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Protein

Mitochondrial intermembrane space import and assembly protein 40

Gene

MIA40

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Required for the import and folding of small cysteine-containing proteins (small Tim) in the mitochondrial intermembrane space (IMS). Forms a redox cycle with ERV1 that involves a disulfide relay system. Precursor proteins to be imported into the IMS are translocated in their reduced form into the mitochondria. The oxidized form of MIA40 forms a transient intermolecular disulfide bridge with the reduced precursor protein, resulting in oxidation of the precursor protein that now contains an intramolecular disulfide bond and is able to undergo folding in the IMS. Reduced MIA40 is reoxidized by FAD-linked sulfhydryl oxidase ERV1.6 Publications

Cofactori

Cu2+, Zn2+Note: Cu2+ or Zn2+.

GO - Molecular functioni

  • 2 iron, 2 sulfur cluster binding Source: SGD
  • oxidoreductase activity Source: SGD
  • protein disulfide isomerase activity Source: SGD
  • protein disulfide oxidoreductase activity Source: Reactome
  • thiol oxidase activity Source: SGD

GO - Biological processi

  • protein folding Source: SGD
  • protein import into mitochondrial intermembrane space Source: SGD
  • protein targeting to mitochondrion Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Protein transport, Translocation, Transport

Enzyme and pathway databases

BioCyciYEAST:G3O-31957-MONOMER.
ReactomeiR-SCE-1268020. Mitochondrial protein import.

Protein family/group databases

TCDBi3.A.8.1.1. the mitochondrial protein translocase (mpt) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitochondrial intermembrane space import and assembly protein 40
Alternative name(s):
Mitochondrial import inner membrane translocase TIM40
Gene namesi
Name:MIA40
Synonyms:TIM40
Ordered Locus Names:YKL195W
OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Taxonomic identifieri559292 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
Proteomesi
  • UP000002311 Componenti: Chromosome XI

Organism-specific databases

EuPathDBiFungiDB:YKL195W.
SGDiS000001678. MIA40.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini33 – 4614Mitochondrial matrixSequence analysisAdd
BLAST
Transmembranei47 – 6620Helical; Signal-anchor for type II membrane proteinSequence analysisAdd
BLAST
Topological domaini67 – 403337Mitochondrial intermembraneSequence analysisAdd
BLAST

GO - Cellular componenti

  • integral component of mitochondrial inner membrane Source: SGD
  • mitochondrial intermembrane space Source: SGD
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion inner membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi296 – 2961C → S: Loss of function; when associated with S-298. 2 Publications
Mutagenesisi298 – 2981C → S: Loss of function; when associated with S-296. 2 Publications
Mutagenesisi307 – 3071C → S: Loss of function; when associated with S-317. 2 Publications
Mutagenesisi317 – 3171C → S: Loss of function; when associated with S-307. 1 Publication
Mutagenesisi330 – 3301C → S: Loss of function; when associated with S-340. 1 Publication
Mutagenesisi340 – 3401C → S: Loss of function; when associated with S-330. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 3131Mitochondrion1 PublicationAdd
BLAST
Chaini32 – 403372Mitochondrial intermembrane space import and assembly protein 40PRO_0000203135Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi296 ↔ 298Redox-active1 Publication
Disulfide bondi307 ↔ 3401 Publication
Disulfide bondi317 ↔ 3301 Publication

Keywords - PTMi

Disulfide bond

Proteomic databases

MaxQBiP36046.

PTM databases

iPTMnetiP36046.

Interactioni

Subunit structurei

Monomer. Interacts with the FAD-linked sulfhydryl oxidase ERV1 and with the substrate proteins COX17, TIM9, and TIM13, forming transient intermolecular disulfide bridges. Interacts with FCJ1.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ATP23P537225EBI-26978,EBI-8059929
ERV1P278822EBI-26978,EBI-6621

Protein-protein interaction databases

BioGridi33926. 74 interactions.
DIPiDIP-5432N.
IntActiP36046. 9 interactions.
MINTiMINT-574280.

Structurei

Secondary structure

1
403
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi282 – 2843Combined sources
Turni287 – 2904Combined sources
Helixi297 – 2993Combined sources
Turni300 – 3034Combined sources
Helixi308 – 31912Combined sources
Beta strandi323 – 3253Combined sources
Turni326 – 3294Combined sources
Helixi331 – 34111Combined sources
Turni345 – 3473Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2ZXTX-ray3.00A282-365[»]
3A3CX-ray2.50A282-353[»]
ProteinModelPortaliP36046.
SMRiP36046. Positions 249-353.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP36046.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini300 – 34344CHCHAdd
BLAST

Domaini

The CHCH domain contains a conserved twin Cys-X(9)-Cys motif which is required for import and stability of MIA40 in mitochondria.Curated

Sequence similaritiesi

Contains 1 CHCH domain.Curated

Keywords - Domaini

Redox-active center, Signal-anchor, Transit peptide, Transmembrane, Transmembrane helix

Phylogenomic databases

GeneTreeiENSGT00390000013132.
InParanoidiP36046.
KOiK17782.
OrthoDBiEOG7JHMH7.

