MIA40_YEAST
ID MIA40_YEAST Reviewed; 403 AA.
AC P36046; D6VX05;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 2.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Mitochondrial intermembrane space import and assembly protein 40;
DE AltName: Full=Mitochondrial import inner membrane translocase TIM40;
DE Flags: Precursor;
GN Name=MIA40; Synonyms=TIM40; OrderedLocusNames=YKL195W;
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 [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 [2]
RP GENOME REANNOTATION.
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 [3]
RP PROTEIN SEQUENCE OF 32-36, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH
RP TIM13, MUTAGENESIS OF CYS-296; CYS-298 AND CYS-307, AND METAL-BINDING.
RX PubMed=15620710; DOI=10.1016/j.febslet.2004.11.072;
RA Terziyska N., Lutz T., Kozany C., Mokranjac D., Mesecke N., Neupert W.,
RA Herrmann J.M., Hell K.;
RT "Mia40, a novel factor for protein import into the intermembrane space of
RT mitochondria is able to bind metal ions.";
RL FEBS Lett. 579:179-184(2005).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=14690591; DOI=10.1016/s1097-2765(03)00476-3;
RA Hazbun T.R., Malmstroem L., Anderson S., Graczyk B.J., Fox B., Riffle M.,
RA Sundin B.A., Aranda J.D., McDonald W.H., Chiu C.-H., Snydsman B.E.,
RA Bradley P., Muller E.G.D., Fields S., Baker D., Yates J.R. III, Davis T.N.;
RT "Assigning function to yeast proteins by integration of technologies.";
RL Mol. Cell 12:1353-1365(2003).
RN [5]
RP IDENTIFICATION OF PROBABLE INITIATION SITE.
RX PubMed=12748633; DOI=10.1038/nature01644;
RA Kellis M., Patterson N., Endrizzi M., Birren B.W., Lander E.S.;
RT "Sequencing and comparison of yeast species to identify genes and
RT regulatory elements.";
RL Nature 423:241-254(2003).
RN [6]
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 [7]
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 [8]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 76625 / YPH499;
RX PubMed=14576278; DOI=10.1073/pnas.2135385100;
RA Sickmann A., Reinders J., Wagner Y., Joppich C., Zahedi R.P., Meyer H.E.,
RA Schoenfisch B., Perschil I., Chacinska A., Guiard B., Rehling P.,
RA Pfanner N., Meisinger C.;
RT "The proteome of Saccharomyces cerevisiae mitochondria.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:13207-13212(2003).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH TIM9.
RX PubMed=15359280; DOI=10.1038/sj.emboj.7600389;
RA Chacinska A., Pfannschmidt S., Wiedemann N., Kozjak V.,
RA Sanjuan Szklarz L.K., Schulze-Specking A., Truscott K.N., Guiard B.,
RA Meisinger C., Pfanner N.;
RT "Essential role of Mia40 in import and assembly of mitochondrial
RT intermembrane space proteins.";
RL EMBO J. 23:3735-3746(2004).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-296; CYS-298;
RP CYS-307; CYS-317; CYS-330 AND CYS-340.
RX PubMed=15364952; DOI=10.1074/jbc.m410272200;
RA Naoe M., Ohwa Y., Ishikawa D., Ohshima C., Nishikawa S., Yamamoto H.,
RA Endo T.;
RT "Identification of Tim40 that mediates protein sorting to the mitochondrial
RT intermembrane space.";
RL J. Biol. Chem. 279:47815-47821(2004).
RN [11]
RP FUNCTION, AND INTERACTION WITH COX17; ERV1 AND TIM13.
RX PubMed=15989955; DOI=10.1016/j.cell.2005.04.011;
RA Mesecke N., Terziyska N., Kozany C., Baumann F., Neupert W., Hell K.,
RA Herrmann J.M.;
RT "A disulfide relay system in the intermembrane space of mitochondria that
RT mediates protein import.";
RL Cell 121:1059-1069(2005).
RN [12]
RP FUNCTION, AND INTERACTION WITH ERV1.
