SPG7_HUMAN
ID SPG7_HUMAN Reviewed; 795 AA.
AC Q9UQ90; O75756; Q2TB70; Q58F00; Q96IB0;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 212.
DE RecName: Full=Paraplegin {ECO:0000250|UniProtKB:Q3ULF4};
DE EC=3.4.24.-;
DE AltName: Full=Cell matrix adhesion regulator {ECO:0000312|HGNC:HGNC:11237};
DE AltName: Full=Spastic paraplegia 7 protein {ECO:0000312|HGNC:HGNC:11237};
DE Flags: Precursor;
GN Name=SPG7 {ECO:0000312|HGNC:HGNC:11237};
GN Synonyms=CAR, CMAR {ECO:0000312|HGNC:HGNC:11237}, PGN;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND
RP INVOLVEMENT IN SPG7.
RX PubMed=9635427; DOI=10.1016/s0092-8674(00)81203-9;
RA Casari G., De Fusco M., Ciarmatori S., Zeviani M., Mora M., Fernandez P.,
RA De Michele G., Filla A., Cocozza S., Marconi R., Duerr A., Fontaine B.,
RA Ballabio A.;
RT "Spastic paraplegia and OXPHOS impairment caused by mutations in
RT paraplegin, a nuclear-encoded mitochondrial metalloprotease.";
RL Cell 93:973-983(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=10480368; DOI=10.1007/s004399900087;
RA Settasatian C., Whitmore S.A., Crawford J., Bilton R.L.,
RA Cleton-Jansen A.-M., Sutherland G.R., Callen D.F.;
RT "Genomic structure and expression analysis of the spastic paraplegia gene,
RT SPG7.";
RL Hum. Genet. 105:139-144(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Duodenum, and Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH AFG3L2.
RX PubMed=14623864; DOI=10.1083/jcb.200304112;
RA Atorino L., Silvestri L., Koppen M., Cassina L., Ballabio A., Marconi R.,
RA Langer T., Casari G.;
RT "Loss of m-AAA protease in mitochondria causes complex I deficiency and
RT increased sensitivity to oxidative stress in hereditary spastic
RT paraplegia.";
RL J. Cell Biol. 163:777-787(2003).
RN [5]
RP INVOLVEMENT IN OSTEOGENESIS IMPERFECTA.
RX PubMed=20579626; DOI=10.1016/j.ajhg.2010.05.016;
RA Lapunzina P., Aglan M., Temtamy S., Caparros-Martin J.A., Valencia M.,
RA Leton R., Martinez-Glez V., Elhossini R., Amr K., Vilaboa N.,
RA Ruiz-Perez V.L.;
RT "Identification of a frameshift mutation in Osterix in a patient with
RT recessive osteogenesis imperfecta.";
RL Am. J. Hum. Genet. 87:110-114(2010).
RN [6]
RP FUNCTION, IDENTIFICATION IN THE MITOCHONDRIAL PERMEABILITY TRANSITION PORE
RP COMPLEX, INTERACTION WITH AFG3L2; PPIF AND VDAC1, AND MUTAGENESIS OF
RP HIS-574; GLU-575 AND GLY-577.
RX PubMed=26387735; DOI=10.1016/j.molcel.2015.08.009;
RA Shanmughapriya S., Rajan S., Hoffman N.E., Higgins A.M., Tomar D.,
RA Nemani N., Hines K.J., Smith D.J., Eguchi A., Vallem S., Shaikh F.,
RA Cheung M., Leonard N.J., Stolakis R.S., Wolfers M.P., Ibetti J.,
RA Chuprun J.K., Jog N.R., Houser S.R., Koch W.J., Elrod J.W., Madesh M.;
RT "SPG7 is an essential and conserved component of the mitochondrial
RT permeability transition pore.";
RL Mol. Cell 60:47-62(2015).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [8]
RP INTERACTION WITH MAIP1.
