AFG3L2

AFG3L2 is 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

Full Name

AFG3 Like Matrix AAA Peptidase Subunit 2

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. Required for the maturation of paraplegin (SPG7) after its cleavage by mitochondrial-processing peptidase (MPP), converting it 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).

Biological Process

Axonogenesis
Calcium import into the mitochondrion
Cristae formation
Membrane protein proteolysis
Mitochondrial calcium ion homeostasis
Mitochondrial calcium ion transmembrane transport
Mitochondrial fusion
Mitochondrial protein processing
Muscle fiber development
Myelination
Nerve development
Neuromuscular junction development
Protein autoprocessing
Protein-containing complex assembly
Protein processing
Proteolysis
Regulation of multicellular organism growth
Righting reflex

Cellular Location

Mitochondrion; Mitochondrion inner membrane

Involvement in disease

Spinocerebellar ataxia 28 (SCA28): 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.
Spastic ataxia 5, autosomal recessive (SPAX5): A neurodegenerative disorder characterized by early onset spasticity, peripheral neuropathy, ptosis, oculomotor apraxia, dystonia, cerebellar atrophy, and progressive myoclonic epilepsy.

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.