Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Orphanet	Ensembl
	HGNC	UniGene	Nucleotide	OMIM		UCSC

Home Page

FLASH GENE

Symbol

AFG3L2

contributors: mct - updated : 01-09-2015

HGNC name	AFG3 ATPase family gene 3-like 2 (S. cerevisiae)
HGNC id	315

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	SCA28 spinocerebellar ataxia 28 SPAX5 ataxia, spastic, 5, autosomal recessive
Location	18p11.21      Physical location : 12.328.943 - 12.377.275
Synonym name	AFG3 ATPase family gene 3-like 2 (yeast)
	paraplegin-like protein
	AFG3-like protein 2
	ATPase family gene 3, yeast
Synonym symbol(s)	FLJ25993, SCA28, SPAX5
EC.number	3.4.24.-

DNA

TYPE	functioning gene
STRUCTURE	48.35 kb     17 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_006796 17 - 3223 NP_006787 88 797 - PMID: 20208537

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 Cardiovascular heart       highly Digestive salivary gland       highly Nervous brain hindbrain cerebellum   specific Skin/Tegument skin       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     highly Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol Nervous Purkinje cell

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	an ATP-binding/ATPase domain (AAA domain), the structural hallmark of the AAA-protease subfamily
	a zinc-dependent metalloprotease domain in a single polypeptide

conjugated

MetalloP

HOMOLOGY

interspecies

homolog to yeast mitochondrial proteins, Yta10p (Afg3p) (Di Bella 2010)

intraspecies

homolog to paraplegin SPG7

Homologene

FAMILY	AAA ATPase family (in the N terminal)
	peptidase M41 family (in the C terminal)

CATEGORY

chaperone/stress , enzyme

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

basic FUNCTION	turn over of mistranslated and misfolded mt DNA encoded polypeptides
	crucial role by linking mitochondrial metabolism and axonal development
	important role of the homo-oligomeric AFG3L2 m-AAA complex in neuronal degeneration
	unexpectedly essential role in protecting the cerebellum from neurodegeneration and expand the spectrum of molecular mechanisms underlying the overlapping features of hereditary ataxias
	is linked to mitochondrial Ca2+ buffering
	cell-autonomous requirement of AFG3L2 for survival of Purkinje cell
	SPG7 assembles with AFG3L2 into the mAAA protease at the inner membrane of mitochondria, degrades damaged proteins, and regulates the synthesis of mitochondrial ribosomes

CELLULAR PROCESS

protein, degradation

PHYSIOLOGICAL PROCESS

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)

INTERACTION

DNA

RNA

small molecule

protein	assembles with the homologous protein paraplegin to form a supracomplex in charge of the essential protein quality control within mitochondria
	mitochondrial processing peptidase PMPCB generates an intermediate form of AFG3L2 that is matured autocatalytically
	AFG3L1, AFG3L2 are also required for maturation of newly imported paraplegin subunits after their cleavage by PMPCB
	SPG7 is cleaved and activated by AFG3L2 upon assembly

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

SCA28 , SPAX5

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       loss of function causes a marked reduction in mitochondrial Ca2+ buffering

Susceptibility

Variant & Polymorphism

Candidate gene	excellent candidate for motoneuron and cerebellar diseases with early onset unknown etiology
Marker
Therapy target

ANIMAL & CELL MODELS

	loss of Afg3l2 in mouse embryonic fibroblasts (MEFs) reduces mitochondrial Ca2+ uptake capacity
	Afg3l2-/- mice resemble patients carrying homozygous mutations, showing a severe neurological syndrome that leads to lethality at P16