SPG7
entrez
6687
canonical
uniprot
Q9UQ90
canonical
ensembl
ENSG00000197912
resolver
ensp
ENSP00000341157
resolver
ensp
ENSP00000493590
resolver
ensp
ENSP00000493908
resolver
ensp
ENSP00000495123
resolver
ensp
ENSP00000495185
resolver
ensp
ENSP00000495219
resolver
ensp
ENSP00000495675
resolver
ensp
ENSP00000495795
resolver
ensp
ENSP00000496434
resolver
ensp
ENSP00000661229
resolver
ensp
ENSP00000732949
resolver
enst
ENST00000644210
resolver
enst
ENST00000645042
resolver
enst
ENST00000645063
resolver
enst
ENST00000646531
resolver
enst
ENST00000646826
resolver
enst
ENST00000646930
resolver
genesymbol
SPG7
resolver
genesymbol_syn
CAR
resolver
genesymbol_syn
CMAR
resolver
genesymbol_syn
PGN
resolver
hgnc
HGNC:11237
resolver
uniprot
A0A2R8Y3M4
resolver
uniprot
A0A2R8Y632
resolver
uniprot
A0A2R8YFJ7
resolver
uniprot
O75756
resolver
uniprot
Q2TB70
resolver
uniprot
Q58F00
resolver
uniprot
Q96IB0
resolver
uniprot_entry
A0A2R8Y3M4_HUMAN
resolver
uniprot_entry
A0A2R8Y632_HUMAN
resolver
uniprot_entry
A0A2R8YFJ7_HUMAN
resolver
uniprot_entry
SPG7_HUMAN
resolver
uniprot_sec
O75756
resolver
uniprot_sec
Q2TB70
resolver
uniprot_sec
Q58F00
resolver
uniprot_sec
Q96IB0
resolver
amino_acid_sequence
MAVLLLLLRALRRGPGPGPRPLWGPGPAWSPGFPARPGRGRPYMASRPPGDLAEAGGRALQSLQLRLLTPTFEGINGLLLKQHLVQNPVRLWQLLGGTFYFNTSRLKQKNKEKDKSKGKAPEEDEEERRRRERDDQMYRERLRTLLVIAVVMSLLNALSTSGGSISWNDFVHEMLAKGEVQRVQVVPESDVVEVYLHPGAVVFGRPRLALMYRMQVANIDKFEEKLRAAEDELNIEAKDRIPVSYKRTGFFGNALYSVGMTAVGLAILWYVFRLAGMTGREGGFSAFNQLKMARFTIVDGKMGKGVSFKDVAGMHEAKLEVREFVDYLKSPERFLQLGAKVPKGALLLGPPGCGKTLLAKAVATEAQVPFLAMAGPEFVEVIGGLGAARVRSLFKEARARAPCIVYIDEIDAVGKKRSTTMSGFSNTEEEQTLNQLLVEMDGMGTTDHVIVLASTNRADILDGALMRPGRLDRHVFIDLPTLQERREIFEQHLKSLKLTQSSTFYSQRLAELTPGFSGADIANICNEAALHAAREGHTSVHTLNFEYAVERVLAGTAKKSKILSKEEQKVVAFHESGHALVGWMLEHTEAVMKVSITPRTNAALGFAQMLPRDQHLFTKEQLFERMCMALGGRASEALSFNEVTSGAQDDLRKVTRIAYSMVKQFGMAPGIGPISFPEAQEGLMGIGRRPFSQGLQQMMDHEARLLVAKAYRHTEKVLQDNLDKLQALANALLEKEVINYEDIEALIGPPPHGPKKMIAPQRWIDAQREKQDLGEEETEETQQPPLGGEEPTWPK
uniprot
proteins
disease_involvement
DISEASE: Spastic paraplegia 7, autosomal recessive, with or without cerebellar ataxia (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}.
uniprot
proteins
ec_number
3.4.24.-
uniprot
proteins
ec_number
3.6.-.-
uniprot
proteins
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:11549317, PubMed:28396416, PubMed:31097542, PubMed:9635427). 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). {ECO:0000250|UniProtKB:Q3ULF4, ECO:0000250|UniProtKB:Q9Y4W6, ECO:0000269|PubMed:11549317, ECO:0000269|PubMed:26387735, ECO:0000269|PubMed:28396416, ECO:0000269|PubMed:31097542, ECO:0000269|PubMed:9635427}.
uniprot
proteins
mass_dalton
88235
uniprot
proteins
mutagenesis
MUTAGEN 574..577; /note="HESG->GGSS: Abolished metalloprotease activity."; /evidence="ECO:0000269|PubMed:31097542"; MUTAGEN 574; /note="H->G: Loss of proteolytic activity but no loss of interaction with PPIF; when associated with G-575 and S-577."; /evidence="ECO:0000269|PubMed:26387735"; MUTAGEN 575; /note="E->G: Loss of proteolytic activity but no loss of interaction with PPIF; when associated with G-574 and S-577."; /evidence="ECO:0000269|PubMed:26387735"; MUTAGEN 577; /note="G->S: 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."; /evidence="ECO:0000269|PubMed:26387735
uniprot
proteins
post_translational_modification
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 AFG3L2 removing an additional N-terminal fragment to generate the proteolytically active mature form. {ECO:0000250|UniProtKB:Q3ULF4}.
uniprot
proteins
protein_family
AAA ATPase family; Peptidase M41 family
uniprot
proteins
pubmed
10480368
uniprot
proteins
pubmed
11549317
uniprot
proteins
pubmed
14623864
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16534102
uniprot
proteins
pubmed
17646629
uniprot
proteins
pubmed
19841671
uniprot
proteins
pubmed
20186691
uniprot
proteins
pubmed
20579626
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26387735
uniprot
proteins
pubmed
27217339
uniprot
proteins
pubmed
27499296
uniprot
proteins
pubmed
28396416
uniprot
proteins
pubmed
31097542
uniprot
proteins
pubmed
9635427
uniprot
proteins
sequence_length
795
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000269|PubMed:9635427}; Multi-pass membrane protein {ECO:0000255}.
uniprot
proteins
transmembrane_region
TRANSMEM 145..165; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 249..269; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins