CHCHD4
entrez
131474
canonical
uniprot
Q8N4Q1
canonical
ensembl
ENSG00000163528
resolver
ensp
ENSP00000295767
resolver
ensp
ENSP00000380122
resolver
genesymbol
CHCHD4
resolver
genesymbol_syn
MIA40
resolver
hgnc
HGNC:26467
resolver
uniprot
A8K3Z9
resolver
uniprot
Q96AI2
resolver
uniprot
Q96MY6
resolver
uniprot_entry
MIA40_HUMAN
resolver
uniprot_sec
A8K3Z9
resolver
uniprot_sec
Q96AI2
resolver
uniprot_sec
Q96MY6
resolver
amino_acid_sequence
MSYCRQEGKDRIIFVTKEDHETPSSAELVADDPNDPYEEHGLILPNGNINWNCPCLGGMASGPCGEQFKSAFSCFHYSTEEIKGSDCVDQFRAMQECMQKYPDLYPQEDEDEEEEREKKPAEQAEETAPIEATATKEEEGSS
uniprot
proteins
function
FUNCTION: Central component of a redox-sensitive mitochondrial intermembrane space import machinery which is required for the biogenesis of respiratory chain complexes (PubMed:26004228). Functions as a chaperone and catalyzes the formation of disulfide bonds in substrate proteins, such as COA7, COX17, COX19, MICU1 and TIMCC/FAM136A (PubMed:16185709, PubMed:19182799, PubMed:21059946, PubMed:23186364, PubMed:23676665, PubMed:26387864, PubMed:30885959, PubMed:41109133). Required for the import and folding of small cysteine-containing proteins (small Tim) in the mitochondrial intermembrane space (IMS). Required for the import of COA7 in the IMS (PubMed:30885959). Precursor proteins to be imported into the IMS are translocated in their reduced form into the mitochondria. The oxidized form of CHCHD4/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 (PubMed:16185709, PubMed:19182799, PubMed:21059946, PubMed:23676665). Reduced CHCHD4/MIA40 is then reoxidized by GFER/ERV1 via a disulfide relay system (PubMed:23186364). Mediates formation of disulfide bond in MICU1 in the IMS, promoting formation of the MICU1-MICU2 heterodimer that regulates mitochondrial calcium uptake (PubMed:26387864). {ECO:0000269|PubMed:16185709, ECO:0000269|PubMed:19182799, ECO:0000269|PubMed:21059946, ECO:0000269|PubMed:23186364, ECO:0000269|PubMed:23676665, ECO:0000269|PubMed:26004228, ECO:0000269|PubMed:26387864, ECO:0000269|PubMed:30885959, ECO:0000269|PubMed:41109133}.
uniprot
proteins
mass_dalton
15996
uniprot
proteins
mutagenesis
MUTAGEN 4; /note="C->S: No effect on interaction with AIFM1."; /evidence="ECO:0000269|PubMed:26004228"; MUTAGEN 53..55; /note="CPC->SPS: No effect on interaction with AIFM1. Reduces interaction with TIMCC."; /evidence="ECO:0000269|PubMed:26004228, ECO:0000269|PubMed:41109133"; MUTAGEN 53; /note="C->S: Does not strongly affect import and stability of CHCHD4 in mitochondria; when associated with S-55. No effect on disulfide exchange with substrate proteins. Does not affect interaction with COA7. No effect on interaction with AIFM1."; /evidence="ECO:0000269|PubMed:16185709, ECO:0000269|PubMed:19182799, ECO:0000269|PubMed:26004228, ECO:0000269|PubMed:26387864, ECO:0000269|PubMed:30885959"; MUTAGEN 55; /note="C->S: Does not strongly affect import and stability of CHCHD4 in mitochondria; when associated with S-53. Nearly abolishes disulfide exchange with substrate proteins. Abolishes interaction with COA7."; /evidence="ECO:0000269|PubMed:16185709, ECO:0000269|PubMed:19182799, ECO:0000269|PubMed:30885959"; MUTAGEN 64; /note="C->S: Affects import and stability of CHCHD4 in mitochondria; when associated with S-74."; /evidence="ECO:0000269|PubMed:16185709"; MUTAGEN 68; /note="F->E: Reduces interaction with TIMCC."; /evidence="ECO:0000269|PubMed:41109133"; MUTAGEN 74; /note="C->S: Affects import and stability of CHCHD4 in mitochondria; when associated with S-64. No effect on interaction with AIFM1."; /evidence="ECO:0000269|PubMed:16185709, ECO:0000269|PubMed:26004228"; MUTAGEN 87; /note="C->S: Strongly affects import and stability of CHCHD4 in mitochondria; when associated with S-97. No effect on interaction with AIFM1."; /evidence="ECO:0000269|PubMed:16185709, ECO:0000269|PubMed:26004228"; MUTAGEN 97; /note="C->S: Strongly affects import and stability of CHCHD4 in mitochondria; when associated with S-87. No effect on interaction with AIFM1."; /evidence="ECO:0000269|PubMed:16185709, ECO:0000269|PubMed:26004228
uniprot
proteins
post_translational_modification
PTM: Forms intrachain disulfide bridges, but exists in different redox states.
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16185709
uniprot
proteins
pubmed
19182799
uniprot
proteins
pubmed
21059946
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23186364
uniprot
proteins
pubmed
23676665
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26004228
uniprot
proteins
pubmed
26387864
uniprot
proteins
pubmed
28040730
uniprot
proteins
pubmed
30885959
uniprot
proteins
pubmed
41109133
uniprot
proteins
sequence_length
142
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion intermembrane space {ECO:0000269|PubMed:16185709, ECO:0000269|PubMed:23186364, ECO:0000269|PubMed:23676665, ECO:0000269|PubMed:26004228}.
uniprot
proteins