AFG32_MOUSE
ID AFG32_MOUSE Reviewed; 802 AA.
AC Q8JZQ2;
DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=AFG3-like protein 2 {ECO:0000305};
DE EC=3.4.24.- {ECO:0000250|UniProtKB:Q9Y4W6};
DE Flags: Precursor;
GN Name=Afg3l2 {ECO:0000312|MGI:MGI:1916847};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Brain, and Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP PROTEIN SEQUENCE OF 39-48 AND 67-74, FUNCTION, PROTEOLYTIC PROCESSING,
RP INTERACTION WITH SPG7 AND AFG3L1, SUBUNIT, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF GLU-574.
RX PubMed=19656850; DOI=10.1091/mbc.e09-03-0218;
RA Koppen M., Bonn F., Ehses S., Langer T.;
RT "Autocatalytic processing of m-AAA protease subunits in mitochondria.";
RL Mol. Biol. Cell 20:4216-4224(2009).
RN [3]
RP PROTEIN SEQUENCE OF 173-181; 283-296 AND 632-650, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [4]
RP SUBUNIT.
RX PubMed=17101804; DOI=10.1128/mcb.01470-06;
RA Koppen M., Metodiev M.D., Casari G., Rugarli E.I., Langer T.;
RT "Variable and tissue-specific subunit composition of mitochondrial m-AAA
RT protease complexes linked to hereditary spastic paraplegia.";
RL Mol. Cell. Biol. 27:758-767(2007).
RN [5]
RP FUNCTION, AND VARIANT PAR GLY-389.
RX PubMed=18337413; DOI=10.1523/jneurosci.4677-07.2008;
RA Maltecca F., Aghaie A., Schroeder D.G., Cassina L., Taylor B.A.,
RA Phillips S.J., Malaguti M., Previtali S., Guenet J.L., Quattrini A.,
RA Cox G.A., Casari G.;
RT "The mitochondrial protease AFG3L2 is essential for axonal development.";
RL J. Neurosci. 28:2827-2836(2008).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=20208537; DOI=10.1038/ng.544;
RA Di Bella D., Lazzaro F., Brusco A., Plumari M., Battaglia G., Pastore A.,
RA Finardi A., Cagnoli C., Tempia F., Frontali M., Veneziano L., Sacco T.,
RA Boda E., Brussino A., Bonn F., Castellotti B., Baratta S., Mariotti C.,
RA Gellera C., Fracasso V., Magri S., Langer T., Plevani P., Di Donato S.,
RA Muzi-Falconi M., Taroni F.;
RT "Mutations in the mitochondrial protease gene AFG3L2 cause dominant
RT hereditary ataxia SCA28.";
RL Nat. Genet. 42:313-321(2010).
RN [8]
RP INTERACTION WITH SPG7.
RX PubMed=22563492; DOI=10.1371/journal.pone.0036337;
RA Mancuso G., Barth E., Crivello P., Rugarli E.I.;
RT "Alternative splicing of Spg7, a gene involved in hereditary spastic
RT paraplegia, encodes a variant of paraplegin targeted to the endoplasmic
RT reticulum.";
RL PLoS ONE 7:E36337-E36337(2012).
RN [9]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-116, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [10]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH DNAJC19 AND PHB2.
RX PubMed=24856930; DOI=10.1016/j.cmet.2014.04.016;
RA Richter-Dennerlein R., Korwitz A., Haag M., Tatsuta T., Dargazanli S.,
RA Baker M., Decker T., Lamkemeyer T., Rugarli E.I., Langer T.;
RT "DNAJC19, a mitochondrial cochaperone associated with cardiomyopathy, forms
RT a complex with prohibitins to regulate cardiolipin remodeling.";
RL Cell Metab. 20:158-171(2014).
RN [11]
RP FUNCTION, AND INTERACTION WITH MAIP1.