RX PubMed=27499296; DOI=10.1016/j.molcel.2016.06.033;
RA Floyd B.J., Wilkerson E.M., Veling M.T., Minogue C.E., Xia C., Beebe E.T.,
RA Wrobel R.L., Cho H., Kremer L.S., Alston C.L., Gromek K.A., Dolan B.K.,
RA Ulbrich A., Stefely J.A., Bohl S.L., Werner K.M., Jochem A.,
RA Westphall M.S., Rensvold J.W., Taylor R.W., Prokisch H., Kim J.J.,
RA Coon J.J., Pagliarini D.J.;
RT "Mitochondrial protein interaction mapping identifies regulators of
RT respiratory chain function.";
RL Mol. Cell 63:621-632(2016).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.22 ANGSTROMS) OF 305-565 IN COMPLEX WITH ATP
RP ANALOG ADP.
RX PubMed=19841671; DOI=10.1371/journal.pone.0006975;
RA Karlberg T., van den Berg S., Hammarstrom M., Sagemark J., Johansson I.,
RA Holmberg-Schiavone L., Schuler H.;
RT "Crystal structure of the ATPase domain of the human AAA+ protein
RT paraplegin/SPG7.";
RL PLoS ONE 4:E6975-E6975(2009).
RN [10]
RP VARIANTS SPG7 VAL-510 AND VAL-581 DEL, AND VARIANTS THR-2; GLN-82 DEL;
RP PRO-284; HIS-294; GLN-486 ALA-503; LEU-545; THR-603; LEU-635; THR-645;
RP HIS-650; GLN-688 AND ASP-730.
RX PubMed=16534102; DOI=10.1212/01.wnl.0000201185.91110.15;
RA Elleuch N., Depienne C., Benomar A., Hernandez A.M., Ferrer X.,
RA Fontaine B., Grid D., Tallaksen C.M.E., Zemmouri R., Stevanin G., Durr A.,
RA Brice A.;
RT "Mutation analysis of the paraplegin gene (SPG7) in patients with
RT hereditary spastic paraplegia.";
RL Neurology 66:654-659(2006).
RN [11]
RP VARIANT SPG7 THR-692.
RX PubMed=17646629; DOI=10.1212/01.wnl.0000266667.91074.fe;
RA Warnecke T., Duning T., Schwan A., Lohmann H., Epplen J.T., Young P.;
RT "A novel form of autosomal recessive hereditary spastic paraplegia caused
RT by a new SPG7 mutation.";
RL Neurology 69:368-375(2007).
RN [12]
RP VARIANTS SPG7 SER-349; VAL-510 AND CYS-583, VARIANTS ALA-503 AND GLN-688,
RP CHARACTERIZATION OF VARIANTS SPG7 SER-349; VAL-510 AND CYS-583, AND
RP CHARACTERIZATION OF VARIANTS ALA-503 AND GLN-688.
RX PubMed=20186691; DOI=10.1002/humu.21226;
RA Bonn F., Pantakani K., Shoukier M., Langer T., Mannan A.U.;
RT "Functional evaluation of paraplegin mutations by a yeast complementation
RT assay.";
RL Hum. Mutat. 31:617-621(2010).
RN [13]
RP VARIANT SPG7 VAL-510.
RX PubMed=27217339; DOI=10.1093/brain/aww111;
RA Kara E., Tucci A., Manzoni C., Lynch D.S., Elpidorou M., Bettencourt C.,
RA Chelban V., Manole A., Hamed S.A., Haridy N.A., Federoff M., Preza E.,
RA Hughes D., Pittman A., Jaunmuktane Z., Brandner S., Xiromerisiou G.,
RA Wiethoff S., Schottlaender L., Proukakis C., Morris H., Warner T.,
RA Bhatia K.P., Korlipara L.V., Singleton A.B., Hardy J., Wood N.W.,
RA Lewis P.A., Houlden H.;
RT "Genetic and phenotypic characterization of complex hereditary spastic
RT paraplegia.";
RL Brain 139:1904-1918(2016).
CC -!- FUNCTION: ATP-dependent zinc metalloprotease. Plays a role in the
CC formation and regulation of the mitochondrial permeability transition
CC pore (mPTP) and its proteolytic activity is dispensable for this
CC function (PubMed:26387735). {ECO:0000269|PubMed:26387735, ECO:0000305}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q9WZ49};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q9WZ49};
CC -!- SUBUNIT: Forms heterooligomers with AFG3L1 and AFG3L2 (By similarity).
CC Component of the mitochondrial permeability transition pore complex
CC (mPTPC), at least composed of SPG7, VDAC1 and PPIF (PubMed:26387735).
CC Interacts with AFG3L2; the interaction is required for the efficient
CC assembly of mitochondrial complex I (PubMed:14623864, PubMed:26387735).
CC Interacts with AFG3L1 (By similarity). Interacts with MAIP1
CC (PubMed:27499296). Interacts with VDAC1 and PPIF (PubMed:26387735).
CC {ECO:0000250|UniProtKB:Q3ULF4, ECO:0000269|PubMed:14623864,
CC ECO:0000269|PubMed:26387735, ECO:0000269|PubMed:27499296}.
CC -!- INTERACTION:
CC Q9UQ90; O95273: CCNDBP1; NbExp=3; IntAct=EBI-717201, EBI-748961;
CC Q9UQ90; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-717201, EBI-3867333;
CC Q9UQ90; P61978: HNRNPK; NbExp=6; IntAct=EBI-717201, EBI-304185;
CC Q9UQ90; P61978-2: HNRNPK; NbExp=3; IntAct=EBI-717201, EBI-7060731;
CC Q9UQ90; O75031: HSF2BP; NbExp=3; IntAct=EBI-717201, EBI-7116203;
CC Q9UQ90; Q5VWX1: KHDRBS2; NbExp=3; IntAct=EBI-717201, EBI-742808;
CC Q9UQ90; Q6A162: KRT40; NbExp=3; IntAct=EBI-717201, EBI-10171697;
CC Q9UQ90; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-717201, EBI-10172290;
CC Q9UQ90; P60411: KRTAP10-9; NbExp=3; IntAct=EBI-717201, EBI-10172052;
CC Q9UQ90; Q9BRK4: LZTS2; NbExp=3; IntAct=EBI-717201, EBI-741037;
CC Q9UQ90; Q99750: MDFI; NbExp=7; IntAct=EBI-717201, EBI-724076;
CC Q9UQ90; Q5JR59: MTUS2; NbExp=4; IntAct=EBI-717201, EBI-742948;
CC Q9UQ90; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-717201, EBI-945833;
CC Q9UQ90; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-717201, EBI-22310682;
CC Q9UQ90; Q8ND90: PNMA1; NbExp=7; IntAct=EBI-717201, EBI-302345;
CC Q9UQ90; P61289: PSME3; NbExp=3; IntAct=EBI-717201, EBI-355546;
CC Q9UQ90; O43586: PSTPIP1; NbExp=3; IntAct=EBI-717201, EBI-1050964;
CC Q9UQ90; Q93062: RBPMS; NbExp=3; IntAct=EBI-717201, EBI-740322;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:9635427}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UQ90-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UQ90-2; Sequence=VSP_009192, VSP_009193;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- PTM: Upon import into the mitochondrion, the N-terminal transit peptide
CC is cleaved by the mitochondrial-processing peptidase (MPP) to generate
CC an intermediate form which undergoes a second proteolytic cleavage
CC mediated by proteases AFG3L1 and/or AFG3L2 removing an additional N-
CC terminal fragment to generate the proteolytically active mature form.
CC {ECO:0000250|UniProtKB:Q3ULF4}.
