Afg3l2
entrez
69597
canonical
uniprot
Q8JZQ2
canonical
ensembl
ENSMUSG00000024527
resolver
ensp
ENSMUSP00000025408
resolver
ensp
ENSMUSP00000330031
resolver
enst
ENSMUST00000025408
resolver
genesymbol
Afg3l2
resolver
uniprot_entry
AFG32_MOUSE
resolver
amino_acid_sequence
MAHRCLLLWSRGGCRRGLPPLLVPRGCLGPDRRPCLRTLYQYATVQTASSRRSLLRDVIAAYQRFCSRPPKGFEKYFPNGKNGKKASEPKEAVGEKKEPQPSGPQPSGGAGGGGGKRRGKKEDSHWWSRFQKGDFPWDDKDFRMYFLWTALFWGGVMIYFVFKSSGREITWKDFVNNYLSKGVVDRLEVVNKRFVRVTFTPGKTPVDGQYVWFNIGSVDTFERNLETLQQELGIEGENRVPVVYIAESDGSFLLSMLPTVLIIAFLLYTIRRGPAGIGRTGRGMGGLFSVGETTAKVLKDEIDVKFKDVAGCEEAKLEIMEFVNFLKNPKQYQDLGAKIPKGAILTGPPGTGKTLLAKATAGEANVPFITVSGSEFLEMFVGVGPARVRDLFALARKNAPCILFIDEIDAVGRKRGRGNFGGQSEQENTLNQLLVEMDGFNTTTNVVILAGTNRPDILDPALLRPGRFDRQIFIGPPDIKGRASIFKVHLRPLKLDSALEKDKLARKLASLTPGFSGADVANVCNEAALIAARHLSDAINEKHFEQAIERVIGGLEKKTQVLQPEEKKTVAYHEAGHAVAGWYLEHADPLLKVSIIPRGKGLGYAQYLPKEQYLYTKEQLLDRMCMTLGGRVSEEIFFGRITTGAQDDLRKVTQSAYAQIVQFGMNEKVGQISFDLPRQGDMVLEKPYSEATARMIDDEVRILISDAYRRTVALLTEKKADVEKVALLLLEKEVLDKNDMVQLLGPRPFTEKSTYEEFVEGTGSLDEDTSLPEGLQDWNKEREKEEKKEKEKEEPLNEKVVS
uniprot
proteins
disease_involvement
DISEASE: Note=Defects in Afg3l2 are the cause of the paralyze (par) phenotype, a spontaneous mutant strain. Par mice have a normal appearance and fertility but are significantly smaller than their littermates at 1 week of age and display a rapidly progressive loss of motor function in all limbs by 12-14 days. As the disease progresses, they lose the ability to support their own weight or turn themselves over when placed on their back and exhibit a typical posture with over extension of all limbs and uncoordinated movements. They rarely survive beyond 16 days of age, when they are completely paralyzed. {ECO:0000269|PubMed:18337413}.
uniprot
proteins
ec_number
3.4.24.-
uniprot
proteins
ec_number
3.6.-.-
uniprot
proteins
function
FUNCTION: Catalytic component of the m-AAA protease, a protease that plays a key role in proteostasis of inner mitochondrial membrane proteins, and which is essential for axonal and neuron development (PubMed:16239145, PubMed:18337413, PubMed:22678058, PubMed:27642048, PubMed:30389403). AFG3L2 possesses both ATPase and protease activities: the ATPase activity is required to unfold substrates, threading them into the internal proteolytic cavity for hydrolysis into small peptide fragments (By similarity). The m-AAA protease carries out protein quality control in the inner membrane of the mitochondria by mediating degradation of mistranslated or misfolded polypeptides (By similarity). The m-AAA protease complex also promotes the processing and maturation of mitochondrial proteins, such as MRPL32/bL32m, PINK1 and SP7 (PubMed:16239145). Mediates protein maturation of the mitochondrial ribosomal subunit MRPL32/bL32m by catalyzing the cleavage of the presequence of MRPL32/bL32m prior to assembly into the mitochondrial ribosome (PubMed:16239145). Required for SPG7 maturation into its active mature form after SPG7 cleavage by mitochondrial-processing peptidase (MPP) (By similarity). Required for the maturation of PINK1 into its 52kDa mature form after its cleavage by mitochondrial-processing peptidase (MPP) (By similarity). Acts as a regulator of calcium in neurons by mediating degradation of SMDT1/EMRE before its assembly with the uniporter complex, limiting the availability of SMDT1/EMRE for MCU assembly and promoting efficient assembly of gatekeeper subunits with MCU (By similarity). Promotes the proteolytic degradation of GHITM upon hyperpolarization of mitochondria: progressive GHITM degradation leads to respiratory complex I degradation and broad reshaping of the mitochondrial proteome by AFG3L2 (By similarity). Also acts as a regulator of mitochondrial glutathione homeostasis by mediating cleavage and degradation of SLC25A39 (By similarity). SLC25A39 cleavage is prevented when SLC25A39 binds iron-sulfur (By similarity). Also acts as a regulator of carnitine biosynthesis by mediating cleavage and degradation of SLC25A45 (By similarity). Involved in the regulation of OMA1-dependent processing of OPA1 (PubMed:17615298, PubMed:20038678). May act by mediating processing of OMA1 precursor, participating in OMA1 maturation (By similarity). {ECO:0000250|UniProtKB:Q9Y4W6, ECO:0000269|PubMed:16239145, ECO:0000269|PubMed:17615298, ECO:0000269|PubMed:18337413, ECO:0000269|PubMed:20038678, ECO:0000269|PubMed:22678058, ECO:0000269|PubMed:27642048, ECO:0000269|PubMed:30389403}.
uniprot
proteins
mass_dalton
89519
uniprot
proteins
mutagenesis
MUTAGEN 574; /note="E->Q: Absence of proteolytic activity. Loss of its processing into the mature form."; /evidence="ECO:0000269|PubMed:19656850"; MUTAGEN 665; /note="M->R: Knockin heterozygous mice develop normally but adult mice show signs of cerebellar ataxia. Cells from mutant mice display altered mitochondrial bioenergetics, with decreased basal oxygen consumption rate, ATP synthesis and mitochondrial membrane potential. Mitochondrial network formation and morphology is also altered, with greatly reduced expression of fusogenic Opa1 isoforms."; /evidence="ECO:0000269|PubMed:30389403
uniprot
proteins
post_translational_modification
PTM: Upon import into the mitochondrion, the N-terminal transit peptide is cleaved to generate an intermediate form which undergoes autocatalytic proteolytic processing to generate the proteolytically active mature form. {ECO:0000269|PubMed:19656850}.
uniprot
proteins
protein_family
AAA ATPase family; Peptidase M41 family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16239145
uniprot
proteins
pubmed
17101804
uniprot
proteins
pubmed
17615298
uniprot
proteins
pubmed
18337413
uniprot
proteins
pubmed
19656850
uniprot
proteins
pubmed
20038678
uniprot
proteins
pubmed
20208537
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
22563492
uniprot
proteins
pubmed
22678058
uniprot
proteins
pubmed
23041622
uniprot
proteins
pubmed
23806337
uniprot
proteins
pubmed
24681487
uniprot
proteins
pubmed
24856930
uniprot
proteins
pubmed
27642048
uniprot
proteins
pubmed
27911893
uniprot
proteins
pubmed
30389403
uniprot
proteins
sequence_length
802
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000269|PubMed:19656850, ECO:0000269|PubMed:24856930}; Multi-pass membrane protein {ECO:0000255}.
uniprot
proteins
transmembrane_region
TRANSMEM 142..162; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 250..270; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins