Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000595
UniProt IDQ8N4Q1
Primary gene name(s)CHCHD4
Synonym gene name(s)MIA40
Protein nameMitochondrial intermembrane space import and assembly protein 40
Protein functionFunctions 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. {ECO:0000269|PubMed:16185709, ECO:0000269|PubMed:19182799, ECO:0000269|PubMed:21059946, ECO:0000269|PubMed:23186364, ECO:0000269|PubMed:26387864}.
Subcellular locationMitochondrion intermembrane space {ECO:0000269|PubMed:16185709, ECO:0000269|PubMed:23186364}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q8N4Q1
Gene Ontology
(Biological Process)
Complete annatation
'de novo' posttranslational protein folding [GO:0051084];
protein import into mitochondrial intermembrane space [GO:0045041];
protein maturation by protein folding [GO:0022417]
Gene Ontology
(Molecular Function)
Complete annatation
protein disulfide oxidoreductase activity [GO:0015035]
Gene Ontology
(Cellular Component)
Complete annatation
mitochondrial intermembrane space [GO:0005758];
mitochondrion [GO:0005739]
Protein-protein interaction126282
Phylogenetic treeQ8N4Q1
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD31.642239705687841.27281927952971e-069.64016692516173e-06
AZA vs. DISU0.04928887665690020.8499097332681370.988692756671169
AZA vs. IL70.4827246780671850.01663010853630560.427642929458849
AZA vs. SAHA-0.3518092511327820.1677211703772970.522711932342297
DISU vs. CD3-1.605032272792841.70126378639113e-050.000119056872405106
DISU vs. IL70.4253231822351350.09933016691925980.417801971626072
DISU vs. SAHA-0.4006551202437850.1804934241444820.546222327905192
DMSO vs. AZA-0.04900283283194630.7857164087713671
DMSO vs. CD3-1.701926723828792.83435306669411e-072.25327329550115e-06
DMSO vs. DISU-0.09996611201895570.6907548211121860.957954410639349
DMSO vs. IL70.5388061150610450.004365181098989760.133863185791214
DMSO vs. SAHA-0.3103001517351430.2076316184208780.548600301756847
HIV vs. Mock in Activation-0.1719752548900380.7827908783245050.999983755607037
HIV vs. Mock in Latency-0.2851330073968290.1065558099893040.999834320637052
IL7 vs. CD3-1.149963916222650.0004486496769617880.00213462644597381
SAHA vs. CD3-2.019399735962944.53760902185962e-085.19562916052392e-07
SAHA vs. IL7-0.8392315429638330.0009217924061996060.0109496443901126
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) FALSE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK -0.179793 0.242403
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
1.032 1.143 1.037 1.03 1.049
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
2K3J NMR - A=1-142.
2L0Y NMR - A=1-142.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

not found

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
not found