Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0009507
UniProt IDP25774
Primary gene name(s)CTSS
Synonym gene name(s)unknown
Protein nameCathepsin S
Protein functionThiol protease. Key protease responsible for the removal of the invariant chain from MHC class II molecules. The bond-specificity of this proteinase is in part similar to the specificities of cathepsin L and cathepsin N.
Subcellular locationLysosome.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P25774
Gene Ontology
(Biological Process)
Complete annatation
adaptive immune response [GO:0002250];
antigen processing and presentation [GO:0019882];
antigen processing and presentation of exogenous peptide antigen via MHC class II [GO:0019886];
antigen processing and presentation of peptide antigen [GO:0048002];
basement membrane disassembly [GO:0034769];
cellular response to thyroid hormone stimulus [GO:0097067];
collagen catabolic process [GO:0030574];
extracellular matrix disassembly [GO:0022617];
immune response [GO:0006955];
positive regulation of cation channel activity [GO:2001259];
protein processing [GO:0016485];
proteolysis [GO:0006508];
proteolysis involved in cellular protein catabolic process [GO:0051603];
response to acidic pH [GO:0010447];
toll-like receptor signaling pathway [GO:0002224]
Gene Ontology
(Molecular Function)
Complete annatation
collagen binding [GO:0005518];
cysteine-type endopeptidase activity [GO:0004197];
fibronectin binding [GO:0001968];
laminin binding [GO:0043236];
proteoglycan binding [GO:0043394];
serine-type endopeptidase activity [GO:0004252]
Gene Ontology
(Cellular Component)
Complete annatation
endolysosome lumen [GO:0036021];
extracellular region [GO:0005576];
extracellular space [GO:0005615];
intracellular membrane-bounded organelle [GO:0043231];
lysosomal lumen [GO:0043202];
lysosome [GO:0005764]
Protein-protein interaction107900
Phylogenetic treeP25774
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      unknown
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
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. CD3-0.7949330794764490.01577089265156250.0383261680174702
AZA vs. DISU0.2104275238938680.4050130773902950.905959666736916
AZA vs. IL7-0.3412287842427760.0761488128146830.772923269734489
AZA vs. SAHA-1.06498574048880.0004308462209305920.0116182038180818
DISU vs. CD30.993673757050140.006584307297304640.0204642985978495
DISU vs. IL7-0.5610210304487190.0262548502318910.206918062767426
DISU vs. SAHA-1.274881054278681.96390994702256e-050.00110126077461006
DMSO vs. AZA-0.1091892998979280.5141964380533251
DMSO vs. CD30.6741439393138310.03574648834747210.0724890088780006
DMSO vs. DISU-0.3217293559542010.1871396139634520.702536983379706
DMSO vs. IL7-0.2247814149818760.2113779911959170.721135647839534
DMSO vs. SAHA-0.9627828044692340.000970257573227440.017575422940037
HIV vs. Mock in Activation-0.3131763984393970.6155075517384480.999983755607037
HIV vs. Mock in Latency0.2322081346924190.1590677175822510.999834320637052
IL7 vs. CD30.4620417997306590.1515873195676790.261068974845022
SAHA vs. CD3-0.2948985723353540.4115836989095130.527210937426251
SAHA vs. IL7-0.7280261928728250.01570837975739030.0860421934821587
(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) unknown
(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 -0.141573 0.344488
(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

