ID SPG7_MOUSE Reviewed; 781 AA. AC Q3ULF4; B2RQY8; D3Z1Z1; Q4V9T9; Q7TNG0; Q80X42; Q811Y5; Q8K414; AC Q8R1A1; Q8R1K2; DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot. DT 11-OCT-2005, sequence version 1. DT 07-NOV-2018, entry version 119. DE RecName: Full=Paraplegin {ECO:0000303|PubMed:14722615}; DE EC=3.4.24.-; DE AltName: Full=Spastic paraplegia 7 protein {ECO:0000312|MGI:MGI:2385906}; DE Flags: Precursor; GN Name=Spg7 {ECO:0000312|MGI:MGI:2385906}; 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 [MRNA], AND DISRUPTION PHENOTYPE. RC STRAIN=Swiss Webster / NIH; RX PubMed=14722615; DOI=10.1172/JCI200420138; RA Ferreirinha F., Quattrini A., Pirozzi M., Valsecchi V., Dina G., RA Broccoli V., Auricchio A., Piemonte F., Tozzi G., Gaeta L., Casari G., RA Ballabio A., Rugarli E.I.; RT "Axonal degeneration in paraplegin-deficient mice is associated with RT abnormal mitochondria and impairment of axonal transport."; RL J. Clin. Invest. 113:231-242(2004). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=BALB/cJ; RA Ungaro P., Milano A., Cocozza S.; RT "Cloning and expression analysis of the mouse Spg7 cDNA."; RL Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., RA Davis M.J., Wilming L.G., Aidinis V., Allen J.E., RA Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., RA Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., RA Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., RA Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., RA di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., RA Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., RA Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., RA Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., RA Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., RA Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., RA Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., RA Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., RA Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., RA Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., RA Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., RA Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., RA Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., RA Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., RA Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., RA Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., RA Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., RA Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., RA Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., RA Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., RA Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., RA Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., RA Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., RA Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., RA Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., RA Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Czech II, and FVB/N; TISSUE=Brain, Kidney, Liver, and Lung; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., RA She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., RA Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., RA Zhou S., Teague B., Potamousis K., Churas C., Place M., Herschleb J., RA Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., RA Lindblad-Toh K., Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of RT the mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [6] RP PROTEIN SEQUENCE OF 44-53 AND 106-115, PROTEOLYTIC PROCESSING, RP SUBUNIT, INTERACTION WITH AFG3L1 AND AFG3L2, MUTAGENESIS OF GLU-575, RP AND SUBCELLULAR LOCATION. 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 RT mitochondria."; RL Mol. Biol. Cell 20:4216-4224(2009). RN [7] RP NITRATION [LARGE SCALE ANALYSIS] AT TYR-505, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain; RX PubMed=16800626; DOI=10.1021/bi060474w; RA Sacksteder C.A., Qian W.-J., Knyushko T.V., Wang H., Chin M.H., RA Lacan G., Melega W.P., Camp D.G. II, Smith R.D., Smith D.J., RA Squier T.C., Bigelow D.J.; RT "Endogenously nitrated proteins in mouse brain: links to RT neurodegenerative disease."; RL Biochemistry 45:8009-8022(2006). RN [8] 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- RT AAA protease complexes linked to hereditary spastic paraplegia."; RL Mol. Cell. Biol. 27:758-767(2007). