PREP_PONAB
ID PREP_PONAB Reviewed; 1037 AA.
AC Q5RDG3;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-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 {ECO:0000250|UniProtKB:Q5JRX3};
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
RG The German cDNA consortium;
RL Submitted (NOV-2004) 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. It is also able to degrade amyloid-beta protein
CC 40, one of the peptides produced by APP processing, when it accumulates
CC in mitochondrion. It is a highly efficient protease, at least toward
CC amyloid-beta protein 40. Cleaves that peptide at a specific position
CC and is probably not processive, releasing digested peptides
CC intermediates that can be further cleaved subsequently. It is also able
CC to degrade amyloid-beta protein 42. {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; CR857947; CAH90194.1; -; mRNA.
DR RefSeq; NP_001128771.1; NM_001135299.1.
DR AlphaFoldDB; Q5RDG3; -.
DR SMR; Q5RDG3; -.
DR STRING; 9601.ENSPPYP00000002367; -.
DR GeneID; 100189669; -.
DR KEGG; pon:100189669; -.
DR CTD; 10531; -.
DR eggNOG; KOG2019; Eukaryota.
DR InParanoid; Q5RDG3; -.
DR OrthoDB; 107079at2759; -.
DR Proteomes; UP000001595; 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: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 Acetylation; Disulfide bond; Hydrolase; Metal-binding; Metalloprotease;
KW Mitochondrion; Protease; Reference proteome; Transit peptide; Zinc.
FT TRANSIT 1..15
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT CHAIN 16..1037
FT /note="Presequence protease, mitochondrial"
FT /id="PRO_0000249933"
FT REGION 803..834
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 803..817
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 107
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q5JRX3"
FT BINDING 104
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q5JRX3"
FT BINDING 108
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q5JRX3"
FT BINDING 205
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q5JRX3"
FT MOD_RES 759
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8K411"
FT MOD_RES 770
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8K411"
FT MOD_RES 770
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8K411"
FT MOD_RES 849
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8K411"
FT MOD_RES 884
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8K411"
FT MOD_RES 946
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8K411"
FT DISULFID 119..556
FT /evidence="ECO:0000250|UniProtKB:Q5JRX3"
SQ SEQUENCE 1037 AA; 117507 MW; D580A804AF94E3CD CRC64;
MWRCGGRQGL GVLRRLSGGH AHHRAWRWNS NRACERALQY KLGDKIHGFT VNQVTSVPEL
FLTAVKLIHD DTGARYLHLA REDTNNLFSV QFRTTPMDST GVPHILEHTV LCGSQKYPCR
DPFFRMLNRS LSTFMNAFTA SDYTLYPFST QNPKDFQNLL SVYLDATFFP CLRELDFWQE
GWRLEHENPR DPQTALVFKG VVFNEMKGAF TDNERIFSQH LQNRLLPDHT YSVVSGGDPL
CILELTWEQL KQFHATHYHP SNARFFTYGN FPLEQHLKQI HEEALSKFQK IEPSTAVPAQ
TPWDKPREFQ ITCGPDSFAT DPSKQTTVSV SFLLPDITDT FEAFTLSLLS SLLTSGPNSP
FYKALIESGL GTDFSPDVGY NGYTREAYFS VGLQGIAEKD IETVRSLVDR TIDEVVEKGF
EDDRIEALLH KIEIQMKHQS TSFGLMLTSY IASCWNHDGD PVELLKLGNQ LAKFRQCLQE
NPKFLQEKVK QYFKNNQHKL TLSMRPDDKY HEKQAQVEAT KLKQKVEALS PGDRQQIYEK
GLELRTQQSK PQDASCLPAL KVSDIEPTIP VTELDVVLTA GDIPVQYCAQ PTNGMVYFRA
FSSLNTLPEE LRPYVPLFCS VLTKLGCGLL DYREQAQQIE LKTGGMSASP HVLPDDSHMD
TYEQGVLFSS LCLDRNLPDM MHLWSEIFNN PCFEEEEHFK VLVKMTAQEL TNAIPDSGHL
YASIRAGRTL TPAGDLQETF SGMDRVRLMK RIAEMTDIKP ILRKLPRIKK HLLNGDNMRC
SVNATPQQMS QTEKAVEDFL RSIGRSKKER RPVRPHTVEK PVPSSSGGDA HVPHGSQIIR
KLVTEPTFKP WQMKTHFLMP FPVNYVGECI RTVPYMDPDH ASLKILARLM TAKFLHTEIR
EKGGAYGGGA KLSHNGIFSL YSYRDPNTIE TLQSFGKAVD WAKSGKFTQQ DIDEAKLSVF
STVDAPIAPS NKGMDYFLYG LSDGMKQAHR EQLFAVSHDK LLAVSNRYLG TGKSTHSLAI
LGPENPKIAK DPSWTIR
