ID   PREP_DANRE              Reviewed;        1023 AA.
AC   Q7ZVZ6;
DT   19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2003, sequence version 1.
DT   03-AUG-2022, entry version 105.
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=zgc:55469 {ECO:0000312|EMBL:AAH45351.1};
OS   Danio rerio (Zebrafish) (Brachydanio rerio).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Danionidae; Danioninae; Danio.
OX   NCBI_TaxID=7955;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=AB;
RG   NIH - Zebrafish Gene Collection (ZGC) project;
RL   Submitted (JAN-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; BC045351; AAH45351.1; -; mRNA.
DR   RefSeq; NP_998652.1; NM_213487.1.
DR   AlphaFoldDB; Q7ZVZ6; -.
DR   SMR; Q7ZVZ6; -.
DR   STRING; 7955.ENSDARP00000056293; -.
DR   PaxDb; Q7ZVZ6; -.
DR   PeptideAtlas; Q7ZVZ6; -.
DR   PRIDE; Q7ZVZ6; -.
DR   GeneID; 406808; -.
DR   KEGG; dre:406808; -.
DR   CTD; 10531; -.
DR   ZFIN; ZDB-GENE-040426-2876; pitrm1.
DR   eggNOG; KOG2019; Eukaryota.
DR   InParanoid; Q7ZVZ6; -.
DR   OrthoDB; 107079at2759; -.
DR   PhylomeDB; Q7ZVZ6; -.
DR   Reactome; R-DRE-1268020; Mitochondrial protein import.
DR   PRO; PR:Q7ZVZ6; -.
DR   Proteomes; UP000000437; Genome assembly.
DR   Proteomes; UP000814640; 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; 1.
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..62
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           63..1023
FT                   /note="Presequence protease, mitochondrial"
FT                   /id="PRO_0000249934"
FT   ACT_SITE        102
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:Q5JRX3"
FT   BINDING         99
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:Q5JRX3"
FT   BINDING         103
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:Q5JRX3"
FT   BINDING         200
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:Q5JRX3"
FT   DISULFID        114..551
FT                   /evidence="ECO:0000250|UniProtKB:Q5JRX3"
SQ   SEQUENCE   1023 AA;  114972 MW;  58F47102CC703477 CRC64;
     MFRQSKTIIT KLTNLSFQGS WRSRGSSAVE KALKYTVGQK IHNFTVKEVT AVPDLFLTAV
     KLSHDATGAQ YLHAARDDSN NLFSVLFRTT PMDSTGVPHI LEHTVLCGSQ RFPCRDPFFK
     MLNRSLSTFM NAFTASDYTM YPFSTQNAKD FQNLLSVYLD AVFFPCLREL DFWQEGWRLE
     HENPTDPSSP LVFKGVVFNE MKGVFSDNER LYAQHLQNKL LPDHTYSVVS GGEPLAIPEL
     TWEQLKHFHA THYHPSNARF FTYGDLPLEQ HLQQIEEEAM SKFERTEPNT AVPPQTPWDK
     PRMDHVSCRP DALAPDPVKQ NTLCMSFLLG DITDTFEMFT LSLLSSLMMS GPNSPFYKAL
     IEPKIGSDFS SSAGFDGSTR QASFTIGLQG MAEDDTETVK HIIAQTIDDI IASGFEEEQI
     EALLHKIEIQ MKHQSTSFGL ALASYIASLW NHDGDPVQLL KISESVSRFR QCLKENPRYL
     QEKVQHYFKN NTHQLTLSMS PDERFLEKQA EAEEQKLQQK IQILSSEDRK DIYEKGLQLL
     AVQSTTQDAS CLPALKVSDI EPIIPYTPVQ PGAAGGVPVQ YCEQPTNGMV YFRAMSNINS
     LPEDLKIYVP LFCSVITKMG SGMLDYRQQA QRIELKTGGL SVSPQIIPDT EDLDLYEQGI
     ILSSSCLERN LPDMFQLWSD LFNSPRFDDE ERLRVLVMMS AQELSNGISY SGHMYAMTRA
     ARSLTPTADL QESFSGMDQV KFMKRIAEMT DLTSILRKLP RIKRHLFNPE NMRCALNATP
     QKMPDVAAEV ERFIGNIAGN RKERKPVRPS VVERALGPEA GAAATRKLIS EAHFKPCQMK
     TYFQLPFNVN FVSECVRTVP FTHADYASLC ILGRMMTAKF LHGEIREKGG AYGGGARMGG
     GGLFSFYSYR DPNSTQTLSA FRGGVEWARA GKFTQQDIDE AKLSVFSAVD APVAPSDKGL
     GRFLNGITDE MKQAHRERLF AVTERNLIDV AGRYLGIGQQ TCGVAILGPE NESIRKDPSW
     VVK