CC -!- DISEASE: Spastic paraplegia 7, autosomal recessive (SPG7) [MIM:607259]:
CC A form of spastic paraplegia, a neurodegenerative disorder
CC characterized by a slow, gradual, progressive weakness and spasticity
CC of the lower limbs. Rate of progression and the severity of symptoms
CC are quite variable. Initial symptoms may include difficulty with
CC balance, weakness and stiffness in the legs, muscle spasms, and
CC dragging the toes when walking. In some forms of the disorder, bladder
CC symptoms (such as incontinence) may appear, or the weakness and
CC stiffness may spread to other parts of the body. SPG7 is a complex
CC form. Additional clinical features are cerebellar syndrome,
CC supranuclear palsy, and cognitive impairment, particularly disturbance
CC of attention and executive functions. {ECO:0000269|PubMed:16534102,
CC ECO:0000269|PubMed:17646629, ECO:0000269|PubMed:20186691,
CC ECO:0000269|PubMed:27217339, ECO:0000269|PubMed:9635427}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Note=Defects in SPG7 may cause autosomal recessive
CC osteogenesis imperfecta (OI). Osteogenesis imperfecta defines a group
CC of connective tissue disorders characterized by bone fragility and low
CC bone mass. Clinical features of SPG7-related osteogenesis imperfecta
CC include recurrent fractures, mild bone deformities, delayed tooth
CC eruption, normal hearing and white sclera.
CC {ECO:0000269|PubMed:20579626}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the AAA ATPase
CC family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the peptidase M41
CC family. {ECO:0000305}.
CC -!- CAUTION: A CDS in the 3'-UTR of SPG7 mRNA had been erroneously
CC identified as a cell matrix adhesion regulator and originally thought
CC to be encoded by the CMAR gene. There is no experimental evidence for
CC the production of endogenous CMAR protein. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH35929.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BC007692; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Osteogenesis imperfecta variant database;
CC Note=Paraplegin (SPG7);
CC URL="http://oi.gene.le.ac.uk/home.php?select_db=SP7";
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DR EMBL; Y16610; CAA76314.1; -; mRNA.
DR EMBL; AF080525; AAD28099.1; -; Genomic_DNA.
DR EMBL; AF080511; AAD28099.1; JOINED; Genomic_DNA.
DR EMBL; AF080512; AAD28099.1; JOINED; Genomic_DNA.
DR EMBL; AF080513; AAD28099.1; JOINED; Genomic_DNA.
DR EMBL; AF080514; AAD28099.1; JOINED; Genomic_DNA.
DR EMBL; AF080515; AAD28099.1; JOINED; Genomic_DNA.
DR EMBL; AF080516; AAD28099.1; JOINED; Genomic_DNA.
DR EMBL; AF080517; AAD28099.1; JOINED; Genomic_DNA.
DR EMBL; AF080518; AAD28099.1; JOINED; Genomic_DNA.
DR EMBL; AF080519; AAD28099.1; JOINED; Genomic_DNA.
DR EMBL; AF080520; AAD28099.1; JOINED; Genomic_DNA.
DR EMBL; AF080521; AAD28099.1; JOINED; Genomic_DNA.
DR EMBL; AF080522; AAD28099.1; JOINED; Genomic_DNA.
DR EMBL; AF080523; AAD28099.1; JOINED; Genomic_DNA.
DR EMBL; AF080524; AAD28099.1; JOINED; Genomic_DNA.
DR EMBL; BC007692; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC035929; AAH35929.1; ALT_INIT; mRNA.
DR EMBL; BC036104; AAH36104.1; -; mRNA.
DR EMBL; BC110530; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC110531; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS10977.1; -. [Q9UQ90-1]
DR CCDS; CCDS10978.1; -. [Q9UQ90-2]
DR RefSeq; NP_003110.1; NM_003119.3. [Q9UQ90-1]
DR RefSeq; NP_955399.1; NM_199367.2. [Q9UQ90-2]
DR RefSeq; XP_016879088.1; XM_017023599.1.
DR PDB; 2QZ4; X-ray; 2.22 A; A=305-565.
DR PDBsum; 2QZ4; -.
