Q9UQ90 · SPG7_HUMAN
- ProteinMitochondrial inner membrane m-AAA protease component paraplegin
- GeneSPG7
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids795 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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 (By similarity).
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 (PubMed:28396416, PubMed:31097542).
Also regulates mitochondrial calcium by catalyzing degradation of MCU (PubMed:31097542).
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).
Catalytic activity
- ATP + H2O = ADP + H+ + phosphateThis reaction proceeds in the forward direction.
Cofactor
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 | peptidase activity | |
Molecular Function | unfolded protein binding | |
Molecular Function | zinc ion binding | |
Biological Process | anterograde axonal transport | |
Biological Process | mitochondrial outer membrane permeabilization involved in programmed cell death | |
Biological Process | mitochondrial protein processing | |
Biological Process | nervous system development | |
Biological Process | proteolysis | |
Biological Process | regulation of calcium import into the mitochondrion | |
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
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9UQ90
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 106-144 | Mitochondrial matrix | ||||
Sequence: LKQKNKEKDKSKGKAPEEDEEERRRRERDDQMYRERLRT | ||||||
Transmembrane | 145-165 | Helical | ||||
Sequence: LLVIAVVMSLLNALSTSGGSI | ||||||
Topological domain | 166-248 | Mitochondrial intermembrane | ||||
Sequence: SWNDFVHEMLAKGEVQRVQVVPESDVVEVYLHPGAVVFGRPRLALMYRMQVANIDKFEEKLRAAEDELNIEAKDRIPVSYKRT | ||||||
Transmembrane | 249-269 | Helical | ||||
Sequence: GFFGNALYSVGMTAVGLAILW | ||||||
Topological domain | 270-795 | Mitochondrial matrix | ||||
Sequence: YVFRLAGMTGREGGFSAFNQLKMARFTIVDGKMGKGVSFKDVAGMHEAKLEVREFVDYLKSPERFLQLGAKVPKGALLLGPPGCGKTLLAKAVATEAQVPFLAMAGPEFVEVIGGLGAARVRSLFKEARARAPCIVYIDEIDAVGKKRSTTMSGFSNTEEEQTLNQLLVEMDGMGTTDHVIVLASTNRADILDGALMRPGRLDRHVFIDLPTLQERREIFEQHLKSLKLTQSSTFYSQRLAELTPGFSGADIANICNEAALHAAREGHTSVHTLNFEYAVERVLAGTAKKSKILSKEEQKVVAFHESGHALVGWMLEHTEAVMKVSITPRTNAALGFAQMLPRDQHLFTKEQLFERMCMALGGRASEALSFNEVTSGAQDDLRKVTRIAYSMVKQFGMAPGIGPISFPEAQEGLMGIGRRPFSQGLQQMMDHEARLLVAKAYRHTEKVLQDNLDKLQALANALLEKEVINYEDIEALIGPPPHGPKKMIAPQRWIDAQREKQDLGEEETEETQQPPLGGEEPTWPK |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Spastic paraplegia 7, autosomal recessive (SPG7)
- Note
- DescriptionA 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.