RX PubMed=16181637; DOI=10.1016/j.jmb.2005.08.051;
RA Rissler M., Wiedemann N., Pfannschmidt S., Gabriel K., Guiard B.,
RA Pfanner N., Chacinska A.;
RT "The essential mitochondrial protein Erv1 cooperates with Mia40 in
RT biogenesis of intermembrane space proteins.";
RL J. Mol. Biol. 353:485-492(2005).
RN [13]
RP SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=16407407; DOI=10.1091/mbc.e05-08-0740;
RA Zahedi R.P., Sickmann A., Boehm A.M., Winkler C., Zufall N.,
RA Schoenfisch B., Guiard B., Pfanner N., Meisinger C.;
RT "Proteomic analysis of the yeast mitochondrial outer membrane reveals
RT accumulation of a subclass of preproteins.";
RL Mol. Biol. Cell 17:1436-1450(2006).
RN [14]
RP INTERACTION WITH FCJ1.
RX PubMed=21944719; DOI=10.1016/j.devcel.2011.08.026;
RA von der Malsburg K., Muller J.M., Bohnert M., Oeljeklaus S.,
RA Kwiatkowska P., Becker T., Loniewska-Lwowska A., Wiese S., Rao S.,
RA Milenkovic D., Hutu D.P., Zerbes R.M., Schulze-Specking A., Meyer H.E.,
RA Martinou J.C., Rospert S., Rehling P., Meisinger C., Veenhuis M.,
RA Warscheid B., van der Klei I.J., Pfanner N., Chacinska A., van der Laan M.;
RT "Dual role of mitofilin in mitochondrial membrane organization and protein
RT biogenesis.";
RL Dev. Cell 21:694-707(2011).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 284-353, FUNCTION, AND DISULFIDE
RP BONDS.
RX PubMed=19667201; DOI=10.1073/pnas.0901793106;
RA Kawano S., Yamano K., Naoe M., Momose T., Terao K., Nishikawa S.,
RA Watanabe N., Endo T.;
RT "Structural basis of yeast Tim40/Mia40 as an oxidative translocator in the
RT mitochondrial intermembrane space.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:14403-14407(2009).
CC -!- FUNCTION: Required for the import and folding of small cysteine-
CC containing proteins (small Tim) in the mitochondrial intermembrane
CC space (IMS). Forms a redox cycle with ERV1 that involves a disulfide
CC relay system. Precursor proteins to be imported into the IMS are
CC translocated in their reduced form into the mitochondria. The oxidized
CC form of MIA40 forms a transient intermolecular disulfide bridge with
CC the reduced precursor protein, resulting in oxidation of the precursor
CC protein that now contains an intramolecular disulfide bond and is able
CC to undergo folding in the IMS. Reduced MIA40 is reoxidized by FAD-
CC linked sulfhydryl oxidase ERV1. {ECO:0000269|PubMed:15359280,
CC ECO:0000269|PubMed:15364952, ECO:0000269|PubMed:15620710,
CC ECO:0000269|PubMed:15989955, ECO:0000269|PubMed:16181637,
CC ECO:0000269|PubMed:19667201}.
CC -!- COFACTOR:
CC Name=Cu(2+); Xref=ChEBI:CHEBI:29036;
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Note=Cu(2+) or Zn(2+).;
CC -!- SUBUNIT: Monomer. Interacts with the FAD-linked sulfhydryl oxidase ERV1
CC and with the substrate proteins COX17, TIM9, and TIM13, forming
CC transient intermolecular disulfide bridges. Interacts with FCJ1.
CC {ECO:0000269|PubMed:15359280, ECO:0000269|PubMed:15620710,
CC ECO:0000269|PubMed:15989955, ECO:0000269|PubMed:16181637,
CC ECO:0000269|PubMed:21944719}.