Family and domain databases

InterProiIPR010625. CHCH.
[Graphical view]
PfamiPF06747. CHCH. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P36046-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLRNLVVRNA CRNRPSIQVA RGLCRHQTRR LMASSPQFGR NSNQEKTAGF
60 70 80 90 100
IMGILSMAGA LYFIAPNRKP LFASRKVESD KTAEEELSSG GEQSPENEDD
110 120 130 140 150
NNSKSDENGD DNDSKNDETE AGPQLGGDKI GASKVAEDGE LVVLAEEDNK
160 170 180 190 200
SSEDKDTDES KVSTKDDEQS NEDNATANNQ KDENISSENS EENTSDKTLD
210 220 230 240 250
NNAGSSEKKD PEHSDDEKSQ QGQSDDKTTT EDNNGEEESS KKTVSDSENS
260 270 280 290 300
AKQSESSDEE KEELRKQEEK QMGPTEEEVQ HEGAYNPDTG EINWDCPCLG
310 320 330 340 350
GMAHGPCGEE FKSAFSCFVY SEAEPKGIDC VEKFQHMQDC FRKYPEHYAE
360 370 380 390 400
QLKETSDDEE PQDKVKVNTI ESAPNVSSAK ENAAKKAEQS DVKKEPLNEE

SKP
Length:403
Mass (Da):44,536
Last modified:March 21, 2006 - v2
Checksum:i5904E8D0213D6EFA
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z28195 Genomic DNA. Translation: CAA82039.1.
BK006944 Genomic DNA. Translation: DAA08971.1.
PIRiS38032.
RefSeqiNP_012726.2. NM_001179761.1.

Genome annotation databases

EnsemblFungiiYKL195W; YKL195W; YKL195W.
GeneIDi853639.
KEGGisce:YKL195W.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z28195 Genomic DNA. Translation: CAA82039.1.
BK006944 Genomic DNA. Translation: DAA08971.1.
PIRiS38032.
RefSeqiNP_012726.2. NM_001179761.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2ZXTX-ray3.00A282-365[»]
3A3CX-ray2.50A282-353[»]
ProteinModelPortaliP36046.
SMRiP36046. Positions 249-353.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi33926. 74 interactions.
DIPiDIP-5432N.
IntActiP36046. 9 interactions.
MINTiMINT-574280.

Protein family/group databases

TCDBi3.A.8.1.1. the mitochondrial protein translocase (mpt) family.

PTM databases

iPTMnetiP36046.

Proteomic databases

MaxQBiP36046.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblFungiiYKL195W; YKL195W; YKL195W.
GeneIDi853639.
KEGGisce:YKL195W.

Organism-specific databases

EuPathDBiFungiDB:YKL195W.
SGDiS000001678. MIA40.

Phylogenomic databases

GeneTreeiENSGT00390000013132.
InParanoidiP36046.
KOiK17782.
OrthoDBiEOG7JHMH7.

Enzyme and pathway databases

BioCyciYEAST:G3O-31957-MONOMER.
ReactomeiR-SCE-1268020. Mitochondrial protein import.

Miscellaneous databases

EvolutionaryTraceiP36046.
PROiP36046.

