ID SPG7_MOUSE Reviewed; 781 AA. AC Q3ULF4; B2RQY8; D3Z1Z1; Q4V9T9; Q7TNG0; Q80X42; Q811Y5; Q8K414; Q8R1A1; AC Q8R1K2; DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot. DT 11-OCT-2005, sequence version 1. DT 02-OCT-2024, entry version 151. DE RecName: Full=Mitochondrial inner membrane m-AAA protease component paraplegin {ECO:0000305}; DE EC=3.4.24.- {ECO:0000269|PubMed:16239145}; DE EC=3.6.-.- {ECO:0000250|UniProtKB:Q9Y4W6}; DE AltName: Full=Paraplegin {ECO:0000303|PubMed:14722615}; 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; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC 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/jci20138; 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., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., 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., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., 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 project: RT 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., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [6] RP PROTEIN SEQUENCE OF 44-53 AND 106-115, PROTEOLYTIC PROCESSING, SUBUNIT, RP INTERACTION WITH AFG3L1 AND AFG3L2, MUTAGENESIS OF GLU-575, AND SUBCELLULAR RP 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 mitochondria."; RL Mol. Biol. Cell 20:4216-4224(2009). RN [7] RP FUNCTION, AND INTERACTION WITH AFG3L2. RX PubMed=16239145; DOI=10.1016/j.cell.2005.08.003; RA Nolden M., Ehses S., Koppen M., Bernacchia A., Rugarli E.I., Langer T.; RT "The m-AAA protease defective in hereditary spastic paraplegia controls RT ribosome assembly in mitochondria."; RL Cell 123:277-289(2005). RN [8] RP NITRATION [LARGE SCALE ANALYSIS] AT TYR-505, AND IDENTIFICATION BY MASS RP 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., Lacan G., RA Melega W.P., Camp D.G. II, Smith R.D., Smith D.J., Squier T.C., RA Bigelow D.J.; RT "Endogenously nitrated proteins in mouse brain: links to neurodegenerative RT disease."; RL Biochemistry 45:8009-8022(2006). RN [9] 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 [10] 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 expression."; RL Cell 143:1174-1189(2010). RN [11] RP SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH AFG3L2, RP 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 endoplasmic RT reticulum."; RL PLoS ONE 7:E36337-E36337(2012). CC -!- FUNCTION: Catalytic component of the m-AAA protease, a protease that CC plays a key role in proteostasis of inner mitochondrial membrane CC proteins, and which is essential for axonal and neuron development CC (PubMed:16239145). SPG7 possesses both ATPase and protease activities: CC the ATPase activity is required to unfold substrates, threading them CC into the internal proteolytic cavity for hydrolysis into small peptide CC fragments (By similarity). The m-AAA protease exerts a dual role in the CC mitochondrial inner membrane: it mediates the processing of specific CC regulatory proteins and ensures protein quality control by degrading CC misfolded polypeptides (By similarity). Mediates protein maturation of CC the mitochondrial ribosomal subunit MRPL32/bL32m by catalyzing the CC cleavage of the presequence of MRPL32/bL32m prior to assembly into the CC mitochondrial ribosome (PubMed:16239145). Acts as a regulator of CC calcium in neurons by mediating degradation of SMDT1/EMRE before its CC assembly with the uniporter complex, limiting the availability of CC SMDT1/EMRE for MCU assembly and promoting efficient assembly of CC gatekeeper subunits with MCU (By similarity). Also regulates CC mitochondrial calcium by catalyzing degradation of MCU (By similarity). CC Plays a role in the formation and regulation of the mitochondrial CC permeability transition pore (mPTP) and its proteolytic activity is CC dispensable for this function (By similarity). CC {ECO:0000250|UniProtKB:Q9UQ90, ECO:0000250|UniProtKB:Q9Y4W6, CC ECO:0000269|PubMed:16239145}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; CC Evidence={ECO:0000250|UniProtKB:Q9Y4W6}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066; CC Evidence={ECO:0000250|UniProtKB:Q9Y4W6}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000250|UniProtKB:Q9Y4W6}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q9Y4W6}; CC -!- SUBUNIT: Forms heterohexamers with SPG7 and AFG3L1 (PubMed:17101804, CC PubMed:19656850, PubMed:22563492). The m-AAA protease is either CC composed of homohexamers of AFG3L2 or heterohexamers of AFG3L1, AFG3L2 CC and/or SPG7 (PubMed:16239145, PubMed:17101804, PubMed:19656850, CC PubMed:22563492). Component of the mitochondrial permeability CC transition pore complex (mPTPC), at least composed of SPG7, VDAC1 and CC PPIF (By similarity). Interacts with MAIP1 (By similarity). CC {ECO:0000250|UniProtKB:Q9UQ90, ECO:0000269|PubMed:16239145, 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-pass CC 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 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: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 first CC signs of swelling and degeneration and correlate with onset of motor CC impairment during a rotarod test. {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 M41 CC family. {ECO:0000305}. CC -!