Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0007897
UniProt IDP98170
Primary gene name(s)XIAP
Synonym gene name(s)API3, BIRC4, IAP3
Protein nameE3 ubiquitin-protein ligase XIAP
Protein functionMulti-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation, as well as cell invasion and metastasis. Acts as a direct caspase inhibitor. Directly bind to the active site pocket of CASP3 and CASP7 and obstructs substrate entry. Inactivates CASP9 by keeping it in a monomeric, inactive state. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and the target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, CASP3, CASP7, CASP8, CASP9, MAP3K2/MEKK2, DIABLO/SMAC, AIFM1, CCS and BIRC5/survivin. Ubiquitinion of CCS leads to enhancement of its chaperone activity toward its physiologic target, SOD1, rather than proteasomal degradation. Ubiquitinion of MAP3K2/MEKK2 and AIFM1 does not lead to proteasomal degradation. Plays a role in copper homeostasis by ubiquitinationg COMMD1 and promoting its proteasomal degradation. Can also function as E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. Regulates the BMP signaling pathway and the SMAD and MAP3K7/TAK1 dependent pathways leading to NF-kappa-B and JNK activation. Acts as an important regulator of innate immune signaling via regulation of Nodlike receptors, NLRs. Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8. Acts as a positive regulator of Wnt signaling and ubiquitinates TLE1, TLE2, TLE3, TLE4 and AES. Ubiquitination of TLE3 results in inhibition of its interaction with TCF7L2/TCF4 thereby allowing efficient recruitment and binding of the transcriptional coactivator beta-catenin to TCF7L2/TCF4 that is required to initiate a Wnt-specific transcriptional program. {ECO:0000269|PubMed:11447297, ECO:0000269|PubMed:12121969, ECO:0000269|PubMed:14645242, ECO:0000269|PubMed:14685266, ECO:0000269|PubMed:17560374, ECO:0000269|PubMed:17967870, ECO:0000269|PubMed:19473982, ECO:0000269|PubMed:20154138, ECO:0000269|PubMed:21145488, ECO:0000269|PubMed:22103349, ECO:0000269|PubMed:22304967, ECO:0000269|PubMed:9230442}.
Subcellular locationCytoplasm. Nucleus. Note=TLE3 promotes its nuclear localization.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P98170
Gene Ontology
(Biological Process)
Complete annatation
cellular response to DNA damage stimulus [GO:0006974];
copper ion homeostasis [GO:0055070];
inhibition of cysteine-type endopeptidase activity involved in apoptotic process [GO:1990001];
negative regulation of apoptotic process [GO:0043066];
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0043154];
positive regulation of canonical Wnt signaling pathway [GO:0090263];
positive regulation of protein linear polyubiquitination [GO:1902530];
positive regulation of protein ubiquitination [GO:0031398];
regulation of BMP signaling pathway [GO:0030510];
regulation of cell proliferation [GO:0042127];
regulation of inflammatory response [GO:0050727];
regulation of innate immune response [GO:0045088];
regulation of nucleotide-binding oligomerization domain containing signaling pathway [GO:0070424];
Wnt signaling pathway [GO:0016055]
Gene Ontology
(Molecular Function)
Complete annatation
cysteine-type endopeptidase inhibitor activity involved in apoptotic process [GO:0043027];
ligase activity [GO:0016874];
ubiquitin protein ligase activity [GO:0061630];
ubiquitin-protein transferase activity [GO:0004842];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
nucleoplasm [GO:0005654];
nucleus [GO:0005634]
Protein-protein interaction106828
Phylogenetic treeP98170
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. CD3-0.2092372663092950.5227352937515630.637897040516845
AZA vs. DISU0.04031560349514170.8736045169805450.991631204917382
