AFG3L2
entrez
10939
canonical
uniprot
Q9Y4W6
canonical
ensembl
ENSG00000141385
resolver
ensp
ENSP00000269143
resolver
ensp
ENSP00000559450
resolver
enst
ENST00000269143
resolver
genesymbol
AFG3L2
resolver
hgnc
HGNC:315
resolver
uniprot
Q6P1L0
resolver
uniprot
Q8TA92
resolver
uniprot_entry
AFG32_HUMAN
resolver
uniprot_entry
Q8TA92_HUMAN
resolver
uniprot_sec
Q6P1L0
resolver
amino_acid_sequence
MAHRCLRLWGRGGCWPRGLQQLLVPGGVGPGEQPCLRTLYRFVTTQARASRNSLLTDIIAAYQRFCSRPPKGFEKYFPNGKNGKKASEPKEVMGEKKESKPAATTRSSGGGGGGGGKRGGKKDDSHWWSRFQKGDIPWDDKDFRMFFLWTALFWGGVMFYLLLKRSGREITWKDFVNNYLSKGVVDRLEVVNKRFVRVTFTPGKTPVDGQYVWFNIGSVDTFERNLETLQQELGIEGENRVPVVYIAESDGSFLLSMLPTVLIIAFLLYTIRRGPAGIGRTGRGMGGLFSVGETTAKVLKDEIDVKFKDVAGCEEAKLEIMEFVNFLKNPKQYQDLGAKIPKGAILTGPPGTGKTLLAKATAGEANVPFITVSGSEFLEMFVGVGPARVRDLFALARKNAPCILFIDEIDAVGRKRGRGNFGGQSEQENTLNQLLVEMDGFNTTTNVVILAGTNRPDILDPALLRPGRFDRQIFIGPPDIKGRASIFKVHLRPLKLDSTLEKDKLARKLASLTPGFSGADVANVCNEAALIAARHLSDSINQKHFEQAIERVIGGLEKKTQVLQPEEKKTVAYHEAGHAVAGWYLEHADPLLKVSIIPRGKGLGYAQYLPKEQYLYTKEQLLDRMCMTLGGRVSEEIFFGRITTGAQDDLRKVTQSAYAQIVQFGMNEKVGQISFDLPRQGDMVLEKPYSEATARLIDDEVRILINDAYKRTVALLTEKKADVEKVALLLLEKEVLDKNDMVELLGPRPFAEKSTYEEFVEGTGSLDEDTSLPEGLKDWNKEREKEKEEPPGEKVAN
uniprot
proteins
disease_involvement
DISEASE: Spinocerebellar ataxia 28 (SCA28) [MIM:610246]: Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA28 is an autosomal dominant cerebellar ataxia (ADCA) with a slow progressive course and no evidence of sensory involvement or cognitive impairment. {ECO:0000269|PubMed:20208537, ECO:0000269|PubMed:20354562, ECO:0000269|PubMed:20725928, ECO:0000269|PubMed:24272953, ECO:0000269|PubMed:24293060, ECO:0000269|PubMed:24814845, ECO:0000269|PubMed:26454370, ECO:0000269|PubMed:26677414, ECO:0000269|PubMed:26868664, ECO:0000269|PubMed:28660440, ECO:0000269|PubMed:29053796, ECO:0000269|PubMed:30252181, ECO:0000269|PubMed:31111429, ECO:0000269|PubMed:31327635}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Spastic ataxia 5, autosomal recessive (SPAX5) [MIM:614487]: A neurodegenerative disorder characterized by early onset spasticity, peripheral neuropathy, ptosis, oculomotor apraxia, dystonia, cerebellar atrophy, and progressive myoclonic epilepsy. {ECO:0000269|PubMed:22022284, ECO:0000269|PubMed:32219868}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Optic atrophy 12 (OPA12) [MIM:618977]: An autosomal dominant disease characterized by progressive visual loss in association with optic atrophy. Atrophy of the optic disk indicates a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts. OPA12 patients manifest slowly progressive visual impairment with onset usually in the first decade. Some patients may exhibit additional features including impaired intellectual development, dystonia, movement disorders, or ataxia. {ECO:0000269|PubMed:26539208, ECO:0000269|PubMed:29181157, ECO:0000269|PubMed:30252181, ECO:0000269|PubMed:32219868, ECO:0000269|PubMed:32548275, ECO:0000269|PubMed:32600459}. Note=The disease is caused by variants affecting the gene represented in this entry.
