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Protein

Paraplegin

Gene

SPG7

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

ATP-dependent zinc metalloprotease.Curated

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei312ATP; via amide nitrogen and carbonyl oxygen1
Binding sitei492ATPCombined sources1 Publication1
Metal bindingi574Zinc; catalyticBy similarity1
Active sitei575By similarity1
Metal bindingi578Zinc; catalyticBy similarity1
Metal bindingi650Zinc; catalyticBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi349 – 357ATPCombined sources1 Publication9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • metalloendopeptidase activity Source: MGI
  • peptidase activity Source: ProtInc
  • unfolded protein binding Source: ProtInc
  • zinc ion binding Source: InterPro

GO - Biological processi

  • anterograde axonal transport Source: Ensembl
  • mitochondrial calcium ion transmembrane transport Source: Reactome
  • mitochondrion organization Source: Ensembl
  • nervous system development Source: ProtInc
  • proteolysis Source: ProtInc

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
LigandATP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDAi3.4.24.B18. 2681.
ReactomeiR-HSA-8949664. Processing of SMDT1.

Protein family/group databases

MEROPSiM41.006.

Names & Taxonomyi

Protein namesi
Recommended name:
ParapleginBy similarity (EC:3.4.24.-)
Alternative name(s):
Cell matrix adhesion regulatorImported
Spastic paraplegia 7 proteinImported
Gene namesi
Name:SPG7Imported
Synonyms:CAR, CMARImported, PGN
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:11237. SPG7.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 144Mitochondrial matrixSequence analysisAdd BLAST144
Transmembranei145 – 165HelicalSequence analysisAdd BLAST21
Topological domaini166 – 248Mitochondrial intermembraneSequence analysisAdd BLAST83
Transmembranei249 – 269HelicalSequence analysisAdd BLAST21
Topological domaini270 – 795Mitochondrial matrixSequence analysisAdd BLAST526

GO - Cellular componenti

  • axon cytoplasm Source: GOC
  • m-AAA complex Source: Ensembl
  • mitochondrial inner membrane Source: Reactome
  • mitochondrion Source: ProtInc

Keywords - Cellular componenti

Membrane, Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Spastic paraplegia 7, autosomal recessive (SPG7)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease 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 also OMIM:607259
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_063607349G → S in SPG7; function impaired. 1 PublicationCorresponds to variant dbSNP:rs141659620Ensembl.1
Natural variantiVAR_063609510A → V in SPG7; function impaired. 3 PublicationsCorresponds to variant dbSNP:rs61755320Ensembl.1
Natural variantiVAR_063611581Missing in SPG7. 1 Publication1
Natural variantiVAR_063612583W → C in SPG7; function impaired. 1 PublicationCorresponds to variant dbSNP:rs267607085Ensembl.1
Natural variantiVAR_045898692S → T in SPG7. 1 PublicationCorresponds to variant dbSNP:rs121918357Ensembl.1
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.1 Publication

Keywords - Diseasei

Disease mutation, Hereditary spastic paraplegia, Neurodegeneration, Osteogenesis imperfecta

Organism-specific databases

DisGeNETi6687.
GeneReviewsiSPG7.
MalaCardsiSPG7.
MIMi607259. phenotype.
OpenTargetsiENSG00000197912.
Orphaneti250932. Autosomal dominant optic atrophy and peripheral neuropathy.
99013. Autosomal recessive spastic paraplegia type 7.
PharmGKBiPA36067.

Polymorphism and mutation databases

BioMutaiSPG7.
DMDMi116242796.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000846751 – 795ParapleginAdd BLAST795

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei505Nitrated tyrosineBy similarity1

Keywords - PTMi

Nitration

Proteomic databases

EPDiQ9UQ90.
PaxDbiQ9UQ90.
PeptideAtlasiQ9UQ90.
PRIDEiQ9UQ90.

PTM databases

iPTMnetiQ9UQ90.
PhosphoSitePlusiQ9UQ90.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000197912.
CleanExiHS_SPG7.
ExpressionAtlasiQ9UQ90. baseline and differential.
GenevisibleiQ9UQ90. HS.

Interactioni

Subunit structurei

Interacts with AFG3L2; the interaction is required for the efficient assembly of mitochondrial complex I (PubMed:14623864, PubMed:19841671). Interacts with MAIP1 (PubMed:27499296).3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • unfolded protein binding Source: ProtInc

Protein-protein interaction databases

BioGridi112565. 59 interactors.
IntActiQ9UQ90. 37 interactors.
MINTiMINT-3083741.
STRINGi9606.ENSP00000268704.

