Q3ULF4 · SPG7_MOUSE
- ProteinMitochondrial inner membrane m-AAA protease component paraplegin
- GeneSpg7
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids781 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalytic component of the m-AAA protease, a protease that plays a key role in proteostasis of inner mitochondrial membrane proteins, and which is essential for axonal and neuron development (PubMed:16239145).
SPG7 possesses both ATPase and protease activities: the ATPase activity is required to unfold substrates, threading them into the internal proteolytic cavity for hydrolysis into small peptide fragments (By similarity).
The m-AAA protease exerts a dual role in the mitochondrial inner membrane: it mediates the processing of specific regulatory proteins and ensures protein quality control by degrading misfolded polypeptides (By similarity).
Mediates protein maturation of the mitochondrial ribosomal subunit MRPL32/bL32m by catalyzing the cleavage of the presequence of MRPL32/bL32m prior to assembly into the mitochondrial ribosome (PubMed:16239145).
Acts as a regulator of calcium in neurons by mediating 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 (By similarity).
Also regulates mitochondrial calcium by catalyzing degradation of MCU (By similarity).
Plays a role in the formation and regulation of the mitochondrial permeability transition pore (mPTP) and its proteolytic activity is dispensable for this function (By similarity).
SPG7 possesses both ATPase and protease activities: the ATPase activity is required to unfold substrates, threading them into the internal proteolytic cavity for hydrolysis into small peptide fragments (By similarity).
The m-AAA protease exerts a dual role in the mitochondrial inner membrane: it mediates the processing of specific regulatory proteins and ensures protein quality control by degrading misfolded polypeptides (By similarity).
Mediates protein maturation of the mitochondrial ribosomal subunit MRPL32/bL32m by catalyzing the cleavage of the presequence of MRPL32/bL32m prior to assembly into the mitochondrial ribosome (PubMed:16239145).
Acts as a regulator of calcium in neurons by mediating 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 (By similarity).
Also regulates mitochondrial calcium by catalyzing degradation of MCU (By similarity).
Plays a role in the formation and regulation of the mitochondrial permeability transition pore (mPTP) and its proteolytic activity is dispensable for this function (By similarity).
Catalytic activity
- ATP + H2O = ADP + H+ + phosphateThis reaction proceeds in the forward direction.
Cofactor
Note: Binds 1 zinc ion per subunit.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 312 | ATP (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 352 | ATP (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 353 | ATP (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 354 | ATP (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 355 | ATP (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 356 | ATP (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 357 | ATP (UniProtKB | ChEBI) | ||||
Sequence: L | ||||||
Binding site | 574 | Zn2+ (UniProtKB | ChEBI); catalytic | ||||
Sequence: H | ||||||
Active site | 575 | |||||
Sequence: E | ||||||
Binding site | 578 | Zn2+ (UniProtKB | ChEBI); catalytic | ||||
Sequence: H | ||||||
Binding site | 650 | Zn2+ (UniProtKB | ChEBI); catalytic | ||||
Sequence: D |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | axon cytoplasm | |
Cellular Component | m-AAA complex | |
Cellular Component | mitochondrial inner membrane | |
Cellular Component | mitochondrial permeability transition pore complex | |
Cellular Component | mitochondrion | |
Molecular Function | ATP binding | |
Molecular Function | ATP hydrolysis activity | |
Molecular Function | ATP-dependent peptidase activity | |
Molecular Function | metalloendopeptidase activity | |
