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AFG3L2 AFG3 like matrix AAA peptidase subunit 2 [ Homo sapiens (human) ]

Gene ID: 10939, updated on 14-Nov-2024

Summary

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Official Symbol
AFG3L2provided by HGNC
Official Full Name
AFG3 like matrix AAA peptidase subunit 2provided by HGNC
Primary source
HGNC:HGNC:315
See related
Ensembl:ENSG00000141385 MIM:604581; AllianceGenome:HGNC:315
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
OPA12; SCA28; SPAX5
Summary
This gene encodes a protein localized in mitochondria and closely related to paraplegin. The paraplegin gene is responsible for an autosomal recessive form of hereditary spastic paraplegia. This gene is a candidate gene for other hereditary spastic paraplegias or neurodegenerative disorders. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in duodenum (RPKM 38.9), heart (RPKM 35.3) and 25 other tissues See more
Orthologs
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Genomic context

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See AFG3L2 in Genome Data Viewer
Location:
18p11.21
Exon count:
17
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 18 NC_000018.10 (12328944..12377227, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 18 NC_060942.1 (12491960..12540204, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 18 NC_000018.9 (12328943..12377226, complement)

Chromosome 18 - NC_000018.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105371996 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr18:12258258-12258758 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9307 Neighboring gene cell death inducing DFFA like effector a Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:12276271-12276894 Neighboring gene VISTA enhancer hs1751 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:12287027-12288022 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:12288023-12289016 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr18:12289267-12290030 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9308 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9309 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9310 Neighboring gene RNA, U6 small nuclear 170, pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr18:12318543-12319043 Neighboring gene tubulin beta 6 class V Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:12327565-12328414 Neighboring gene uncharacterized LOC107985154 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:12334195-12335050 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:12335909-12336764 Neighboring gene H3K27ac hESC enhancer GRCh37_chr18:12377463-12377994 Neighboring gene H3K27ac hESC enhancer GRCh37_chr18:12377995-12378524 Neighboring gene Sharpr-MPRA regulatory region 1882 Neighboring gene hESC enhancers GRCh37_chr18:12407327-12407988 and GRCh37_chr18:12407989-12408648 Neighboring gene RNA, U7 small nuclear 129 pseudogene Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:12415673-12416623 Neighboring gene PRELI domain containing 3A Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9313 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr18:12431759-12432277

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Identification and characterization of AFG3L2, a novel paraplegin-related gene. Banfi S, et al. Genomics, 1999 Jul 1. PMID 10395799
  2. Spinocerebellar Ataxia Type 28. Adam MP, et al. , 1993. PMID 21595125
  3. Spinocerebellar ataxia type 28. Mariotti C, et al. Handb Clin Neurol, 2012. PMID 21827917
  4. AFG3L2 Biallelic Mutation: Clinical Heterogeneity in Two Italian Patients. Colucci F, et al. Cerebellum, 2023 Dec. PMID 36447112
  5. Translation of MT-ATP6 pathogenic variants reveals distinct regulatory consequences from the co-translational quality control of mitochondrial protein synthesis. Ng KY, et al. Hum Mol Genet, 2022 Apr 22. PMID 34718584, Free PMC Article

See all (164) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. AFG3L2 and ACO2-Linked Dominant Optic Atrophy: Genotype-Phenotype Characterization Compared to OPA1 Patients.
    Title: AFG3L2 and ACO2-Linked Dominant Optic Atrophy: Genotype-Phenotype Characterization Compared to OPA1 Patients.
  2. Dual regulation of SLC25A39 by AFG3L2 and iron controls mitochondrial glutathione homeostasis.
    Title: Dual regulation of SLC25A39 by AFG3L2 and iron controls mitochondrial glutathione homeostasis.
  3. Autoregulatory control of mitochondrial glutathione homeostasis.
    Title: Autoregulatory control of mitochondrial glutathione homeostasis.
  4. AFG3L2 Biallelic Mutation: Clinical Heterogeneity in Two Italian Patients.
    Title: AFG3L2 Biallelic Mutation: Clinical Heterogeneity in Two Italian Patients.
  5. Expanding the phenotype of AFG3L2 mutations: Late-onset autosomal recessive spinocerebellar ataxia.
    Title: Expanding the phenotype of AFG3L2 mutations: Late-onset autosomal recessive spinocerebellar ataxia.
  6. A novel AFG3L2 mutation close to AAA domain leads to aberrant OMA1 and OPA1 processing in a family with optic atrophy.
    Title: A novel AFG3L2 mutation close to AAA domain leads to aberrant OMA1 and OPA1 processing in a family with optic atrophy.
  7. Spastic ataxia with eye-of-the-tiger-like sign in 4 siblings due to novel compound heterozygous AFG3L2 mutation.
    Title: Spastic ataxia with eye-of-the-tiger-like sign in 4 siblings due to novel compound heterozygous AFG3L2 mutation.
  8. Inactivation of the mitochondrial protease Afg3l2 results in severely diminished respiratory chain activity and widespread defects in mitochondrial gene expression.
    Title: Inactivation of the mitochondrial protease Afg3l2 results in severely diminished respiratory chain activity and widespread defects in mitochondrial gene expression.
  9. ATPase Domain AFG3L2 Mutations Alter OPA1 Processing and Cause Optic Neuropathy.
    Title: ATPase Domain AFG3L2 Mutations Alter OPA1 Processing and Cause Optic Neuropathy.
  10. 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.
Submit: New GeneRIF Correction See all GeneRIFs (30)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction Pubs
Knockdown of AFG3 ATPase family gene 3-like 2 (AFG3L2) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1 PubMed

