Search Results

Overview

Uniprot IDQ8JZQ2
Protein NameMitochondrial inner membrane m-AAA protease component AFG3L2
Gene NameAfg3l2
OrganismMus musculus

Kla Sites from experimental identification

Position Flanking peptide
121 GGKRRGKKEDSHWWS
307 DEIDVKFKDVAGCEE
330 VNFLKNPKQYQDLGA
487 KGRASIFKVHLRPLK
558 VIGGLEKKTQVLQPE
792 EEKKEKEKEEPLNEK
90 GKKASEPKEAVGEKK

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)

Protein Sequence

10 MAHRCLLLWS 20 RGGCRRGLPP 30 LLVPRGCLGP 40 DRRPCLRTLY 50 QYATVQTASS 60 RRSLLRDVIA 70 AYQRFCSRPP 80 KGFEKYFPNG 90 KNGKKASEPK 100 EAVGEKKEPQ 110 PSGPQPSGGA 120 GGGGGKRRGK 130 KEDSHWWSRF 140 QKGDFPWDDK 150 DFRMYFLWTA 160 LFWGGVMIYF 170 VFKSSGREIT 180 WKDFVNNYLS 190 KGVVDRLEVV 200 NKRFVRVTFT 210 PGKTPVDGQY 220 VWFNIGSVDT 230 FERNLETLQQ 240 ELGIEGENRV 250 PVVYIAESDG 260 SFLLSMLPTV 270 LIIAFLLYTI 280 RRGPAGIGRT 290 GRGMGGLFSV 300 GETTAKVLKD 310 EIDVKFKDVA 320 GCEEAKLEIM 330 EFVNFLKNPK 340 QYQDLGAKIP 350 KGAILTGPPG 360 TGKTLLAKAT 370 AGEANVPFIT 380 VSGSEFLEMF 390 VGVGPARVRD 400 LFALARKNAP 410 CILFIDEIDA 420 VGRKRGRGNF 430 GGQSEQENTL 440 NQLLVEMDGF 450 NTTTNVVILA 460 GTNRPDILDP 470 ALLRPGRFDR 480 QIFIGPPDIK 490 GRASIFKVHL 500 RPLKLDSALE 510 KDKLARKLAS 520 LTPGFSGADV 530 ANVCNEAALI 540 AARHLSDAIN 550 EKHFEQAIER 560 VIGGLEKKTQ 570 VLQPEEKKTV 580 AYHEAGHAVA 590 GWYLEHADPL 600 LKVSIIPRGK 610 GLGYAQYLPK 620 EQYLYTKEQL 630 LDRMCMTLGG 640 RVSEEIFFGR 650 ITTGAQDDLR 660 KVTQSAYAQI 670 VQFGMNEKVG 680 QISFDLPRQG 690 DMVLEKPYSE 700 ATARMIDDEV 710 RILISDAYRR 720 TVALLTEKKA 730 DVEKVALLLL 740 EKEVLDKNDM 750 VQLLGPRPFT 760 EKSTYEEFVE 770 GTGSLDEDTS 780 LPEGLQDWNK 790 EREKEEKKEK 800 EKEEPLNEKV VS

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005745 m-AAA complex
Cellular Component GO:0005743 mitochondrial inner membrane
Cellular Component GO:0005739 mitochondrion
Cellular Component GO:0033011 perinuclear theca
Cellular Component GO:0120238 sperm glycocalyx
Cellular Component GO:0120212 sperm head-tail coupling apparatus
Cellular Component GO:0097225 sperm midpiece
Cellular Component GO:0097228 sperm principal piece
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0016887 ATP hydrolysis activity
Molecular Function GO:0004176 ATP-dependent peptidase activity
Molecular Function GO:0140567 membrane protein dislocase activity
Molecular Function GO:0004222 metalloendopeptidase activity
Molecular Function GO:0008237 metallopeptidase activity
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:0042407 cristae formation
Biological Process GO:0160007 glutathione import into mitochondrion
Biological Process GO:0033619 membrane protein proteolysis
Biological Process GO:0051560 mitochondrial calcium ion homeostasis
Biological Process GO:0008053 mitochondrial fusion
Biological Process GO:0034982 mitochondrial protein processing
Biological Process GO:0141164 mitochondrial protein quality control
Biological Process GO:0007005 mitochondrion organization
Biological Process GO:0055001 muscle cell development
Biological Process GO:0042552 myelination
Biological Process GO:0021675 nerve development
Biological Process GO:0007528 neuromuscular junction development
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:0006508 proteolysis
Biological Process GO:0110097 regulation of calcium import into the mitochondrion
Biological Process GO:0040014 regulation of multicellular organism growth
Biological Process GO:0060013 righting reflex

Reference

[1] Zhuo W, Zhang M, Tan J, Gao Y, Wang Y et al.. Lysine lactylation analysis of proteins in the heart of the Kawasaki disease mouse model.. Front Cell Dev Biol 13:1550220. 2025. PMID: 40114965.

[2] Wu D, Tang Y, Li X, Xiong S, Zhang Z et al.. Characterization of protein lactylation in healthy and ischemic mouse hearts.. Front Cardiovasc Med 12:1644886. 2025. PMID: 41089239.