Search Results

Overview

Uniprot IDQ9Y4W6
Protein NameMitochondrial inner membrane m-AAA protease component AFG3L2
Gene NameAFG3L2
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
100 MGEKKESKPAATTRS
117 GGGGGGGKRGGKKDD
300 ETTAKVLKDEIDVKF
308 DEIDVKFKDVAGCEE
331 VNFLKNPKQYQDLGA
398 DLFALARKNAPCILF
481 FIGPPDIKGRASIFK
502 KLDSTLEKDKLARKL
559 VIGGLEKKTQVLQPE
601 VSIIPRGKGLGYAQY
719 TVALLTEKKADVEKV

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)

Protein Sequence

10 MAHRCLRLWG 20 RGGCWPRGLQ 30 QLLVPGGVGP 40 GEQPCLRTLY 50 RFVTTQARAS 60 RNSLLTDIIA 70 AYQRFCSRPP 80 KGFEKYFPNG 90 KNGKKASEPK 100 EVMGEKKESK 110 PAATTRSSGG 120 GGGGGGKRGG 130 KKDDSHWWSR 140 FQKGDIPWDD 150 KDFRMFFLWT 160 ALFWGGVMFY 170 LLLKRSGREI 180 TWKDFVNNYL 190 SKGVVDRLEV 200 VNKRFVRVTF 210 TPGKTPVDGQ 220 YVWFNIGSVD 230 TFERNLETLQ 240 QELGIEGENR 250 VPVVYIAESD 260 GSFLLSMLPT 270 VLIIAFLLYT 280 IRRGPAGIGR 290 TGRGMGGLFS 300 VGETTAKVLK 310 DEIDVKFKDV 320 AGCEEAKLEI 330 MEFVNFLKNP 340 KQYQDLGAKI 350 PKGAILTGPP 360 GTGKTLLAKA 370 TAGEANVPFI 380 TVSGSEFLEM 390 FVGVGPARVR 400 DLFALARKNA 410 PCILFIDEID 420 AVGRKRGRGN 430 FGGQSEQENT 440 LNQLLVEMDG 450 FNTTTNVVIL 460 AGTNRPDILD 470 PALLRPGRFD 480 RQIFIGPPDI 490 KGRASIFKVH 500 LRPLKLDSTL 510 EKDKLARKLA 520 SLTPGFSGAD 530 VANVCNEAAL 540 IAARHLSDSI 550 NQKHFEQAIE 560 RVIGGLEKKT 570 QVLQPEEKKT 580 VAYHEAGHAV 590 AGWYLEHADP 600 LLKVSIIPRG 610 KGLGYAQYLP 620 KEQYLYTKEQ 630 LLDRMCMTLG 640 GRVSEEIFFG 650 RITTGAQDDL 660 RKVTQSAYAQ 670 IVQFGMNEKV 680 GQISFDLPRQ 690 GDMVLEKPYS 700 EATARLIDDE 710 VRILINDAYK 720 RTVALLTEKK 730 ADVEKVALLL 740 LEKEVLDKND 750 MVELLGPRPF 760 AEKSTYEEFV 770 EGTGSLDEDT 780 SLPEGLKDWN 790 KEREKEKEEP PGEKVAN

Gene Ontology

Classification GO ID Description
Biological Process GO:0006508 proteolysis
Cellular Component GO:0005745 m-AAA complex
Cellular Component GO:0005743 mitochondrial inner membrane
Cellular Component GO:0005739 mitochondrion
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0016887 ATP hydrolysis activity
Molecular Function GO:0004176 ATP-dependent peptidase activity
Molecular Function GO:0004222 metalloendopeptidase activity
Molecular Function GO:0008237 metallopeptidase activity
Molecular Function GO:0051082 unfolded protein binding
Molecular Function GO:0008270 zinc ion binding
Biological Process GO:0007409 axonogenesis
Biological Process GO:0036444 calcium import into the mitochondrion
Biological Process GO:0072753 cellular response to glutathione
Biological Process GO:0033619 membrane protein proteolysis
Biological Process GO:0051560 mitochondrial calcium ion homeostasis
Biological Process GO:0034982 mitochondrial protein processing
Biological Process GO:0141164 mitochondrial protein quality control
Biological Process GO:0016540 protein autoprocessing
Biological Process GO:0030163 protein catabolic process
Biological Process GO:0051604 protein maturation
Biological Process GO:0016485 protein processing
Biological Process GO:0110097 regulation of calcium import into the mitochondrion

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.

[3] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.