PREP_XENTR
ID PREP_XENTR Reviewed; 1027 AA.
AC Q28BR5;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 04-APR-2006, sequence version 1.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=Presequence protease, mitochondrial {ECO:0000305};
DE EC=3.4.24.- {ECO:0000250|UniProtKB:Q5JRX3};
DE AltName: Full=Pitrilysin metalloproteinase 1 {ECO:0000250|UniProtKB:Q5JRX3};
DE Flags: Precursor;
GN Name=pitrm1; ORFNames=TNeu116i05.1 {ECO:0000312|EMBL:CAJ82697.1};
OS Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX NCBI_TaxID=8364;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Neurula;
RG Sanger Xenopus tropicalis EST/cDNA project;
RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Metalloendopeptidase of the mitochondrial matrix that
CC functions in peptide cleavage and degradation rather than in protein
CC processing. Has an ATP-independent activity. Specifically cleaves
CC peptides in the range of 5 to 65 residues. Shows a preference for
CC cleavage after small polar residues and before basic residues, but
CC without any positional preference. Degrades the transit peptides of
CC mitochondrial proteins after their cleavage. Also degrades other
CC unstructured peptides. {ECO:0000250|UniProtKB:Q5JRX3}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q5JRX3};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q5JRX3};
CC -!- ACTIVITY REGULATION: Mainly exists in a closed and catalytically
CC competent conformation but a closed-to-open switch allows substrate
CC entry into the catalytic chamber. Substrate binding induces closure and
CC dimerization. A disulfide bond may lock the enzyme in a closed
CC conformation preventing substrate entry into the catalytic chamber,
CC participating in redox regulation of the enzyme. Inhibited by metal-
CC chelating agents. Inhibited by nickel and zinc excess, and slightly
CC activated by manganese. {ECO:0000250|UniProtKB:Q5JRX3}.
CC -!- SUBUNIT: Monomer and homodimer; homodimerization is induced by binding
CC of the substrate. {ECO:0000250|UniProtKB:Q5JRX3}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000250|UniProtKB:Q5JRX3}.
CC -!- PTM: A disulfide bond locks the enzyme in the closed conformation
CC preventing substrate entry into the catalytic chamber.
CC {ECO:0000250|UniProtKB:Q5JRX3}.
CC -!- SIMILARITY: Belongs to the peptidase M16 family. PreP subfamily.
CC {ECO:0000305}.
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DR EMBL; CR942684; CAJ82697.1; -; mRNA.
DR RefSeq; NP_001039262.1; NM_001045797.1.
DR AlphaFoldDB; Q28BR5; -.
DR SMR; Q28BR5; -.
DR PaxDb; Q28BR5; -.
DR GeneID; 734137; -.
DR KEGG; xtr:734137; -.
DR CTD; 10531; -.
DR Xenbase; XB-GENE-952658; pitrm1.
DR eggNOG; KOG2019; Eukaryota.
DR InParanoid; Q28BR5; -.
DR OrthoDB; 107079at2759; -.
DR Reactome; R-XTR-1268020; Mitochondrial protein import.
DR Proteomes; UP000008143; Chromosome 6.
DR Proteomes; UP000790000; Unplaced.
DR GO; GO:0005759; C:mitochondrial matrix; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; ISS:UniProtKB.
DR GO; GO:0016485; P:protein processing; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; ISS:UniProtKB.
DR InterPro; IPR011249; Metalloenz_LuxS/M16.
DR InterPro; IPR011765; Pept_M16_N.
DR InterPro; IPR007863; Peptidase_M16_C.
DR InterPro; IPR013578; Peptidase_M16C_assoc.
DR Pfam; PF08367; M16C_assoc; 1.
DR Pfam; PF00675; Peptidase_M16; 1.
DR Pfam; PF05193; Peptidase_M16_C; 2.
DR SMART; SM01264; M16C_associated; 1.
DR SUPFAM; SSF63411; SSF63411; 4.
PE 2: Evidence at transcript level;
KW Disulfide bond; Hydrolase; Metal-binding; Metalloprotease; Mitochondrion;
KW Protease; Reference proteome; Transit peptide; Zinc.
FT TRANSIT 1..22
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 23..1027
FT /note="Presequence protease, mitochondrial"
FT /id="PRO_0000249936"
FT REGION 800..829
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 811..826
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 101
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q5JRX3"
FT BINDING 98
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q5JRX3"
FT BINDING 102
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q5JRX3"
FT BINDING 199
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q5JRX3"
FT DISULFID 113..550
FT /evidence="ECO:0000250|UniProtKB:Q5JRX3"
SQ SEQUENCE 1027 AA; 116221 MW; 336BA9545BC4EEEA CRC64;
MIRQCRAGLR LCRALYQTSY RWHGKSACER ALRYAPGESI HGFTVNEVTP VPELFLTAVK
LSHDNTGAKY LHVAREDSNN LFSVQFRTTP LDSTGVPHIL EHTVLCGSQK YPCRDPFFKM
LNRSLSTFMN AFTASDYTMY PFSTQNAKDF QNLLSVYLDA VFFPCLRELD FWQEGWRLEH
ENPEDPNSPL IFKGIVFNEM KGAFTDNEKV FSQHLQNKLL PDHTYSVVSG GEPLNIPDLT
WEQLKQFHAT HYHPSNARFF TYGNLPLEIH LKQIHEDALS KFERIDPKTS VPPQERWQSP
REYSISCGTD SFASDPEKQT TVSVNFLLSE ITDTFEAFTL SLLSSLMVDG PNSPFYKALI
EANLGTDFSP DTGFNNYTRE TYFSIGLQGI NKEDSEKVKA IINKTINEVA EHGIEAERIE
ALLHKLEIQM KHQSTSFGLT LASYVASCWN HEGDPVDLLK IGDKISRFRE CLKENPKFLQ
DKVKQYFQVS QHRMTLSMSP DEQHYDKEAQ LEAEKLTQKV KALSEEERKQ IYEKGLELIR
LQSKPQDASC LPALKVSDIE PKIPLTDLDI TYAGDVPVQY CAQPTNGMVY FRAVSSLNTL
PEELKPYVPL FCSVITKLGC GVYNYREQAQ QMELTTGGMS VCPHIITDDS NLDTYEQGVV
FSSLCLDRNL PDMMHLWSEI FNSPHFDDEE RLRVLVRMSA QEMSNGIPDS GHVYASIRAG
RTLTPAGELQ ELFSGMDQVK MIKRIAEMPE MGPILRKLSR IRKYVLLSDN MRCSVNATPQ
QMPVASKEIE HFLAGISRSK KERKSIRPHV VEKSSSPSSS GSEISRRATR KLVGDPTFKP
CQMKTHFSLS FPVNYIGECV RTVPYTHPDY ASLRILARIM TAKFLHGEIR EKGGAYGGGA
KLSFDGIFGF YSYRDPNSLS TLSTFQKAAD WAKSGQFTQQ DVDEAKLSVF SAVDSPIAPS
DKGMNHFLHG ISDEMKQKHR EQLFAVTHSD LTNASNKYLT AGQCTRGTAI LGPENRNIAK
DPSWIIR
