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Q9UQ90 (SPG7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Paraplegin

EC=3.4.24.-
Alternative name(s):
Spastic paraplegia 7 protein
Gene names
Name:SPG7
Synonyms:CAR, CMAR, PGN
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length795 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Putative ATP-dependent zinc metalloprotease. HAMAP-Rule MF_01458

Subunit structure

Interacts with AFG3L2; the interaction is required for the efficient assembly of mitochondrial complex I. Ref.4

Subcellular location

Mitochondrion membrane; Multi-pass membrane protein Ref.1.

Tissue specificity

Ubiquitous.

Involvement in disease

Spastic paraplegia 7, autosomal recessive (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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.7 Ref.8 Ref.9

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.

Sequence similarities

In the N-terminal section; belongs to the AAA ATPase family.

In the C-terminal section; belongs to the peptidase M41 family.

Caution

A CDS in the 3'-UTR of SPG7 mRNA had been erroneously identified as a cell matrix adhesion regulator and originally thought to be encoded by the CMAR gene. There is no experimental evidence for the production of endogenous CMAR protein.

Sequence caution

The sequence AAH35929.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence BC007692 differs from that shown. Reason: Erroneous termination at position 428. Translated as Glu.

Ontologies

Keywords
   Cellular componentMembrane
Mitochondrion
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Hereditary spastic paraplegia
Neurodegeneration
Osteogenesis imperfecta
   DomainTransmembrane
Transmembrane helix
   LigandATP-binding
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionHydrolase
Metalloprotease
Protease
   PTMNitration
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processanterograde axon cargo transport

Inferred from electronic annotation. Source: Ensembl

cell death

Inferred from electronic annotation. Source: UniProtKB-KW

mitochondrion organization

Inferred from electronic annotation. Source: Ensembl

nervous system development

Traceable author statement Ref.1. Source: ProtInc

proteolysis

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentintegral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

mitochondrial membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrion

Traceable author statement Ref.1. Source: ProtInc

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

metalloendopeptidase activity

Inferred from direct assay PubMed 11549317. Source: MGI

nucleoside-triphosphatase activity

Inferred from electronic annotation. Source: InterPro

peptidase activity

Traceable author statement Ref.1. Source: ProtInc

protein binding

Inferred from physical interaction Ref.4. Source: UniProtKB

unfolded protein binding

Traceable author statement Ref.1. Source: ProtInc

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: 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.
Isoform 2 (identifier: Q9UQ90-2)

The sequence of this isoform differs from the canonical sequence as follows:
     443-489: MGTTDHVIVL...PTLQERREIF → ASLDQLPSQG...HSLCWGCLLH
     490-795: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 795795Paraplegin HAMAP-Rule MF_01458
PRO_0000084675

Regions

Topological domain1 – 144144Mitochondrial matrix Potential
Transmembrane145 – 16521Helical; Potential
Topological domain166 – 24883Mitochondrial intermembrane Potential
Transmembrane249 – 26921Helical; Potential
Topological domain270 – 795526Mitochondrial matrix Potential
Nucleotide binding349 – 3579ATP HAMAP-Rule MF_01458

Sites

Active site5751 By similarity
Metal binding5741Zinc; catalytic By similarity
Metal binding5781Zinc; catalytic By similarity
Metal binding6501Zinc; catalytic By similarity
Binding site1731ATP; via amide nitrogen and carbonyl oxygen
Binding site4921ATP

