MIA40_MOUSE
ID MIA40_MOUSE Reviewed; 139 AA.
AC Q8VEA4;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Mitochondrial intermembrane space import and assembly protein 40;
DE AltName: Full=Coiled-coil-helix-coiled-coil-helix domain-containing protein 4;
GN Name=Chchd4; Synonyms=Mia40;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=16185709; DOI=10.1016/j.jmb.2005.08.064;
RA Hofmann S., Rothbauer U., Muehlenbein N., Baiker K., Hell K., Bauer M.F.;
RT "Functional and mutational characterization of human MIA40 acting during
RT import into the mitochondrial intermembrane space.";
RL J. Mol. Biol. 353:517-528(2005).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26004228; DOI=10.1016/j.molcel.2015.04.020;
RA Hangen E., Feraud O., Lachkar S., Mou H., Doti N., Fimia G.M., Lam N.V.,
RA Zhu C., Godin I., Muller K., Chatzi A., Nuebel E., Ciccosanti F.,
RA Flamant S., Benit P., Perfettini J.L., Sauvat A., Bennaceur-Griscelli A.,
RA Ser-Le Roux K., Gonin P., Tokatlidis K., Rustin P., Piacentini M., Ruvo M.,
RA Blomgren K., Kroemer G., Modjtahedi N.;
RT "Interaction between AIF and CHCHD4 Regulates Respiratory Chain
RT Biogenesis.";
RL Mol. Cell 58:1001-1014(2015).
CC -!- FUNCTION: Central component of a redox-sensitive mitochondrial
CC intermembrane space import machinery which is required for the
CC biogenesis of respiratory chain complexes (PubMed:26004228). Functions
CC as chaperone and catalyzes the formation of disulfide bonds in
CC substrate proteins, such as COX17, COX19, MICU1 and COA7. Required for
CC the import and folding of small cysteine-containing proteins (small
CC Tim) in the mitochondrial intermembrane space (IMS). Required for the
CC import of COA7 in the IMS. Precursor proteins to be imported into the
CC IMS are translocated in their reduced form into the mitochondria. The
CC oxidized form of CHCHD4/MIA40 forms a transient intermolecular
CC disulfide bridge with the reduced precursor protein, resulting in
CC oxidation of the precursor protein that now contains an intramolecular
CC disulfide bond and is able to undergo folding in the IMS. Reduced
CC CHCHD4/MIA40 is then reoxidized by GFER/ERV1 via a disulfide relay
CC system. Mediates formation of disulfide bond in MICU1 in the IMS,
CC promoting formation of the MICU1-MICU2 heterodimer that regulates
CC mitochondrial calcium uptake. {ECO:0000250|UniProtKB:Q8N4Q1,
CC ECO:0000269|PubMed:26004228}.
CC -!- SUBUNIT: Monomer. Can form homooligomers. Interacts with GFER and forms
CC transient disulfide bonds with GFER. Interacts with MICU1. Interacts
CC with COX19 forming transient intermolecular disulfide bridges.
CC Interacts with COA7 through transient intermolecular disulfide bonds.
CC Interacts with AIFM1; the interaction increases in presence of NADH.
CC Interacts with NDUFB10. {ECO:0000250|UniProtKB:Q8N4Q1}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion intermembrane space
CC {ECO:0000250|UniProtKB:Q8N4Q1}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Present at high level in liver
CC and kidney, followed by lung, brain, heart and spleen (at protein
CC level). {ECO:0000269|PubMed:16185709}.
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:0000250}.
CC -!- PTM: Forms intrachain disulfide bridges, but exists in different redox
CC states. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mutants have a developmental arrest coupled with
CC embryonic lethality at 8.5 dpc. They show a major defect in the
CC expression of respiratory chain complex I subunit NDUFS7/CI-20.
CC {ECO:0000269|PubMed:26004228}.
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DR EMBL; AK012745; BAC25375.1; -; mRNA.
DR EMBL; BC019405; AAH19405.1; -; mRNA.
DR CCDS; CCDS20367.1; -.
DR RefSeq; NP_598689.1; NM_133928.2.
