General Information of Target

Target ID LDTP08874
Target Name Mitochondrial intermembrane space import and assembly protein 40 (CHCHD4)
Gene Name CHCHD4
Gene ID 131474
Synonyms
MIA40; Mitochondrial intermembrane space import and assembly protein 40; Coiled-coil-helix-coiled-coil-helix domain-containing protein 4
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MSYCRQEGKDRIIFVTKEDHETPSSAELVADDPNDPYEEHGLILPNGNINWNCPCLGGMA
SGPCGEQFKSAFSCFHYSTEEIKGSDCVDQFRAMQECMQKYPDLYPQEDEDEEEEREKKP
AEQAEETAPIEATATKEEEGSS
Target Bioclass
Other
Subcellular location
Mitochondrion intermembrane space
Function
Central component of a redox-sensitive mitochondrial intermembrane space import machinery which is required for the biogenesis of respiratory chain complexes. Functions as chaperone and catalyzes the formation of disulfide bonds in substrate proteins, such as COX17, COX19, MICU1 and COA7. 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. 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. Reduced CHCHD4/MIA40 is then reoxidized by GFER/ERV1 via a disulfide relay system. Mediates formation of disulfide bond in MICU1 in the IMS, promoting formation of the MICU1-MICU2 heterodimer that regulates mitochondrial calcium uptake.
Uniprot ID
Q8N4Q1
Ensemble ID
ENST00000295767.9
HGNC ID
HGNC:26467

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
HCT15 SNV: p.L104R .
MDAMB157 SNV: p.E122K .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 12 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
FBP2
 Probe Info 
3.26  LDD0323  [1]
Probe 1
 Probe Info 
Y101(12.62); Y105(11.12)  LDD3495  [2]
Acrolein
 Probe Info 
N.A.  LDD0222  [3]
5E-2FA
 Probe Info 
N.A.  LDD2235  [4]
m-APA
 Probe Info 
N.A.  LDD2231  [4]
4-Iodoacetamidophenylacetylene
 Probe Info 
C97(0.00); C74(0.00)  LDD0038  [5]
IA-alkyne
 Probe Info 
C97(0.00); C87(0.00); C74(0.00)  LDD0036  [5]
Lodoacetamide azide
 Probe Info 
C87(0.00); C74(0.00)  LDD0037  [5]
TFBX
 Probe Info 
N.A.  LDD0027  [6]
Phosphinate-6
 Probe Info 
N.A.  LDD0018  [7]
AOyne
 Probe Info 
15.00  LDD0443  [8]
NAIA_5
 Probe Info 
C97(0.00); C87(0.00); C74(0.00); C4(0.00)  LDD2223  [9]
PAL-AfBPP Probe
Click To Hide/Show 4 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
C265
 Probe Info 
17.88  LDD1936  [10]
C342
 Probe Info 
6.32  LDD2004  [10]
C343
 Probe Info 
11.31  LDD2005  [10]
C431
 Probe Info 
13.83  LDD2086  [10]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0108  Chloroacetamide HeLa N.A.  LDD0222  [3]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Calcium uptake protein 1, mitochondrial (MICU1) MICU1 family Q9BPX6
Other
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Cytochrome c oxidase copper chaperone (COX17) COX17 family Q14061

References

1 Tranylcypromine specificity for monoamine oxidase is limited by promiscuous protein labelling and lysosomal trapping. RSC Chem Biol. 2020 Aug 12;1(4):209-213. doi: 10.1039/d0cb00048e. eCollection 2020 Oct 1.
Mass spectrometry data entry: PXD018580
2 An Azo Coupling-Based Chemoproteomic Approach to Systematically Profile the Tyrosine Reactivity in the Human Proteome. Anal Chem. 2021 Jul 27;93(29):10334-10342. doi: 10.1021/acs.analchem.1c01935. Epub 2021 Jul 12.
3 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.
4 Global profiling of functional histidines in live cells using small-molecule photosensitizer and chemical probe relay labelling. Nat Chem. 2024 Jun 4. doi: 10.1038/s41557-024-01545-6. Online ahead of print.
Mass spectrometry data entry: PXD042377
5 Enhancing Cysteine Chemoproteomic Coverage through Systematic Assessment of Click Chemistry Product Fragmentation. Anal Chem. 2022 Mar 8;94(9):3800-3810. doi: 10.1021/acs.analchem.1c04402. Epub 2022 Feb 23.
Mass spectrometry data entry: PXD028853
6 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255
7 DFT-Guided Discovery of Ethynyl-Triazolyl-Phosphinates as Modular Electrophiles for Chemoselective Cysteine Bioconjugation and Profiling. Angew Chem Int Ed Engl. 2022 Oct 10;61(41):e202205348. doi: 10.1002/anie.202205348. Epub 2022 Aug 22.
Mass spectrometry data entry: PXD033004
8 Chemoproteomic profiling of targets of lipid-derived electrophiles by bioorthogonal aminooxy probe. Redox Biol. 2017 Aug;12:712-718. doi: 10.1016/j.redox.2017.04.001. Epub 2017 Apr 5.
9 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264
10 Large-scale chemoproteomics expedites ligand discovery and predicts ligand behavior in cells. Science. 2024 Apr 26;384(6694):eadk5864. doi: 10.1126/science.adk5864. Epub 2024 Apr 26.
Mass spectrometry data entry: PXD041587