UniProt functional annotation for Q9UQ90



	UniProt functional annotation for Q9UQ90

UniProt code: Q9UQ90.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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). {ECO:0000269|PubMed:26387735, ECO:0000305}.

Cofactor: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:Q9WZ49}; Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q9WZ49};

Subunit: Forms heterooligomers with AFG3L1 and AFG3L2 (By similarity). Component of the mitochondrial permeability transition pore complex (mPTPC), at least composed of SPG7, VDAC1 and PPIF (PubMed:26387735). Interacts with AFG3L2; the interaction is required for the efficient assembly of mitochondrial complex I (PubMed:14623864, PubMed:26387735). Interacts with AFG3L1 (By similarity). Interacts with MAIP1 (PubMed:27499296). Interacts with VDAC1 and PPIF (PubMed:26387735). {ECO:0000250|UniProtKB:Q3ULF4, ECO:0000269|PubMed:14623864, ECO:0000269|PubMed:26387735, ECO:0000269|PubMed:27499296}.

Subcellular location: Mitochondrion inner membrane {ECO:0000269|PubMed:9635427}; Multi-pass membrane protein {ECO:0000255}.

Tissue specificity: Ubiquitous.

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. {ECO:0000250|UniProtKB:Q3ULF4}.

Disease: Spastic paraplegia 7, autosomal recessive (SPG7) [MIM:607259]: 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. {ECO:0000269|PubMed:16534102, ECO:0000269|PubMed:17646629, ECO:0000269|PubMed:20186691, ECO:0000269|PubMed:27217339, ECO:0000269|PubMed:9635427}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Note=Defects in SPG7 may cause autosomal recessive osteogenesis imperfecta (OI). Osteogenesis imperfecta defines a group of connective tissue disorders characterized by bone fragility and low bone mass. Clinical features of SPG7-related osteogenesis imperfecta include recurrent fractures, mild bone deformities, delayed tooth eruption, normal hearing and white sclera. {ECO:0000269|PubMed:20579626}.

Similarity: In the N-terminal section; belongs to the AAA ATPase family. {ECO:0000305}.

Similarity: In the C-terminal section; belongs to the peptidase M41 family. {ECO:0000305}.

Sequence caution: Sequence=AAH35929.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=BC007692; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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). {ECO:0000269\|PubMed:26387735, ECO:0000305}.


Cofactor:		Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250\|UniProtKB:Q9WZ49}; Note=Binds 1 zinc ion per subunit. {ECO:0000250\|UniProtKB:Q9WZ49};
Subunit:		Forms heterooligomers with AFG3L1 and AFG3L2 (By similarity). Component of the mitochondrial permeability transition pore complex (mPTPC), at least composed of SPG7, VDAC1 and PPIF (PubMed:26387735). Interacts with AFG3L2; the interaction is required for the efficient assembly of mitochondrial complex I (PubMed:14623864, PubMed:26387735). Interacts with AFG3L1 (By similarity). Interacts with MAIP1 (PubMed:27499296). Interacts with VDAC1 and PPIF (PubMed:26387735). {ECO:0000250\|UniProtKB:Q3ULF4, ECO:0000269\|PubMed:14623864, ECO:0000269\|PubMed:26387735, ECO:0000269\|PubMed:27499296}.
Subcellular location:		Mitochondrion inner membrane {ECO:0000269\|PubMed:9635427}; Multi-pass membrane protein {ECO:0000255}.
Tissue specificity:		Ubiquitous.
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. {ECO:0000250\|UniProtKB:Q3ULF4}.
Disease:		Spastic paraplegia 7, autosomal recessive (SPG7) [MIM:607259]: 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. {ECO:0000269\|PubMed:16534102, ECO:0000269\|PubMed:17646629, ECO:0000269\|PubMed:20186691, ECO:0000269\|PubMed:27217339, ECO:0000269\|PubMed:9635427}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Note=Defects in SPG7 may cause autosomal recessive osteogenesis imperfecta (OI). Osteogenesis imperfecta defines a group of connective tissue disorders characterized by bone fragility and low bone mass. Clinical features of SPG7-related osteogenesis imperfecta include recurrent fractures, mild bone deformities, delayed tooth eruption, normal hearing and white sclera. {ECO:0000269\|PubMed:20579626}.
Similarity:		In the N-terminal section; belongs to the AAA ATPase family. {ECO:0000305}.
Similarity:		In the C-terminal section; belongs to the peptidase M41 family. {ECO:0000305}.
Sequence caution:		Sequence=AAH35929.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=BC007692; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};