Go to the HIV-1, Human Interaction Database

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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Markers

Homology

Clone Names

  • FLJ25993

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables ATP hydrolysis activity IDA
Inferred from Direct Assay
more info
 PubMed 
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 metalloendopeptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables metalloendopeptidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables metallopeptidase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables unfolded protein binding TAS
Traceable Author Statement
more info
 PubMed 
enables zinc ion binding IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in axonogenesis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in calcium import into the mitochondrion IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cellular response to glutathione IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in chromatin looping IEA
Inferred from Electronic Annotation
more info
  
involved_in chromatin remodeling IEA
Inferred from Electronic Annotation
more info
  
involved_in cristae formation IEA
Inferred from Electronic Annotation
more info
  
involved_in membrane protein proteolysis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in mitochondrial calcium ion homeostasis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in mitochondrial fusion IEA
Inferred from Electronic Annotation
more info
  
involved_in mitochondrial protein processing IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in mitochondrial protein quality control IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in muscle cell development IEA
Inferred from Electronic Annotation
more info
  
involved_in myelination IEA
Inferred from Electronic Annotation
more info
  
involved_in nerve development IEA
Inferred from Electronic Annotation
more info
  
involved_in neuromuscular junction development IEA
Inferred from Electronic Annotation
more info
  
involved_in protein autoprocessing ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in protein catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein maturation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein processing ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in proteolysis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in proteolysis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of calcium import into the mitochondrion IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of multicellular organism growth IEA
Inferred from Electronic Annotation
more info
  
involved_in righting reflex IEA
Inferred from Electronic Annotation
more info
  
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 
is_active_in mitochondrial inner membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in mitochondrial inner membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
is_active_in mitochondrial inner membrane TAS
Traceable Author Statement
more info
 PubMed 
located_in mitochondrial inner membrane TAS
Traceable Author Statement
more info
  
located_in mitochondrion HTP PubMed 
located_in mitochondrion IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
mitochondrial inner membrane m-AAA protease component AFG3L2
Names
AFG3 ATPase family gene 3-like 2
AFG3 ATPase family member 3-like 2
AFG3 like AAA ATPase 2
AFG3-like protein 2
ATPase family gene 3, yeast
paraplegin-like protein

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.

Genomic

  1. NG_023361.1 RefSeqGene

    Range
    5001..53333
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_666

mRNA and Protein(s)

  1. NM_006796.3 → NP_006787.2  mitochondrial inner membrane m-AAA protease component AFG3L2

    See identical proteins and their annotated locations for NP_006787.2

    Status: REVIEWED

    Source sequence(s)
    BC024282, BU786821, BX091241, DN993083
    Consensus CDS
    CCDS11859.1
    UniProtKB/Swiss-Prot
    Q6P1L0, Q9Y4W6
    UniProtKB/TrEMBL
    A0A8I5KVV1
    Related
    ENSP00000269143.2, ENST00000269143.8
    Conserved Domains (2) summary
    pfam06480
    Location:146 → 242
    FtsH_ext; FtsH Extracellular
    cl27568
    Location:253 → 746
    TIP49; TIP49 C-terminus

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000018.10 Reference GRCh38.p14 Primary Assembly

    Range
    12328944..12377227 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011525601.4 → XP_011523903.1  mitochondrial inner membrane m-AAA protease component AFG3L2 isoform X1

    UniProtKB/TrEMBL
    A0A8I5KVV1
    Conserved Domains (4) summary
    TIGR01241
    Location:253 → 679
    FtsH_fam; ATP-dependent metalloprotease FtsH
    pfam00004
    Location:345 → 476
    AAA; ATPase family associated with various cellular activities (AAA)
    pfam01434
    Location:562 → 677
    Peptidase_M41; Peptidase family M41
    pfam06480
    Location:146 → 242
    FtsH_ext; FtsH Extracellular

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060942.1 Alternate T2T-CHM13v2.0

    Range
    12491960..12540204 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054318163.1 → XP_054174138.1  mitochondrial inner membrane m-AAA protease component AFG3L2 isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9Y4W6.2 GenPept UniProtKB/Swiss-Prot:Q9Y4W6

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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