- CAUTION: According to PubMed:22563492, alternative splicing gives rise CC to an isoform (Paraplegin-2) which is identical to the sequence of the CC mature protein and localizes to the endoplasmic reticulum. CC {ECO:0000305|PubMed:19656850}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH55488.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAH96690.1; Type=Erroneous initiation; Note=Extended N-terminus.; 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 AlphaFoldDB; Q3ULF4; -. DR SMR; Q3ULF4; -. DR BioGRID; 231586; 3. DR STRING; 10090.ENSMUSP00000119552; -. DR MEROPS; M41.006; -. DR iPTMnet; Q3ULF4; -. DR PhosphoSitePlus; Q3ULF4; -. DR PaxDb; 10090-ENSMUSP00000119552; -. DR ProteomicsDB; 261134; -. DR Pumba; Q3ULF4; -. DR Antibodypedia; 30863; 455 antibodies from 21 providers. DR DNASU; 234847; -. DR Ensembl; ENSMUST00000149248.9; ENSMUSP00000119552.3; ENSMUSG00000000738.19. DR GeneID; 234847; -. DR KEGG; mmu:234847; -. DR UCSC; uc009nuc.1; mouse. DR AGR; MGI:2385906; -. DR CTD; 6687; -. DR MGI; MGI:2385906; Spg7. DR VEuPathDB; HostDB:ENSMUSG00000000738; -. DR eggNOG; KOG0731; Eukaryota. DR GeneTree; ENSGT00940000156329; -. DR InParanoid; Q3ULF4; -. DR OMA; TRMKSMK; -. DR OrthoDB; 9585at2759; -. DR TreeFam; TF105003; -. DR BRENDA; 3.4.24.B18; 3474. DR Reactome; R-MMU-8949664; Processing of SMDT1. DR Reactome; R-MMU-9837999; Mitochondrial protein degradation. DR BioGRID-ORCS; 234847; 0 hits in 80 CRISPR screens. DR ChiTaRS; Spg7; mouse. DR PRO; PR:Q3ULF4; -. DR Proteomes; UP000000589; Chromosome 8. DR RNAct; Q3ULF4; protein. DR Bgee; ENSMUSG00000000738; Expressed in retinal neural layer and 202 other cell types or tissues. DR ExpressionAtlas; Q3ULF4; baseline and differential. 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: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; ISS:UniProtKB. 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:0034982; P:mitochondrial protein processing; IBA:GO_Central. DR GO; GO:0007005; P:mitochondrion organization; IMP:MGI. DR GO; GO:0110097; P:regulation of calcium import into the mitochondrion; ISS:UniProtKB. DR GO; GO:0030155; P:regulation of cell adhesion; TAS:MGI. DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; ISS:UniProtKB. DR CDD; cd19501; RecA-like_FtsH; 1. DR Gene3D; 1.10.8.60; -; 1. DR Gene3D; 3.40.1690.20; -; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR Gene3D; 1.20.58.760; Peptidase M41; 1. DR HAMAP; MF_01458; FtsH; 1. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR041569; AAA_lid_3. DR InterPro; IPR050928; ATP-dep_Zn_Metalloprotease. 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 NCBIfam; TIGR01241; FtsH_fam; 1. DR PANTHER; PTHR43655; ATP-DEPENDENT PROTEASE; 1. DR PANTHER; PTHR43655:SF8; PARAPLEGIN; 1. 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; FtsH protease domain-like; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. PE 1: Evidence at protein level; KW ATP-binding; Direct protein sequencing; 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:0000269|PubMed:19656850" FT PROPEP 44..105 FT /note="Removed in mature form" FT /evidence="ECO:0000305|PubMed:19656850" FT /id="PRO_0000442306" FT CHAIN 106..781 FT /note="Mitochondrial inner membrane m-AAA protease FT component paraplegin" FT /id="PRO_0000442307" FT TOPO_DOM 106..144 FT /note="Mitochondrial matrix" FT /evidence="ECO:0000305" FT TRANSMEM 145..165 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 166..248 FT /note="Mitochondrial intermembrane" FT /evidence="ECO:0000305" FT TRANSMEM 249..269 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 270..781 FT /note="Mitochondrial matrix" FT /evidence="ECO:0000305" FT REGION 22..56 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 103..135 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..135 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 352 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q9UQ90" FT BINDING 353 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q9UQ90" FT BINDING 354 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q9UQ90" FT BINDING 355 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q9UQ90" FT BINDING 356 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q9UQ90" FT BINDING 357 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:Q9Y4W6" FT BINDING 578 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:Q9Y4W6" FT BINDING 650 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:Q9Y4W6" FT MOD_RES 505 FT /note="3'-nitrotyrosine" FT /evidence="ECO:0007744|PubMed:16800626" FT MUTAGEN 575 FT /note="E->Q: Absence of proteolytic activity. No loss of FT its processing into the mature form." FT /evidence="ECO:0000269|PubMed:19656850" FT CONFLICT 165 FT /note="I -> T (in Ref. 2; AAO21098)" FT /evidence="ECO:0000305" FT CONFLICT 168 FT /note="A -> S (in Ref. 5; AAI38142)" FT /evidence="ECO:0000305" FT CONFLICT 310 FT /note="D -> G (in Ref. 2; AAO21098)" FT /evidence="ECO:0000305" FT CONFLICT 471 FT /note="L -> F (in Ref. 1; AAN03852)" FT /evidence="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 //