Structurei

Secondary structure

1795
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi315 – 329Combined sources15
Beta strandi344 – 349Combined sources6
Helixi355 – 366Combined sources12
Beta strandi370 – 374Combined sources5
Turni375 – 378Combined sources4
Beta strandi379 – 382Combined sources4
Helixi385 – 399Combined sources15
Beta strandi402 – 408Combined sources7
Helixi431 – 441Combined sources11
Beta strandi449 – 456Combined sources8
Helixi458 – 462Combined sources5
Helixi464 – 466Combined sources3
Beta strandi473 – 476Combined sources4
Helixi482 – 495Combined sources14
Helixi502 – 511Combined sources10
Helixi518 – 529Combined sources12
Helixi545 – 557Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2QZ4X-ray2.22A305-565[»]
ProteinModelPortaliQ9UQ90.
SMRiQ9UQ90.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UQ90.

Family & Domainsi

Sequence similaritiesi

In the N-terminal section; belongs to the AAA ATPase family.Curated
In the C-terminal section; belongs to the peptidase M41 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0731. Eukaryota.
COG0465. LUCA.
GeneTreeiENSGT00890000139410.
HOGENOMiHOG000217277.
HOVERGENiHBG050184.
InParanoidiQ9UQ90.
KOiK09552.
OMAiKMEVKEF.
OrthoDBiEOG091G03B4.
PhylomeDBiQ9UQ90.
TreeFamiTF105003.

Family and domain databases

HAMAPiMF_01458. FtsH. 1 hit.
InterProiView protein in InterPro
IPR003593. AAA+_ATPase.
IPR003959. ATPase_AAA_core.
IPR005936. FtsH.
IPR027417. P-loop_NTPase.
IPR011546. Pept_M41_FtsH_extracell.
IPR000642. Peptidase_M41.
PfamiView protein in Pfam
PF00004. AAA. 1 hit.
PF06480. FtsH_ext. 1 hit.
PF01434. Peptidase_M41. 1 hit.
SMARTiView protein in SMART
SM00382. AAA. 1 hit.
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR01241. FtsH_fam. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9UQ90-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAVLLLLLRA LRRGPGPGPR PLWGPGPAWS PGFPARPGRG RPYMASRPPG
60 70 80 90 100
DLAEAGGRAL QSLQLRLLTP TFEGINGLLL KQHLVQNPVR LWQLLGGTFY
110 120 130 140 150
FNTSRLKQKN KEKDKSKGKA PEEDEEERRR RERDDQMYRE RLRTLLVIAV
160 170 180 190 200
VMSLLNALST SGGSISWNDF VHEMLAKGEV QRVQVVPESD VVEVYLHPGA
210 220 230 240 250
VVFGRPRLAL MYRMQVANID KFEEKLRAAE DELNIEAKDR IPVSYKRTGF
260 270 280 290 300
FGNALYSVGM TAVGLAILWY VFRLAGMTGR EGGFSAFNQL KMARFTIVDG
310 320 330 340 350
KMGKGVSFKD VAGMHEAKLE VREFVDYLKS PERFLQLGAK VPKGALLLGP
360 370 380 390 400
PGCGKTLLAK AVATEAQVPF LAMAGPEFVE VIGGLGAARV RSLFKEARAR
410 420 430 440 450
APCIVYIDEI DAVGKKRSTT MSGFSNTEEE QTLNQLLVEM DGMGTTDHVI
460 470 480 490 500
VLASTNRADI LDGALMRPGR LDRHVFIDLP TLQERREIFE QHLKSLKLTQ
510 520 530 540 550
SSTFYSQRLA ELTPGFSGAD IANICNEAAL HAAREGHTSV HTLNFEYAVE
560 570 580 590 600
RVLAGTAKKS KILSKEEQKV VAFHESGHAL VGWMLEHTEA VMKVSITPRT
610 620 630 640 650
NAALGFAQML PRDQHLFTKE QLFERMCMAL GGRASEALSF NEVTSGAQDD
660 670 680 690 700
LRKVTRIAYS MVKQFGMAPG IGPISFPEAQ EGLMGIGRRP FSQGLQQMMD
710 720 730 740 750
HEARLLVAKA YRHTEKVLQD NLDKLQALAN ALLEKEVINY EDIEALIGPP
760 770 780 790
PHGPKKMIAP QRWIDAQREK QDLGEEETEE TQQPPLGGEE PTWPK
Length:795
Mass (Da):88,235
Last modified:October 17, 2006 - v2
Checksum:i453D4BF8553A0632
GO
Isoform 2 (identifier: Q9UQ90-2) [UniParc]FASTAAdd to basket