- See alsoMIM:607259
Natural variants in SPG7
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_063607 | 349 | G>S | in SPG7; function impaired; dbSNP:rs141659620 | |
VAR_063609 | 510 | A>V | in SPG7; function impaired; dbSNP:rs61755320 | |
VAR_063611 | 581 | missing | in SPG7 | |
VAR_063612 | 583 | W>C | in SPG7; function impaired; dbSNP:rs267607085 | |
VAR_045898 | 692 | S>T | in SPG7; dbSNP:rs121918357 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_063603 | 2 | in dbSNP:rs535030441 | |||
Sequence: A → T | ||||||
Natural variant | VAR_063604 | 82 | might be implicated in the hereditary spastic paraplegia phenotype | |||
Sequence: Missing | ||||||
Natural variant | VAR_063605 | 284 | might be implicated in the hereditary spastic paraplegia phenotype; requires 2 nucleotide substitutions | |||
Sequence: F → P | ||||||
Natural variant | VAR_063606 | 294 | in dbSNP:rs115661328 | |||
Sequence: R → H | ||||||
Natural variant | VAR_063607 | 349 | in SPG7; function impaired; dbSNP:rs141659620 | |||
Sequence: G → S | ||||||
Natural variant | VAR_063608 | 486 | in dbSNP:rs111475461 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_017433 | 503 | in dbSNP:rs2292954 | |||
Sequence: T → A | ||||||
Natural variant | VAR_063609 | 510 | in SPG7; function impaired; dbSNP:rs61755320 | |||
Sequence: A → V | ||||||
Natural variant | VAR_063610 | 545 | in dbSNP:rs758338586 | |||
Sequence: F → L | ||||||
Mutagenesis | 574 | Loss of proteolytic activity but no loss of interaction with PPIF; when associated with G-575 and S-577. | ||||
Sequence: H → G | ||||||
Mutagenesis | 574-577 | Abolished metalloprotease activity. | ||||
Sequence: HESG → GGSS | ||||||
Mutagenesis | 575 | Loss of proteolytic activity but no loss of interaction with PPIF; when associated with G-574 and S-577. | ||||
Sequence: E → G | ||||||
Mutagenesis | 577 | No loss of interaction with PPIF. Loss of proteolytic activity but no loss of interaction with PPIF; when associated with G-574 and G-575. | ||||
Sequence: G → S | ||||||
Natural variant | VAR_063611 | 581 | in SPG7 | |||
Sequence: Missing | ||||||
Natural variant | VAR_063612 | 583 | in SPG7; function impaired; dbSNP:rs267607085 | |||
Sequence: W → C | ||||||
Natural variant | VAR_063613 | 603 | in dbSNP:rs370852816 | |||
Sequence: A → T | ||||||
Natural variant | VAR_048117 | 623 | in dbSNP:rs17783943 | |||
Sequence: F → C | ||||||
Natural variant | VAR_063614 | 635 | might be implicated in the hereditary spastic paraplegia phenotype; dbSNP:rs864622507 | |||
Sequence: S → L | ||||||
Natural variant | VAR_059086 | 645 | in dbSNP:rs2099104 | |||
Sequence: S → T | ||||||
Natural variant | VAR_063615 | 650 | might be implicated in the hereditary spastic paraplegia phenotype | |||
Sequence: D → H | ||||||
Natural variant | VAR_017434 | 688 | in dbSNP:rs12960 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_045898 | 692 | in SPG7; dbSNP:rs121918357 | |||
Sequence: S → T | ||||||
Natural variant | VAR_048118 | 730 | in dbSNP:rs35749032 | |||
Sequence: N → D |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,149 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for transit peptide, propeptide, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transit peptide | 1-43 | Mitochondrion | ||||
Sequence: MAVLLLLLRALRRGPGPGPRPLWGPGPAWSPGFPARPGRGRPY | ||||||
Propeptide | PRO_0000442305 | 44-105 | Removed in mature form | |||
Sequence: MASRPPGDLAEAGGRALQSLQLRLLTPTFEGINGLLLKQHLVQNPVRLWQLLGGTFYFNTSR | ||||||
Chain | PRO_0000084675 | 106-795 | Mitochondrial inner membrane m-AAA protease component paraplegin | |||
Sequence: LKQKNKEKDKSKGKAPEEDEEERRRRERDDQMYRERLRTLLVIAVVMSLLNALSTSGGSISWNDFVHEMLAKGEVQRVQVVPESDVVEVYLHPGAVVFGRPRLALMYRMQVANIDKFEEKLRAAEDELNIEAKDRIPVSYKRTGFFGNALYSVGMTAVGLAILWYVFRLAGMTGREGGFSAFNQLKMARFTIVDGKMGKGVSFKDVAGMHEAKLEVREFVDYLKSPERFLQLGAKVPKGALLLGPPGCGKTLLAKAVATEAQVPFLAMAGPEFVEVIGGLGAARVRSLFKEARARAPCIVYIDEIDAVGKKRSTTMSGFSNTEEEQTLNQLLVEMDGMGTTDHVIVLASTNRADILDGALMRPGRLDRHVFIDLPTLQERREIFEQHLKSLKLTQSSTFYSQRLAELTPGFSGADIANICNEAALHAAREGHTSVHTLNFEYAVERVLAGTAKKSKILSKEEQKVVAFHESGHALVGWMLEHTEAVMKVSITPRTNAALGFAQMLPRDQHLFTKEQLFERMCMALGGRASEALSFNEVTSGAQDDLRKVTRIAYSMVKQFGMAPGIGPISFPEAQEGLMGIGRRPFSQGLQQMMDHEARLLVAKAYRHTEKVLQDNLDKLQALANALLEKEVINYEDIEALIGPPPHGPKKMIAPQRWIDAQREKQDLGEEETEETQQPPLGGEEPTWPK | ||||||
Modified residue | 505 | 3'-nitrotyrosine | ||||
Sequence: Y |
Post-translational modification
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Gene expression databases
Organism-specific databases
Interaction
Subunit
Component of the mitochondrial permeability transition pore complex (mPTPC), at least composed of SPG7, VDAC1 and PPIF (PubMed:26387735).
