG10360-PA; CG10360-PB; p62 polyubiquitin; ref(2)P-PA; ref(2)P-PB; refractaire; refractaire(2)Paris; sequestosome; sequestosome-1

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_033779.5 Reference assembly

Range

19542468..19545548

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001014491.2 → NP_001014491.1 refractory to sigma P, isoform B [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_001014491.1

Status: REVIEWED

UniProtKB/Swiss-Prot

A6PX28, A6PX29, A6PX30, A6PX31, A6PX32, A6PX33, A6PX35, A6PX37, A6PX38, A6PX44, A6PX45, A6PX46, A6PX51, A6PX56, A6PX61, A6PX72, A6PX73, A6PX89, A6PX90, A6PXA2, A6PXA4, A6PXB0, A6PXB1, P14199, Q04576, Q04577, Q04578, Q24063, Q24064, Q24065, Q24066, Q24067, Q24068, Q24069, Q24070, Q24071, Q24072, Q541D1, Q9VIU1

Conserved Domains (3) summary

cd14320
Location:555 → 593

UBA_SQSTM; UBA domain of sequestosome-1 (SQSTM) and similar proteins

pfam00569
Location:121 → 165

ZZ; Zinc finger, ZZ type

cl02720
Location:6 → 88

PB1; The PB1 domain is a modular domain mediating specific protein-protein interactions which play a role in many critical cell processes, such as osteoclastogenesis, angiogenesis, early cardiovascular development, and cell polarity. A canonical PB1-PB1 ...
NM_057352.4 → NP_476700.1 refractory to sigma P, isoform A [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_476700.1

Status: REVIEWED

UniProtKB/Swiss-Prot

A6PX28, A6PX29, A6PX30, A6PX31, A6PX32, A6PX33, A6PX35, A6PX37, A6PX38, A6PX44, A6PX45, A6PX46, A6PX51, A6PX56, A6PX61, A6PX72, A6PX73, A6PX89, A6PX90, A6PXA2, A6PXA4, A6PXB0, A6PXB1, P14199, Q04576, Q04577, Q04578, Q24063, Q24064, Q24065, Q24066, Q24067, Q24068, Q24069, Q24070, Q24071, Q24072, Q541D1, Q9VIU1

Related

FBpp0080794

Conserved Domains (3) summary

cd14320
Location:555 → 593

UBA_SQSTM; UBA domain of sequestosome-1 (SQSTM) and similar proteins

pfam00569
Location:121 → 165

ZZ; Zinc finger, ZZ type

cl02720
Location:6 → 88

PB1; The PB1 domain is a modular domain mediating specific protein-protein interactions which play a role in many critical cell processes, such as osteoclastogenesis, angiogenesis, early cardiovascular development, and cell polarity. A canonical PB1-PB1 ...