DR AlphaFoldDB; Q8VEA4; -.
DR SMR; Q8VEA4; -.
DR BioGRID; 215197; 6.
DR STRING; 10090.ENSMUSP00000041380; -.
DR PhosphoSitePlus; Q8VEA4; -.
DR EPD; Q8VEA4; -.
DR MaxQB; Q8VEA4; -.
DR PaxDb; Q8VEA4; -.
DR PeptideAtlas; Q8VEA4; -.
DR PRIDE; Q8VEA4; -.
DR ProteomicsDB; 252550; -.
DR Ensembl; ENSMUST00000040835; ENSMUSP00000041380; ENSMUSG00000034203.
DR GeneID; 72170; -.
DR KEGG; mmu:72170; -.
DR UCSC; uc009cyb.1; mouse.
DR CTD; 131474; -.
DR MGI; MGI:1919420; Chchd4.
DR VEuPathDB; HostDB:ENSMUSG00000034203; -.
DR eggNOG; KOG4149; Eukaryota.
DR GeneTree; ENSGT00390000013132; -.
DR HOGENOM; CLU_127296_1_0_1; -.
DR InParanoid; Q8VEA4; -.
DR OMA; MECAMRT; -.
DR OrthoDB; 1594252at2759; -.
DR PhylomeDB; Q8VEA4; -.
DR TreeFam; TF314054; -.
DR BioGRID-ORCS; 72170; 15 hits in 110 CRISPR screens.
DR ChiTaRS; Chchd4; mouse.
DR PRO; PR:Q8VEA4; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q8VEA4; protein.
DR Bgee; ENSMUSG00000034203; Expressed in otic placode and 248 other tissues.
DR Genevisible; Q8VEA4; MM.
DR GO; GO:0005758; C:mitochondrial intermembrane space; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0015035; F:protein-disulfide reductase activity; ISS:UniProtKB.
DR GO; GO:0051084; P:'de novo' post-translational protein folding; ISS:UniProtKB.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEP:MGI.
DR GO; GO:0034599; P:cellular response to oxidative stress; IDA:MGI.
DR GO; GO:0072655; P:establishment of protein localization to mitochondrion; IMP:MGI.
DR GO; GO:0043504; P:mitochondrial DNA repair; IDA:MGI.
DR GO; GO:0033108; P:mitochondrial respiratory chain complex assembly; IMP:UniProtKB.
DR GO; GO:0018171; P:peptidyl-cysteine oxidation; ISS:UniProtKB.
DR GO; GO:1901857; P:positive regulation of cellular respiration; IMP:MGI.
DR GO; GO:0045041; P:protein import into mitochondrial intermembrane space; ISS:UniProtKB.
DR GO; GO:0022417; P:protein maturation by protein folding; ISS:UniProtKB.
DR GO; GO:0046825; P:regulation of protein export from nucleus; IMP:MGI.
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 Disulfide bond; Mitochondrion; Oxidoreductase; Protein transport;
KW Redox-active center; Reference proteome; Translocation; Transport.
FT CHAIN 1..139
FT /note="Mitochondrial intermembrane space import and
FT assembly protein 40"
FT /id="PRO_0000129166"
FT DOMAIN 61..105
FT /note="CHCH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150"
FT REGION 102..139
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 64..74
FT /note="Cx9C motif 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150"
FT MOTIF 87..97
FT /note="Cx9C motif 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150"
FT DISULFID 53..55
FT /note="Redox-active"
FT /evidence="ECO:0000250|UniProtKB:Q8N4Q1"
FT DISULFID 64..97
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150"
FT DISULFID 74..87
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150"
SQ SEQUENCE 139 AA; 15525 MW; 624DCB0613A102FF CRC64;
MSYCRQEGKD RIIFVTKEDH ETPSSAELVA DDPNDPYEEH GLILPNGDIN WNCPCLGGMA
SGPCGEQFKS AFSCFHYSTE DIKGSDCIDQ FRAMQECMQK YPDLYPQDEE EEEEAKPVEP
VEETADTKVS AAKEQGTSS
