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FLASH GENE

Symbol

SPG7

contributors: mct/npt - updated : 09-04-2020

HGNC name	SPG7 matrix AAA peptidase subunit, paraplegin
HGNC id	11237

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	49.39 kb     17 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Text	CMAR cDNA with a 5'region highly homolog to the 5'utr of murine variant in kinase (vik)

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003119 17 - 3076 NP_003110 - 795 - 1999 10480368 NM_199367 10 - 2296 NP_955399 - 489 - 1999 10480368 NM_001363850 18 - 3301 NP_001350779 - 809 - 1999 10480368

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine neuroendocrine pituitary     highly Nervous brain diencephalon amygdala       brain basal nuclei caudate nucleus       brain diencephalon thalamus       nerve       highly   spinal cord         Reproductive female system ovary     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous central

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

HOMOLOGY

interspecies	homolog to yeast AFG3 (of the AAA family adenosine triphosphatases associated with diverse activities)
	homolog to to murine variant in kinase (vik)

Homologene

FAMILY

peptidase family M41

CATEGORY

adhesion , chaperone/stress , enzyme , tumor suppressor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria,inner
	intracellular,cytoplasm,organelle,membrane

basic FUNCTION	nuclear-encoded mitochondrial metalloprotease
	potentially involved in the turnover of mitochondrial proteins
	cell matrix adhesion regulator influencing cell adhesion to collagen
	important role of the homo-oligomeric AFG3L2 m-AAA complex in neuronal degeneration (Martinelli 2009)
	SPG7 assembles with AFG3L2 into the mAAA protease at the inner membrane of mitochondria, degrades damaged proteins, and regulates the synthesis of mitochondrial ribosomes
	is an essential and conserved component of the mitochondrial permeability transition pore
	does not constitute a core component of the mitochondrial permeability transition pore (mPTP) but can modulate mPTP through regulation of the basal mitochondrial Ca2+ concentration

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

text	neuronal development

PATHWAY

metabolism

signaling

a component

component of the m-AAA protease, a high molecular weight complex in the inner mitochondrial membrane evolutionary conserved from yeast to mammals (exists in a hetero-oligomeric form, composed of paraplegin and AFG3L2)(Martinelli 2009)

INTERACTION

DNA

RNA

small molecule

protein

interacting with MRPL32 for importing of MRPL32 into mitochondria

cell & other

REGULATION

Other

SPG7 is cleaved and activated by AFG3L2 upon assembly

ASSOCIATED DISORDERS

corresponding disease(s)

SPG7

related resource

MITOP database

Susceptibility

to sporadic spastic paraparesis

Variant & Polymorphism other	mutations are a frequent cause of sporadic spastic paraparesis (Brugman 2008)

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	Drosophila Spg7 mutants exhibited shortened lifespan, progressive locomotor defects, sensitivity to chemical and environmental stress, and muscular and neuronal degeneration
	mouse model of Spg7-linked hereditary spastic paraplegia is an isoform-specific knock-out, in which mitochondrial paraplegin is specifically ablated, while expression of paraplegin-2 is retained