RX PubMed=27642048; DOI=10.1016/j.molcel.2016.08.020;
RA Koenig T., Troeder S.E., Bakka K., Korwitz A., Richter-Dennerlein R.,
RA Lampe P.A., Patron M., Muehlmeister M., Guerrero-Castillo S., Brandt U.,
RA Decker T., Lauria I., Paggio A., Rizzuto R., Rugarli E.I., De Stefani D.,
RA Langer T.;
RT "The m-AAA protease associated with neurodegeneration limits MCU activity
RT in mitochondria.";
RL Mol. Cell 64:148-162(2016).
CC -!- FUNCTION: ATP-dependent protease which is essential for axonal and
CC neuron development (PubMed:18337413, PubMed:27642048). In neurons,
CC mediates degradation of SMDT1/EMRE before its assembly with the
CC uniporter complex, limiting the availability of SMDT1/EMRE for MCU
CC assembly and promoting efficient assembly of gatekeeper subunits with
CC MCU (By similarity). Required for the maturation of paraplegin (SPG7)
CC after its cleavage by mitochondrial-processing peptidase (MPP),
CC converting it into a proteolytically active mature form. Required for
CC the maturation of PINK1 into its 52kDa mature form after its cleavage
CC by mitochondrial-processing peptidase (MPP) (By similarity). Involved
CC in the regulation of OMA1-dependent processing of OPA1 (By similarity).
CC {ECO:0000250|UniProtKB:Q9Y4W6, ECO:0000269|PubMed:18337413,
CC ECO:0000269|PubMed:27642048}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q9WZ49};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q9WZ49};
CC -!- SUBUNIT: Homooligomer (PubMed:17101804). Forms heterooligomers with
CC SPG7 and AFG3L1 (PubMed:17101804, PubMed:19656850). Interacts with
CC SPG7; the interaction is required for the efficient assembly of
CC mitochondrial complex I (PubMed:22563492, PubMed:19656850). Interacts
CC with AFG3L1 (PubMed:19656850). Interacts with MAIP1 (PubMed:27642048).
CC Interacts with DNAJC19 and PHB2 (PubMed:24856930).
CC {ECO:0000250|UniProtKB:Q9Y4W6, ECO:0000269|PubMed:17101804,
CC ECO:0000269|PubMed:19656850, ECO:0000269|PubMed:22563492,
CC ECO:0000269|PubMed:24856930, ECO:0000269|PubMed:27642048}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:19656850, ECO:0000269|PubMed:24856930}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the cerebellar Purkinje cells.
CC {ECO:0000269|PubMed:20208537}.
CC -!- PTM: Upon import into the mitochondrion, the N-terminal transit peptide
CC is cleaved to generate an intermediate form which undergoes
CC autocatalytic proteolytic processing to generate the proteolytically
CC active mature form. {ECO:0000269|PubMed:19656850}.
CC -!- DISEASE: Note=Defects in Afg3l2 are the cause of the paralyze (par)
CC phenotype, a spontaneous mutant strain. Par mice have a normal
CC appearance and fertility but are significantly smaller than their
CC littermates at 1 week of age and display a rapidly progressive loss of
CC motor function in all limbs by 12-14 days. As the disease progresses,
CC they lose the ability to support their own weight or turn themselves
CC over when placed on their back and exhibit a typical posture with over
CC extension of all limbs and uncoordinated movements. They rarely survive
CC beyond 16 days of age, when they are completely paralyzed.
CC {ECO:0000269|PubMed:18337413}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the AAA ATPase
CC family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the peptidase M41
CC family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BC036999; AAH36999.1; -; mRNA.
DR EMBL; BC043056; AAH43056.1; -; mRNA.
DR CCDS; CCDS37847.1; -.
DR RefSeq; NP_081406.1; NM_027130.1.
DR AlphaFoldDB; Q8JZQ2; -.
DR BMRB; Q8JZQ2; -.
DR SMR; Q8JZQ2; -.
DR BioGRID; 213561; 17.
DR IntAct; Q8JZQ2; 5.
DR MINT; Q8JZQ2; -.
DR STRING; 10090.ENSMUSP00000025408; -.
DR MEROPS; M41.007; -.
DR iPTMnet; Q8JZQ2; -.
DR PhosphoSitePlus; Q8JZQ2; -.
DR SwissPalm; Q8JZQ2; -.
DR EPD; Q8JZQ2; -.
DR jPOST; Q8JZQ2; -.
DR MaxQB; Q8JZQ2; -.
DR PaxDb; Q8JZQ2; -.
DR PeptideAtlas; Q8JZQ2; -.
DR PRIDE; Q8JZQ2; -.
DR ProteomicsDB; 296075; -.
DR Antibodypedia; 1387; 274 antibodies from 31 providers.
DR Ensembl; ENSMUST00000025408; ENSMUSP00000025408; ENSMUSG00000024527.
DR GeneID; 69597; -.
DR KEGG; mmu:69597; -.
DR UCSC; uc008fmf.1; mouse.
DR CTD; 10939; -.
DR MGI; MGI:1916847; Afg3l2.
DR VEuPathDB; HostDB:ENSMUSG00000024527; -.
DR eggNOG; KOG0731; Eukaryota.
DR GeneTree; ENSGT00940000159566; -.
DR HOGENOM; CLU_000688_23_1_1; -.
DR InParanoid; Q8JZQ2; -.
DR OMA; KSHEPTN; -.
DR OrthoDB; 217929at2759; -.
DR PhylomeDB; Q8JZQ2; -.
DR TreeFam; TF105004; -.
DR BRENDA; 3.4.24.B18; 3474.
DR Reactome; R-MMU-8949664; Processing of SMDT1.
DR BioGRID-ORCS; 69597; 9 hits in 73 CRISPR screens.
DR ChiTaRS; Afg3l2; mouse.
DR PRO; PR:Q8JZQ2; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q8JZQ2; protein.
DR Bgee; ENSMUSG00000024527; Expressed in interventricular septum and 250 other tissues.
DR Genevisible; Q8JZQ2; MM.
DR GO; GO:0005745; C:m-AAA complex; IDA:MGI.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0004176; F:ATP-dependent peptidase activity; IEA:InterPro.
DR GO; GO:0004222; F:metalloendopeptidase activity; ISO:MGI.
DR GO; GO:0008237; F:metallopeptidase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0007409; P:axonogenesis; IMP:MGI.
DR GO; GO:0036444; P:calcium import into the mitochondrion; ISS:UniProtKB.
DR GO; GO:0042407; P:cristae formation; IGI:MGI.
DR GO; GO:0033619; P:membrane protein proteolysis; ISO:MGI.
DR GO; GO:0051560; P:mitochondrial calcium ion homeostasis; ISS:UniProtKB.
DR GO; GO:0008053; P:mitochondrial fusion; IGI:MGI.
DR GO; GO:0034982; P:mitochondrial protein processing; IDA:MGI.
DR GO; GO:0007005; P:mitochondrion organization; IGI:MGI.
DR GO; GO:0055001; P:muscle cell development; IMP:MGI.
DR GO; GO:0042552; P:myelination; IMP:MGI.
DR GO; GO:0021675; P:nerve development; IMP:MGI.
DR GO; GO:0007528; P:neuromuscular junction development; IMP:MGI.
DR GO; GO:0016540; P:protein autoprocessing; IMP:UniProtKB.
DR GO; GO:0016485; P:protein processing; IDA:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; ISO:MGI.
DR GO; GO:0040014; P:regulation of multicellular organism growth; IMP:MGI.
DR GO; GO:0060013; P:righting reflex; IMP:MGI.
DR Gene3D; 1.20.58.760; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR HAMAP; MF_01458; FtsH; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR041569; AAA_lid_3.
DR InterPro; IPR003959; ATPase_AAA_core.
DR InterPro; IPR003960; ATPase_AAA_CS.