DR AlphaFoldDB; Q9UQ90; -.
DR SMR; Q9UQ90; -.
DR BioGRID; 112565; 142.
DR CORUM; Q9UQ90; -.
DR IntAct; Q9UQ90; 55.
DR MINT; Q9UQ90; -.
DR STRING; 9606.ENSP00000268704; -.
DR MEROPS; M41.006; -.
DR iPTMnet; Q9UQ90; -.
DR PhosphoSitePlus; Q9UQ90; -.
DR BioMuta; SPG7; -.
DR DMDM; 116242796; -.
DR EPD; Q9UQ90; -.
DR jPOST; Q9UQ90; -.
DR MassIVE; Q9UQ90; -.
DR MaxQB; Q9UQ90; -.
DR PaxDb; Q9UQ90; -.
DR PeptideAtlas; Q9UQ90; -.
DR PRIDE; Q9UQ90; -.
DR ProteomicsDB; 85528; -. [Q9UQ90-1]
DR ProteomicsDB; 85529; -. [Q9UQ90-2]
DR Antibodypedia; 30863; 406 antibodies from 21 providers.
DR DNASU; 6687; -.
DR Ensembl; ENST00000341316.6; ENSP00000341157.2; ENSG00000197912.16. [Q9UQ90-2]
DR Ensembl; ENST00000645818.2; ENSP00000495795.2; ENSG00000197912.16. [Q9UQ90-1]
DR Ensembl; ENST00000646263.1; ENSP00000494119.1; ENSG00000197912.16. [Q9UQ90-2]
DR GeneID; 6687; -.
DR KEGG; hsa:6687; -.
DR MANE-Select; ENST00000645818.2; ENSP00000495795.2; NM_003119.4; NP_003110.1.
DR UCSC; uc002fni.4; human. [Q9UQ90-1]
DR CTD; 6687; -.
DR DisGeNET; 6687; -.
DR GeneCards; SPG7; -.
DR GeneReviews; SPG7; -.
DR HGNC; HGNC:11237; SPG7.
DR HPA; ENSG00000197912; Low tissue specificity.
DR MalaCards; SPG7; -.
DR MIM; 602783; gene.
DR MIM; 607259; phenotype.
DR neXtProt; NX_Q9UQ90; -.
DR OpenTargets; ENSG00000197912; -.
DR Orphanet; 35689; Primary lateral sclerosis.
DR Orphanet; 99013; Spastic paraplegia type 7.
DR PharmGKB; PA36067; -.
DR VEuPathDB; HostDB:ENSG00000197912; -.
DR eggNOG; KOG0731; Eukaryota.
DR GeneTree; ENSGT00940000156329; -.
DR HOGENOM; CLU_000688_23_2_1; -.
DR InParanoid; Q9UQ90; -.
DR OMA; TRMKSMK; -.
DR OrthoDB; 217929at2759; -.
DR PhylomeDB; Q9UQ90; -.
DR TreeFam; TF105003; -.
DR BRENDA; 3.4.24.B18; 2681.
DR PathwayCommons; Q9UQ90; -.
DR Reactome; R-HSA-8949664; Processing of SMDT1.
DR SignaLink; Q9UQ90; -.
DR BioGRID-ORCS; 6687; 11 hits in 1078 CRISPR screens.
DR ChiTaRS; SPG7; human.
DR EvolutionaryTrace; Q9UQ90; -.
DR GeneWiki; Paraplegin; -.
DR GeneWiki; SPG7; -.
DR GenomeRNAi; 6687; -.
DR Pharos; Q9UQ90; Tbio.
DR PRO; PR:Q9UQ90; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9UQ90; protein.
DR Bgee; ENSG00000197912; Expressed in sural nerve and 201 other tissues.
DR ExpressionAtlas; Q9UQ90; baseline and differential.
DR Genevisible; Q9UQ90; HS.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0005745; C:m-AAA complex; IBA:GO_Central.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005757; C:mitochondrial permeability transition pore complex; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; TAS:ProtInc.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0004176; F:ATP-dependent peptidase activity; IEA:InterPro.
DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:MGI.
DR GO; GO:0008233; F:peptidase activity; TAS:ProtInc.
DR GO; GO:0051082; F:unfolded protein binding; TAS:ProtInc.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0008089; P:anterograde axonal transport; IEA:Ensembl.
DR GO; GO:1902686; P:mitochondrial outer membrane permeabilization involved in programmed cell death; IMP:UniProtKB.
DR GO; GO:0034982; P:mitochondrial protein processing; IBA:GO_Central.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0065003; P:protein-containing complex assembly; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; TAS:ProtInc.
DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; IMP:UniProtKB.
DR Gene3D; 1.20.58.760; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR HAMAP; MF_01458; FtsH; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR041569; AAA_lid_3.
DR InterPro; IPR003959; ATPase_AAA_core.
DR InterPro; IPR005936; FtsH.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR011546; Pept_M41_FtsH_extracell.
DR InterPro; IPR000642; Peptidase_M41.
DR InterPro; IPR037219; Peptidase_M41-like.
DR Pfam; PF00004; AAA; 1.
DR Pfam; PF17862; AAA_lid_3; 1.
DR Pfam; PF06480; FtsH_ext; 1.
DR Pfam; PF01434; Peptidase_M41; 1.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF140990; SSF140990; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR01241; FtsH_fam; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Disease variant;
KW Hereditary spastic paraplegia; Hydrolase; Membrane; Metal-binding;
KW Metalloprotease; Mitochondrion; Mitochondrion inner membrane;
KW Neurodegeneration; Nitration; Nucleotide-binding; Osteogenesis imperfecta;
KW Protease; Reference proteome; Transit peptide; Transmembrane;
KW Transmembrane helix; Zinc.
FT TRANSIT 1..43
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:Q3ULF4"
FT PROPEP 44..105
FT /note="Removed in mature form"
FT /evidence="ECO:0000250|UniProtKB:Q3ULF4"
FT /id="PRO_0000442305"
FT CHAIN 106..795
FT /note="Paraplegin"
FT /id="PRO_0000084675"
FT TOPO_DOM 106..144
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000255"
FT TRANSMEM 145..165
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 166..248
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT TRANSMEM 249..269
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 270..795
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000255"
FT REGION 108..133
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 701..795
FT /note="Interaction with PPIF"
FT /evidence="ECO:0000269|PubMed:26387735"
FT REGION 751..795
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 762..777
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 575
FT /evidence="ECO:0000250|UniProtKB:Q9WZ49"
FT BINDING 312
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 349..357
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:19841671,
FT ECO:0007744|PDB:2QZ4"
FT BINDING 492
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:19841671,
FT ECO:0007744|PDB:2QZ4"
FT BINDING 574
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9WZ49"
FT BINDING 578
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9WZ49"
FT BINDING 650
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9WZ49"
FT MOD_RES 505
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q3ULF4"
FT VAR_SEQ 443..489
FT /note="MGTTDHVIVLASTNRADILDGALMRPGRLDRHVFIDLPTLQERREIF -> A