Molecular Function | zinc ion binding | |
Biological Process | anterograde axonal transport | |
Biological Process | cell adhesion | |
Biological Process | mitochondrial outer membrane permeabilization involved in programmed cell death | |
Biological Process | mitochondrial protein processing | |
Biological Process | mitochondrion organization | |
Biological Process | regulation of calcium import into the mitochondrion | |
Biological Process | regulation of cell adhesion | |
Biological Process | regulation of mitochondrial membrane permeability |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameMitochondrial inner membrane m-AAA protease component paraplegin
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ3ULF4
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Mitochondrion inner membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 106-144 | Mitochondrial matrix | ||||
Sequence: MKQKNKDNDKPKGKTPEDDEEEKRRKEREDQMYRERLRT | ||||||
Transmembrane | 145-165 | Helical; Name=1 | ||||
Sequence: LFIIALVMSLLNSLSTSGGSI | ||||||
Topological domain | 166-248 | Mitochondrial intermembrane | ||||
Sequence: SWADFVNEMLAKGEVQRVQVVPESDVVEVYLHPGAVVFGRPRLALMYRMQVANIDKFEEKLRAAEDELNIESKDRIPVSYKRT | ||||||
Transmembrane | 249-269 | Helical; Name=2 | ||||
Sequence: GFFGNALYALGMTAVGLAILW | ||||||
Topological domain | 270-781 | Mitochondrial matrix | ||||
Sequence: YVFRLAGMTGREGGFSAFNQLKMARFTIVDGKTGKGVSFQDVAGMHEAKLEVREFVDYLKSPERFLQLGAKVPKGALLLGPPGCGKTLLAKAVATEAQVPFLAMAGPEFVEVIGGLGAARVRSLFKEARARAPCIVYIDEIDAVGKKRSTSMSGFSNTEEEQTLNQLLVEMDGMGTTDHVIVLASTNRADVLDNALMRPGRLDRHVFIDLPTLQERREIFEQHLKGLKLTQPSSFYSQRLAELTPGFSGADIANICNEAALHAAREGHTSVHTFNFEYAVERVIAGTAKKSKILSKEEQRVVAFHESGHALVGWLLEHTEAVMKVSIAPRTNAALGFSQMLPRDQYLFTKEQLFERMCMALGGRAAEAISFSRVTSGAQDDLRKVTRIAYSMVKQFGMAPSIGPVSFPEAQEGLMGIGRRPFSQGLQQMMDHEAKLLVAKAYRHTEKVLLDNLDKLQALANALLEKEVINYEDIEALIGPPPHGPKKMIAPQKWIDAEKERQASGEEEAPAP |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Mice are affected by a distal axonopathy of spinal and peripheral axons, characterized by axonal swelling and degeneration. Mitochondrial morphological abnormalities occur in synaptic terminals and in distal regions of axons long before the first signs of swelling and degeneration and correlate with onset of motor impairment during a rotarod test.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 575 | Absence of proteolytic activity. No loss of its processing into the mature form. | ||||
Sequence: E → Q |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 35 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for transit peptide, propeptide, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transit peptide | 1-43 | Mitochondrion | ||||
Sequence: MAAALLLLRGLRPGPEPRPRRLWGLLSGRGPGLSSGAGARRPY | ||||||
Propeptide | PRO_0000442306 | 44-105 | Removed in mature form | |||
Sequence: AARGTPVGPAAAGGHAPQSLLLRILTPSFEGISGLLLKQHIVPNAVRLWPLSGSTLYFNTSR | ||||||
Chain | PRO_0000442307 | 106-781 | Mitochondrial inner membrane m-AAA protease component paraplegin | |||
Sequence: MKQKNKDNDKPKGKTPEDDEEEKRRKEREDQMYRERLRTLFIIALVMSLLNSLSTSGGSISWADFVNEMLAKGEVQRVQVVPESDVVEVYLHPGAVVFGRPRLALMYRMQVANIDKFEEKLRAAEDELNIESKDRIPVSYKRTGFFGNALYALGMTAVGLAILWYVFRLAGMTGREGGFSAFNQLKMARFTIVDGKTGKGVSFQDVAGMHEAKLEVREFVDYLKSPERFLQLGAKVPKGALLLGPPGCGKTLLAKAVATEAQVPFLAMAGPEFVEVIGGLGAARVRSLFKEARARAPCIVYIDEIDAVGKKRSTSMSGFSNTEEEQTLNQLLVEMDGMGTTDHVIVLASTNRADVLDNALMRPGRLDRHVFIDLPTLQERREIFEQHLKGLKLTQPSSFYSQRLAELTPGFSGADIANICNEAALHAAREGHTSVHTFNFEYAVERVIAGTAKKSKILSKEEQRVVAFHESGHALVGWLLEHTEAVMKVSIAPRTNAALGFSQMLPRDQYLFTKEQLFERMCMALGGRAAEAISFSRVTSGAQDDLRKVTRIAYSMVKQFGMAPSIGPVSFPEAQEGLMGIGRRPFSQGLQQMMDHEAKLLVAKAYRHTEKVLLDNLDKLQALANALLEKEVINYEDIEALIGPPPHGPKKMIAPQKWIDAEKERQASGEEEAPAP | ||||||
Modified residue | 505 | 3'-nitrotyrosine | ||||
Sequence: Y |
Post-translational modification
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.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in the brain and retina (at protein level).