DR InterPro; IPR005936; FtsH.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR011546; Pept_M41_FtsH_extracell.
DR InterPro; IPR000642; Peptidase_M41.
DR InterPro; IPR037219; Peptidase_M41-like.
DR Pfam; PF00004; AAA; 1.
DR Pfam; PF17862; AAA_lid_3; 1.
DR Pfam; PF06480; FtsH_ext; 1.
DR Pfam; PF01434; Peptidase_M41; 1.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF140990; SSF140990; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR01241; FtsH_fam; 1.
DR PROSITE; PS00674; AAA; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Direct protein sequencing; Disease variant; Hydrolase;
KW Membrane; Metal-binding; Metalloprotease; Mitochondrion;
KW Mitochondrion inner membrane; Nucleotide-binding; Protease;
KW Reference proteome; Transit peptide; Transmembrane; Transmembrane helix;
KW Zinc.
FT TRANSIT 1..38
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:19656850"
FT PROPEP 39..66
FT /note="Removed in mature form"
FT /evidence="ECO:0000305|PubMed:19656850"
FT /id="PRO_0000442313"
FT CHAIN 67..802
FT /note="AFG3-like protein 2"
FT /id="PRO_0000442314"
FT TRANSMEM 142..162
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 250..270
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 76..124
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 759..802
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 773..802
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 574
FT /evidence="ECO:0000250|UniProtKB:Q9WZ49"
FT BINDING 347..354
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT BINDING 573
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9WZ49"
FT BINDING 577
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9WZ49"
FT BINDING 648
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9WZ49"
FT MOD_RES 116
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT VARIANT 389
FT /note="R -> G (in par)"
FT /evidence="ECO:0000269|PubMed:18337413"
FT MUTAGEN 574
FT /note="E->Q: Absence of proteolytic activity. Loss of its
FT processing into the mature form."
FT /evidence="ECO:0000269|PubMed:19656850"
SQ SEQUENCE 802 AA; 89519 MW; E7300BD686532D2D CRC64;
MAHRCLLLWS RGGCRRGLPP LLVPRGCLGP DRRPCLRTLY QYATVQTASS RRSLLRDVIA
AYQRFCSRPP KGFEKYFPNG KNGKKASEPK EAVGEKKEPQ PSGPQPSGGA GGGGGKRRGK
KEDSHWWSRF QKGDFPWDDK DFRMYFLWTA LFWGGVMIYF VFKSSGREIT WKDFVNNYLS
KGVVDRLEVV NKRFVRVTFT PGKTPVDGQY VWFNIGSVDT FERNLETLQQ ELGIEGENRV
PVVYIAESDG SFLLSMLPTV LIIAFLLYTI RRGPAGIGRT GRGMGGLFSV GETTAKVLKD
EIDVKFKDVA GCEEAKLEIM EFVNFLKNPK QYQDLGAKIP KGAILTGPPG TGKTLLAKAT
AGEANVPFIT VSGSEFLEMF VGVGPARVRD LFALARKNAP CILFIDEIDA VGRKRGRGNF
GGQSEQENTL NQLLVEMDGF NTTTNVVILA GTNRPDILDP ALLRPGRFDR QIFIGPPDIK
GRASIFKVHL RPLKLDSALE KDKLARKLAS LTPGFSGADV ANVCNEAALI AARHLSDAIN
EKHFEQAIER VIGGLEKKTQ VLQPEEKKTV AYHEAGHAVA GWYLEHADPL LKVSIIPRGK
GLGYAQYLPK EQYLYTKEQL LDRMCMTLGG RVSEEIFFGR ITTGAQDDLR KVTQSAYAQI
VQFGMNEKVG QISFDLPRQG DMVLEKPYSE ATARMIDDEV RILISDAYRR TVALLTEKKA
DVEKVALLLL EKEVLDKNDM VQLLGPRPFT EKSTYEEFVE GTGSLDEDTS LPEGLQDWNK
EREKEEKKEK EKEEPLNEKV VS
