MPPB_RAT
ID MPPB_RAT Reviewed; 489 AA.
AC Q03346; Q68G08;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Mitochondrial-processing peptidase subunit beta;
DE EC=3.4.24.64 {ECO:0000269|PubMed:12433926, ECO:0000305|PubMed:22354088};
DE AltName: Full=Beta-MPP;
DE AltName: Full=P-52;
DE Flags: Precursor;
GN Name=Pmpcb; Synonyms=Mppb;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=8506385; DOI=10.1073/pnas.90.11.5355;
RA Paces V., Rosenberg L.E., Fenton W.A., Kalousek F.;
RT "The beta subunit of the mitochondrial processing peptidase from rat liver:
RT cloning and sequencing of a cDNA and comparison with a proposed family of
RT metallopeptidases.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:5355-5358(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-489.
RC TISSUE=Liver;
RX PubMed=8422255; DOI=10.1006/bbrc.1993.1044;
RA Kitada S., Niidome T., Nagano T., Ogishima T., Ito A.;
RT "Molecular cloning of the smaller subunit(P52) of rat liver mitochondrial
RT processing protease.";
RL Biochem. Biophys. Res. Commun. 190:289-293(1993).
RN [4]
RP SEQUENCE REVISION.
RA Kitada S.;
RL Submitted (SEP-1993) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP PROTEIN SEQUENCE OF 153-173, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Spinal cord;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (NOV-2006) to UniProtKB.
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF GLU-191 AND ASP-195.
RX PubMed=12433926; DOI=10.1074/jbc.m209263200;
RA Kitada S., Yamasaki E., Kojima K., Ito A.;
RT "Determination of the cleavage site of the presequence by mitochondrial
RT processing peptidase on the substrate binding scaffold and the multiple
RT subsites inside a molecular cavity.";
RL J. Biol. Chem. 278:1879-1885(2003).
RN [7]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=22354088; DOI=10.1038/embor.2012.14;
RA Greene A.W., Grenier K., Aguileta M.A., Muise S., Farazifard R.,
RA Haque M.E., McBride H.M., Park D.S., Fon E.A.;
RT "Mitochondrial processing peptidase regulates PINK1 processing, import and
RT Parkin recruitment.";
RL EMBO Rep. 13:378-385(2012).
CC -!- FUNCTION: Catalytic subunit of the essential mitochondrial processing
CC protease (MPP), which cleaves the mitochondrial sequence off newly
CC imported precursors proteins (PubMed:12433926) (Probable).
CC Preferentially, cleaves after an arginine at position P2
CC (PubMed:12433926). Required for PINK1 turnover by coupling PINK1
CC mitochondrial import and cleavage, which results in subsequent PINK1
CC proteolysis (PubMed:22354088). {ECO:0000269|PubMed:12433926,
CC ECO:0000269|PubMed:22354088, ECO:0000305|PubMed:22354088}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of N-terminal transit peptides from precursor proteins
CC imported into the mitochondrion, typically with Arg in position P2.;
CC EC=3.4.24.64; Evidence={ECO:0000269|PubMed:12433926,
CC ECO:0000305|PubMed:22354088};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P10507};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P10507};
CC -!- ACTIVITY REGULATION: Binding to PMPCA is required for catalytic
CC activity. {ECO:0000250|UniProtKB:P10507}.
CC -!- SUBUNIT: Heterodimer of PMPCA (alpha) and PMPCB (beta) subunits,
CC forming the mitochondrial processing protease (MPP) in which PMPCA is
CC involved in substrate recognition and binding and PMPCB is the
CC catalytic subunit. {ECO:0000250|UniProtKB:P10507}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000250|UniProtKB:O75439}.
CC -!- SIMILARITY: Belongs to the peptidase M16 family. {ECO:0000305}.
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DR EMBL; L12965; AAA41633.1; -; mRNA.
DR EMBL; BC078826; AAH78826.1; -; mRNA.
DR EMBL; D13907; BAA03007.1; -; mRNA.
DR PIR; S36390; S36390.
DR RefSeq; NP_071790.1; NM_022395.2.
DR AlphaFoldDB; Q03346; -.
DR SMR; Q03346; -.
DR STRING; 10116.ENSRNOP00000017017; -.
DR MEROPS; M16.973; -.
DR MEROPS; M16.981; -.
DR iPTMnet; Q03346; -.
DR PhosphoSitePlus; Q03346; -.
DR jPOST; Q03346; -.
DR PaxDb; Q03346; -.
DR PRIDE; Q03346; -.