Gene expression databases
Interaction
Subunit
Forms heterohexamers with SPG7 and AFG3L1 (PubMed:17101804, PubMed:19656850, PubMed:22563492).
The m-AAA protease is either composed of homohexamers of AFG3L2 or heterohexamers of AFG3L1, AFG3L2 and/or SPG7 (PubMed:16239145, PubMed:17101804, PubMed:19656850, PubMed:22563492).
Component of the mitochondrial permeability transition pore complex (mPTPC), at least composed of SPG7, VDAC1 and PPIF (By similarity).
Interacts with MAIP1 (By similarity).
The m-AAA protease is either composed of homohexamers of AFG3L2 or heterohexamers of AFG3L1, AFG3L2 and/or SPG7 (PubMed:16239145, PubMed:17101804, PubMed:19656850, PubMed:22563492).
Component of the mitochondrial permeability transition pore complex (mPTPC), at least composed of SPG7, VDAC1 and PPIF (By similarity).
Interacts with MAIP1 (By similarity).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 22-56 | Disordered | ||||
Sequence: LWGLLSGRGPGLSSGAGARRPYAARGTPVGPAAAG | ||||||
Region | 103-135 | Disordered | ||||
Sequence: TSRMKQKNKDNDKPKGKTPEDDEEEKRRKERED | ||||||
Compositional bias | 107-135 | Basic and acidic residues | ||||
Sequence: KQKNKDNDKPKGKTPEDDEEEKRRKERED | ||||||
Region | 701-781 | Interaction with PPIF | ||||
Sequence: HEAKLLVAKAYRHTEKVLLDNLDKLQALANALLEKEVINYEDIEALIGPPPHGPKKMIAPQKWIDAEKERQASGEEEAPAP |
Sequence similarities
In the N-terminal section; belongs to the AAA ATPase family.
In the C-terminal section; belongs to the peptidase M41 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length781
- Mass (Da)85,996
- Last updated2005-10-11 v1
- Checksum35CCFB8F24B249D8
Computationally mapped potential isoform sequences
There are 7 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 107-135 | Basic and acidic residues | ||||
Sequence: KQKNKDNDKPKGKTPEDDEEEKRRKERED | ||||||
Sequence conflict | 165 | in Ref. 2; AAO21098 | ||||
Sequence: I → T | ||||||
Sequence conflict | 168 | in Ref. 5; AAI38142 | ||||
Sequence: A → S | ||||||
Sequence conflict | 310 | in Ref. 2; AAO21098 | ||||
Sequence: D → G | ||||||
Sequence conflict | 471 | in Ref. 1; AAN03852 | ||||
Sequence: L → F |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF512565 EMBL· GenBank· DDBJ | AAN03852.1 EMBL· GenBank· DDBJ | mRNA | ||
AF547215 EMBL· GenBank· DDBJ | AAO21098.1 EMBL· GenBank· DDBJ | mRNA | ||
AK145540 EMBL· GenBank· DDBJ | BAE26494.1 EMBL· GenBank· DDBJ | mRNA | ||
AC121819 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC024466 EMBL· GenBank· DDBJ | AAH24466.1 EMBL· GenBank· DDBJ | mRNA | ||
BC024986 EMBL· GenBank· DDBJ | AAH24986.1 EMBL· GenBank· DDBJ | mRNA | ||
BC051051 EMBL· GenBank· DDBJ | AAH51051.1 EMBL· GenBank· DDBJ | mRNA | ||
BC096690 EMBL· GenBank· DDBJ | AAH96690.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC055488 EMBL· GenBank· DDBJ | AAH55488.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC138141 EMBL· GenBank· DDBJ | AAI38142.1 EMBL· GenBank· DDBJ | mRNA |