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB03767 Morpholine-4-Carboxylic Acid [1s-(2-Benzyloxy-1r-Cyano-Ethylcarbamoyl)-3-Methyl-Butyl]Amide experimental unknown unknown
DB03837 Morpholine-4-Carboxylic Acid (1-(3-Benzenesulfonyl-1-Phenethylallylcarbamoyl)-3-Methylbutyl)-Amide experimental unknown unknown
DB03984 Morpholine-4-Carboxylic Acid [1-(2-Benzylsulfanyl-1-Formyl-Ethylcarbamoyl)-2-Phenyl-Ethyl]-Amide experimental unknown unknown
DB07520 N-[1-(AMINOMETHYL)CYCLOPROPYL]-3-(MORPHOLIN-4-YLSULFONYL)-N~2~-[(1S)-2,2,2-TRIFLUORO-1-(4-FLUOROPHENYL)ETHYL]-L-ALANINAMIDE experimental unknown unknown
DB07587 N-(1-CYANOCYCLOPROPYL)-3-({[(2S)-5-OXOPYRROLIDIN-2-YL]METHYL}SULFONYL)-N~2~-[(1S)-2,2,2-TRIFLUORO-1-(4-FLUOROPHENYL)ETHYL]-L-ALANINAMIDE experimental unknown unknown
DB07589 N-[1-(AMINOMETHYL)CYCLOPROPYL]-3-(BENZYLSULFONYL)-N~2~-[(1S)-2,2,2-TRIFLUORO-1-(4-HYDROXYPHENYL)ETHYL]-L-ALANINAMIDE experimental unknown unknown
DB07839 N~2~-1,3-BENZOXAZOL-2-YL-3-CYCLOHEXYL-N-{2-[(4-METHOXYPHENYL)AMINO]ETHYL}-L-ALANINAMIDE experimental unknown unknown
DB07878 N-[(1S)-1-{1-[(1R,3E)-1-ACETYLPENT-3-EN-1-YL]-1H-1,2,3-TRIAZOL-4-YL}-1,2-DIMETHYLPROPYL]BENZAMIDE experimental unknown unknown
DB08195 (1R)-2-[(CYANOMETHYL)AMINO]-1-({[2-(DIFLUOROMETHOXY)BENZYL]SULFONYL}METHYL)-2-OXOETHYL MORPHOLINE-4-CARBOXYLATE experimental unknown unknown
DB08611 2-[(2&,39;,3&,39;,4&,39;-TRIFLUOROBIPHENYL-2-YL)OXY]ETHANOL experimental unknown unknown
DB08752 N-[(1S)-2-[(4-cyano-1-methylpiperidin-4-yl)amino]-1-(cyclohexylmethyl)-2-oxoethyl]morpholine-4-carboxamide experimental unknown unknown
DB08755 N-[(1S)-2-{[(1R)-2-(benzyloxy)-1-cyano-1-methylethyl]amino}-1-(cyclohexylmethyl)-2-oxoethyl]morpholine-4-carboxamide experimental unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1BXF Model - A=115-331.
1GLO X-ray 2.2Å A=115-331.
1MS6 X-ray 1.9Å A=115-331.
1NPZ X-ray 2.0Å A/B=115-331.
1NQC X-ray 1.8Å A=115-331.
2C0Y X-ray 2.1Å A=17-331.
2F1G X-ray 1.9Å A/B=112-331.
2FQ9 X-ray 1.6Å A/B=114-331.
2FRA X-ray 1.9Å A/B=114-330.
2FRQ X-ray 1.6Å A/B=114-331.
2FT2 X-ray 1.7Å A/B=114-331.
2FUD X-ray 1.9Å A/B=114-331.
2FYE X-ray 2.2Å A=115-331.
2G6D X-ray 2.5Å A=115-331.
2G7Y X-ray 2.0Å A/B=114-330.
2H7J X-ray 1.5Å A/B=112-331.
2HH5 X-ray 1.8Å A/B=112-331.
2HHN X-ray 1.5Å A/B=112-331.
2HXZ X-ray 1.9Å A/B/C=112-331.
2OP3 X-ray 1.6Å A/B=112-331.
2R9M X-ray 1.9Å A/B=115-331.
2R9N X-ray 2.0Å A/B=115-331.
2R9O X-ray 2.0Å A/B=115-331.
3IEJ X-ray 2.1Å A/B=115-331.
3KWN X-ray 2.1Å A/B=115-331.
3MPE X-ray 2.2Å A/B=114-331.
3MPF X-ray 1.8Å A/B=115-331.
3N3G X-ray 1.6Å A/B=115-331.
3N4C X-ray 1.9Å A/B=115-331.
3OVX X-ray 1.4Å A/B=114-331.
4P6E X-ray 1.8Å A/B=109-331.
4P6G X-ray 1.5Å A/B/C/D=114-331.

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

HIV Partner Interaction Type PubMed
Envelope surface glycoprotein gp120 cleaved by 19939935
Tat upregulates 24667918

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04142 Lysosome - Homo sapiens (human)
hsa04145 Phagosome - Homo sapiens (human)
hsa04210 Apoptosis - Homo sapiens (human)
hsa04612 Antigen processing and presentation - Homo sapiens (human)
hsa05152 Tuberculosis - Homo sapiens (human)
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