PMIP_YEAST
ID PMIP_YEAST Reviewed; 772 AA.
AC P35999; D6VX62; P51980;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Mitochondrial intermediate peptidase;
DE Short=MIP;
DE EC=3.4.24.59;
DE Flags: Precursor;
GN Name=OCT1; Synonyms=MIP1; OrderedLocusNames=YKL134C;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RX PubMed=8035833; DOI=10.1128/mcb.14.8.5603-5616.1994;
RA Isaya G., Miklos D., Rollins R.A.;
RT "MIP1, a new yeast gene homologous to the rat mitochondrial intermediate
RT peptidase gene, is required for oxidative metabolism in Saccharomyces
RT cerevisiae.";
RL Mol. Cell. Biol. 14:5603-5616(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8196765; DOI=10.1038/369371a0;
RA Dujon B., Alexandraki D., Andre B., Ansorge W., Baladron V.,
RA Ballesta J.P.G., Banrevi A., Bolle P.-A., Bolotin-Fukuhara M., Bossier P.,
RA Bou G., Boyer J., Buitrago M.J., Cheret G., Colleaux L.,
RA Daignan-Fornier B., del Rey F., Dion C., Domdey H., Duesterhoeft A.,
RA Duesterhus S., Entian K.-D., Erfle H., Esteban P.F., Feldmann H.,
RA Fernandes L., Fobo G.M., Fritz C., Fukuhara H., Gabel C., Gaillon L.,
RA Garcia-Cantalejo J.M., Garcia-Ramirez J.J., Gent M.E., Ghazvini M.,
RA Goffeau A., Gonzalez A., Grothues D., Guerreiro P., Hegemann J.H.,
RA Hewitt N., Hilger F., Hollenberg C.P., Horaitis O., Indge K.J.,
RA Jacquier A., James C.M., Jauniaux J.-C., Jimenez A., Keuchel H.,
RA Kirchrath L., Kleine K., Koetter P., Legrain P., Liebl S., Louis E.J.,
RA Maia e Silva A., Marck C., Monnier A.-L., Moestl D., Mueller S.,
RA Obermaier B., Oliver S.G., Pallier C., Pascolo S., Pfeiffer F.,
RA Philippsen P., Planta R.J., Pohl F.M., Pohl T.M., Poehlmann R.,
RA Portetelle D., Purnelle B., Puzos V., Ramezani Rad M., Rasmussen S.W.,
RA Remacha M.A., Revuelta J.L., Richard G.-F., Rieger M.,
RA Rodrigues-Pousada C., Rose M., Rupp T., Santos M.A., Schwager C.,
RA Sensen C., Skala J., Soares H., Sor F., Stegemann J., Tettelin H.,
RA Thierry A., Tzermia M., Urrestarazu L.A., van Dyck L.,
RA van Vliet-Reedijk J.C., Valens M., Vandenbol M., Vilela C., Vissers S.,
RA von Wettstein D., Voss H., Wiemann S., Xu G., Zimmermann J., Haasemann M.,
RA Becker I., Mewes H.-W.;
RT "Complete DNA sequence of yeast chromosome XI.";
RL Nature 369:371-378(1994).
RN [3]
RP GENOME REANNOTATION, AND SEQUENCE REVISION TO 343-350 AND 694-702.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP FUNCTION.
RX PubMed=7593000; DOI=10.1074/jbc.270.45.27366;
RA Branda S.S., Isaya G.;
RT "Prediction and identification of new natural substrates of the yeast
RT mitochondrial intermediate peptidase.";
RL J. Biol. Chem. 270:27366-27373(1995).
RN [5]
RP MUTAGENESIS OF CYS-131; PHE-557; HIS-558; GLU-559; GLY-561; HIS-562;
RP HIS-565; GLY-578; CYS-581; ASP-584; GLU-587; PRO-589; SER-590 AND GLU-594,
RP AND SUBCELLULAR LOCATION.
RX PubMed=8831696; DOI=10.1006/bbrc.1996.1435;
RA Chew A., Rollins R.A., Sakati W.R., Isaya G.;
RT "Mutations in a putative zinc-binding domain inactivate the mitochondrial
RT intermediate peptidase.";
RL Biochem. Biophys. Res. Commun. 226:822-829(1996).
RN [6]
RP ACTIVITY REGULATION.
RX PubMed=10332043; DOI=10.1093/hmg/8.6.1099;
RA Branda S.S., Yang Z.Y., Chew A., Isaya G.;
RT "Mitochondrial intermediate peptidase and the yeast frataxin homolog
RT together maintain mitochondrial iron homeostasis in Saccharomyces
RT cerevisiae.";
RL Hum. Mol. Genet. 8:1099-1110(1999).
RN [7]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [8]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [9]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=16823961; DOI=10.1021/pr050477f;
RA Reinders J., Zahedi R.P., Pfanner N., Meisinger C., Sickmann A.;
RT "Toward the complete yeast mitochondrial proteome: multidimensional
RT separation techniques for mitochondrial proteomics.";
RL J. Proteome Res. 5:1543-1554(2006).
CC -!- FUNCTION: Cleaves proteins, imported into the mitochondrion, to their
CC mature size. While most mitochondrial precursor proteins are processed
CC to the mature form in one step by mitochondrial processing peptidase
CC (MPP), the sequential cleavage by MIP of an octapeptide after initial
CC processing by MPP is a required step for a subgroup of nuclear-encoded
CC precursor proteins destined for the matrix or the inner membrane.
CC Cleaves precursor proteins of respiratory components, including
CC subunits of the electron transport chain and tricarboxylic acid cycle
CC enzymes, and components of the mitochondrial genetic machinery,
CC including ribosomal proteins, translation factors, and proteins
CC required for mitochondrial DNA metabolism. {ECO:0000269|PubMed:7593000,
CC ECO:0000269|PubMed:8035833}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of an N-terminal octapeptide as second stage of
CC processing of some proteins imported into the mitochondrion.;
CC EC=3.4.24.59;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Stimulated by Fe(2+).
CC {ECO:0000269|PubMed:10332043}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:14562095, ECO:0000269|PubMed:16823961,
CC ECO:0000269|PubMed:8831696}.
CC -!- MISCELLANEOUS: Present with 2690 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the peptidase M3 family. {ECO:0000305}.
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DR EMBL; U10243; AAA21278.1; -; Genomic_DNA.
DR EMBL; Z28134; CAA81975.1; -; Genomic_DNA.
DR EMBL; BK006944; DAA09028.2; -; Genomic_DNA.
DR PIR; S37963; S37963.
DR RefSeq; NP_012788.2; NM_001179700.2.
DR AlphaFoldDB; P35999; -.
DR SMR; P35999; -.
DR BioGRID; 34002; 83.
DR DIP; DIP-2670N; -.
DR IntAct; P35999; 1.
DR MINT; P35999; -.
DR STRING; 4932.YKL134C; -.
DR MEROPS; M03.006; -.
DR MaxQB; P35999; -.
DR PaxDb; P35999; -.
DR PRIDE; P35999; -.
DR EnsemblFungi; YKL134C_mRNA; YKL134C; YKL134C.
DR GeneID; 853724; -.
DR KEGG; sce:YKL134C; -.
DR SGD; S000001617; OCT1.
DR VEuPathDB; FungiDB:YKL134C; -.
DR eggNOG; KOG2090; Eukaryota.
DR GeneTree; ENSGT00950000183171; -.
DR HOGENOM; CLU_001805_0_0_1; -.
DR InParanoid; P35999; -.
DR OMA; VVYCDLF; -.
DR BioCyc; YEAST:YKL134C-MON; -.
DR PRO; PR:P35999; -.
DR Proteomes; UP000002311; Chromosome XI.
DR RNAct; P35999; protein.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:SGD.
DR GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:SGD.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IMP:SGD.
DR GO; GO:0006518; P:peptide metabolic process; IBA:GO_Central.
DR GO; GO:0006627; P:protein processing involved in protein targeting to mitochondrion; IMP:SGD.
DR GO; GO:0050821; P:protein stabilization; IMP:SGD.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR Gene3D; 1.10.1370.10; -; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR024077; Neurolysin/TOP_dom2.
DR InterPro; IPR045090; Pept_M3A_M3B.
DR InterPro; IPR001567; Pept_M3A_M3B_dom.
DR PANTHER; PTHR11804; PTHR11804; 1.
DR Pfam; PF01432; Peptidase_M3; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Hydrolase; Metal-binding; Metalloprotease; Mitochondrion; Protease;
KW Reference proteome; Transit peptide; Zinc.
FT TRANSIT 1..37
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 38..772
FT /note="Mitochondrial intermediate peptidase"
FT /id="PRO_0000028583"
FT ACT_SITE 559
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 558
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 562
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 587
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305"
FT MUTAGEN 131
FT /note="C->S,V: Affects protein stability, but has no effect
FT on peptidase activity."
FT /evidence="ECO:0000269|PubMed:8831696"
FT MUTAGEN 557
FT /note="F->R: Affects protein stability."
FT /evidence="ECO:0000269|PubMed:8831696"
FT MUTAGEN 558
FT /note="H->R: Abolishes proteolytic activity."
FT /evidence="ECO:0000269|PubMed:8831696"
FT MUTAGEN 559
FT /note="E->D: Abolishes proteolytic activity."
FT /evidence="ECO:0000269|PubMed:8831696"
FT MUTAGEN 561
FT /note="G->L: Affects protein stability."
FT /evidence="ECO:0000269|PubMed:8831696"
FT MUTAGEN 562
FT /note="H->R: Abolishes proteolytic activity."
FT /evidence="ECO:0000269|PubMed:8831696"
FT MUTAGEN 565
FT /note="H->R: Temperature sensitive; abolishes proteolytic
FT activity for RIP1, but not for COX4."
FT /evidence="ECO:0000269|PubMed:8831696"
FT MUTAGEN 578
FT /note="G->L: Temperature sensitive; abolishes proteolytic
FT activity for RIP1, but not for COX4."
FT /evidence="ECO:0000269|PubMed:8831696"
FT MUTAGEN 581
FT /note="C->S,V: Affects protein stability, but has no effect
FT on peptidase activity."
FT /evidence="ECO:0000269|PubMed:8831696"
FT MUTAGEN 584
FT /note="D->E: No effect."
FT /evidence="ECO:0000269|PubMed:8831696"
FT MUTAGEN 587
FT /note="E->D: Abolishes proteolytic activity."
FT /evidence="ECO:0000269|PubMed:8831696"
FT MUTAGEN 589
FT /note="P->L: No effect."
FT /evidence="ECO:0000269|PubMed:8831696"
FT MUTAGEN 590
FT /note="S->Y: Affects protein stability."
FT /evidence="ECO:0000269|PubMed:8831696"
FT MUTAGEN 594
FT /note="E->D: No effect."
FT /evidence="ECO:0000269|PubMed:8831696"
FT CONFLICT 343..350
FT /note="MAKNPKDV -> WQDRRC (in Ref. 2; CAA81975)"
FT /evidence="ECO:0000305"
FT CONFLICT 694..702
FT /note="YGATYYSYL -> SGQLITATY (in Ref. 2; CAA81975)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 772 AA; 88183 MW; 1C19A0655FAAE7CA CRC64;
MLRTIILKAG SNASIPSPSR QNKLLRFFAT AGAVSRTSPG SIKKIFDDNS YWRNINGQDA
NNSKISQYLF KKNKTGLFKN PYLTSPDGLR KFSQVSLQQA QELLDKMRND FSESGKLTYI
MNLDRLSDTL CRVIDLCEFI RSTHPDDAFV RAAQDCHEQM FEFMNVLNTD VSLCNILKSV
LNNPEVSSKL SAEELKVGKI LLDDFEKSGI YMNPDVREKF IQLSQEISLV GQEFINHTDY
PGSNSVKIPC KDLDNSKVST FLLKQLNKDV KGQNYKVPTF GYAAYALLKS CENEMVRKKL
WTALHSCSDK QVKRLSHLIK LRAILANLMH KTSYAEYQLE GKMAKNPKDV QDFILTLMNN
TIEKTANELK FIAELKAKDL KKPLTTNTDE ILKLVRPWDR DYYTGKYFQL NPSNSPNAKE
ISYYFTLGNV IQGLSDLFQQ IYGIRLEPAI TDEGETWSPD VRRLNVISEE EGIIGIIYCD
LFERNGKTSN PAHFTVCCSR QIYPSETDFS TIQVGENPDG TYFQLPVISL VCNFSPILIA
SKKSLCFLQL SEVETLFHEM GHAMHSMLGR THMQNISGTR CATDFVELPS ILMEHFAKDI
RILTKIGKHY GTGETIQADM LQRFMKSTNF LQNCETYSQA KMAMLDQSFH DEKIISDIDN
FDVVENYQAL ERRLKVLVDD QSNWCGRFGH LFGYGATYYS YLFDRTIASK IWYALFEDDP
YSRKNGDKFK KHLLKWGGLK DPWKCIADVL ECPMLEKGGS DAMEFIAQSH KS
