SPG7

This gene encodes a mitochondrial metalloprotease protein that is a member of the AAA family. Members of this protein family share an ATPase domain and have roles in diverse cellular processes including membrane trafficking, intracellular motility, organelle biogenesis, protein folding, and proteolysis. Mutations in this gene cause autosomal recessive spastic paraplegia 7. Two transcript variants encoding distinct isoforms have been identified.

Full Name

SPG7, Paraplegin Matrix AAA Peptidase Subunit

Function

ATP-dependent zinc metalloprotease. Plays a role in the formation and regulation of the mitochondrial permeability transition pore (mPTP) and its proteolytic activity is dispensable for this function (PubMed:26387735).

Biological Process

Biological Process anterograde axonal transportIEA:Ensembl
Biological Process mitochondrial outer membrane permeabilization involved in programmed cell deathManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process mitochondrial protein processingManual Assertion Based On ExperimentIBA:GO_Central
Biological Process nervous system developmentManual Assertion Based On ExperimentTAS:ProtInc
Biological Process protein-containing complex assemblyManual Assertion Based On ExperimentIBA:GO_Central
Biological Process proteolysisManual Assertion Based On ExperimentTAS:ProtInc
Biological Process regulation of mitochondrial membrane permeabilityManual Assertion Based On ExperimentIMP:UniProtKB

Cellular Location

Mitochondrion inner membrane

Involvement in disease

Spastic paraplegia 7, autosomal recessive (SPG7):
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG7 is a complex form. Additional clinical features are cerebellar syndrome, supranuclear palsy, and cognitive impairment, particularly disturbance of attention and executive functions.

Topology

Mitochondrial matrix: 106-144
Helical: 145-165
Mitochondrial intermembrane: 166-248
Helical: 249-269
Mitochondrial matrix: 270-795

PTM

Upon import into the mitochondrion, the N-terminal transit peptide is cleaved by the mitochondrial-processing peptidase (MPP) to generate an intermediate form which undergoes a second proteolytic cleavage mediated by proteases AFG3L1 and/or AFG3L2 removing an additional N-terminal fragment to generate the proteolytically active mature form.