P36046 (MIA40_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mitochondrial intermembrane space import and assembly protein 40

Alternative name(s):
Mitochondrial import inner membrane translocase TIM40

Gene names

Name:	MIA40
Synonyms:	TIM40
Ordered Locus Names:	YKL195W

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces

Protein attributes

Sequence length	403 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.3 Ref.8 Ref.9 Ref.10 Ref.11
Cofactor	Copper or zinc.
Subunit structure	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. Ref.3 Ref.8 Ref.10 Ref.11 Ref.14
Subcellular location	Mitochondrion inner membrane; Single-pass type II membrane protein; Intermembrane side Ref.3 Ref.5 Ref.7 Ref.8 Ref.9 Ref.12.
Domain	The CHCH domain contains a conserved twin Cys-X(9)-Cys motif which is required for import and stability of MIA40 in mitochondria Probable.
Miscellaneous	Present with 5040 molecules/cell in log phase SD medium. Ref.6
Sequence similarities	Contains 1 CHCH domain.

Ontologies

Keywords
Biological process	Protein transport Translocation Transport
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Domain	Signal-anchor Transit peptide Transmembrane Transmembrane helix
PTM	Disulfide bond Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	protein import into mitochondrial intermembrane space Inferred from mutant phenotype Ref.8Ref.9. Source: SGD
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial inner membrane Inferred from direct assay Ref.9. Source: SGD mitochondrial intermembrane space Inferred from direct assay Ref.8. Source: SGD mitochondrial outer membrane translocase complex Inferred from direct assay Ref.3. Source: SGD
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 31

31

Mitochondrion Ref.3

Chain

32 – 403

372

Mitochondrial intermembrane space import and assembly protein 40

PRO_0000203135

Regions

Topological domain

33 – 46

14

Mitochondrial matrix Potential

Transmembrane

47 – 66

20

Helical; Signal-anchor for type II membrane protein; Potential

Topological domain

67 – 403

337

Mitochondrial intermembrane Potential

Domain

300 – 343

44

CHCH

Amino acid modifications

Modified residue

372

1

Phosphoserine Ref.13

Experimental info

Mutagenesis

296

1

C → S: Loss of function; when associated with S-298. Ref.3 Ref.9

Mutagenesis

298

1

C → S: Loss of function; when associated with S-296. Ref.3 Ref.9

Mutagenesis

307

1

C → S: Loss of function; when associated with S-317. Ref.3 Ref.9

Mutagenesis

317

1

C → S: Loss of function; when associated with S-307. Ref.9

Mutagenesis

330

1

C → S: Loss of function; when associated with S-340. Ref.9

Mutagenesis

340

1

C → S: Loss of function; when associated with S-330. Ref.9

Secondary structure

1

.

.

.

.

.

.

.

403

Helix Strand Turn

Details...

Helix

310 – 319

10

Helix

331 – 341

11

Turn

345 – 347

3

Sequences

	Sequence		Length	Mass (Da)
	P36046 [UniParc]. Last modified March 21, 2006. Version 2. Checksum: 5904E8D0213D6EFA	FASTA	403	44,536
	10 20 30 40 50 60 MLRNLVVRNA CRNRPSIQVA RGLCRHQTRR LMASSPQFGR NSNQEKTAGF IMGILSMAGA 70 80 90 100 110 120 LYFIAPNRKP LFASRKVESD KTAEEELSSG GEQSPENEDD NNSKSDENGD DNDSKNDETE 130 140 150 160 170 180 AGPQLGGDKI GASKVAEDGE LVVLAEEDNK SSEDKDTDES KVSTKDDEQS NEDNATANNQ 190 200 210 220 230 240 KDENISSENS EENTSDKTLD NNAGSSEKKD PEHSDDEKSQ QGQSDDKTTT EDNNGEEESS 250 260 270 280 290 300 KKTVSDSENS AKQSESSDEE KEELRKQEEK QMGPTEEEVQ HEGAYNPDTG EINWDCPCLG 310 320 330 340 350 360 GMAHGPCGEE FKSAFSCFVY SEAEPKGIDC VEKFQHMQDC FRKYPEHYAE QLKETSDDEE 370 380 390 400 PQDKVKVNTI ESAPNVSSAK ENAAKKAEQS DVKKEPLNEE SKP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 8196765] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 96604 / S288c / FY1679.
[2]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases 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: 15620710] [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: 12748633] [Abstract] Cited for: IDENTIFICATION OF PROBABLE INITIATION SITE.
[5]	"Global analysis of protein localization in budding yeast." Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., Weissman J.S., O'Shea E.K. Nature 425:686-691(2003) [PubMed: 14562095] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
[6]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed: 14562106] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[7]	"The proteome of Saccharomyces cerevisiae mitochondria." Sickmann A., Reinders J., Wagner Y., Joppich C., Zahedi R.P., Meyer H.E., Schoenfisch B., Perschil I., Chacinska A., Guiard B., Rehling P., Pfanner N., Meisinger C. Proc. Natl. Acad. Sci. U.S.A. 100:13207-13212(2003) [PubMed: 14576278] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. 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: 15359280] [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: 15364952] [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: 15989955] [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: 16181637] [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: 16407407] [Abstract] Cited for: SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY.
[13]	"A multidimensional chromatography technology for in-depth phosphoproteome analysis." Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H. Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed: 18407956] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-372, MASS SPECTROMETRY.
[14]	"Dual role of mitofilin in mitochondrial membrane organization and protein biogenesis." von der Malsburg K., Muller J.M., Bohnert M., Oeljeklaus S., Kwiatkowska P., Becker T., Loniewska-Lwowska A., Wiese S., Rao S., Milenkovic D., Hutu D.P., Zerbes R.M., Schulze-Specking A., Meyer H.E., Martinou J.C., Rospert S., Rehling P., Meisinger C. , Veenhuis M., Warscheid B., van der Klei I.J., Pfanner N., Chacinska A., van der Laan M. Dev. Cell 21:694-707(2011) [PubMed: 21944719] [Abstract] Cited for: INTERACTION WITH FCJ1.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z28195 Genomic DNA. Translation: CAA82039.1.
BK006944 Genomic DNA. Translation: DAA08971.1.

PIR

S38032.

RefSeq

NP_012726.2. NM_001179761.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ZXT	X-ray	3.00	A	284-365	[»]
3A3C	X-ray	2.50	A	284-353	[»]

ProteinModelPortal

P36046.

SMR

P36046. Positions 249-353.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5432N.

IntAct

P36046. 4 interactions.

MINT

MINT-574280.

STRING

P36046.

Protein family/group databases

TCDB

3.A.8.1.1. mitochondrial protein translocase (MPT) family.

Proteomic databases

PeptideAtlas

P36046.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblFungi

YKL195W; YKL195W; YKL195W.

GeneID

853639.

KEGG

sce:YKL195W.

NMPDR

fig|4932.3.peg.3703.

Organism-specific databases

CYGD

YKL195w.

SGD

S000001678. MIA40.

Phylogenomic databases

eggNOG

fuNOG11502.

GeneTree

EFGT00050000000165.

OrthoDB

EOG4BGD4X.

Gene expression databases

ArrayExpress

P36046.

Genevestigator

P36046.

GermOnline

YKL195W. Saccharomyces cerevisiae.

Family and domain databases

InterPro

IPR010625. CHCH.
[Graphical view]

Pfam

PF06747. CHCH. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

974528.

Entry information

Entry name

MIA40_YEAST

Accession

Primary (citable) accession number: P36046
Secondary accession number(s): D6VX05

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	March 21, 2006
Last modified:	January 25, 2012
This is version 84 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program