Afg3l2 AFG3-like AAA ATPase 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Afg3l2provided by MGI
Official Full Name: AFG3-like AAA ATPase 2provided by MGI
Primary source: MGI:MGI:1916847
See related: Ensembl:ENSMUSG00000024527 AllianceGenome:MGI:1916847
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: par; Emv66; 2310036I02Rik
Summary: Enables metallopeptidase activity. Involved in protein autoprocessing and regulation of calcium import into the mitochondrion. Acts upstream of or within several processes, including mitochondrion organization; nervous system development; and righting reflex. Located in mitochondrial inner membrane. Part of m-AAA complex. Is expressed in central nervous system and sensory organ. Used to study spinocerebellar ataxia type 28. Human ortholog(s) of this gene implicated in optic atrophy 12; spastic ataxia; spastic ataxia 5; and spinocerebellar ataxia type 28. Orthologous to human AFG3L2 (AFG3 like matrix AAA peptidase subunit 2). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Ubiquitous expression in colon adult (RPKM 22.4), adrenal adult (RPKM 20.7) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 18 E1; 18 39.96 cM

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	18	NC_000084.7 (67537830..67582277, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	18	NC_000084.6 (67404764..67449192, complement)

Chromosome 18 - NC_000084.7 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

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Our data identify the earliest events in SCA28 pathogenesis and open new perspectives for therapy. By identifying similar mitochondrial phenotypes between SCA28 cells and AFG3L2(+/-) cells, our results support haploinsufficiency as the mechanism for the studied pathogenic variants.
Title: Pathogenic variants in the AFG3L2 proteolytic domain cause SCA28 through haploinsufficiency and proteostatic stress-driven OMA1 activation.
Upregulation of Peroxiredoxin 3 Protects Afg3l2-KO Cortical Neurons In Vitro from Oxidative Stress: A Paradigm for Neuronal Cell Survival under Neurodegenerative Conditions.
Title: Upregulation of Peroxiredoxin 3 Protects Afg3l2-KO Cortical Neurons In Vitro from Oxidative Stress: A Paradigm for Neuronal Cell Survival under Neurodegenerative Conditions.
Astrocyte-specific deletion of Afg3l2 in the mouse leads to late-onset motor impairment and to degeneration of BG, which display aberrant morphology, altered expression of the glutamate transporter EAAT2, and a reactive inflammatory signature. The neurological and glial phenotypes are drastically exacerbated when astrocytes lack both Afg31l and Afg3l2, and therefore, are totally depleted of the m-AAA protease.
Title: Astrocyte-specific deletion of the mitochondrial m-AAA protease reveals glial contribution to neurodegeneration.
total ablation of the m-AAA protease, by deleting both Afg3l2 and its paralogue Afg3l1, triggers progressive motor dysfunction and demyelination, owing to rapid oligodendrocyte cell death
Title: The Mitochondrial m-AAA Protease Prevents Demyelination and Hair Greying.
AFG3L2 is critical to the surveillance mechanism that acts as a sensor to couple the synthesis of mitochondrial proteins with organelle fitness, thus ensuring coordinated assembly of the oxidative phosphorylation complexes from two sets of ribosomes.
Title: Quality control of mitochondrial protein synthesis is required for membrane integrity and cell fitness.
Reactive oxygen species signaling leads to cytoskeletal modifications that impair mitochondrial transport in neurons lacking AFGL.
Title: Loss of the m-AAA protease subunit AFG₃L₂ causes mitochondrial transport defects and tau hyperphosphorylation.
defective mitochondrial protein synthesis, leading to early-onset fragmentation of the mitochondrial network, is a central causative factor in AFG3L2-related neurodegeneration.
Title: AFG3L2 supports mitochondrial protein synthesis and Purkinje cell survival.
These findings shed new light in the molecular mechanisms underlining neurodegeneration caused by AFG3L2 mutations.
Title: Respiratory dysfunction by AFG3L2 deficiency causes decreased mitochondrial calcium uptake via organellar network fragmentation.
Data show that Afg3l1 or Afg3l2 are required for maturation of newly imported paraplegin subunits after their cleavage by MPP.
Title: Autocatalytic processing of m-AAA protease subunits in mitochondria.
demonstrate that cerebellum is the neuronal tissue with the highest susceptibility to reduced Afg3l2 dosage; propose that the Afg3l2 heterozygous mouse is an excellent model to unravel the pathological cascade leading to spinocerebellar ataxia type 28
Title: Haploinsufficiency of AFG3L2, the gene responsible for spinocerebellar ataxia type 28, causes mitochondria-mediated Purkinje cell dark degeneration.