CC -!- INTERACTION:
CC P36046; P53722: ATP23; NbExp=5; IntAct=EBI-26978, EBI-8059929;
CC P36046; P27882: ERV1; NbExp=4; IntAct=EBI-26978, EBI-6621;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:14562095, ECO:0000269|PubMed:14576278,
CC ECO:0000269|PubMed:15359280, ECO:0000269|PubMed:15364952,
CC ECO:0000269|PubMed:15620710, ECO:0000269|PubMed:16407407}; Single-pass
CC type II membrane protein {ECO:0000269|PubMed:14562095,
CC ECO:0000269|PubMed:14576278, ECO:0000269|PubMed:15359280,
CC ECO:0000269|PubMed:15364952, ECO:0000269|PubMed:15620710,
CC ECO:0000269|PubMed:16407407}; Intermembrane side
CC {ECO:0000269|PubMed:14562095, ECO:0000269|PubMed:14576278,
CC ECO:0000269|PubMed:15359280, ECO:0000269|PubMed:15364952,
CC ECO:0000269|PubMed:15620710, ECO:0000269|PubMed:16407407}.
CC -!- DOMAIN: The CHCH domain contains a conserved twin Cys-X(9)-Cys motif
CC which is required for import and stability of MIA40 in mitochondria.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: Present with 5040 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
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DR EMBL; Z28195; CAA82039.1; -; Genomic_DNA.
DR EMBL; BK006944; DAA08971.1; -; Genomic_DNA.
DR PIR; S38032; S38032.
DR RefSeq; NP_012726.2; NM_001179761.1.
DR PDB; 2ZXT; X-ray; 3.00 A; A=282-365.
DR PDB; 3A3C; X-ray; 2.50 A; A=282-353.
DR PDBsum; 2ZXT; -.
DR PDBsum; 3A3C; -.
DR AlphaFoldDB; P36046; -.
DR SMR; P36046; -.
DR BioGRID; 33926; 215.
DR DIP; DIP-5432N; -.
DR IntAct; P36046; 11.
DR MINT; P36046; -.
DR STRING; 4932.YKL195W; -.
DR TCDB; 3.A.8.1.1; the mitochondrial protein translocase (mpt) family.
DR iPTMnet; P36046; -.
DR MaxQB; P36046; -.
DR PaxDb; P36046; -.
DR PRIDE; P36046; -.
DR EnsemblFungi; YKL195W_mRNA; YKL195W; YKL195W.
DR GeneID; 853639; -.
DR KEGG; sce:YKL195W; -.
DR SGD; S000001678; MIA40.
DR VEuPathDB; FungiDB:YKL195W; -.
DR eggNOG; KOG4149; Eukaryota.
DR GeneTree; ENSGT00940000170392; -.
DR HOGENOM; CLU_683707_0_0_1; -.
DR InParanoid; P36046; -.
DR BioCyc; YEAST:G3O-31957-MON; -.
DR EvolutionaryTrace; P36046; -.
DR PRO; PR:P36046; -.
DR Proteomes; UP000002311; Chromosome XI.
DR RNAct; P36046; protein.
DR GO; GO:0031305; C:integral component of mitochondrial inner membrane; IDA:SGD.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:SGD.
DR GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; IDA:SGD.
DR GO; GO:0016491; F:oxidoreductase activity; IMP:SGD.
DR GO; GO:0003756; F:protein disulfide isomerase activity; IDA:SGD.
DR GO; GO:0015035; F:protein-disulfide reductase activity; IBA:GO_Central.
DR GO; GO:0016972; F:thiol oxidase activity; IDA:SGD.
DR GO; GO:0006457; P:protein folding; IDA:SGD.
DR GO; GO:0045041; P:protein import into mitochondrial intermembrane space; IMP:SGD.
DR GO; GO:0022417; P:protein maturation by protein folding; IBA:GO_Central.
DR InterPro; IPR010625; CHCH.
DR InterPro; IPR039289; CHCHD4.
DR PANTHER; PTHR21622; PTHR21622; 1.
DR Pfam; PF06747; CHCH; 1.
DR PROSITE; PS51808; CHCH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond; Membrane;
KW Mitochondrion; Mitochondrion inner membrane; Oxidoreductase;
KW Protein transport; Redox-active center; Reference proteome; Signal-anchor;
KW Transit peptide; Translocation; Transmembrane; Transmembrane helix;
KW Transport.
