Q3ULF4 · SPG7_MOUSE

  • Protein
    Mitochondrial inner membrane m-AAA protease component paraplegin
  • Gene
    Spg7
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

Caution

According to PubMed:22563492, alternative splicing gives rise to an isoform (Paraplegin-2) which is identical to the sequence of the mature protein and localizes to the endoplasmic reticulum.

Catalytic activity

Cofactor

Zn2+ (UniProtKB | Rhea| CHEBI:29105 )

Note: Binds 1 zinc ion per subunit.

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site312ATP (UniProtKB | ChEBI)
Binding site352ATP (UniProtKB | ChEBI)
Binding site353ATP (UniProtKB | ChEBI)
Binding site354ATP (UniProtKB | ChEBI)
Binding site355ATP (UniProtKB | ChEBI)
Binding site356ATP (UniProtKB | ChEBI)
Binding site357ATP (UniProtKB | ChEBI)
Binding site574Zn2+ (UniProtKB | ChEBI); catalytic
Active site575
Binding site578Zn2+ (UniProtKB | ChEBI); catalytic
Binding site650Zn2+ (UniProtKB | ChEBI); catalytic

GO annotations

AspectTerm
Cellular Componentaxon cytoplasm
Cellular Componentm-AAA complex
Cellular Componentmitochondrial inner membrane
Cellular Componentmitochondrial permeability transition pore complex
Cellular Componentmitochondrion
Molecular FunctionATP binding
Molecular FunctionATP hydrolysis activity
Molecular FunctionATP-dependent peptidase activity
Molecular Functionmetalloendopeptidase activity
Molecular Functionzinc ion binding
Biological Processanterograde axonal transport
Biological Processcell adhesion
Biological Processmitochondrial outer membrane permeabilization involved in programmed cell death
Biological Processmitochondrial protein processing
Biological Processmitochondrion organization
Biological Processregulation of calcium import into the mitochondrion
Biological Processregulation of cell adhesion
Biological Processregulation of mitochondrial membrane permeability

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Mitochondrial inner membrane m-AAA protease component paraplegin
  • EC number
  • Alternative names
    • Paraplegin
    • Spastic paraplegia 7 protein

Gene names

    • Name
      Spg7

Organism names

  • Taxonomic identifier
  • Strains
    • Swiss Webster / NIH
    • BALB/cJ
    • C57BL/6J
    • Czech II
    • FVB/N
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q3ULF4
  • Secondary accessions
    • B2RQY8
    • D3Z1Z1
    • Q4V9T9
    • Q7TNG0
    • Q80X42

Proteomes

Organism-specific databases

Subcellular Location

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain106-144Mitochondrial matrix
Transmembrane145-165Helical; Name=1
Topological domain166-248Mitochondrial intermembrane
Transmembrane249-269Helical; Name=2
Topological domain270-781Mitochondrial matrix

Keywords

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.

TypeIDPosition(s)Description
Mutagenesis575Absence of proteolytic activity. No loss of its processing into the mature form.

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.

Go to variant viewer

PTM/Processing

Features

Showing features for transit peptide, propeptide, chain, modified residue.

TypeIDPosition(s)Description
Transit peptide1-43Mitochondrion
PropeptidePRO_000044230644-105Removed in mature form
ChainPRO_0000442307106-781Mitochondrial inner membrane m-AAA protease component paraplegin
Modified residue5053'-nitrotyrosine

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

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).

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for region, compositional bias.

TypeIDPosition(s)Description
Region22-56Disordered
Region103-135Disordered
Compositional bias107-135Basic and acidic residues
Region701-781Interaction with PPIF

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

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    781
  • Mass (Da)
    85,996
  • Last updated
    2005-10-11 v1
  • Checksum
    35CCFB8F24B249D8
MAAALLLLRGLRPGPEPRPRRLWGLLSGRGPGLSSGAGARRPYAARGTPVGPAAAGGHAPQSLLLRILTPSFEGISGLLLKQHIVPNAVRLWPLSGSTLYFNTSRMKQKNKDNDKPKGKTPEDDEEEKRRKEREDQMYRERLRTLFIIALVMSLLNSLSTSGGSISWADFVNEMLAKGEVQRVQVVPESDVVEVYLHPGAVVFGRPRLALMYRMQVANIDKFEEKLRAAEDELNIESKDRIPVSYKRTGFFGNALYALGMTAVGLAILWYVFRLAGMTGREGGFSAFNQLKMARFTIVDGKTGKGVSFQDVAGMHEAKLEVREFVDYLKSPERFLQLGAKVPKGALLLGPPGCGKTLLAKAVATEAQVPFLAMAGPEFVEVIGGLGAARVRSLFKEARARAPCIVYIDEIDAVGKKRSTSMSGFSNTEEEQTLNQLLVEMDGMGTTDHVIVLASTNRADVLDNALMRPGRLDRHVFIDLPTLQERREIFEQHLKGLKLTQPSSFYSQRLAELTPGFSGADIANICNEAALHAAREGHTSVHTFNFEYAVERVIAGTAKKSKILSKEEQRVVAFHESGHALVGWLLEHTEAVMKVSIAPRTNAALGFSQMLPRDQYLFTKEQLFERMCMALGGRAAEAISFSRVTSGAQDDLRKVTRIAYSMVKQFGMAPSIGPVSFPEAQEGLMGIGRRPFSQGLQQMMDHEAKLLVAKAYRHTEKVLLDNLDKLQALANALLEKEVINYEDIEALIGPPPHGPKKMIAPQKWIDAEKERQASGEEEAPAP

Computationally mapped potential isoform sequences

There are 7 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A1I7Q4C2A0A1I7Q4C2_MOUSESpg7145
D3YXB7D3YXB7_MOUSESpg7744
D3YZN4D3YZN4_MOUSESpg7676
D3Z342D3Z342_MOUSESpg7230
G3UX97G3UX97_MOUSESpg7209
F6W695F6W695_MOUSESpg7253
F6VTG4F6VTG4_MOUSESpg790

Sequence caution

The sequence AAH55488.1 differs from that shown. Reason: Erroneous initiation Extended N-terminus.
The sequence AAH96690.1 differs from that shown. Reason: Erroneous initiation Extended N-terminus.

Features

Showing features for compositional bias, sequence conflict.

TypeIDPosition(s)Description
Compositional bias107-135Basic and acidic residues
Sequence conflict165in Ref. 2; AAO21098
Sequence conflict168in Ref. 5; AAI38142
Sequence conflict310in Ref. 2; AAO21098
Sequence conflict471in Ref. 1; AAN03852

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice.
We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.
FeedbackHelp