Human Gene AFG3L2 (ENST00000269143.8_5) from GENCODE V45lift37
Description: Homo sapiens AFG3 like matrix AAA peptidase subunit 2 (AFG3L2), mRNA. (from RefSeq NM_006796) RefSeq Summary (NM_006796): 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]. Gencode Transcript: ENST00000269143.8_5 Gencode Gene: ENSG00000141385.12_9 Transcript (Including UTRs) Position: hg19 chr18:12,328,943-12,377,226 Size: 48,284 Total Exon Count: 17 Strand: - Coding Region Position: hg19 chr18:12,329,564-12,377,081 Size: 47,518 Coding Exon Count: 17
ID:AFG32_HUMAN DESCRIPTION: RecName: Full=AFG3-like protein 2 ; EC=3.4.24.- ; AltName: Full=Paraplegin-like protein; Flags: Precursor; FUNCTION: ATP-dependent protease which is essential for axonal and neuron development. In neurons, mediates degradation of SMDT1/EMRE before its assembly with the uniporter complex, limiting the availability of SMDT1/EMRE for MCU assembly and promoting efficient assembly of gatekeeper subunits with MCU (PubMed:27642048). Required for paraplegin (SPG7) maturation (PubMed:30252181). After its cleavage by mitochondrial-processing peptidase (MPP), it converts paraplegin into a proteolytically active mature form (By similarity). Required for the maturation of PINK1 into its 52kDa mature form after its cleavage by mitochondrial-processing peptidase (MPP) (PubMed:22354088, PubMed:30252181). Involved in the regulation of OMA1-dependent processing of OPA1 (PubMed:32600459, PubMed:30252181). Contributes to the proteolytic degradation of GHITM upon hyperpolarization of mitochondria (PubMed:35912435). Progressive GHITM degradation upon persistent hyperpolarization leads to respiratory complex I degradation and broad reshaping of the mitochondrial proteome by AFG3L2 (PubMed:35912435). COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence=; Note=Binds 1 zinc ion per subunit. ; SUBUNIT: Homooligomer. Forms heterooligomers with SPG7 and AFG3L1 (PubMed:17101804). Interacts with SPG7; the interaction is required for the efficient assembly of mitochondrial complex I (PubMed:14623864, PubMed:26387735, PubMed:30252181). Interacts with AFG3L1 (By similarity). Interacts with MAIP1 (PubMed:27499296, PubMed:27642048). Interacts with DNAJC19 and PHB2 (By similarity). Interacts with GHITM (PubMed:35912435). INTERACTION: Q9Y4W6; P42858: HTT; NbExp=3; IntAct=EBI-358755, EBI-466029; SUBCELLULAR LOCATION: Mitochondrion tochondrion inner membrane ; Multi-pass membrane protein TISSUE SPECIFICITY: Ubiquitous. Highly expressed in the cerebellar Purkinje cells. PTM: Upon import into the mitochondrion, the N-terminal transit peptide is cleaved to generate an intermediate form which undergoes autocatalytic proteolytic processing to generate the proteolytically active mature form. DISEASE: Spinocerebellar ataxia 28 (SCA28) [MIM:610246]: Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA28 is an autosomal dominant cerebellar ataxia (ADCA) with a slow progressive course and no evidence of sensory involvement or cognitive impairment. te=The disease is caused by variants affecting the gene represented in this entry. DISEASE: Spastic ataxia 5, autosomal recessive (SPAX5) [MIM:614487]: A neurodegenerative disorder characterized by early onset spasticity, peripheral neuropathy, ptosis, oculomotor apraxia, dystonia, cerebellar atrophy, and progressive myoclonic epilepsy. Note=The disease is caused by variants affecting the gene represented in this entry. DISEASE: Optic atrophy 12 (OPA12) [MIM:618977]: An autosomal dominant disease characterized by progressive visual loss in association with optic atrophy. Atrophy of the optic disk indicates a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts. OPA12 patients manifest slowly progressive visual impairment with onset usually in the first decade. Some patients may exhibit additional features including impaired intellectual development, dystonia, movement disorders, or ataxia. te=The disease is caused by variants affecting the gene represented in this entry. SIMILARITY: In the N-terminal section; belongs to the AAA ATPase family. SIMILARITY: In the C-terminal section; belongs to the peptidase M41 family.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9Y4W6
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Gene Ontology (GO) Annotations with Structured Vocabulary
KJ898315 - Synthetic construct Homo sapiens clone ccsbBroadEn_07709 AFG3L2 gene, encodes complete protein. Y18314 - Homo sapiens mRNA for paraplegin-like protein. BC065016 - Homo sapiens AFG3 ATPase family gene 3-like 2 (yeast), mRNA (cDNA clone MGC:70766 IMAGE:6169804), complete cds. BC024282 - Homo sapiens, Similar to AFG3 ATPase family gene 3-like 2 (yeast), clone IMAGE:4840336, mRNA, partial cds. AK129504 - Homo sapiens cDNA FLJ25993 fis, clone DMC03573, highly similar to AFG3-like protein 2 (EC 3.4.24.-). JD428662 - Sequence 409686 from Patent EP1572962. JD498123 - Sequence 479147 from Patent EP1572962. JD144904 - Sequence 125928 from Patent EP1572962. JD316339 - Sequence 297363 from Patent EP1572962. JD491866 - Sequence 472890 from Patent EP1572962. JD079953 - Sequence 60977 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q9Y4W6 (Reactome details) participates in the following event(s):
R-HSA-8949661 C2orf47:AFG3L2 binds the transit peptide of SMDT1 R-HSA-8949649 PMPCA:PMPCB cleaves the transit peptide of proSMDT1 (proEMRE) R-HSA-8949664 Processing of SMDT1 R-HSA-8949215 Mitochondrial calcium ion transport R-HSA-382551 Transport of small molecules
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
