SPG7

Protein identityUniProt · HPA

UniProt accession

Q9UQ90

Gene

SPG7

Ensembl

ENSG00000197912

Chromosome

16

Canonical length

795 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins

OverviewNCBI Gene

This gene encodes a mitochondrial metalloprotease protein that is a member of the AAA family. Members of this protein family share an ATPase domain and have roles in diverse cellular processes including membrane trafficking, intracellular motility, organelle biogenesis, protein folding, and proteolysis. Mutations in this gene cause autosomal recessive spastic paraplegia 7. Two transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Mar 2014]

Canonical amino-acid sequenceUniProt

795 residues, UniProt reviewed canonical sequence.

>Q9UQ90|SPG7
     1  MAVLLLLLRA LRRGPGPGPR PLWGPGPAWS PGFPARPGRG RPYMASRPPG DLAEAGGRAL
    61  QSLQLRLLTP TFEGINGLLL KQHLVQNPVR LWQLLGGTFY FNTSRLKQKN KEKDKSKGKA
   121  PEEDEEERRR RERDDQMYRE RLRTLLVIAV VMSLLNALST SGGSISWNDF VHEMLAKGEV
   181  QRVQVVPESD VVEVYLHPGA VVFGRPRLAL MYRMQVANID KFEEKLRAAE DELNIEAKDR
   241  IPVSYKRTGF FGNALYSVGM TAVGLAILWY VFRLAGMTGR EGGFSAFNQL KMARFTIVDG
   301  KMGKGVSFKD VAGMHEAKLE VREFVDYLKS PERFLQLGAK VPKGALLLGP PGCGKTLLAK
   361  AVATEAQVPF LAMAGPEFVE VIGGLGAARV RSLFKEARAR APCIVYIDEI DAVGKKRSTT
   421  MSGFSNTEEE QTLNQLLVEM DGMGTTDHVI VLASTNRADI LDGALMRPGR LDRHVFIDLP
   481  TLQERREIFE QHLKSLKLTQ SSTFYSQRLA ELTPGFSGAD IANICNEAAL HAAREGHTSV
   541  HTLNFEYAVE RVLAGTAKKS KILSKEEQKV VAFHESGHAL VGWMLEHTEA VMKVSITPRT
   601  NAALGFAQML PRDQHLFTKE QLFERMCMAL GGRASEALSF NEVTSGAQDD LRKVTRIAYS
   661  MVKQFGMAPG IGPISFPEAQ EGLMGIGRRP FSQGLQQMMD HEARLLVAKA YRHTEKVLQD
   721  NLDKLQALAN ALLEKEVINY EDIEALIGPP PHGPKKMIAP QRWIDAQREK QDLGEEETEE
   781  TQQPPLGGEE PTWPK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SPG7 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

2

Mean surface accessibility (rSASA)

0.39

Highest tissue expression

49 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SPG7.

Disease | AllUniProt

Conditions SPG7 is implicated in, by any mechanism.

• Spastic paraplegia 7, autosomal recessive (SPG7) MIM:607259

Disease | GeneticClinVar

193 pathogenic / likely-pathogenic of 1,249 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hereditary spastic paraplegia 7
• Hereditary spastic paraplegia
• SPG7-related disorder
• Inborn genetic diseases
• Retinal dystrophy

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.65

gnomAD pLI

0

gnomAD missense Z

-0.87

DepMap mean gene effect

0.03

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• anterograde axonal transport
• mitochondrial outer membrane permeabilization involved in programmed cell death
• mitochondrial protein processing
• nervous system development
• proteolysis
• regulation of calcium import into the mitochondrion
• regulation of mitochondrial membrane permeability

Molecular functions

• ATP binding
• ATP hydrolysis activity
• ATP-dependent peptidase activity
• metalloendopeptidase activity
• peptidase activity
• unfolded protein binding
• zinc ion binding

Cellular components

• axon cytoplasm
• m-AAA complex
• mitochondrial inner membrane
• mitochondrial permeability transition pore complex
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Peptidase M41
• AAA+ ATPase domain
• ATPase, AAA-type, core
• ATP-dependent zinc metalloprotease, FtsH
• Peptidase M41, FtsH extracellular
• P-loop containing nucleoside triphosphate hydrolase
• Peptidase M41-like
• AAA ATPase, AAA+ lid domain
• ATP-dependent Zinc Metalloprotease
• ATPase family associated with various cellular activities (AAA)
• Peptidase family M41
• FtsH Extracellular
• AAA+ lid domain

KeywordsUniProt

• ATP-binding
• Hereditary spastic paraplegia
• Hydrolase
• Membrane
• Metal-binding
• Metalloprotease
• Mitochondrion
• Mitochondrion inner membrane
• Neurodegeneration
• Nitration
• Nucleotide-binding
• Osteogenesis imperfecta
• Protease
• Transit peptide
• Transmembrane
• Transmembrane helix
• Zinc

InteractionsUniProt · HPA

Protein binding partners of SPG7 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MAIP1
• PPIF
• VDAC1