BIRC3 (baculoviral IAP repeat-containing 3)

2001-09-01   Mathijs Baens , Peter Marynen 

Center for Human Genetics, Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, Catholic University of Leuven, Leuven, Belgium

Identity

HGNC
LOCATION
11q22.2
LOCUSID
ALIAS
AIP1,API2,CIAP2,HAIP1,HIAP1,IAP-1,MALT2,MIHC,RNF49,c-IAP2
FUSION GENES

DNA/RNA

Description

centromere to telomere orientation; 10 exons; large 5 untranslated region, start codon in exon 3, stop codon in exon 10.

Transcription

6.5 kb mRNA

Proteins

Atlas Image
BIRC3 protein - Mathijs Baens, Peter Marynen

Description

68 kDa; 604 amino acids. The protein contains three baculovirus inhibition of apoptosis (BIR) repeats, a caspace recruitment domain or CARD and a carboxyterminal Zn-binding RING domain.

Expression

wide, most abundantly in kidney, liver, small intestine and lung

Function

Member of the inhibitor of apoptosis (IAP) protein family. Binds to the tumor necrosis factor receptor via its associated factors TRAF1 and TRAF2 and inhibits apoptosis, probably by interfering with activation of caspaces.

Homology

with Baculovirus IAP proteins, Drosophila DIAP1 and DIAP2

Implicated in

Disease
B-cell non Hodgkin lymphoma (NHL); marginal zone B-cell lymphoma (MZBCL) of mucosa-associated lymphoid tissue (MALT); found in extranodal MZBCL or MALT-type, absent in splenic and nodal MZBCL
Prognosis
For gastric MALT-type lymphomas, t(11;18) is a clonal marker for resistance to Helicobacter pylori eradication therapy and antigen independent growth
Cytogenetics
t(11;18) is frequently associated with deletions affecting 3 API2 on chromosome 11 or 5 MALT1 on chromosome 18.
Hybrid gene
5 API2 on chromosome 11q21 translocated on chromosome 18 in frame with 3 MALT1. Deletions often exclude the expression of the reciprocal 5 MLT API2 3 transcript.
Fusion protein
All MALT-type lymphomas reported with a t(11;18) express an in frame API2-MLT fusion protein with consistently the three BIR domains of API2 fused to the caspace p20 domain and VDJ4-like domain of MLT.
Atlas Image
BIRC3/MALT1 fusion protein - Mathijs Baens, Peter Marynen
Oncogenesis
Transient expression of the API2-MLT fusion protein acitvates an NF-KB luciferase reporter construct, suggesting the involvement of this signaling cascade in MALT lymphomagenesis

Bibliography

Pubmed IDLast YearTitleAuthors
107513672000The product of the t(11;18), an API2-MLT fusion, marks nearly half of gastric MALT type lymphomas without large cell proliferation.Baens M et al
110660712000Structure of the MLT gene and molecular characterization of the genomic breakpoint junctions in the t(11;18)(q21;q21) of marginal zone B-cell lymphomas of MALT type.Baens M et al
109799682000Detection of t(11;18)(q21;q21) by interphase fluorescence in situ hybridization using API2 and MLT specific probes.Dierlamm J et al
109079432000The product of the t(11;18), an API2-MLT fusion, is an almost exclusive finding in marginal zone cell lymphoma of extranodal MALT-type.Maes B et al

Other Information

Locus ID:

NCBI: 330
MIM: 601721
HGNC: 591
Ensembl: ENSG00000023445

Variants:

dbSNP: 330
ClinVar: 330
TCGA: ENSG00000023445
COSMIC: BIRC3

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000023445ENST00000263464Q13489
ENSG00000023445ENST00000527309H0YCJ5
ENSG00000023445ENST00000532808Q13489
ENSG00000023445ENST00000615299Q13489

Expression (GTEx)