AZA vs. IL70.03903310124657820.8391279619978470.999311006273513
AZA vs. SAHA-0.4376586229686420.07421465497855340.338081507750594
DISU vs. CD30.2370532380973810.5132479490938140.637027549167572
DISU vs. IL7-0.00987976207546820.9687352243405460.995379686713869
DISU vs. SAHA-0.4777802223187940.1016437206849880.40762972710044
DMSO vs. AZA-0.09377099699451670.5759253347786611
DMSO vs. CD30.1038035667094520.7452877321359350.816089524976585
DMSO vs. DISU-0.1359394744713830.5779827721751390.932467317571925
DMSO vs. IL70.1400567156135580.4361789593285350.861245067843667
DMSO vs. SAHA-0.3514732035666210.1374055901740880.443664524375346
HIV vs. Mock in Activation0.02641502078197990.9663330376999210.999983755607037
HIV vs. Mock in Latency0.09447288660207760.5667608134742630.999834320637052
IL7 vs. CD30.2572609254463780.4230508263294170.55925671858124
SAHA vs. CD3-0.2542492664207270.4721707304871640.583414255032484
SAHA vs. IL7-0.4813169744083680.04893186816324820.18131735021947
(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 -0.0278608 0.886681
(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
0.901 0.823 0.734 0.78 0.869
(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
DB02628 1-[3,3-Dimethyl-2-(2-Methylamino-Propionylamino)-Butyryl]-Pyrrolidine-2-Carboxylic Acid(1,2,3,4-Tetrahydro-Naphthalen-1-Yl)-Amide experimental unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1C9Q NMR - A=124-240.
1F9X NMR - A=241-356.
1G3F NMR - A=241-356.
1G73 X-ray 2.0Å C/D=238-358.
1I3O X-ray 2.7Å E/F=124-240.
1I4O X-ray 2.4Å C/D=120-260.
1I51 X-ray 2.4Å E/F=124-240.
1KMC X-ray 2.9Å C/D=124-242.
1NW9 X-ray 2.4Å A=253-350.
1TFQ NMR - A=241-356.
1TFT NMR - A=241-356.
2ECG NMR - A=430-497.
2JK7 X-ray 2.8Å A=241-356.
2KNA NMR - A=357-449.
2OPY X-ray 2.8Å A=249-354.
2OPZ X-ray 3.0Å A/B/C/D=249-357.
2POI X-ray 1.8Å A=10-99.
2POP X-ray 3.1Å B/D=10-100.
2QRA X-ray 2.5Å A/B/C/D=10-99.
2VSL X-ray 2.1Å A=250-345.
3CLX X-ray 2.7Å A/B/C/D=241-356.
3CM2 X-ray 2.5Å A/B/C/D/E/F/G/H/I/J=241-356.
3CM7 X-ray 3.1Å A/B/C/D=241-356.
3EYL X-ray 3.0Å A/B=241-356.
3G76 X-ray 3.0Å A/B/C/D/E/F/G/H=241-356.
3HL5 X-ray 1.8Å A/B=256-346.
3UW4 X-ray 1.7Å A=338-348.
3UW5 X-ray 1.7Å A/B=336-348.
4EC4 X-ray 3.3Å A/B/C/D/E/F/G/J/K/L=241-356.
4HY0 X-ray 2.8Å A/B/C/D/E/F/G/H=238-357.
4IC2 X-ray 2.2Å A/B=429-497.
4IC3 X-ray 1.7Å A/B=429-497.
4J3Y X-ray 1.4Å A/C=152-236.
4J44 X-ray 1.3Å A/C=152-236.
4J45 X-ray 1.4Å A/C=152-236.
4J46 X-ray 1.4Å A/C=152-236.
4J47 X-ray 1.3Å A/C=152-236.
4J48 X-ray 2.1Å A/C=152-236.
4KJU X-ray 1.6Å A/C=152-236.
4KJV X-ray 1.7Å A/C=152-236.
4KMP X-ray 1.9Å A/B=256-348.
4MTZ X-ray 2.1Å A/B/C/D=10-99.
4OXC X-ray 2.9Å A/B/C/D=10-99.
4WVS X-ray 2.0Å A=156-231.
4WVT X-ray 1.9Å A/B=156-231.
4WVU X-ray 2.0Å A=156-231.
5C0K X-ray 2.2Å A=249-354.
5C0L X-ray 2.6Å A=246-354.
5C3H X-ray 2.6Å A=249-354.
5C3K X-ray 2.0Å A=249-354.
5C7A X-ray 2.3Å A=249-354.
5C7B X-ray 2.6Å A=249-354.
5C7C X-ray 2.3Å A=249-354.
5C7D X-ray 2.2Å A=249-354.
5C83 X-ray 2.3Å A=249-354.
5C84 X-ray 2.3Å A=249-354.

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

HIV Partner Interaction Type PubMed
HIV-1 virus replication enhanced by expression of human gene 18854154

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa01524 Platinum drug resistance - Homo sapiens (human)
hsa04064 NF-kappa B signaling pathway - Homo sapiens (human)
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)
hsa04210 Apoptosis - Homo sapiens (human)
hsa04215 Apoptosis - multiple species - Homo sapiens (human)
hsa04510 Focal adhesion - Homo sapiens (human)
hsa04621 NOD-like receptor signaling pathway - Homo sapiens (human)
hsa05145 Toxoplasmosis - Homo sapiens (human)
hsa05166 HTLV-I infection - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05222 Small cell lung cancer - Homo sapiens (human)