FT TRANSIT 1..31
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:15620710"
FT CHAIN 32..403
FT /note="Mitochondrial intermembrane space import and
FT assembly protein 40"
FT /id="PRO_0000203135"
FT TOPO_DOM 33..46
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000255"
FT TRANSMEM 47..66
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 67..403
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT DOMAIN 304..348
FT /note="CHCH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150"
FT REGION 75..292
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 351..403
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 307..317
FT /note="Cx9C motif 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150"
FT MOTIF 330..340
FT /note="Cx9C motif 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150"
FT COMPBIAS 97..118
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 140..172
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 202..245
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 252..284
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 351..366
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 368..383
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 384..403
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 296..298
FT /note="Redox-active"
FT /evidence="ECO:0000269|PubMed:19667201"
FT DISULFID 307..340
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150,
FT ECO:0000269|PubMed:19667201"
FT DISULFID 317..330
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150,
FT ECO:0000269|PubMed:19667201"
FT MUTAGEN 296
FT /note="C->S: Loss of function; when associated with S-298."
FT /evidence="ECO:0000269|PubMed:15364952,
FT ECO:0000269|PubMed:15620710"
FT MUTAGEN 298
FT /note="C->S: Loss of function; when associated with S-296."
FT /evidence="ECO:0000269|PubMed:15364952,
FT ECO:0000269|PubMed:15620710"
FT MUTAGEN 307
FT /note="C->S: Loss of function; when associated with S-317."
FT /evidence="ECO:0000269|PubMed:15364952,
FT ECO:0000269|PubMed:15620710"
FT MUTAGEN 317
FT /note="C->S: Loss of function; when associated with S-307."
FT /evidence="ECO:0000269|PubMed:15364952"
FT MUTAGEN 330
FT /note="C->S: Loss of function; when associated with S-340."
FT /evidence="ECO:0000269|PubMed:15364952"
FT MUTAGEN 340
FT /note="C->S: Loss of function; when associated with S-330."
FT /evidence="ECO:0000269|PubMed:15364952"
FT HELIX 274..277
FT /evidence="ECO:0007829|PDB:3A3C"
FT HELIX 280..284
FT /evidence="ECO:0007829|PDB:3A3C"
FT TURN 287..290
FT /evidence="ECO:0007829|PDB:3A3C"
FT HELIX 297..299
FT /evidence="ECO:0007829|PDB:3A3C"
FT TURN 300..303
FT /evidence="ECO:0007829|PDB:3A3C"
FT HELIX 308..319
FT /evidence="ECO:0007829|PDB:3A3C"
FT STRAND 323..325
FT /evidence="ECO:0007829|PDB:3A3C"
FT TURN 326..329
FT /evidence="ECO:0007829|PDB:3A3C"
FT HELIX 331..341
FT /evidence="ECO:0007829|PDB:3A3C"
FT TURN 345..347
FT /evidence="ECO:0007829|PDB:3A3C"
SQ SEQUENCE 403 AA; 44536 MW; 5904E8D0213D6EFA CRC64;
MLRNLVVRNA CRNRPSIQVA RGLCRHQTRR LMASSPQFGR NSNQEKTAGF IMGILSMAGA
LYFIAPNRKP LFASRKVESD KTAEEELSSG GEQSPENEDD NNSKSDENGD DNDSKNDETE
AGPQLGGDKI GASKVAEDGE LVVLAEEDNK SSEDKDTDES KVSTKDDEQS NEDNATANNQ
KDENISSENS EENTSDKTLD NNAGSSEKKD PEHSDDEKSQ QGQSDDKTTT EDNNGEEESS
KKTVSDSENS AKQSESSDEE KEELRKQEEK QMGPTEEEVQ HEGAYNPDTG EINWDCPCLG
GMAHGPCGEE FKSAFSCFVY SEAEPKGIDC VEKFQHMQDC FRKYPEHYAE QLKETSDDEE
PQDKVKVNTI ESAPNVSSAK ENAAKKAEQS DVKKEPLNEE SKP