0
50
100
150

Pathways

PathwaySourceExternal ID
Ubiquitin mediated proteolysisKEGGko04120
ApoptosisKEGGko04210
Focal adhesionKEGGko04510
Small cell lung cancerKEGGko05222
Ubiquitin mediated proteolysisKEGGhsa04120
ApoptosisKEGGhsa04210
Focal adhesionKEGGhsa04510
Pathways in cancerKEGGhsa05200
Small cell lung cancerKEGGhsa05222
NOD-like receptor signaling pathwayKEGGko04621
NOD-like receptor signaling pathwayKEGGhsa04621
ToxoplasmosisKEGGko05145
ToxoplasmosisKEGGhsa05145
Transcriptional misregulation in cancerKEGGko05202
Transcriptional misregulation in cancerKEGGhsa05202
NF-kappa B signaling pathwayKEGGhsa04064
NF-kappa B signaling pathwayKEGGko04064
TNF signaling pathwayKEGGhsa04668
TNF signaling pathwayKEGGko04668
Metabolism of proteinsREACTOMER-HSA-392499
Post-translational protein modificationREACTOMER-HSA-597592
Immune SystemREACTOMER-HSA-168256
Innate Immune SystemREACTOMER-HSA-168249
Toll-Like Receptors CascadesREACTOMER-HSA-168898
Toll Like Receptor 3 (TLR3) CascadeREACTOMER-HSA-168164
MyD88-independent TLR3/TLR4 cascadeREACTOMER-HSA-166166
TRIF-mediated TLR3/TLR4 signalingREACTOMER-HSA-937061
IKK complex recruitment mediated by RIP1REACTOMER-HSA-937041
Toll Like Receptor 4 (TLR4) CascadeREACTOMER-HSA-166016
Activated TLR4 signallingREACTOMER-HSA-166054
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathwaysREACTOMER-HSA-168643
NOD1/2 Signaling PathwayREACTOMER-HSA-168638
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
TNFR2 non-canonical NF-kB pathwayREACTOMER-HSA-5668541
TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathwayREACTOMER-HSA-5676594
Signal TransductionREACTOMER-HSA-162582
Death Receptor SignallingREACTOMER-HSA-73887
TNF signalingREACTOMER-HSA-75893
Programmed Cell DeathREACTOMER-HSA-5357801
Regulated NecrosisREACTOMER-HSA-5218859
RIPK1-mediated regulated necrosisREACTOMER-HSA-5213460
Regulation of necroptotic cell deathREACTOMER-HSA-5675482
TNFR1-induced NFkappaB signaling pathwayREACTOMER-HSA-5357956
Regulation of TNFR1 signalingREACTOMER-HSA-5357905
Apoptosis - multiple speciesKEGGko04215
Apoptosis - multiple speciesKEGGhsa04215
Platinum drug resistanceKEGGko01524
Platinum drug resistanceKEGGhsa01524
DeubiquitinationREACTOMER-HSA-5688426
Ub-specific processing proteasesREACTOMER-HSA-5689880

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
185708722008cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination.383
186217372008c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation.200
163391512006The human anti-apoptotic proteins cIAP1 and cIAP2 bind but do not inhibit caspases.121
232432742013Integrated mutational and cytogenetic analysis identifies new prognostic subgroups in chronic lymphocytic leukemia.120
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
189316632008IAPs contain an evolutionarily conserved ubiquitin-binding domain that regulates NF-kappaB as well as cell survival and oncogenesis.79
125255022003Cellular inhibitor of apoptosis 1 and 2 are ubiquitin ligases for the apoptosis inducer Smac/DIABLO.70
203850932010Crystal structures of the TRAF2: cIAP2 and the TRAF1: TRAF2: cIAP2 complexes: affinity, specificity, and regulation.65
126518742003A comprehensive search for DNA amplification in lung cancer identifies inhibitors of apoptosis cIAP1 and cIAP2 as candidate oncogenes.63
128150692003Omi/HtrA2 catalytic cleavage of inhibitor of apoptosis (IAP) irreversibly inactivates IAPs and facilitates caspase activity in apoptosis.63

Citation

Mathijs Baens ; Peter Marynen

BIRC3 (baculoviral IAP repeat-containing 3)

Atlas Genet Cytogenet Oncol Haematol. 2001-09-01

Online version: http://atlasgeneticsoncology.org/gene/239/birc3