Interacts with MAIP1 (PubMed:27499296).
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 108-133 | Disordered | ||||
Sequence: QKNKEKDKSKGKAPEEDEEERRRRER | ||||||
Region | 701-795 | Interaction with PPIF | ||||
Sequence: HEARLLVAKAYRHTEKVLQDNLDKLQALANALLEKEVINYEDIEALIGPPPHGPKKMIAPQRWIDAQREKQDLGEEETEETQQPPLGGEEPTWPK | ||||||
Region | 751-795 | Disordered | ||||
Sequence: PHGPKKMIAPQRWIDAQREKQDLGEEETEETQQPPLGGEEPTWPK | ||||||
Compositional bias | 762-777 | Basic and acidic residues | ||||
Sequence: RWIDAQREKQDLGEEE |
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 2 isoforms produced by Alternative splicing.
Q9UQ90-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length795
- Mass (Da)88,235
- Last updated2006-10-17 v2
- Checksum453D4BF8553A0632
Q9UQ90-2
- Name2
Computationally mapped potential isoform sequences
There are 42 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
J3KRF6 | J3KRF6_HUMAN | SPG7 | 357 | ||
A0A2R8Y856 | A0A2R8Y856_HUMAN | SPG7 | 107 | ||
A0A2R8Y7N2 | A0A2R8Y7N2_HUMAN | SPG7 | 456 | ||
A0A2R8Y7E2 | A0A2R8Y7E2_HUMAN | SPG7 | 617 | ||
A0A2R8Y7B8 | A0A2R8Y7B8_HUMAN | SPG7 | 681 | ||
A0A2R8Y6Z7 | A0A2R8Y6Z7_HUMAN | SPG7 | 339 | ||
A0A2R8Y726 | A0A2R8Y726_HUMAN | SPG7 | 659 | ||
A0A2R8Y729 | A0A2R8Y729_HUMAN | SPG7 | 507 | ||
A0A2R8Y6K2 | A0A2R8Y6K2_HUMAN | SPG7 | 641 | ||
A0A2R8Y3M4 | A0A2R8Y3M4_HUMAN | SPG7 | 809 | ||
A0A2R8Y6E8 | A0A2R8Y6E8_HUMAN | SPG7 | 485 | ||
A0A2R8Y617 | A0A2R8Y617_HUMAN | SPG7 | 162 | ||
A0A2R8Y632 | A0A2R8Y632_HUMAN | SPG7 | 463 | ||
A0A2R8Y4Y7 | A0A2R8Y4Y7_HUMAN | SPG7 | 751 | ||
A0A2R8Y4Z7 | A0A2R8Y4Z7_HUMAN | SPG7 | 206 | ||
A0A2R8Y530 | A0A2R8Y530_HUMAN | SPG7 | 107 | ||
A0A2R8Y4L0 | A0A2R8Y4L0_HUMAN | SPG7 | 278 | ||
A0A2R8Y4L7 | A0A2R8Y4L7_HUMAN | SPG7 | 250 | ||
A0A2R8Y4M0 | A0A2R8Y4M0_HUMAN | SPG7 | 383 | ||
A0A2R8Y4M8 | A0A2R8Y4M8_HUMAN | SPG7 | 320 | ||
A0A2R8YGZ0 | A0A2R8YGZ0_HUMAN | SPG7 | 415 | ||
A0A2R8YGV4 | A0A2R8YGV4_HUMAN | SPG7 | 258 | ||
A0A2R8YDU1 | A0A2R8YDU1_HUMAN | SPG7 | 164 | ||
A0A2R8YDW8 | A0A2R8YDW8_HUMAN | SPG7 | 81 | ||
A0A2R8YDQ1 | A0A2R8YDQ1_HUMAN | SPG7 | 758 | ||
A0A2R8YDS3 | A0A2R8YDS3_HUMAN | SPG7 | 56 | ||
A0A2R8YDM8 | A0A2R8YDM8_HUMAN | SPG7 | 128 | ||
A0A2R8YCU3 | A0A2R8YCU3_HUMAN | SPG7 | 126 | ||
A0A2R8YFW4 | A0A2R8YFW4_HUMAN | SPG7 | 780 | ||
A0A2R8YG90 | A0A2R8YG90_HUMAN | SPG7 | 27 | ||
A0A2R8YG79 | A0A2R8YG79_HUMAN | SPG7 | 358 | ||
A0A2R8YFQ9 | A0A2R8YFQ9_HUMAN | SPG7 | 208 | ||
A0A2R8YFJ7 | A0A2R8YFJ7_HUMAN | SPG7 | 511 | ||
A0A2R8YFN9 | A0A2R8YFN9_HUMAN | SPG7 | 181 | ||
A0A2R8YFF4 | A0A2R8YFF4_HUMAN | SPG7 | 421 | ||
H3BTR8 | H3BTR8_HUMAN | SPG7 | 106 | ||
A0A2R8YEH4 | A0A2R8YEH4_HUMAN | SPG7 | 493 | ||
H3BTY6 | H3BTY6_HUMAN | SPG7 | 210 | ||