FT SLDQLPSQGTMRKLRGKTPACSCLTEPTGSRRAMEGHSLCWGCLLH (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009192"
FT VAR_SEQ 490..795
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009193"
FT VARIANT 2
FT /note="A -> T (in dbSNP:rs535030441)"
FT /evidence="ECO:0000269|PubMed:16534102"
FT /id="VAR_063603"
FT VARIANT 82
FT /note="Missing (might be implicated in the hereditary
FT spastic paraplegia phenotype)"
FT /evidence="ECO:0000269|PubMed:16534102"
FT /id="VAR_063604"
FT VARIANT 284
FT /note="F -> P (requires 2 nucleotide substitutions; might
FT be implicated in the hereditary spastic paraplegia
FT phenotype)"
FT /evidence="ECO:0000269|PubMed:16534102"
FT /id="VAR_063605"
FT VARIANT 294
FT /note="R -> H (in dbSNP:rs115661328)"
FT /evidence="ECO:0000269|PubMed:16534102"
FT /id="VAR_063606"
FT VARIANT 349
FT /note="G -> S (in SPG7; function impaired;
FT dbSNP:rs141659620)"
FT /evidence="ECO:0000269|PubMed:20186691"
FT /id="VAR_063607"
FT VARIANT 486
FT /note="R -> Q (in dbSNP:rs111475461)"
FT /id="VAR_063608"
FT VARIANT 503
FT /note="T -> A (in dbSNP:rs2292954)"
FT /evidence="ECO:0000269|PubMed:16534102,
FT ECO:0000269|PubMed:20186691"
FT /id="VAR_017433"
FT VARIANT 510
FT /note="A -> V (in SPG7; function impaired;
FT dbSNP:rs61755320)"
FT /evidence="ECO:0000269|PubMed:16534102,
FT ECO:0000269|PubMed:20186691, ECO:0000269|PubMed:27217339"
FT /id="VAR_063609"
FT VARIANT 545
FT /note="F -> L (in dbSNP:rs758338586)"
FT /evidence="ECO:0000269|PubMed:16534102"
FT /id="VAR_063610"
FT VARIANT 581
FT /note="Missing (in SPG7)"
FT /evidence="ECO:0000269|PubMed:16534102"
FT /id="VAR_063611"
FT VARIANT 583
FT /note="W -> C (in SPG7; function impaired;
FT dbSNP:rs267607085)"
FT /evidence="ECO:0000269|PubMed:20186691"
FT /id="VAR_063612"
FT VARIANT 603
FT /note="A -> T (in dbSNP:rs370852816)"
FT /evidence="ECO:0000269|PubMed:16534102"
FT /id="VAR_063613"
FT VARIANT 623
FT /note="F -> C (in dbSNP:rs17783943)"
FT /id="VAR_048117"
FT VARIANT 635
FT /note="S -> L (might be implicated in the hereditary
FT spastic paraplegia phenotype; dbSNP:rs864622507)"
FT /evidence="ECO:0000269|PubMed:16534102"
FT /id="VAR_063614"
FT VARIANT 645
FT /note="S -> T (in dbSNP:rs2099104)"
FT /evidence="ECO:0000269|PubMed:16534102"
FT /id="VAR_059086"
FT VARIANT 650
FT /note="D -> H (might be implicated in the hereditary
FT spastic paraplegia phenotype)"
FT /evidence="ECO:0000269|PubMed:16534102"
FT /id="VAR_063615"
FT VARIANT 688
FT /note="R -> Q (in dbSNP:rs12960)"
FT /evidence="ECO:0000269|PubMed:16534102,
FT ECO:0000269|PubMed:20186691"
FT /id="VAR_017434"
FT VARIANT 692
FT /note="S -> T (in SPG7; dbSNP:rs121918357)"
FT /evidence="ECO:0000269|PubMed:17646629"
FT /id="VAR_045898"
FT VARIANT 730
FT /note="N -> D (in dbSNP:rs35749032)"
FT /evidence="ECO:0000269|PubMed:16534102"
FT /id="VAR_048118"
FT MUTAGEN 574
FT /note="H->G: Loss of proteolytic activity but no loss of
FT interaction with PPIF; when associated with G-575 and S-
FT 577."
FT /evidence="ECO:0000269|PubMed:26387735"
FT MUTAGEN 575
FT /note="E->G: Loss of proteolytic activity but no loss of
FT interaction with PPIF; when associated with G-574 and S-
FT 577."
FT /evidence="ECO:0000269|PubMed:26387735"
FT MUTAGEN 577
FT /note="G->S: No loss of interaction with PPIF. Loss of
FT proteolytic activity but no loss of interaction with PPIF;
FT when associated with G-574 and G-575."
