Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000181
UniProt IDQ86TL0
Primary gene name(s)ATG4D
Synonym gene name(s)APG4D, AUTL4
Protein nameCysteine protease ATG4D
Protein functionCysteine protease ATG4D: Cysteine protease required for the cytoplasm to vacuole transport, Cvt and autophagy. Cleaves the C-terminal amino acid of ATG8 family proteins MAP1LC3 and GABARAPL2, to reveal a C-terminal glycine. Exposure of the glycine at the C-terminus is essential for ATG8 proteins conjugation to phosphatidylethanolamine, PE and insertion to membranes, which is necessary for autophagy. Has also an activity of delipidating enzyme for the PE-conjugated forms.; FUNCTION: Cysteine protease ATG4D, mitochondrial: Plays a role as an autophagy regulator that links mitochondrial dysfunction with apoptosis. The mitochondrial import of ATG4D during cellular stress and differentiation may play important roles in the regulation of mitochondrial physiology, ROS, mitophagy and cell viability.
Subcellular locationCysteine protease ATG4D: Cytoplasm {ECO:0000269|PubMed:19549685}.;
SUBCELLULAR LOCATION: Cysteine protease ATG4D, mitochondrial: Cytoplasm {ECO:0000269|PubMed:19549685}. Mitochondrion matrix {ECO:0000269|PubMed:19549685, ECO:0000269|PubMed:22441018}. Note=Imported into mitochondrial matrix after cleavage by CASP3 during oxidative stress and cell death. {ECO:0000269|PubMed:22441018}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q86TL0
Gene Ontology
(Biological Process)
Complete annatation
apoptotic process [GO:0006915];
autophagosome assembly [GO:0000045];
C-terminal protein lipidation [GO:0006501];
mitophagy [GO:0000422];
nucleophagy [GO:0044804];
protein delipidation [GO:0051697];
protein processing [GO:0016485];
protein targeting to membrane [GO:0006612]
Gene Ontology
(Molecular Function)
Complete annatation
cysteine-type endopeptidase activity [GO:0004197]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
mitochondrial matrix [GO:0005759]
Protein-protein interaction124401
Phylogenetic treeQ86TL0
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. CD3-0.5953066386158910.07199170447646870.134367686805906
AZA vs. DISU0.1354897773117050.5960599322357360.955158276076142
AZA vs. IL7-0.2057516302788440.2955056962475060.999311006273513
AZA vs. SAHA-0.339241227548460.1709826457987060.527397667847289
DISU vs. CD30.7180058528699880.04977235527265620.107457531277574
DISU vs. IL7-0.3511172738346520.1680564948705850.530565792706611
DISU vs. SAHA-0.4720018480239740.1089866370684710.423699662367598
DMSO vs. AZA0.02881244784131120.8671397994068161
DMSO vs. CD30.6097992362930090.05906696825710440.110801130219559
DMSO vs. DISU-0.1092797303248750.6574958525291330.950156143725546
DMSO vs. IL7-0.2268475212187180.2178443960948010.726228277560621
DMSO vs. SAHA-0.3722000654561160.1198938336926270.412068407658284
HIV vs. Mock in Activation0.2970546003777810.6365258790001990.999983755607037
HIV vs. Mock in Latency-0.03997738725360010.8132568100427960.999834320637052
IL7 vs. CD30.3944460411080370.2237771715552270.351609851647236
SAHA vs. CD30.2330817627921380.5125026935278790.620554040773351
SAHA vs. IL7-0.1354576567441180.583855371525920.786526043435332
(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) TRUE
(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 0.127849 0.778042
(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
unknown unknown unknown unknown unknown
(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

not found

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

HIV Partner Interaction Type PubMed
Vif interacts with 25490467

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04140 Autophagy - Homo sapiens (human)