CHCHD2

Protein identityUniProt · HPA

UniProt accession

Q9Y6H1

Gene

CHCHD2

Ensembl

ENSG00000106153

Chromosome

7

Canonical length

151 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins

Subcellular location

Mitochondria

OverviewNCBI Gene

The protein encoded by this gene belongs to a class of eukaryotic CX(9)C proteins characterized by four cysteine residues spaced ten amino acids apart from one another. These residues form disulfide linkages that define a CHCH fold. In response to stress, the protein translocates from the mitochondrial intermembrane space to the nucleus where it binds to a highly conserved 13 nucleotide oxygen responsive element in the promoter of cytochrome oxidase 4I2, a subunit of the terminal enzyme of the electron transport chain. In concert with recombination signal sequence-binding protein J, binding of this protein activates the oxygen responsive element at four percent oxygen. In addition, it has been shown that this protein is a negative regulator of mitochondria-mediated apoptosis. In response to apoptotic stimuli, mitochondrial levels of this protein decrease, allowing BCL2-associated X protein to oligomerize and activate the caspase cascade. Pseudogenes of this gene are found on multiple chromosomes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

Canonical amino-acid sequenceUniProt

151 residues, UniProt reviewed canonical sequence.

>Q9Y6H1|CHCHD2
     1  MPRGSRSRTS RMAPPASRAP QMRAAPRPAP VAQPPAAAPP SAVGSSAAAP RQPGLMAQMA
    61  TTAAGVAVGS AVGHTLGHAI TGGFSGGSNA EPARPDITYQ EPQGTQPAQQ QQPCLYEIKQ
   121  FLECAQNQGD IKLCEGFNEV LKQCRLANGL A

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CHCHD2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.66

Highest tissue expression

854 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CHCHD2.

Disease | AllUniProt

Conditions CHCHD2 is implicated in, by any mechanism.

• Parkinson disease 22 (PARK22) MIM:616710

Disease | GeneticClinVar

2 pathogenic / likely-pathogenic of 113 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Parkinson disease 22, autosomal dominant

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.9

gnomAD pLI

0

gnomAD missense Z

0.12

DepMap mean gene effect

-0.37

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 10% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cellular response to oxidative stress
• mitochondrion organization
• positive regulation of mitochondrial ATP synthesis coupled electron transport
• positive regulation of transcription by RNA polymerase II
• regulation of cellular response to hypoxia
• regulation of generation of precursor metabolites and energy

Molecular functions

• DNA-binding transcription factor binding
• sequence-specific DNA binding

Cellular components

• mitochondrial intermembrane space
• mitochondrion
• nucleus

Protein domainsUniProt · Pfam · InterPro

• CHCH
• Coiled-coil-helix-coiled-coil-helix domain-containing protein 2/10-like
• CHCH domain

KeywordsUniProt

• Activator
• Disulfide bond
• Mitochondrion
• Neurodegeneration
• Nucleus
• Parkinson disease
• Parkinsonism
• Transcription

InteractionsUniProt · HPA

Protein binding partners of CHCHD2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• RBPJ
• C1QBP
• CHCHD10
• POLDIP2
• YBX1