Entry euk: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   10-MAY-2017, entry version 126.
DE   RecName: Full=AFG3-like protein 2;
DE            EC=3.4.24.- {ECO:0000250|UniProtKB:Q9Y4W6};
GN   Name=Afg3l2;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; 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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [2]
RP   PROTEIN SEQUENCE OF 173-181; 283-296 AND 632-650, AND IDENTIFICATION
RP   BY MASS SPECTROMETRY.
RC   STRAIN=C57BL/6J; TISSUE=Brain;
RA   Lubec G., Kang S.U.;
RL   Submitted (APR-2007) to UniProtKB.
RN   [3]
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
RT   development.";
RL   J. Neurosci. 28:2827-2836(2008).
RN   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
RC   Pancreas, 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
RT   expression.";
RL   Cell 143:1174-1189(2010).
RN   [5]
RP   TISSUE SPECIFICITY.
RX   PubMed=20208537; DOI=10.1038/ng.544;
RA   Di Bella D., Lazzaro F., Brusco A., Plumari M., Battaglia G.,
RA   Pastore A., Finardi A., Cagnoli C., Tempia F., Frontali M.,
RA   Veneziano L., Sacco T., Boda E., Brussino A., Bonn F., Castellotti B.,
RA   Baratta S., Mariotti C., Gellera C., Fracasso V., Magri S., Langer T.,
RA   Plevani P., Di Donato S., 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   [6]
RP   SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-116, AND IDENTIFICATION BY
RP   MASS 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.,
RA   Zhang Y., 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   [7]
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.,
RA   Brandt U., Decker T., Lauria I., Paggio A., Rizzuto R., Rugarli E.I.,
RA   De Stefani D., Langer T.;
RT   "The m-AAA protease associated with neurodegeneration limits MCU
RT   activity 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
CC       with MCU (By similarity). {ECO:0000250|UniProtKB:Q9Y4W6,
CC       ECO:0000269|PubMed:18337413, 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. Interacts with SPG7; the interaction is
CC       required for the efficient assembly of mitochondrial complex I.
CC       Interacts with MAIP1 (PubMed:27642048).
CC       {ECO:0000250|UniProtKB:Q9Y4W6, ECO:0000269|PubMed:27642048}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion membrane
CC       {ECO:0000250|UniProtKB:Q9Y4W6}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:Q9Y4W6}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in the cerebellar Purkinje
CC       cells. {ECO:0000269|PubMed:20208537}.
CC   -!- DISEASE: Note=Defects in Afg3l2 are the cause of the paralyze
CC       (par) phenotype, a spontaneous mutant strain. Par mice have a
CC       normal appearance and fertility but are significantly smaller than
CC       their littermates at 1 week of age and display a rapidly
CC       progressive loss of motor function in all limbs by 12-14 days. As
CC       the disease progresses, they lose the ability to support their own
CC       weight or turn themselves over when placed on their back and
CC       exhibit a typical posture with over extension of all limbs and
CC       uncoordinated movements. They rarely survive beyond 16 days of
CC       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
CC       M41 family. {ECO:0000305}.
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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   UniGene; Mm.426052; -.
DR   ProteinModelPortal; Q8JZQ2; -.
DR   SMR; Q8JZQ2; -.
DR   IntAct; Q8JZQ2; 3.
DR   MINT; MINT-4116623; -.
DR   STRING; 10090.ENSMUSP00000025408; -.
DR   MEROPS; M41.007; -.
DR   iPTMnet; Q8JZQ2; -.
DR   PhosphoSitePlus; Q8JZQ2; -.
DR   EPD; Q8JZQ2; -.
DR   MaxQB; Q8JZQ2; -.
DR   PaxDb; Q8JZQ2; -.
DR   PeptideAtlas; Q8JZQ2; -.
DR   PRIDE; Q8JZQ2; -.
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   eggNOG; KOG0731; Eukaryota.
DR   eggNOG; COG0465; LUCA.
DR   GeneTree; ENSGT00870000136452; -.
DR   HOGENOM; HOG000217277; -.
DR   HOVERGEN; HBG050184; -.
DR   InParanoid; Q8JZQ2; -.
DR   KO; K08956; -.
DR   OMA; CLRLWGR; -.
DR   OrthoDB; EOG091G03EQ; -.
DR   PhylomeDB; Q8JZQ2; -.
DR   TreeFam; TF105004; -.
DR   BRENDA; 3.4.24.B18; 3474.
DR   PRO; PR:Q8JZQ2; -.
DR   Proteomes; UP000000589; Chromosome 18.
DR   Bgee; ENSMUSG00000024527; -.
DR   CleanEx; MM_AFG3L2; -.
DR   Genevisible; Q8JZQ2; MM.
DR   GO; GO:0005745; C:m-AAA complex; IDA:MGI.
DR   GO; GO:0005743; C:mitochondrial inner membrane; IDA:MGI.
DR   GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
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:0042407; P:cristae formation; IGI:MGI.
DR   GO; GO:0051560; P:mitochondrial calcium ion homeostasis; ISS:UniProtKB.
DR   GO; GO:0036444; P:mitochondrial calcium uptake; 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:0048747; P:muscle fiber 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: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   HAMAP; MF_01458; FtsH; 1.
DR   InterPro; IPR003593; AAA+_ATPase.
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   Pfam; PF00004; AAA; 1.
DR   Pfam; PF06480; FtsH_ext; 1.
DR   Pfam; PF01434; Peptidase_M41; 1.
DR   SMART; SM00382; AAA; 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; Complete proteome; Direct protein sequencing;
KW   Disease mutation; Hydrolase; Membrane; Metal-binding; Metalloprotease;
KW   Mitochondrion; Nucleotide-binding; Protease; Reference proteome;
KW   Transmembrane; Transmembrane helix; Zinc.
FT   CHAIN         1    802       AFG3-like protein 2.
FT                                /FTId=PRO_0000084674.
FT   TRANSMEM    142    162       Helical. {ECO:0000255}.
FT   TRANSMEM    250    270       Helical. {ECO:0000255}.
FT   NP_BIND     347    354       ATP. {ECO:0000255}.
FT   ACT_SITE    574    574       {ECO:0000250|UniProtKB:Q9WZ49}.
FT   METAL       573    573       Zinc; catalytic.
FT                                {ECO:0000250|UniProtKB:Q9WZ49}.
FT   METAL       577    577       Zinc; catalytic.
FT                                {ECO:0000250|UniProtKB:Q9WZ49}.
FT   METAL       648    648       Zinc; catalytic.
FT                                {ECO:0000250|UniProtKB:Q9WZ49}.
FT   MOD_RES     116    116       N6-succinyllysine.
FT                                {ECO:0000244|PubMed:23806337}.
FT   VARIANT     389    389       R -> G (in par).
FT                                {ECO:0000269|PubMed:18337413}.
CC   --------------------------------------------------------------------------
CC   The following FT lines are automated annotations from the MyHits database.
CC   --------------------------------------------------------------------------
FT   MYHIT       339    478       ismart:AAA [T]
FT   MYHIT       344    475       ipfam:AAA [T]
FT   MYHIT         4    787       ihamap:FtsH [T]
FT   MYHIT       446    464       ipat:AAA [T]
FT   MYHIT       541    743       ipfam:Peptidase_M41 [T]
FT   MYHIT       148    239       ipfam:FtsH_ext [T]
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
//