H3BNE4 | H3BNE4_HUMAN | SPG7 | 70 | ||
A0A2U3TZH1 | A0A2U3TZH1_HUMAN | SPG7 | 788 | ||
H3BMP1 | H3BMP1_HUMAN | SPG7 | 238 | ||
A0A087X0F5 | A0A087X0F5_HUMAN | SPG7 | 114 |
Sequence caution
Features
Showing features for sequence conflict, alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 12 | in Ref. 2; AAD28099 | ||||
Sequence: R → G | ||||||
Sequence conflict | 376 | in Ref. 3; AAH36104 | ||||
Sequence: P → A | ||||||
Alternative sequence | VSP_009192 | 443-489 | in isoform 2 | |||
Sequence: MGTTDHVIVLASTNRADILDGALMRPGRLDRHVFIDLPTLQERREIF → ASLDQLPSQGTMRKLRGKTPACSCLTEPTGSRRAMEGHSLCWGCLLH | ||||||
Alternative sequence | VSP_009193 | 490-795 | in isoform 2 | |||
Sequence: Missing | ||||||
Compositional bias | 762-777 | Basic and acidic residues | ||||
Sequence: RWIDAQREKQDLGEEE |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
Y16610 EMBL· GenBank· DDBJ | CAA76314.1 EMBL· GenBank· DDBJ | mRNA | ||
AF080525 EMBL· GenBank· DDBJ | AAD28099.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF080511 EMBL· GenBank· DDBJ | AAD28099.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF080512 EMBL· GenBank· DDBJ | AAD28099.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF080513 EMBL· GenBank· DDBJ | AAD28099.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF080514 EMBL· GenBank· DDBJ | AAD28099.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF080515 EMBL· GenBank· DDBJ | AAD28099.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF080516 EMBL· GenBank· DDBJ | AAD28099.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF080517 EMBL· GenBank· DDBJ | AAD28099.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF080518 EMBL· GenBank· DDBJ | AAD28099.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF080519 EMBL· GenBank· DDBJ | AAD28099.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF080520 EMBL· GenBank· DDBJ | AAD28099.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF080521 EMBL· GenBank· DDBJ | AAD28099.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF080522 EMBL· GenBank· DDBJ | AAD28099.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF080523 EMBL· GenBank· DDBJ | AAD28099.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF080524 EMBL· GenBank· DDBJ | AAD28099.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC007692 EMBL· GenBank· DDBJ | - | mRNA | No translation available. | |
BC035929 EMBL· GenBank· DDBJ | AAH35929.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC036104 EMBL· GenBank· DDBJ | AAH36104.1 EMBL· GenBank· DDBJ | mRNA | ||
BC110530 EMBL· GenBank· DDBJ | - | mRNA | No translation available. | |
BC110531 EMBL· GenBank· DDBJ | - | mRNA | No translation available. |