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:19748354, PubMed:28396416, PubMed:29932645, PubMed:30683687, PubMed:31327635, PubMed:37917749, PubMed:38157846, PubMed:41075794). 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 (PubMed:19748354, PubMed:31327635). The m-AAA protease carries out quality control in the inner membrane of the mitochondria by mediating degradation of mistranslated or misfolded polypeptides (PubMed:26504172, PubMed:30683687, PubMed:34718584). The m-AAA protease complex also promotes the processing and maturation of mitochondrial proteins, such as MRPL32/bL32m, PINK1 and SP7 (PubMed:22354088, PubMed:29932645, PubMed:30252181). 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:29932645). Required for SPG7 maturation into its active mature form after SPG7 cleavage by mitochondrial-processing peptidase (MPP) (PubMed:30252181). Required for the maturation of PINK1 into its 52kDa mature form after its cleavage by mitochondrial-processing peptidase (MPP) (PubMed:22354088). 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 (PubMed:27642048, PubMed:28396416). 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 (PubMed:35912435). Also acts as a regulator of mitochondrial glutathione homeostasis by mediating cleavage and degradation of SLC25A39 (PubMed:37917749, PubMed:38157846). SLC25A39 cleavage is prevented when SLC25A39 binds iron-sulfur (PubMed:37917749, PubMed:38157846). Also acts as a regulator of carnitine biosynthesis by mediating cleavage and degradation of SLC25A45 (PubMed:41075794). Involved in the regulation of OMA1-dependent processing of OPA1 (PubMed:17615298, PubMed:29545505, PubMed:30252181, PubMed:30683687, PubMed:32600459). May act by mediating processing of OMA1 precursor, participating in OMA1 maturation (PubMed:29545505). {ECO:0000269|PubMed:17615298, ECO:0000269|PubMed:19748354, ECO:0000269|PubMed:22354088, ECO:0000269|PubMed:26504172, ECO:0000269|PubMed:27642048, ECO:0000269|PubMed:28396416, ECO:0000269|PubMed:29545505, ECO:0000269|PubMed:29932645, ECO:0000269|PubMed:30252181, ECO:0000269|PubMed:30683687, ECO:0000269|PubMed:31327635, ECO:0000269|PubMed:32600459, ECO:0000269|PubMed:34718584, ECO:0000269|PubMed:35912435, ECO:0000269|PubMed:37917749, ECO:0000269|PubMed:38157846, ECO:0000269|PubMed:41075794}.
uniprot
proteins
mass_dalton
88584
uniprot
proteins
mutagenesis
MUTAGEN 289; /note="F->A: Reduced rate of protein degradation."; /evidence="ECO:0000269|PubMed:31327635"; MUTAGEN 299; /note="L->A: Reduced rate of protein degradation."; /evidence="ECO:0000269|PubMed:31327635"; MUTAGEN 354; /note="K->A: Does not effect activity of the m-AAA protease complex."; /evidence="ECO:0000269|PubMed:19748354"; MUTAGEN 380; /note="M->K: Abolished ATPase and protease activities."; /evidence="ECO:0000269|PubMed:31327635"; MUTAGEN 380; /note="M->V: Increased ATP hydrolysis."; /evidence="ECO:0000269|PubMed:31327635"; MUTAGEN 408; /note="E->Q: Abolished ATPase activity, leading to impaired activity of the m-AAA protease complex, preventing cleavage and degradation of substrate proteins."; /evidence="ECO:0000269|PubMed:19748354, ECO:0000269|PubMed:29932645, ECO:0000269|PubMed:37917749"; MUTAGEN 421; /note="F->A: Impairted protease activity without affecting the ATPase activity."; /evidence="ECO:0000269|PubMed:31327635"; MUTAGEN 575; /note="E->Q: Abolished protease activity. Loss of autocatalytic processing. Impaired proteolytic maturation of SPG7."; /evidence="ECO:0000269|PubMed:29932645, ECO:0000269|PubMed:30252181, ECO:0000269|PubMed:31327635"; MUTAGEN 779; /note="W->R: Impaired ability to degrade substrates without affecting the ATPase activity."; /evidence="ECO:0000269|PubMed:31327635
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:30252181}.
uniprot
proteins
protein_family
AAA ATPase family; Peptidase M41 family
uniprot
proteins
pubmed
10395799
uniprot
proteins
pubmed
14623864
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17101804
uniprot
proteins
pubmed
17615298
uniprot
proteins
pubmed
19748354
uniprot
proteins
pubmed
20208537
uniprot
proteins
pubmed
20354562
uniprot
proteins
pubmed
20725928
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22022284
uniprot
proteins
pubmed
22354088
uniprot
proteins
pubmed
24055473
uniprot
proteins
pubmed
24272953
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24293060
uniprot
proteins
pubmed
24814845
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26387735
uniprot
proteins
pubmed
26454370
uniprot
proteins
pubmed
26504172
uniprot
proteins
pubmed
26539208
uniprot
proteins
pubmed
26677414
uniprot
proteins
pubmed
26868664
uniprot
proteins
pubmed
27499296
uniprot
proteins
pubmed
27642048
uniprot
proteins
pubmed
28396416
uniprot
proteins
pubmed
28449981
uniprot
proteins
pubmed
28660440
uniprot
proteins
pubmed
29053796
uniprot
proteins
pubmed
29181157
uniprot
proteins
pubmed
29545505
uniprot
proteins
pubmed
29932645
uniprot
proteins
pubmed
30252181
uniprot
proteins
pubmed
30683687
uniprot
proteins
pubmed
31111429
uniprot
proteins
pubmed
31327635
uniprot
proteins
pubmed
32219868
uniprot
proteins
pubmed
32548275
uniprot
proteins
pubmed
32600459
uniprot
proteins
pubmed
34718584
uniprot
proteins
pubmed
35912435
uniprot
proteins
pubmed
37917749
uniprot
proteins
pubmed
38157846
uniprot
proteins
pubmed
41075794
uniprot
proteins
sequence_length
797
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000305|PubMed:10395799, ECO:0000305|PubMed:22354088, ECO:0000305|PubMed:31327635}; Multi-pass membrane protein {ECO:0000255}.
uniprot
proteins
transmembrane_region
TRANSMEM 143..163; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 251..271; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins