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 27-MAR-2024, entry version 185. 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). RN [10] RP DISRUPTION PHENOTYPE. RX PubMed=25176146; DOI=10.1016/j.cmet.2014.07.024; RA Mossmann D., Voegtle F.N., Taskin A.A., Teixeira P.F., Ring J., RA Burkhart J.M., Burger N., Pinho C.M., Tadic J., Loreth D., Graff C., RA Metzger F., Sickmann A., Kretz O., Wiedemann N., Zahedi R.P., Madeo F., RA Glaser E., Meisinger C.; RT "Amyloid-beta peptide induces mitochondrial dysfunction by inhibition of RT preprotein maturation."; RL Cell Metab. 20:662-669(2014). 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 -!- DISRUPTION PHENOTYPE: Simultaneous disruption of the mitochondrial CC presequence protease CYM1 results in synthetic lethality in respiratory CC conditions. {ECO:0000269|PubMed:25176146}. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 85. DR DIP; DIP-2670N; -. DR IntAct; P35999; 1. DR MINT; P35999; -. DR STRING; 4932.YKL134C; -. DR MEROPS; M03.006; -. DR MaxQB; P35999; -. DR PaxDb; 4932-YKL134C; -. DR PeptideAtlas; P35999; -. DR EnsemblFungi; YKL134C_mRNA; YKL134C; YKL134C. DR GeneID; 853724; -. DR KEGG; sce:YKL134C; -. DR AGR; SGD:S000001617; -. 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; ALMFEYM; -. DR OrthoDB; 735202at2759; -. DR BioCyc; YEAST:YKL134C-MONOMER; -. DR BioGRID-ORCS; 853724; 5 hits in 10 CRISPR screens. 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:intracellular 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 CDD; cd06457; M3A_MIP; 1. DR Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 1. DR Gene3D; 1.10.1370.10; Neurolysin, domain 3; 1. DR InterPro; IPR033851; M3A_MIP. 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:SF79; MITOCHONDRIAL INTERMEDIATE PEPTIDASE; 1. DR PANTHER; PTHR11804; PROTEASE M3 THIMET OLIGOPEPTIDASE-RELATED; 1. DR Pfam; PF01432; Peptidase_M3; 1. DR SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 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 //