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.
Show »
Length:489
Mass (Da):53,940
Checksum:i32CDE9E69A1918F9
GO

Sequence cautioni

The sequence AAH35929 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BC007692 differs from that shown. Reason: Erroneous termination at position 428. Translated as Glu.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti12R → G in AAD28099 (PubMed:10480368).Curated1
Sequence conflicti376P → A in AAH36104 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0636032A → T1 PublicationCorresponds to variant dbSNP:rs535030441Ensembl.1
Natural variantiVAR_06360482Missing Might be implicated in the hereditary spastic paraplegia phenotype. 1 Publication1
Natural variantiVAR_063605284F → P Requires 2 nucleotide substitutions; might be implicated in the hereditary spastic paraplegia phenotype. 1 Publication1
Natural variantiVAR_063606294R → H1 PublicationCorresponds to variant dbSNP:rs115661328Ensembl.1
Natural variantiVAR_063607349G → S in SPG7; function impaired. 1 PublicationCorresponds to variant dbSNP:rs141659620Ensembl.1
Natural variantiVAR_063608486R → Q. Corresponds to variant dbSNP:rs111475461Ensembl.1
Natural variantiVAR_017433503T → A Neutral polymorphism. 2 PublicationsCorresponds to variant dbSNP:rs2292954Ensembl.1
Natural variantiVAR_063609510A → V in SPG7; function impaired. 3 PublicationsCorresponds to variant dbSNP:rs61755320Ensembl.1
Natural variantiVAR_063610545F → L1 Publication1
Natural variantiVAR_063611581Missing in SPG7. 1 Publication1
Natural variantiVAR_063612583W → C in SPG7; function impaired. 1 PublicationCorresponds to variant dbSNP:rs267607085Ensembl.1
Natural variantiVAR_063613603A → T1 PublicationCorresponds to variant dbSNP:rs370852816Ensembl.1
Natural variantiVAR_048117623F → C. Corresponds to variant dbSNP:rs17783943Ensembl.1
Natural variantiVAR_063614635S → L Might be implicated in the hereditary spastic paraplegia phenotype. 1 PublicationCorresponds to variant dbSNP:rs864622507Ensembl.1
Natural variantiVAR_059086645S → T1 PublicationCorresponds to variant dbSNP:rs2099104Ensembl.1
Natural variantiVAR_063615650D → H Might be implicated in the hereditary spastic paraplegia phenotype. 1 Publication1
Natural variantiVAR_017434688R → Q Neutral polymorphism. 2 PublicationsCorresponds to variant dbSNP:rs12960Ensembl.1
Natural variantiVAR_045898692S → T in SPG7. 1 PublicationCorresponds to variant dbSNP:rs121918357Ensembl.1
Natural variantiVAR_048118730N → D1 PublicationCorresponds to variant dbSNP:rs35749032Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_009192443 – 489MGTTD…RREIF → ASLDQLPSQGTMRKLRGKTP ACSCLTEPTGSRRAMEGHSL CWGCLLH in isoform 2. 1 PublicationAdd BLAST47
Alternative sequenceiVSP_009193490 – 795Missing in isoform 2. 1 PublicationAdd BLAST306

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y16610 mRNA. Translation: CAA76314.1.
AF080525
, 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.
CCDSiCCDS10977.1. [Q9UQ90-1]
CCDS10978.1. [Q9UQ90-2]
RefSeqiNP_003110.1. NM_003119.3. [Q9UQ90-1]
NP_955399.1. NM_199367.2. [Q9UQ90-2]
XP_016879088.1. XM_017023599.1. [Q9UQ90-2]
UniGeneiHs.185597.

Genome annotation databases

EnsembliENST00000268704; ENSP00000268704; ENSG00000197912. [Q9UQ90-1]
ENST00000341316; ENSP00000341157; ENSG00000197912. [Q9UQ90-2]
GeneIDi6687.
KEGGihsa:6687.
UCSCiuc002fni.4. human. [Q9UQ90-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSPG7_HUMAN
AccessioniPrimary (citable) accession number: Q9UQ90
Secondary accession number(s): O75756
, Q2TB70, Q58F00, Q96IB0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: October 17, 2006
Last modified: August 30, 2017
This is version 179 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

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.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families