FT /evidence="ECO:0000269|PubMed:26387735"
FT CONFLICT 12
FT /note="R -> G (in Ref. 2; AAD28099)"
FT /evidence="ECO:0000305"
FT CONFLICT 376
FT /note="P -> A (in Ref. 3; AAH36104)"
FT /evidence="ECO:0000305"
FT HELIX 315..329
FT /evidence="ECO:0007829|PDB:2QZ4"
FT STRAND 344..349
FT /evidence="ECO:0007829|PDB:2QZ4"
FT HELIX 355..366
FT /evidence="ECO:0007829|PDB:2QZ4"
FT STRAND 370..374
FT /evidence="ECO:0007829|PDB:2QZ4"
FT TURN 375..378
FT /evidence="ECO:0007829|PDB:2QZ4"
FT STRAND 379..382
FT /evidence="ECO:0007829|PDB:2QZ4"
FT HELIX 385..399
FT /evidence="ECO:0007829|PDB:2QZ4"
FT STRAND 402..408
FT /evidence="ECO:0007829|PDB:2QZ4"
FT HELIX 431..441
FT /evidence="ECO:0007829|PDB:2QZ4"
FT STRAND 449..456
FT /evidence="ECO:0007829|PDB:2QZ4"
FT HELIX 458..462
FT /evidence="ECO:0007829|PDB:2QZ4"
FT HELIX 464..466
FT /evidence="ECO:0007829|PDB:2QZ4"
FT STRAND 473..476
FT /evidence="ECO:0007829|PDB:2QZ4"
FT HELIX 482..495
FT /evidence="ECO:0007829|PDB:2QZ4"
FT HELIX 502..511
FT /evidence="ECO:0007829|PDB:2QZ4"
FT HELIX 518..529
FT /evidence="ECO:0007829|PDB:2QZ4"
FT HELIX 545..557
FT /evidence="ECO:0007829|PDB:2QZ4"
SQ SEQUENCE 795 AA; 88235 MW; 453D4BF8553A0632 CRC64;
MAVLLLLLRA LRRGPGPGPR PLWGPGPAWS PGFPARPGRG RPYMASRPPG DLAEAGGRAL
QSLQLRLLTP TFEGINGLLL KQHLVQNPVR LWQLLGGTFY FNTSRLKQKN KEKDKSKGKA
PEEDEEERRR RERDDQMYRE RLRTLLVIAV VMSLLNALST SGGSISWNDF VHEMLAKGEV
QRVQVVPESD VVEVYLHPGA VVFGRPRLAL MYRMQVANID KFEEKLRAAE DELNIEAKDR
IPVSYKRTGF FGNALYSVGM TAVGLAILWY VFRLAGMTGR EGGFSAFNQL KMARFTIVDG
KMGKGVSFKD VAGMHEAKLE VREFVDYLKS PERFLQLGAK VPKGALLLGP PGCGKTLLAK
AVATEAQVPF LAMAGPEFVE VIGGLGAARV RSLFKEARAR APCIVYIDEI DAVGKKRSTT
MSGFSNTEEE QTLNQLLVEM DGMGTTDHVI VLASTNRADI LDGALMRPGR LDRHVFIDLP
TLQERREIFE QHLKSLKLTQ SSTFYSQRLA ELTPGFSGAD IANICNEAAL HAAREGHTSV
HTLNFEYAVE RVLAGTAKKS KILSKEEQKV VAFHESGHAL VGWMLEHTEA VMKVSITPRT
NAALGFAQML PRDQHLFTKE QLFERMCMAL GGRASEALSF NEVTSGAQDD LRKVTRIAYS
MVKQFGMAPG IGPISFPEAQ EGLMGIGRRP FSQGLQQMMD HEARLLVAKA YRHTEKVLQD
NLDKLQALAN ALLEKEVINY EDIEALIGPP PHGPKKMIAP QRWIDAQREK QDLGEEETEE
TQQPPLGGEE PTWPK
