PREP_XENLA
ID PREP_XENLA Reviewed; 1027 AA.
AC Q6PF24;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, 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;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (SEP-2003) 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; BC057754; AAH57754.1; -; mRNA.
DR RefSeq; NP_001079981.1; NM_001086512.1.
DR AlphaFoldDB; Q6PF24; -.
DR SMR; Q6PF24; -.
DR DNASU; 379672; -.
DR GeneID; 379672; -.
DR KEGG; xla:379672; -.
DR CTD; 379672; -.
DR Xenbase; XB-GENE-952663; pitrm1.L.
DR OrthoDB; 107079at2759; -.
DR Proteomes; UP000186698; Chromosome 6L.
DR Bgee; 379672; Expressed in blastula and 19 other tissues.
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: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_0000249935"
FT REGION 803..827
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 813..827
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; 116680 MW; 64174B1B6ED59822 CRC64;
MIRQCWAGLR LCRALYQTSY RWHGKSACER ALRYSPGESI HGFTVNEVTP VPELFLTAVK
LSHDNTGAKY LHVAREDSNN LFSVQFRTTP LDSTGVPHIL EHTVLCGSQK YPCRDPFFKM
LNRSLSTFMN AFTASDYTMY PFSTQNAKDF QNLLSVYLDA VFFPCLRELD FWQEGWRLEH
ENPEDPNSPL IFKGIVFNEM KGAFTDNEKV FSQHLQNKLL PDHTYSVVSG GEPLNIPDLT
WEQLKEFHAT HYHPSNARFF TYGNLPLEMH LKQIHEDALS KFGRIDPKTS VPPQERWQSP
REYSISCGVD SFASDPEKQT MVSVNFLLSE ITDSFEAFTL SLLSSLMVDG PNSPFYKALI
EANLGTDFSP DTGFNNYTRE TYFSIGLQGI NKEDSEKVKH IINRTINEIA EQGIEPERIE
ALLHKLEIQM KHQSTSFGLT LASYIASCWN HEGDPVDLLK IGDKISRFRQ CLKENPKFLQ
DKVKQYFQVN QHRMMLSMSP DEQHYDKEEQ LEEEKLTQKV KALSEEERKQ IYEKGLELIS
LQSKPQDFSC LPALKVSDIE PQIPLTDLEI AYAGDVPVQY CTQPTNGMVY FRAVSSLNTL
PEELKPYVPL FCSVITKLGC GVYNYREQAQ QMELTTGGMS VCPHIISDDS SLDTYEQGIL
FSSLCLDRNM PDMMHLWSEI FNSPHFDDEE RLRVLVRMSA QEMSNGIPDS GHVYASIRAS
RTLTPTGELQ ELFSGMDQVK MIKRIAEMPD MGSILRKLSR IRKYVLLSDN MRCSINAAPQ
QMETASKEME HFLTGITRSK KERKAIRPHV VEKSSNPSPS GSEISRTATR KLVGDPTFKP
CQMKTHFCLS FPVNYIGECV RTVPYTHPDY ASLRILARIM TAKFLHGEIR EKGGAYGGGA
KLSFDGIFGF YSYRDPNSLS TLSTFQKATD WAKSGQFSQQ DVDEAKLSVF SAVDSPIAPS
DKGMNHFLHG ISDEMKQRHR EELFAVTHSD LTNASNKYLT AGQCTRGTAI LGPENKNIAK
DPSWIIR