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, 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 [10] RP SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH RP AFG3L2, AND CAUTION. 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 RT endoplasmic reticulum."; RL PLoS ONE 7:E36337-E36337(2012). CC -!- FUNCTION: ATP-dependent zinc metalloprotease. Plays a role in the CC formation and regulation of the mitochondrial permeability CC transition pore (mPTP) and its proteolytic activity is dispensable CC for this function (By similarity). {ECO:0000250|UniProtKB:Q9UQ90, CC ECO:0000305}. 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: Forms heterooligomers with AFG3L1 and AFG3L2 CC (PubMed:22563492, PubMed:17101804, PubMed:19656850). Component of CC the mitochondrial permeability transition pore complex (mPTPC), at CC least composed of SPG7, VDAC1 and PPIF (By similarity). Interacts CC with AFG3L2; the interaction is required for the efficient CC assembly of mitochondrial complex I (PubMed:22563492, CC PubMed:19656850). Interacts with AFG3L1 (PubMed:19656850). CC Interacts with MAIP1. Interacts with VDAC1 and PPIF (By CC similarity). {ECO:0000250|UniProtKB:Q9UQ90, CC ECO:0000269|PubMed:17101804, ECO:0000269|PubMed:19656850, CC ECO:0000269|PubMed:22563492}. CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:19656850, ECO:0000269|PubMed:22563492}; Multi- CC pass membrane protein {ECO:0000255}. CC -!- TISSUE SPECIFICITY: Expressed in the brain and retina (at protein CC level). {ECO:0000269|PubMed:22563492}. CC -!- PTM: Upon import into the mitochondrion, the N-terminal transit CC peptide is cleaved by the mitochondrial-processing peptidase (MPP) CC to generate an intermediate form which undergoes a second CC proteolytic cleavage mediated by proteases AFG3L1 and/or AFG3L2 CC removing an additional N-terminal fragment to generate the CC proteolytically active mature form. {ECO:0000269|PubMed:19656850}. CC -!- DISRUPTION PHENOTYPE: Mice are affected by a distal axonopathy of CC spinal and peripheral axons, characterized by axonal swelling and CC degeneration. Mitochondrial morphological abnormalities occur in CC synaptic terminals and in distal regions of axons long before the CC first signs of swelling and degeneration and correlate with onset CC of motor impairment during a rotarod test. CC {ECO:0000269|PubMed:14722615}. 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}. CC -!- CAUTION: According to PubMed:22563492, alternative splicing gives CC rise to an isoform (Paraplegin-2) which is identical to the CC sequence of the mature protein and localizes to the endoplasmic CC reticulum. {ECO:0000305|PubMed:19656850}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH55488.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC Sequence=AAH96690.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={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; AF512565; AAN03852.1; -; mRNA. DR EMBL; AF547215; AAO21098.1; -; mRNA. DR EMBL; AK145540; BAE26494.1; -; mRNA. DR EMBL; AC121819; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC024466; AAH24466.1; -; mRNA. DR EMBL; BC024986; AAH24986.1; -; mRNA. DR EMBL; BC051051; AAH51051.1; -; mRNA. DR EMBL; BC096690; AAH96690.1; ALT_INIT; mRNA. DR EMBL; BC055488; AAH55488.1; ALT_INIT; mRNA. DR EMBL; BC138141; AAI38142.1; -; mRNA. DR CCDS; CCDS40508.1; -. DR RefSeq; NP_694816.3; NM_153176.4. DR UniGene; Mm.292075; -. DR ProteinModelPortal; Q3ULF4; -. DR SMR; Q3ULF4; -. DR BioGrid; 231586; 1. DR STRING; 10090.ENSMUSP00000104496; -. DR MEROPS; M41.006; -. DR iPTMnet; Q3ULF4; -. DR PhosphoSitePlus; Q3ULF4; -. DR EPD; Q3ULF4; -. DR MaxQB; Q3ULF4; -. DR PaxDb; Q3ULF4; -. DR PRIDE; Q3ULF4; -. DR Ensembl; ENSMUST00000149248; ENSMUSP00000119552; ENSMUSG00000000738. DR GeneID; 234847; -. DR KEGG; mmu:234847; -. DR UCSC; uc009nuc.1; mouse. DR CTD; 6687; -. DR MGI; MGI:2385906; Spg7. DR eggNOG; KOG0731; Eukaryota. DR eggNOG; COG0465; LUCA. DR GeneTree; ENSGT00890000139410; -. DR HOGENOM; HOG000217277; -. DR HOVERGEN; HBG050184; -. DR InParanoid; Q3ULF4; -. DR KO; K09552; -. DR OrthoDB; EOG091G03B4; -. DR TreeFam; TF105003; -. DR BRENDA; 3.4.24.B18; 3474. DR Reactome; R-MMU-8949664; Processing of SMDT1. DR ChiTaRS; Spg7; mouse. DR PRO; PR:Q3ULF4; -. DR Proteomes; UP000000589; Chromosome 8. DR Bgee; ENSMUSG00000000738; Expressed in 213 organ(s), highest expression level in brown adipose tissue. DR CleanEx; MM_SPG7; -. DR ExpressionAtlas; Q3ULF4; baseline and differential. DR Genevisible; Q3ULF4; MM. DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC. DR GO; GO:0005745; C:m-AAA complex; IDA:MGI. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB. DR GO; GO:0005757; C:mitochondrial permeability transition pore complex; ISS:UniProtKB. 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:Ensembl. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0008089; P:anterograde axonal transport; IMP:MGI. DR GO; GO:0007155; P:cell adhesion; TAS:MGI. DR GO; GO:1902686; P:mitochondrial outer membrane permeabilization involved in programmed cell death; ISS:UniProtKB. DR GO; GO:0007005; P:mitochondrion organization; IMP:MGI. DR GO; GO:0030155; P:regulation of cell adhesion; TAS:MGI. DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; ISS:UniProtKB. DR HAMAP; MF_01458; FtsH; 1. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR003959; ATPase_AAA_core. 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; 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. PE 1: Evidence at protein level; KW ATP-binding; Complete proteome; Direct protein sequencing; Hydrolase; KW Membrane; Metal-binding; Metalloprotease; Mitochondrion; KW Mitochondrion inner membrane; Nitration; Nucleotide-binding; Protease; KW Reference proteome; Transit peptide; Transmembrane; KW Transmembrane helix; Zinc. FT TRANSIT 1 43 Mitochondrion. FT {ECO:0000269|PubMed:19656850}. FT PROPEP 44 105 Removed in mature form. FT {ECO:0000305|PubMed:19656850}. FT /FTId=PRO_0000442306. FT CHAIN 106 781 Paraplegin. FT /FTId=PRO_0000442307. FT TOPO_DOM 106 144 Mitochondrial matrix. {ECO:0000305}. FT TRANSMEM 145 165 Helical; Name=1. {ECO:0000255}. FT TOPO_DOM 166 248 Mitochondrial intermembrane. FT {ECO:0000305}. FT TRANSMEM 249 269 Helical; Name=2. {ECO:0000255}. FT TOPO_DOM 270 781 Mitochondrial matrix. {ECO:0000305}. FT NP_BIND 349 357 ATP. {ECO:0000250|UniProtKB:Q9UQ90}. FT REGION 701 781 Interaction with PPIF. FT {ECO:0000250|UniProtKB:Q9UQ90}. FT ACT_SITE 575 575 {ECO:0000250|UniProtKB:Q9WZ49}. FT METAL 574 574 Zinc; catalytic. FT {ECO:0000250|UniProtKB:Q9WZ49}. FT METAL 578 578 Zinc; catalytic. FT {ECO:0000250|UniProtKB:Q9WZ49}. FT METAL 650 650 Zinc; catalytic. FT {ECO:0000250|UniProtKB:Q9WZ49}. FT BINDING 312 312 ATP; via amide nitrogen and carbonyl FT oxygen. {ECO:0000250|UniProtKB:Q9UQ90}. FT BINDING 492 492 ATP. {ECO:0000250|UniProtKB:Q9UQ90}. FT MOD_RES 505 505 Nitrated tyrosine. FT {ECO:0000244|PubMed:16800626}. FT MUTAGEN 575 575 E->Q: Absence of proteolytic activity. No FT loss of its processing into the mature FT form. {ECO:0000269|PubMed:19656850}. FT CONFLICT 165 165 I -> T (in Ref. 2; AAO21098). FT {ECO:0000305}. FT CONFLICT 168 168 A -> S (in Ref. 5; AAI38142). FT {ECO:0000305}. FT CONFLICT 310 310 D -> G (in Ref. 2; AAO21098). FT {ECO:0000305}. FT CONFLICT 471 471 L -> F (in Ref. 1; AAN03852). FT {ECO:0000305}. SQ SEQUENCE 781 AA; 85996 MW; 35CCFB8F24B249D8 CRC64; MAAALLLLRG LRPGPEPRPR RLWGLLSGRG PGLSSGAGAR RPYAARGTPV GPAAAGGHAP QSLLLRILTP SFEGISGLLL KQHIVPNAVR LWPLSGSTLY FNTSRMKQKN KDNDKPKGKT PEDDEEEKRR KEREDQMYRE RLRTLFIIAL VMSLLNSLST SGGSISWADF VNEMLAKGEV QRVQVVPESD VVEVYLHPGA VVFGRPRLAL MYRMQVANID KFEEKLRAAE DELNIESKDR IPVSYKRTGF FGNALYALGM TAVGLAILWY VFRLAGMTGR EGGFSAFNQL KMARFTIVDG KTGKGVSFQD VAGMHEAKLE VREFVDYLKS PERFLQLGAK VPKGALLLGP PGCGKTLLAK AVATEAQVPF LAMAGPEFVE VIGGLGAARV RSLFKEARAR APCIVYIDEI DAVGKKRSTS MSGFSNTEEE QTLNQLLVEM DGMGTTDHVI VLASTNRADV LDNALMRPGR LDRHVFIDLP TLQERREIFE QHLKGLKLTQ PSSFYSQRLA ELTPGFSGAD IANICNEAAL HAAREGHTSV HTFNFEYAVE RVIAGTAKKS KILSKEEQRV VAFHESGHAL VGWLLEHTEA VMKVSIAPRT NAALGFSQML PRDQYLFTKE QLFERMCMAL GGRAAEAISF SRVTSGAQDD LRKVTRIAYS MVKQFGMAPS IGPVSFPEAQ EGLMGIGRRP FSQGLQQMMD HEAKLLVAKA YRHTEKVLLD NLDKLQALAN ALLEKEVINY EDIEALIGPP PHGPKKMIAP QKWIDAEKER QASGEEEAPA P //