DR GeneID; 64198; -.
DR KEGG; rno:64198; -.
DR CTD; 9512; -.
DR RGD; 621297; Pmpcb.
DR VEuPathDB; HostDB:ENSRNOG00000012693; -.
DR eggNOG; KOG0960; Eukaryota.
DR HOGENOM; CLU_009902_4_0_1; -.
DR InParanoid; Q03346; -.
DR OMA; IDVVCDM; -.
DR OrthoDB; 638125at2759; -.
DR PhylomeDB; Q03346; -.
DR TreeFam; TF105032; -.
DR Reactome; R-RNO-8949664; Processing of SMDT1.
DR PRO; PR:Q03346; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000012693; Expressed in heart and 20 other tissues.
DR Genevisible; Q03346; RN.
DR GO; GO:0017087; C:mitochondrial processing peptidase complex; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0004175; F:endopeptidase activity; IDA:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:UniProtKB.
DR GO; GO:0016485; P:protein processing; IDA:UniProtKB.
DR GO; GO:0006627; P:protein processing involved in protein targeting to mitochondrion; IDA:UniProtKB.
DR InterPro; IPR011249; Metalloenz_LuxS/M16.
DR InterPro; IPR037718; MPP_beat.
DR InterPro; IPR011765; Pept_M16_N.
DR InterPro; IPR001431; Pept_M16_Zn_BS.
DR InterPro; IPR007863; Peptidase_M16_C.
DR PANTHER; PTHR11851:SF103; PTHR11851:SF103; 1.
DR Pfam; PF00675; Peptidase_M16; 1.
DR Pfam; PF05193; Peptidase_M16_C; 1.
DR SUPFAM; SSF63411; SSF63411; 2.
DR PROSITE; PS00143; INSULINASE; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Hydrolase; Metal-binding; Metalloprotease;
KW Mitochondrion; Protease; Reference proteome; Transit peptide; Zinc.
FT TRANSIT 1..45
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:O75439"
FT CHAIN 46..489
FT /note="Mitochondrial-processing peptidase subunit beta"
FT /id="PRO_0000026779"
FT ACT_SITE 104
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10096"
FT BINDING 101
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10096"
FT BINDING 105
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10096"
FT BINDING 181
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10096"
FT SITE 191
FT /note="Required for the specific determination of the
FT substrate cleavage site"
FT /evidence="ECO:0000269|PubMed:12433926"
FT SITE 195
FT /note="Required for the specific determination of the
FT substrate cleavage site"
FT /evidence="ECO:0000269|PubMed:12433926"
FT MUTAGEN 191
FT /note="E->A: Loss of substrate cleavage site specificity.
FT Complete loss of cleavage site specificity following an
FT arginine at position P2; when associated with A-195."
FT /evidence="ECO:0000269|PubMed:12433926"
FT MUTAGEN 195
FT /note="D->A: Severe loss of cleavage site specificity
FT following an arginine at position P2. The loss is complete;
FT when associated with A-191."
FT /evidence="ECO:0000269|PubMed:12433926"
FT CONFLICT 167
FT /note="G -> R (in Ref. 3; BAA03007)"
FT /evidence="ECO:0000305"
FT CONFLICT 312
FT /note="C -> R (in Ref. 1; AAA41633)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 489 AA; 54265 MW; 79B9C1ED7385533F CRC64;
MAAAAVSRTL LPVAGRRLWG FTRRLPLRAA AAQPLYFGGD RLRSTQAAPQ VVLNVPETQV
TCLENGLRVA SENSGISTCT VGLWIDAGSR YENEKNNGTA HFLEHMAFKG TKKRSQLDLE
LEIENMGAHL NAYTSREQTV YYAKAFSKDL PRAVEILADI IQNSTLGEAE IERERGVILR
EMQEVETNLQ EVVFDYLHAT AYQNTALGRT ILGPTENIKS ISRKDLVDYI TTHYKGPRIV
LAAAGGVCHN ELLELAKFHF GDSLCAHKGD VPALPPCKFT GSEIRVRDDK MPLAHLAVAI
EAVGWTHPDT ICLMVANTLI GNWDRSFGGG MNLSSKLAQL TCHGNLCHSF QSFNTSYTDT
GLWGLYMVCE QATVADMLHA VQKEWMRLCT AVSESEVARA KNLLKTNMLL QLDGSTPICE
DIGRQMLCYN RRIPIPELEA RIDAVDAEMV REVCTKYIYG KSPAIAALGP IERLPDFNQI
CSNMRWTRD