Submit: New GeneRIF Correction See all GeneRIFs (12)

Phenotypes

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Associated conditions

Description	Tests
paralyse GeneReviews: Not available

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (2)
Gene trapped (1)
Not Applicable (1) 1 citation
Spontaneous (1)
Targeted (2) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

1810073H04Rik (e-PCR), detects polymorphism
- UniSTS:478976

D8Mit9 (e-PCR), detects polymorphism
- UniSTS:131636

D10Chm206 (e-PCR)
- UniSTS:518213

Afg3l2 (e-PCR), detects polymorphism
- UniSTS:479067

AW260507 (e-PCR)
- UniSTS:181141

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ATP hydrolysis activity	ISO Inferred from Sequence Orthology more info
enables ATP hydrolysis activity	ISS Inferred from Sequence or Structural Similarity more info
enables ATP-dependent H2AZ histone chaperone activity	IEA Inferred from Electronic Annotation more info
enables ATP-dependent H3-H4 histone complex chaperone activity	IEA Inferred from Electronic Annotation more info
enables ATP-dependent peptidase activity	IEA Inferred from Electronic Annotation more info
enables DNA clamp loader activity	IEA Inferred from Electronic Annotation more info
enables chromatin extrusion motor activity	IEA Inferred from Electronic Annotation more info
enables cohesin loader activity	IEA Inferred from Electronic Annotation more info
enables membrane protein dislocase activity	ISS Inferred from Sequence or Structural Similarity more info
enables metalloendopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables metalloendopeptidase activity	ISO Inferred from Sequence Orthology more info
enables metalloendopeptidase activity	ISS Inferred from Sequence or Structural Similarity more info
enables metallopeptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables metallopeptidase activity	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within axonogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in axonogenesis	ISO Inferred from Sequence Orthology more info
involved_in axonogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in calcium import into the mitochondrion	ISO Inferred from Sequence Orthology more info
involved_in calcium import into the mitochondrion	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to glutathione	ISO Inferred from Sequence Orthology more info
involved_in cellular response to glutathione	ISS Inferred from Sequence or Structural Similarity more info
involved_in chromatin looping	IEA Inferred from Electronic Annotation more info
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within cristae formation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in membrane protein proteolysis	IEA Inferred from Electronic Annotation more info
involved_in membrane protein proteolysis	ISO Inferred from Sequence Orthology more info
involved_in mitochondrial calcium ion homeostasis	ISO Inferred from Sequence Orthology more info
involved_in mitochondrial calcium ion homeostasis	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within mitochondrial fusion	IGI Inferred from Genetic Interaction more info	PubMed
involved_in mitochondrial protein processing	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within mitochondrial protein processing	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within mitochondrial protein processing	IGI Inferred from Genetic Interaction more info	PubMed
involved_in mitochondrial protein quality control	ISO Inferred from Sequence Orthology more info
involved_in mitochondrial protein quality control	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within mitochondrion organization	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within muscle cell development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within myelination	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within nerve development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within neuromuscular junction development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein autoprocessing	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in protein catabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein maturation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein maturation	ISO Inferred from Sequence Orthology more info
involved_in protein processing	IDA Inferred from Direct Assay more info	PubMed
involved_in proteolysis	ISO Inferred from Sequence Orthology more info
involved_in regulation of calcium import into the mitochondrion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of calcium import into the mitochondrion	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of multicellular organism growth	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within righting reflex	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of m-AAA complex	IBA Inferred from Biological aspect of Ancestor more info
part_of m-AAA complex	IDA Inferred from Direct Assay more info	PubMed
part_of m-AAA complex	ISO Inferred from Sequence Orthology more info
located_in mitochondrial inner membrane	HDA more info	PubMed
located_in mitochondrial inner membrane	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrion	HDA more info	PubMed
located_in mitochondrion	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: mitochondrial inner membrane m-AAA protease component AFG3L2; AFG3-like protein 2

Names: AFG3 (ATPase family gene 3)-like 2

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_027130.2 → NP_081406.1 mitochondrial inner membrane m-AAA protease component AFG3L2

See identical proteins and their annotated locations for NP_081406.1

Status: VALIDATED

Source sequence(s)

AK168668, BC043056

Consensus CDS

CCDS37847.1

UniProtKB/Swiss-Prot

Q8JZQ2

UniProtKB/TrEMBL

Q3U7C0

Related

ENSMUSP00000025408.9, ENSMUST00000025408.10

Conserved Domains (4) summary

TIGR01241
Location:252 → 745

FtsH_fam; ATP-dependent metalloprotease FtsH

pfam00004
Location:344 → 475

AAA; ATPase family associated with various cellular activities (AAA)

pfam01434
Location:561 → 743

Peptidase_M41; Peptidase family M41

pfam06480
Location:145 → 241

FtsH_ext; FtsH Extracellular

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000084.7 Reference GRCm39 C57BL/6J

Range

67537830..67582277 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_036161273.1 → XP_036017166.1 AFG3-like protein 2 isoform X2

Conserved Domains (1) summary

TIGR01241
Location:4 → 497

FtsH_fam; ATP-dependent metalloprotease FtsH
XM_011246998.3 → XP_011245300.1 AFG3-like protein 2 isoform X1

UniProtKB/TrEMBL

Q3U7C0

Conserved Domains (2) summary

TIGR01241
Location:174 → 667

FtsH_fam; ATP-dependent metalloprotease FtsH

pfam06480
Location:67 → 163

FtsH_ext; FtsH Extracellular
XM_036161274.1 → XP_036017167.1 AFG3-like protein 2 isoform X2

Conserved Domains (1) summary

TIGR01241
Location:4 → 497

FtsH_fam; ATP-dependent metalloprotease FtsH