SPG7_RAT
ID SPG7_RAT Reviewed; 781 AA.
AC Q7TT47; A0A0G2K536;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 22-NOV-2017, sequence version 2.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Paraplegin;
DE EC=3.4.24.-;
DE Flags: Precursor;
GN Name=Spg7;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Shan Y.X., Guo Z.K., Pan J., Geng D.C., Yu L.;
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3]
RP FUNCTION.
RX PubMed=26387735; DOI=10.1016/j.molcel.2015.08.009;
RA Shanmughapriya S., Rajan S., Hoffman N.E., Higgins A.M., Tomar D.,
RA Nemani N., Hines K.J., Smith D.J., Eguchi A., Vallem S., Shaikh F.,
RA Cheung M., Leonard N.J., Stolakis R.S., Wolfers M.P., Ibetti J.,
RA Chuprun J.K., Jog N.R., Houser S.R., Koch W.J., Elrod J.W., Madesh M.;
RT "SPG7 is an essential and conserved component of the mitochondrial
RT permeability transition pore.";
RL Mol. Cell 60:47-62(2015).
CC -!- FUNCTION: ATP-dependent zinc metalloprotease. Plays a role in the
CC formation and regulation of the mitochondrial permeability transition
CC pore (mPTP) and its proteolytic activity is dispensable for this
CC function (PubMed:26387735). {ECO:0000269|PubMed:26387735, 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. Component of the
CC mitochondrial permeability transition pore complex (mPTPC), at least
CC composed of SPG7, VDAC1 and PPIF. Interacts with AFG3L2; the
CC interaction is required for the efficient assembly of mitochondrial
CC complex I. Interacts with AFG3L1. Interacts with MAIP1. Interacts with
CC VDAC1 and PPIF. {ECO:0000250|UniProtKB:Q3ULF4,
CC ECO:0000250|UniProtKB:Q9UQ90}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:Q9UQ90}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q7TT47-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7TT47-2; Sequence=VSP_059223;
CC -!- PTM: Upon import into the mitochondrion, the N-terminal transit peptide
CC is cleaved by the mitochondrial-processing peptidase (MPP) to generate
CC an intermediate form which undergoes a second proteolytic cleavage
CC mediated by proteases AFG3L1 and/or AFG3L2 removing an additional N-
CC terminal fragment to generate the proteolytically active mature form.
CC {ECO:0000250|UniProtKB:Q3ULF4}.
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}.
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DR EMBL; AY278739; AAP35059.1; -; mRNA.
DR EMBL; AC119635; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC141337; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_852053.1; NM_181388.2.
DR RefSeq; XP_008770841.1; XM_008772619.2. [Q7TT47-1]
DR AlphaFoldDB; Q7TT47; -.
DR SMR; Q7TT47; -.
DR STRING; 10116.ENSRNOP00000048848; -.
DR MEROPS; M41.006; -.
DR SwissPalm; Q7TT47; -.
DR jPOST; Q7TT47; -.
DR PaxDb; Q7TT47; -.
DR PRIDE; Q7TT47; -.
DR GeneID; 353231; -.
DR KEGG; rno:353231; -.
DR UCSC; RGD:727940; rat. [Q7TT47-1]
DR CTD; 6687; -.
DR RGD; 727940; Spg7.
DR VEuPathDB; HostDB:ENSRNOG00000015150; -.
DR eggNOG; KOG0731; Eukaryota.
DR InParanoid; Q7TT47; -.
DR OMA; TRMKSMK; -.
DR OrthoDB; 217929at2759; -.
DR Reactome; R-RNO-8949664; Processing of SMDT1.
DR PRO; PR:Q7TT47; -.
DR Proteomes; UP000002494; Chromosome 19.
DR Bgee; ENSRNOG00000015150; Expressed in skeletal muscle tissue and 20 other tissues.
DR ExpressionAtlas; Q7TT47; baseline and differential.
DR Genevisible; Q7TT47; RN.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0005745; C:m-AAA complex; ISO:RGD.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005757; C:mitochondrial permeability transition pore complex; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
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; IEA:Ensembl.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0008089; P:anterograde axonal transport; ISO:RGD.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; ISO:RGD.
DR GO; GO:1902686; P:mitochondrial outer membrane permeabilization involved in programmed cell death; IMP:UniProtKB.
DR GO; GO:0034982; P:mitochondrial protein processing; IBA:GO_Central.
DR GO; GO:0007005; P:mitochondrion organization; ISO:RGD.
DR GO; GO:0001954; P:positive regulation of cell-matrix adhesion; ISO:RGD.
DR GO; GO:0065003; P:protein-containing complex assembly; IBA:GO_Central.
DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; IMP:UniProtKB.
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; 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.
PE 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; Hydrolase; Membrane; Metal-binding;
KW Metalloprotease; Mitochondrion; Mitochondrion inner membrane; Nitration;
KW Nucleotide-binding; Protease; Reference proteome; Transit peptide;
KW Transmembrane; Transmembrane helix; Zinc.
FT TRANSIT 1..43
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:Q3ULF4"
FT PROPEP 44..105
FT /note="Removed in mature form"
FT /evidence="ECO:0000250|UniProtKB:Q3ULF4"
FT /id="PRO_0000442308"
FT CHAIN 106..781
FT /note="Paraplegin"
FT /id="PRO_0000304933"
FT TOPO_DOM 106..144
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305"
FT TRANSMEM 145..165
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 166..248
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT TRANSMEM 249..269
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 270..781
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305"
FT REGION 105..134
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 701..781
FT /note="Interaction with PPIF"
FT /evidence="ECO:0000250|UniProtKB:Q9UQ90"
FT COMPBIAS 107..134
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 575
FT /evidence="ECO:0000250|UniProtKB:Q9WZ49"
FT BINDING 312
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9UQ90"
FT BINDING 349..357
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9UQ90"
FT BINDING 492
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9UQ90"
FT BINDING 574
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9WZ49"
FT BINDING 578
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9WZ49"
FT BINDING 650
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9WZ49"
FT MOD_RES 505
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q3ULF4"
FT VAR_SEQ 517..554
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_059223"
SQ SEQUENCE 781 AA; 86103 MW; F4C5D4673F5BCFD2 CRC64;
MAAALLLLRA LRQSPEPGPW RLWAQLSGRS PGLFSGAGGR RPYVVRGTPI GLAAAGGHTP
QSLLLRILTP SFEGVSGLLL KRHIVPSAIR LWQLSGSTLY FNTSGLKQKN KDDDKPKGKA
PEDDEEERRR KEREDQMYRE RLRTLFIIAI 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 DGMGTADHVI VLASTNRADV LDNALMRPGR LDRHVFIDLP
TLQERREIFE QHLKGLKLTQ PSSFYSQRLA ELTPGFSGAD IANICNEAAL HAAREGHTSV
HTFNFEYAVE RVIAGTAKKS KILSKEEQRV VAFHESGHAL VGWLLEHTEA VMKVSIAPRT
NAALGFSQML PRDQYLFTKE QLFERMCMAL GGRAAEAISF SRVTSGAQDD LRKVTRIAYS
MVKQFGMAPS IGPVSFPEAQ EGLVGIGRRP FSQGLQQMMD HEARLLVARA YRHTEKVLLD
NLDKLQALAN ALLEKEVINY EDIEALIGPP PHGPKKMIAP QKWIDAEKEK QASGEEEAPA
P
