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Protein

Mitochondrial intermembrane space import and assembly protein 40

Gene

CHCHD4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Functions as chaperone and catalyzes the formation of disulfide bonds in substrate proteins, such as COX17 or MICU1 (PubMed:16185709, PubMed:26387864, PubMed:19182799, PubMed:21059946, PubMed:23186364). Required for the import and folding of small cysteine-containing proteins (small Tim) in the mitochondrial intermembrane space (IMS) (PubMed:16185709, PubMed:19182799, PubMed:21059946). Precursor proteins to be imported into the IMS are translocated in their reduced form into the mitochondria (PubMed:16185709, PubMed:19182799, PubMed:21059946). 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). 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).5 Publications

GO - Molecular functioni

  • protein disulfide oxidoreductase activity Source: UniProtKB

GO - Biological processi

  • 'de novo' posttranslational protein folding Source: UniProtKB
  • protein import into mitochondrial intermembrane space Source: UniProtKB
  • protein maturation by protein folding Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Protein transport, Translocation, Transport

Enzyme and pathway databases

ReactomeiR-HSA-1268020. Mitochondrial protein import.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitochondrial intermembrane space import and assembly protein 40
Alternative name(s):
Coiled-coil-helix-coiled-coil-helix domain-containing protein 4
Gene namesi
Name:CHCHD4
Synonyms:MIA40
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:26467. CHCHD4.

Subcellular locationi

GO - Cellular componenti

  • mitochondrial intermembrane space Source: UniProtKB
  • mitochondrion Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi53 – 531C → 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. 3 Publications
Mutagenesisi55 – 551C → S: Does not strongly affect import and stability of CHCHD4 in mitochondria; when associated with S-53. Nearly abolishes disulfide exchange with substrate proteins. 2 Publications
Mutagenesisi64 – 641C → S: Affects import and stability of CHCHD4 in mitochondria; when associated with S-74. 1 Publication
Mutagenesisi74 – 741C → S: Affects import and stability of CHCHD4 in mitochondria; when associated with S-64. 1 Publication
Mutagenesisi87 – 871C → S: Strongly affects import and stability of CHCHD4 in mitochondria; when associated with S-97. 1 Publication
Mutagenesisi97 – 971C → S: Strongly affects import and stability of CHCHD4 in mitochondria; when associated with S-87. 1 Publication

Organism-specific databases

PharmGKBiPA134990707.

Polymorphism and mutation databases

BioMutaiCHCHD4.
DMDMi62510498.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 142142Mitochondrial intermembrane space import and assembly protein 40PRO_0000129165Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi53 ↔ 55Redox-active1 Publication1 Publication
Disulfide bondi64 ↔ 97Combined sources2 Publications
Disulfide bondi74 ↔ 87Combined sources2 Publications

Post-translational modificationi

Forms intrachain disulfide bridges, but exists in different redox states.

Keywords - PTMi

Disulfide bond

Proteomic databases

EPDiQ8N4Q1.
MaxQBiQ8N4Q1.
PaxDbiQ8N4Q1.
PeptideAtlasiQ8N4Q1.
PRIDEiQ8N4Q1.
TopDownProteomicsiQ8N4Q1-1. [Q8N4Q1-1]

PTM databases

iPTMnetiQ8N4Q1.
PhosphoSiteiQ8N4Q1.

Expressioni

Tissue specificityi

Expressed in all tissues tested, suggesting an ubiquitous expression.1 Publication

Gene expression databases

BgeeiENSG00000163528.
CleanExiHS_CHCHD4.
ExpressionAtlasiQ8N4Q1. baseline and differential.
GenevisibleiQ8N4Q1. HS.

Organism-specific databases

HPAiHPA034688.
HPA063727.

Interactioni

Subunit structurei

Monomer (PubMed:19182799). Can form homooligomers (PubMed:16185709). Interacts with GFER and forms transient disulfide bonds with GFER (PubMed:23186364). Interacts with MICU1 (PubMed:26387864).3 Publications

Protein-protein interaction databases

BioGridi126282. 20 interactions.
DIPiDIP-48483N.
IntActiQ8N4Q1. 6 interactions.
STRINGi9606.ENSP00000295767.

Structurei

Secondary structure

1
142
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi47 – 493Combined sources
Helixi54 – 596Combined sources
Beta strandi61 – 633Combined sources
Helixi65 – 7814Combined sources
Beta strandi80 – 823Combined sources
Turni83 – 875Combined sources
Helixi88 – 10013Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2K3JNMR-A1-142[»]
2L0YNMR-A1-142[»]
ProteinModelPortaliQ8N4Q1.
SMRiQ8N4Q1. Positions 41-105.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8N4Q1.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini57 – 10044CHCHSequence analysisAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi108 – 11710Asp/Glu-rich (acidic)Curated

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

Phylogenomic databases

eggNOGiKOG4149. Eukaryota.
ENOG4111V0I. LUCA.
GeneTreeiENSGT00390000013132.
HOGENOMiHOG000013070.
HOVERGENiHBG050937.
InParanoidiQ8N4Q1.
KOiK17782.
OMAiTTRYYHR.
PhylomeDBiQ8N4Q1.
TreeFamiTF314054.