Amino acid modifications

Modified residue5051Nitrated tyrosine By similarity

Natural variations

Alternative sequence443 – 48947MGTTD…RREIF → ASLDQLPSQGTMRKLRGKTP ACSCLTEPTGSRRAMEGHSL CWGCLLH in isoform 2.
VSP_009192
Alternative sequence490 – 795306Missing in isoform 2.
VSP_009193
Natural variant21A → T. Ref.7
VAR_063603
Natural variant821Missing Might be implicated in the hereditary spastic paraplegia phenotype. Ref.7
VAR_063604
Natural variant2841F → P Requires 2 nucleotide substitutions; might be implicated in the hereditary spastic paraplegia phenotype. Ref.7
VAR_063605
Natural variant2941R → H. Ref.7
Corresponds to variant rs115661328 [ dbSNP | Ensembl ].
VAR_063606
Natural variant3491G → S in SPG7; function impaired. Ref.9
Corresponds to variant rs141659620 [ dbSNP | Ensembl ].
VAR_063607
Natural variant4861R → Q. Ref.7
Corresponds to variant rs111475461 [ dbSNP | Ensembl ].
VAR_063608
Natural variant5031T → A Neutral polymorphism. Ref.7 Ref.9
Corresponds to variant rs2292954 [ dbSNP | Ensembl ].
VAR_017433
Natural variant5101A → V in SPG7; function impaired. Ref.7 Ref.9
Corresponds to variant rs61755320 [ dbSNP | Ensembl ].
VAR_063609
Natural variant5451F → L. Ref.7
VAR_063610
Natural variant5811Missing in SPG7. Ref.7
VAR_063611
Natural variant5831W → C in SPG7; function impaired. Ref.9
VAR_063612
Natural variant6031A → T. Ref.7
VAR_063613
Natural variant6231F → C.
Corresponds to variant rs17783943 [ dbSNP | Ensembl ].
VAR_048117
Natural variant6351S → L Might be implicated in the hereditary spastic paraplegia phenotype. Ref.7
VAR_063614
Natural variant6451S → T. Ref.7
Corresponds to variant rs2099104 [ dbSNP | Ensembl ].
VAR_059086
Natural variant6501D → H Might be implicated in the hereditary spastic paraplegia phenotype. Ref.7
VAR_063615
Natural variant6881R → Q Neutral polymorphism. Ref.7 Ref.9
Corresponds to variant rs12960 [ dbSNP | Ensembl ].
VAR_017434
Natural variant6921S → T in SPG7. Ref.8
VAR_045898
Natural variant7301N → D. Ref.7
Corresponds to variant rs35749032 [ dbSNP | Ensembl ].
VAR_048118

Experimental info

Sequence conflict121R → G in AAD28099. Ref.2
Sequence conflict3761P → A in AAH36104. Ref.3

Secondary structure

................................. 795
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 17, 2006. Version 2.
Checksum: 453D4BF8553A0632

FASTA79588,235
        10         20         30         40         50         60 
MAVLLLLLRA LRRGPGPGPR PLWGPGPAWS PGFPARPGRG RPYMASRPPG DLAEAGGRAL 

        70         80         90        100        110        120 
QSLQLRLLTP TFEGINGLLL KQHLVQNPVR LWQLLGGTFY FNTSRLKQKN KEKDKSKGKA 

       130        140        150        160        170        180 
PEEDEEERRR RERDDQMYRE RLRTLLVIAV VMSLLNALST SGGSISWNDF VHEMLAKGEV 

       190        200        210        220        230        240 
QRVQVVPESD VVEVYLHPGA VVFGRPRLAL MYRMQVANID KFEEKLRAAE DELNIEAKDR 

       250        260        270        280        290        300 
IPVSYKRTGF FGNALYSVGM TAVGLAILWY VFRLAGMTGR EGGFSAFNQL KMARFTIVDG 

       310        320        330        340        350        360 
KMGKGVSFKD VAGMHEAKLE VREFVDYLKS PERFLQLGAK VPKGALLLGP PGCGKTLLAK 

       370        380        390        400        410        420 
AVATEAQVPF LAMAGPEFVE VIGGLGAARV RSLFKEARAR APCIVYIDEI DAVGKKRSTT 

       430        440        450        460        470        480 
MSGFSNTEEE QTLNQLLVEM DGMGTTDHVI VLASTNRADI LDGALMRPGR LDRHVFIDLP 

       490        500        510        520        530        540 
TLQERREIFE QHLKSLKLTQ SSTFYSQRLA ELTPGFSGAD IANICNEAAL HAAREGHTSV 