Family and domain databases

InterProiIPR010625. CHCH.
[Graphical view]
PfamiPF06747. CHCH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Complete DNA sequence of yeast chromosome XI."
    Dujon B., Alexandraki D., Andre B., Ansorge W., Baladron V., Ballesta J.P.G., Banrevi A., Bolle P.-A., Bolotin-Fukuhara M., Bossier P., Bou G., Boyer J., Buitrago M.J., Cheret G., Colleaux L., Daignan-Fornier B., del Rey F., Dion C.
    , Domdey H., Duesterhoeft A., Duesterhus S., Entian K.-D., Erfle H., Esteban P.F., Feldmann H., Fernandes L., Fobo G.M., Fritz C., Fukuhara H., Gabel C., Gaillon L., Garcia-Cantalejo J.M., Garcia-Ramirez J.J., Gent M.E., Ghazvini M., Goffeau A., Gonzalez A., Grothues D., Guerreiro P., Hegemann J.H., Hewitt N., Hilger F., Hollenberg C.P., Horaitis O., Indge K.J., Jacquier A., James C.M., Jauniaux J.-C., Jimenez A., Keuchel H., Kirchrath L., Kleine K., Koetter P., Legrain P., Liebl S., Louis E.J., Maia e Silva A., Marck C., Monnier A.-L., Moestl D., Mueller S., Obermaier B., Oliver S.G., Pallier C., Pascolo S., Pfeiffer F., Philippsen P., Planta R.J., Pohl F.M., Pohl T.M., Poehlmann R., Portetelle D., Purnelle B., Puzos V., Ramezani Rad M., Rasmussen S.W., Remacha M.A., Revuelta J.L., Richard G.-F., Rieger M., Rodrigues-Pousada C., Rose M., Rupp T., Santos M.A., Schwager C., Sensen C., Skala J., Soares H., Sor F., Stegemann J., Tettelin H., Thierry A., Tzermia M., Urrestarazu L.A., van Dyck L., van Vliet-Reedijk J.C., Valens M., Vandenbol M., Vilela C., Vissers S., von Wettstein D., Voss H., Wiemann S., Xu G., Zimmermann J., Haasemann M., Becker I., Mewes H.-W.
    Nature 369:371-378(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: ATCC 204508 / S288c.
  2. Cited for: GENOME REANNOTATION.
    Strain: ATCC 204508 / S288c.
  3. "Mia40, a novel factor for protein import into the intermembrane space of mitochondria is able to bind metal ions."
    Terziyska N., Lutz T., Kozany C., Mokranjac D., Mesecke N., Neupert W., Herrmann J.M., Hell K.
    FEBS Lett. 579:179-184(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 32-36, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH TIM13, MUTAGENESIS OF CYS-296; CYS-298 AND CYS-307, METAL-BINDING.
  4. "Sequencing and comparison of yeast species to identify genes and regulatory elements."
    Kellis M., Patterson N., Endrizzi M., Birren B.W., Lander E.S.
    Nature 423:241-254(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION OF PROBABLE INITIATION SITE.
  5. Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
  6. Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
  7. Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
    Strain: ATCC 76625 / YPH499.
  8. "Essential role of Mia40 in import and assembly of mitochondrial intermembrane space proteins."
    Chacinska A., Pfannschmidt S., Wiedemann N., Kozjak V., Sanjuan Szklarz L.K., Schulze-Specking A., Truscott K.N., Guiard B., Meisinger C., Pfanner N.
    EMBO J. 23:3735-3746(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH TIM9.
  9. "Identification of Tim40 that mediates protein sorting to the mitochondrial intermembrane space."
    Naoe M., Ohwa Y., Ishikawa D., Ohshima C., Nishikawa S., Yamamoto H., Endo T.
    J. Biol. Chem. 279:47815-47821(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-296; CYS-298; CYS-307; CYS-317; CYS-330 AND CYS-340.
  10. "A disulfide relay system in the intermembrane space of mitochondria that mediates protein import."
    Mesecke N., Terziyska N., Kozany C., Baumann F., Neupert W., Hell K., Herrmann J.M.
    Cell 121:1059-1069(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH COX17; ERV1 AND TIM13.
  11. "The essential mitochondrial protein Erv1 cooperates with Mia40 in biogenesis of intermembrane space proteins."
    Rissler M., Wiedemann N., Pfannschmidt S., Gabriel K., Guiard B., Pfanner N., Chacinska A.
    J. Mol. Biol. 353:485-492(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH ERV1.
  12. "Proteomic analysis of the yeast mitochondrial outer membrane reveals accumulation of a subclass of preproteins."
    Zahedi R.P., Sickmann A., Boehm A.M., Winkler C., Zufall N., Schoenfisch B., Guiard B., Pfanner N., Meisinger C.
    Mol. Biol. Cell 17:1436-1450(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY.
  13. Cited for: INTERACTION WITH FCJ1.
  14. "Structural basis of yeast Tim40/Mia40 as an oxidative translocator in the mitochondrial intermembrane space."
    Kawano S., Yamano K., Naoe M., Momose T., Terao K., Nishikawa S., Watanabe N., Endo T.
    Proc. Natl. Acad. Sci. U.S.A. 106:14403-14407(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 284-353, FUNCTION, DISULFIDE BONDS.

Entry informationi

Entry nameiMIA40_YEAST
AccessioniPrimary (citable) accession number: P36046
Secondary accession number(s): D6VX05
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: March 21, 2006
Last modified: July 6, 2016
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Miscellaneous

Present with 5040 molecules/cell in log phase SD medium.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Yeast
    Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
  4. Yeast chromosome XI
    Yeast (Saccharomyces cerevisiae) chromosome XI: entries and gene names

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.