Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0009945
UniProt IDQ13489
Primary gene name(s)BIRC3
Synonym gene name(s)API2, MIHC, RNF49
Protein nameBaculoviral IAP repeat-containing protein 3
Protein functionMulti-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, mitogenic kinase signaling and cell proliferation, as well as cell invasion and metastasis. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and regulates both canonical and non-canonical NF-kappa-B signaling by acting in opposite directions: acts as a positive regulator of the canonical pathway and suppresses constitutive activation of non-canonical NF-kappa-B signaling. The target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, RIPK2, RIPK3, RIPK4, CASP3, CASP7, CASP8, IKBKE, TRAF1, and BCL10. Acts as an important regulator of innate immune signaling via regulation of Toll-like receptors, TLRs, Nodlike receptors, NLRs and RIG-I like receptors, RLRs, collectively referred to as pattern recognition receptors, PRRs. 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. {ECO:0000269|PubMed:21931591, ECO:0000269|PubMed:23453969}.
Subcellular locationCytoplasm {ECO:0000269|PubMed:15665297}. Nucleus {ECO:0000269|PubMed:15665297}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q13489
Gene Ontology
(Biological Process)
Complete annatation
cell surface receptor signaling pathway [GO:0007166];
I-kappaB kinase/NF-kappaB signaling [GO:0007249];
inhibition of cysteine-type endopeptidase activity involved in apoptotic process [GO:1990001];
negative regulation of apoptotic process [GO:0043066];
negative regulation of necroptotic process [GO:0060546];
NIK/NF-kappaB signaling [GO:0038061];
positive regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043123];
positive regulation of protein ubiquitination [GO:0031398];
protein heterooligomerization [GO:0051291];
regulation of apoptotic process [GO:0042981];
regulation of cysteine-type endopeptidase activity [GO:2000116];
regulation of inflammatory response [GO:0050727];
regulation of innate immune response [GO:0045088];
regulation of necroptotic process [GO:0060544];
regulation of necrotic cell death [GO:0010939];
regulation of nucleotide-binding oligomerization domain containing signaling pathway [GO:0070424];
regulation of RIG-I signaling pathway [GO:0039535];
regulation of toll-like receptor signaling pathway [GO:0034121];
regulation of tumor necrosis factor-mediated signaling pathway [GO:0010803];
spermatogenesis [GO:0007283];
TRIF-dependent toll-like receptor signaling pathway [GO:0035666];
tumor necrosis factor-mediated signaling pathway [GO:0033209]
Gene Ontology
(Molecular Function)
Complete annatation
cysteine-type endopeptidase inhibitor activity involved in apoptotic process [GO:0043027];
ligase activity [GO:0016874];
transferase activity [GO:0016740];
ubiquitin-protein transferase activity [GO:0004842];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
membrane raft [GO:0045121];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
protein complex [GO:0043234]
Protein-protein interaction106827
Phylogenetic treeQ13489
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. CD34.2316389701246900
AZA vs. DISU0.8235937225005110.007780190811406910.221590064552732
AZA vs. IL7-0.2840478857471680.1860763834439180.952505417553304
AZA vs. SAHA0.7211116519727090.02146853256534360.161808329944995
DISU vs. CD3-3.421715048305500
DISU vs. IL7-1.116378104168120.0001631055729492960.00763607612487775
DISU vs. SAHA-0.1024379602024320.7811149104490060.940086709960701
DMSO vs. AZA-0.140610501251040.4655376888177771
DMSO vs. CD3-4.3851390860090500
DMSO vs. DISU-0.966562767431450.0005420551331621890.0461512477782723
DMSO vs. IL7-0.1361301580090750.4481510308425220.868701134765033
DMSO vs. SAHA0.8537332856329940.002957821002309790.0383625820359818
HIV vs. Mock in Activation0.2472299520748780.6911325401367450.999983755607037
HIV vs. Mock in Latency-0.1383483651260060.4002977601647220.999834320637052
IL7 vs. CD3-4.506526520161300
SAHA vs. CD3-3.5370628007340800
SAHA vs. IL71.00008708188130.0009614124623245070.0113019339796041
(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 0.374092 0.00362272
(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

PDB Accession Method Resolution Chain Structure Preview
2UVL X-ray 1.9Å A/B=244-337.
3EB5 X-ray 2.0Å A=536-604.
3EB6 X-ray 3.4Å A=536-604.
3M0A X-ray 2.6Å D=26-99.
3M0D X-ray 2.8Å D=26-99.

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

HIV Partner Interaction Type PubMed
Vpr inhibited by 22403404
Tat upregulates 12539042
Envelope surface glycoprotein gp120 upregulates 23867815

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)
hsa04668 TNF signaling pathway - Homo sapiens (human)
hsa05145 Toxoplasmosis - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05202 Transcriptional misregulation in cancer - Homo sapiens (human)
hsa05222 Small cell lung cancer - Homo sapiens (human)