       550        560        570        580        590        600 
HTLNFEYAVE RVLAGTAKKS KILSKEEQKV VAFHESGHAL VGWMLEHTEA VMKVSITPRT 

       610        620        630        640        650        660 
NAALGFAQML PRDQHLFTKE QLFERMCMAL GGRASEALSF NEVTSGAQDD LRKVTRIAYS 

       670        680        690        700        710        720 
MVKQFGMAPG IGPISFPEAQ EGLMGIGRRP FSQGLQQMMD HEARLLVAKA YRHTEKVLQD 

       730        740        750        760        770        780 
NLDKLQALAN ALLEKEVINY EDIEALIGPP PHGPKKMIAP QRWIDAQREK QDLGEEETEE 

       790 
TQQPPLGGEE PTWPK 

« Hide

Isoform 2 [UniParc].

Checksum: 32CDE9E69A1918F9
Show »

FASTA48953,940

References

« Hide 'large scale' references
[1]"Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease."
Casari G., De Fusco M., Ciarmatori S., Zeviani M., Mora M., Fernandez P., De Michele G., Filla A., Cocozza S., Marconi R., Duerr A., Fontaine B., Ballabio A.
Cell 93:973-983(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, INVOLVEMENT IN SPG7.
[2]"Genomic structure and expression analysis of the spastic paraplegia gene, SPG7."
Settasatian C., Whitmore S.A., Crawford J., Bilton R.L., Cleton-Jansen A.-M., Sutherland G.R., Callen D.F.
Hum. Genet. 105:139-144(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Duodenum and Placenta.
[4]"Loss of m-AAA protease in mitochondria causes complex I deficiency and increased sensitivity to oxidative stress in hereditary spastic paraplegia."
Atorino L., Silvestri L., Koppen M., Cassina L., Ballabio A., Marconi R., Langer T., Casari G.
J. Cell Biol. 163:777-787(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AFG3L2.
[5]"Identification of a frameshift mutation in Osterix in a patient with recessive osteogenesis imperfecta."
Lapunzina P., Aglan M., Temtamy S., Caparros-Martin J.A., Valencia M., Leton R., Martinez-Glez V., Elhossini R., Amr K., Vilaboa N., Ruiz-Perez V.L.
Am. J. Hum. Genet. 87:110-114(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN OSTEOGENESIS IMPERFECTA.
[6]"Crystal structure of the ATPase domain of the human AAA+ protein paraplegin/SPG7."
Karlberg T., van den Berg S., Hammarstrom M., Sagemark J., Johansson I., Holmberg-Schiavone L., Schuler H.
PLoS ONE 4:E6975-E6975(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.22 ANGSTROMS) OF 305-565 IN COMPLEX WITH ADP.
[7]"Mutation analysis of the paraplegin gene (SPG7) in patients with hereditary spastic paraplegia."
Elleuch N., Depienne C., Benomar A., Hernandez A.M., Ferrer X., Fontaine B., Grid D., Tallaksen C.M.E., Zemmouri R., Stevanin G., Durr A., Brice A.
Neurology 66:654-659(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SPG7 VAL-510 AND VAL-581 DEL, VARIANTS THR-2; GLN-82 DEL; PRO-284; HIS-294; GLN-486 ALA-503; LEU-545; THR-603; LEU-635; THR-645; HIS-650; GLN-688 AND ASP-730.
[8]"A novel form of autosomal recessive hereditary spastic paraplegia caused by a new SPG7 mutation."
Warnecke T., Duning T., Schwan A., Lohmann H., Epplen J.T., Young P.
Neurology 69:368-375(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SPG7 THR-692.
[9]"Functional evaluation of paraplegin mutations by a yeast complementation assay."
Bonn F., Pantakani K., Shoukier M., Langer T., Mannan A.U.
Hum. Mutat. 31:617-621(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SPG7 SER-349; VAL-510 AND CYS-583, VARIANTS ALA-503 AND GLN-688, CHARACTERIZATION OF VARIANTS SPG7 SER-349; VAL-510 AND CYS-583, CHARACTERIZATION OF VARIANTS ALA-503 AND GLN-688.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y16610 mRNA. Translation: CAA76314.1.
AF080525 expand/collapse EMBL AC list , AF080511, AF080512, AF080513, AF080514, AF080515, AF080516, AF080517, AF080518, AF080519, AF080520, AF080521, AF080522, AF080523, AF080524 Genomic DNA. Translation: AAD28099.1.
BC007692 mRNA. No translation available.
BC035929 mRNA. Translation: AAH35929.1. Different initiation.
BC036104 mRNA. Translation: AAH36104.1.
BC110530 mRNA. No translation available.
BC110531 mRNA. No translation available.
CCDSCCDS10977.1. [Q9UQ90-1]
CCDS10978.1. [Q9UQ90-2]
RefSeqNP_003110.1. NM_003119.3. [Q9UQ90-1]
NP_955399.1. NM_199367.2. [Q9UQ90-2]
UniGeneHs.185597.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2QZ4X-ray2.22A305-565[»]
ProteinModelPortalQ9UQ90.
SMRQ9UQ90. Positions 158-245, 305-755.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112565. 14 interactions.
IntActQ9UQ90. 15 interactions.
MINTMINT-3083741.
STRING9606.ENSP00000268704.