Family and domain databases

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

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8N4Q1-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSYCRQEGKD RIIFVTKEDH ETPSSAELVA DDPNDPYEEH GLILPNGNIN
60 70 80 90 100
WNCPCLGGMA SGPCGEQFKS AFSCFHYSTE EIKGSDCVDQ FRAMQECMQK
110 120 130 140
YPDLYPQEDE DEEEEREKKP AEQAEETAPI EATATKEEEG SS
Length:142
Mass (Da):15,996
Last modified:October 1, 2002 - v1
Checksum:i87563CADF249800C
GO
Isoform 2 (identifier: Q8N4Q1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-6: MSYCRQ → MPVSYSSVTTRYYHRAGAE

Note: No experimental confirmation available.
Show »
Length:155
Mass (Da):17,385
Checksum:iC0477CE14E8775FD
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 66MSYCRQ → MPVSYSSVTTRYYHRAGAE in isoform 2. 1 PublicationVSP_018433

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK056271 mRNA. Translation: BAB71132.1.
AK290764 mRNA. Translation: BAF83453.1.
CH471055 Genomic DNA. Translation: EAW64180.1.
BC017082 mRNA. Translation: AAH17082.2.
BC033775 mRNA. Translation: AAH33775.1.
CCDSiCCDS2617.1. [Q8N4Q1-2]
CCDS43054.1. [Q8N4Q1-1]
RefSeqiNP_001091972.1. NM_001098502.1. [Q8N4Q1-1]
NP_653237.1. NM_144636.2. [Q8N4Q1-2]
UniGeneiHs.517815.

Genome annotation databases

EnsembliENST00000295767; ENSP00000295767; ENSG00000163528. [Q8N4Q1-2]
ENST00000396914; ENSP00000380122; ENSG00000163528. [Q8N4Q1-1]
GeneIDi131474.
KEGGihsa:131474.
UCSCiuc003byi.5. human. [Q8N4Q1-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK056271 mRNA. Translation: BAB71132.1.
AK290764 mRNA. Translation: BAF83453.1.
CH471055 Genomic DNA. Translation: EAW64180.1.
BC017082 mRNA. Translation: AAH17082.2.
BC033775 mRNA. Translation: AAH33775.1.
CCDSiCCDS2617.1. [Q8N4Q1-2]
CCDS43054.1. [Q8N4Q1-1]
RefSeqiNP_001091972.1. NM_001098502.1. [Q8N4Q1-1]
NP_653237.1. NM_144636.2. [Q8N4Q1-2]
UniGeneiHs.517815.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2K3JNMR-A1-142[»]
2L0YNMR-A1-142[»]
ProteinModelPortaliQ8N4Q1.
SMRiQ8N4Q1. Positions 41-105.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi126282. 20 interactions.
DIPiDIP-48483N.
IntActiQ8N4Q1. 6 interactions.
STRINGi9606.ENSP00000295767.

PTM databases

iPTMnetiQ8N4Q1.
PhosphoSiteiQ8N4Q1.

Polymorphism and mutation databases

BioMutaiCHCHD4.
DMDMi62510498.

Proteomic databases

EPDiQ8N4Q1.
MaxQBiQ8N4Q1.
PaxDbiQ8N4Q1.
PeptideAtlasiQ8N4Q1.
PRIDEiQ8N4Q1.
TopDownProteomicsiQ8N4Q1-1. [Q8N4Q1-1]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000295767; ENSP00000295767; ENSG00000163528. [Q8N4Q1-2]
ENST00000396914; ENSP00000380122; ENSG00000163528. [Q8N4Q1-1]
GeneIDi131474.
KEGGihsa:131474.
UCSCiuc003byi.5. human. [Q8N4Q1-1]

Organism-specific databases

CTDi131474.
GeneCardsiCHCHD4.
HGNCiHGNC:26467. CHCHD4.
HPAiHPA034688.
HPA063727.
MIMi611077. gene.
neXtProtiNX_Q8N4Q1.
PharmGKBiPA134990707.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4149. Eukaryota.
ENOG4111V0I. LUCA.
GeneTreeiENSGT00390000013132.
HOGENOMiHOG000013070.
HOVERGENiHBG050937.
InParanoidiQ8N4Q1.
KOiK17782.
OMAiTTRYYHR.
PhylomeDBiQ8N4Q1.
TreeFamiTF314054.

Enzyme and pathway databases

ReactomeiR-HSA-1268020. Mitochondrial protein import.

Miscellaneous databases

ChiTaRSiCHCHD4. human.
EvolutionaryTraceiQ8N4Q1.
GenomeRNAii131474.
PROiQ8N4Q1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000163528.
CleanExiHS_CHCHD4.
ExpressionAtlasiQ8N4Q1. baseline and differential.
GenevisibleiQ8N4Q1. HS.

Family and domain databases

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

Entry informationi

Entry nameiMIA40_HUMAN
AccessioniPrimary (citable) accession number: Q8N4Q1
Secondary accession number(s): A8K3Z9, Q96AI2, Q96MY6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: October 1, 2002
Last modified: September 7, 2016
This is version 111 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

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.