Protein family/group databases

MEROPSM41.006.

PTM databases

PhosphoSiteQ9UQ90.

Polymorphism databases

DMDM116242796.

Proteomic databases

MaxQBQ9UQ90.
PaxDbQ9UQ90.
PRIDEQ9UQ90.

Protocols and materials databases

DNASU6687.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000268704; ENSP00000268704; ENSG00000197912. [Q9UQ90-1]
ENST00000341316; ENSP00000341157; ENSG00000197912. [Q9UQ90-2]
GeneID6687.
KEGGhsa:6687.
UCSCuc002fni.3. human. [Q9UQ90-2]
uc002fnj.3. human. [Q9UQ90-1]

Organism-specific databases

CTD6687.
GeneCardsGC16P089559.
GeneReviewsSPG7.
HGNCHGNC:11237. SPG7.
MIM602783. gene.
607259. phenotype.
neXtProtNX_Q9UQ90.
Orphanet250932. Autosomal dominant optic atrophy and peripheral neuropathy.
99013. Autosomal recessive spastic paraplegia type 7.
PharmGKBPA36067.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0465.
HOGENOMHOG000217277.
HOVERGENHBG050184.
InParanoidQ9UQ90.
KOK09552.
OMAMMDHEAK.
OrthoDBEOG7HF1HP.
PhylomeDBQ9UQ90.
TreeFamTF105003.

Gene expression databases

ArrayExpressQ9UQ90.
BgeeQ9UQ90.
CleanExHS_SPG7.
GenevestigatorQ9UQ90.

Family and domain databases

Gene3D3.40.50.300. 1 hit.
HAMAPMF_01458. FtsH.
InterProIPR003593. AAA+_ATPase.
IPR003959. ATPase_AAA_core.
IPR005936. FtsH.
IPR027417. P-loop_NTPase.
IPR011546. Pept_M41_FtsH_extracell.
IPR000642. Peptidase_M41.
[Graphical view]
PfamPF00004. AAA. 1 hit.
PF06480. FtsH_ext. 1 hit.
PF01434. Peptidase_M41. 1 hit.
[Graphical view]
SMARTSM00382. AAA. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 1 hit.
TIGRFAMsTIGR01241. FtsH_fam. 1 hit.
ProtoNetSearch...

Other

ChiTaRSSPG7. human.
EvolutionaryTraceQ9UQ90.
GeneWikiParaplegin.
SPG7.
GenomeRNAi6687.
NextBio26057.
PROQ9UQ90.
SOURCESearch...

Entry information

Entry nameSPG7_HUMAN
AccessionPrimary (citable) accession number: Q9UQ90
Secondary accession number(s): O75756 expand/collapse secondary AC list , Q2TB70, Q58F00, Q96IB0
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: October 17, 2006
Last modified: July 9, 2014
This is version 146 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM