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BIRC6 (Baculoviral IAP repeat-containing 6)

Identity

Other namesBaculoviral IAP repeat-containing ubiquitin-conjugating enzyme (BRUCE)
Baculoviral IAP repeat-containing 6 (Apollon)
FLJ13726
FLJ13786
KIAA1289
HGNC (Hugo) BIRC6
LocusID (NCBI) 57448
Location 2p22.3
Location_base_pair Starts at 32582096 and ends at 32843965 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order CARD12 (caspase recruitment domain family member 12) {encoded on minus strand, 32.303.029-32.344.427}
YPF4 (YIP1 domain family member 4) {32.356.483-32.385.159}
BIRC6 {32.435.234-32.697.467}
TTC27 (tetratricopeptide repeat domain 27) {32.706.633-32.899.620}
LTBP1 (latent transforming growth factor beta binding protein 1) {33.025.896-33.478.077}

DNA/RNA

Description The BIRC6 gene comprises 75 exons resulting in a transcript of 16066 bps. The ATG is in the first exon.
Transcription Only one variant of BIRC6 has been found so far which comprises 14490 bps. There are several synonymous and nonsynonymous SNPs reported for BIRC6 (E589K, L1742F, R2187T, T2646S, T3708N, E3864K, Q4323H, N4324Y, S4325C, N4326T, P4329R).
Pseudogene Not known. There is evidence for a processed pseudogene in M. musculus.

Protein

 
  BRUCE is component of the apoptosis regulatory network. Multiple protein-protein interactions allow a switch from apoptosis inhibition to inactivation in later steps in apoptosis. BRUCEšs action on activated caspases and other pro-apoptotic molecules might be restricted to the trans-Golgi network and the vesicular system.
Description BIRC6 contains two functionally validated domains: A N-terminal BIR repeat (SMART SM00238, aa: 256-332) and a C-terminal UBC domain (SMART SM00212, aa: 4548 ­ 4712). The BIR repeat is needed for interactions with caspases and IAP-binding motiv (IBM) containing proteins (HtrA2, Smac). The UBC domain can form a thiolester linkage with ubiquitin transferred by E1.
Between aa 1589-1633 a coiled-coil region can be found.
Expression BRUCE is highly expressed in brain, testis, lymphatic cells and secretory organs and also found in any other tissue. It is highly expressed in the mouse embryos up to E11 and then transcript levels drop.
Localisation Localized to membranes of the trans Golgi network (TGN) and the endosomal system.
Function BRUCE is a peripheral membrane protein of the trans-Golgi network that protects cells from apoptosis by functioning as an inhibitor of apoptosis protein (IAP). BRUCE can bind and inhibit activated caspases CASP-3, CASP-6, CASP-7, CASP-8 and CASP-9. Furthermore it ubiquitylates caspase-9, HtrA2 (a pro-apoptotic serine protease) and DIABLO/Smac (a competitor for caspase-IAP interactions) thereby most likely targeting them for proteasomal degradation. The ubiquityltion reactions do not require an ubiquitin E3 ligase making BRUCE a chimeric E2/E3 ubiquitin ligase.
Homology ubc-17 (C. elegans)
IAP6 (A. gambiae)
Bruce (D. melanogaster)
BIRC6 (X. tropicalis)
Birc6 (M. musculus).

Mutations

Note There are several synonymous and nonsynonymous SNPs reported for BIRC6 (E589K, L1742F, R2187T, T2646S, T3708N, E3864K, Q4323H, N4324Y, S4325C, N4326T, P4329R).

Implicated in

Entity Overexpression of BRUCE is found in several cancer cell lines (brain SF-268, SNB-78 ­ ovarian cancer OVCAR-8). High level expression of BRUCE in these cell lines seems to correlate with their resistance to apoptotic reagents. Furthermore, bone marrow cells of myelodysplastic syndromes exhibit significant expression of BIRC6.
  

External links

Nomenclature
HGNC (Hugo)BIRC6   13516
Cards
AtlasBIRC6ID798ch2p22
Entrez_Gene (NCBI)BIRC6  57448  baculoviral IAP repeat containing 6
GeneCards (Weizmann)BIRC6
Ensembl (Hinxton)ENSG00000115760 [Gene_View]  chr2:32582096-32843965 [Contig_View]  BIRC6 [Vega]
ICGC DataPortalENSG00000115760
AceView (NCBI)BIRC6
Genatlas (Paris)BIRC6
WikiGenes57448
SOURCE (Princeton)NM_016252
Genomic and cartography
GoldenPath (UCSC)BIRC6  -  2p22.3   chr2:32582096-32843965 +  2p22.3   [Description]    (hg19-Feb_2009)
EnsemblBIRC6 - 2p22.3 [CytoView]
Mapping of homologs : NCBIBIRC6 [Mapview]
OMIM605638   
Gene and transcription
Genbank (Entrez)AA315620 AB033115 AF265555 AK023788 AK023848
RefSeq transcript (Entrez)NM_016252
RefSeq genomic (Entrez)AC_000134 NC_000002 NC_018913 NT_022184 NW_001838769 NW_004929300
Consensus coding sequences : CCDS (NCBI)BIRC6
Cluster EST : UnigeneHs.150107 [ NCBI ]
CGAP (NCI)Hs.150107
Alternative Splicing : Fast-db (Paris)GSHG0016362
Alternative Splicing GalleryENSG00000115760
Gene ExpressionBIRC6 [ NCBI-GEO ]     BIRC6 [ SEEK ]   BIRC6 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9NR09 (Uniprot)
NextProtQ9NR09  [Medical]
With graphics : InterProQ9NR09
Splice isoforms : SwissVarQ9NR09 (Swissvar)
Catalytic activity : Enzyme6.3.2.- [ Enzyme-Expasy ]   6.3.2.-6.3.2.- [ IntEnz-EBI ]   6.3.2.- [ BRENDA ]   6.3.2.- [ KEGG ]   
Domaine pattern : Prosite (Expaxy)BIR_REPEAT_2 (PS50143)    UBIQUITIN_CONJUGAT_2 (PS50127)   
Domains : Interpro (EBI)BIR    BIRC6    UBQ-conjugat_E2    UBQ-conjugating_enzyme/RWD    WD40/YVTN_repeat-like_dom   
Related proteins : CluSTrQ9NR09
Domain families : Pfam (Sanger)BIR (PF00653)    DUF3643 (PF12356)    UQ_con (PF00179)   
Domain families : Pfam (NCBI)pfam00653    pfam12356    pfam00179   
Domain families : Smart (EMBL)BIR (SM00238)  
DMDM Disease mutations57448
Blocks (Seattle)Q9NR09
PDB (SRS)3CEG   
PDB (PDBSum)3CEG   
PDB (IMB)3CEG   
PDB (RSDB)3CEG   
Human Protein AtlasENSG00000115760
Peptide AtlasQ9NR09
HPRD05731
IPIIPI00939720   IPI00893564   IPI00893758   
Protein Interaction databases
DIP (DOE-UCLA)Q9NR09
IntAct (EBI)Q9NR09
FunCoupENSG00000115760
BioGRIDBIRC6
IntegromeDBBIRC6
STRING (EMBL)BIRC6
Ontologies - Pathways
QuickGOQ9NR09
Ontology : AmiGOspindle pole  ubiquitin-protein transferase activity  cysteine-type endopeptidase inhibitor activity  protein binding  endosome  trans-Golgi network  microtubule organizing center  protein phosphorylation  apoptotic process  mitotic nuclear division  positive regulation of cell proliferation  negative regulation of endopeptidase activity  negative regulation of endopeptidase activity  membrane  protein ubiquitination  acid-amino acid ligase activity  midbody  regulation of cytokinesis  regulation of cell proliferation  negative regulation of apoptotic process  negative regulation of apoptotic process  labyrinthine layer development  spongiotrophoblast layer development  negative regulation of extrinsic apoptotic signaling pathway  
Ontology : EGO-EBIspindle pole  ubiquitin-protein transferase activity  cysteine-type endopeptidase inhibitor activity  protein binding  endosome  trans-Golgi network  microtubule organizing center  protein phosphorylation  apoptotic process  mitotic nuclear division  positive regulation of cell proliferation  negative regulation of endopeptidase activity  negative regulation of endopeptidase activity  membrane  protein ubiquitination  acid-amino acid ligase activity  midbody  regulation of cytokinesis  regulation of cell proliferation  negative regulation of apoptotic process  negative regulation of apoptotic process  labyrinthine layer development  spongiotrophoblast layer development  negative regulation of extrinsic apoptotic signaling pathway  
Pathways : KEGGUbiquitin mediated proteolysis   
Protein Interaction DatabaseBIRC6
Wikipedia pathwaysBIRC6
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)BIRC6
SNP (GeneSNP Utah)BIRC6
SNP : HGBaseBIRC6
Genetic variants : HAPMAPBIRC6
1000_GenomesBIRC6 
ICGC programENSG00000115760 
CONAN: Copy Number AnalysisBIRC6 
Somatic Mutations in Cancer : COSMICBIRC6 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
DECIPHER (Syndromes)2:32582096-32843965
Mutations and Diseases : HGMDBIRC6
OMIM605638   
MedgenBIRC6
GENETestsBIRC6
Disease Genetic AssociationBIRC6
Huge Navigator BIRC6 [HugePedia]  BIRC6 [HugeCancerGEM]
Genomic VariantsBIRC6  BIRC6 [DGVbeta]
Exome VariantBIRC6
dbVarBIRC6
ClinVarBIRC6
snp3D : Map Gene to Disease57448
General knowledge
Homologs : HomoloGeneBIRC6
Homology/Alignments : Family Browser (UCSC)BIRC6
Phylogenetic Trees/Animal Genes : TreeFamBIRC6
Chemical/Protein Interactions : CTD57448
Chemical/Pharm GKB GenePA25363
Clinical trialBIRC6
Cancer Resource (Charite)ENSG00000115760
Other databases
Probes
Litterature
PubMed45 Pubmed reference(s) in Entrez
CoreMineBIRC6
GoPubMedBIRC6
iHOPBIRC6

Bibliography

A giant ubiquitin-conjugating enzyme related to IAP apoptosis inhibitors.
Hauser HP, Bardroff M, Pyrowolakis G, Jentsch S
The Journal of cell biology. 1998 ; 141 (6) : 1415-1422.
PMID 9628897
 
A human IAP-family gene, apollon, expressed in human brain cancer cells.
Chen Z, Naito M, Hori S, Mashima T, Yamori T, Tsuruo T
Biochemical and biophysical research communications. 1999 ; 264 (3) : 847-854.
PMID 10544019
 
Inhibitor of apoptosis proteins and their relatives: IAPs and other BIRPs.
Verhagen AM, Coulson EJ, Vaux DL
Genome biology. 2001 ; 2 (7) : page REVIEWS3009.
PMID 11516343
 
Drosophila Bruce can potently suppress Rpr- and Grim-dependent but not Hid-dependent cell death.
Vernooy SY, Chow V, Su J, Verbrugghe K, Yang J, Cole S, Olson MR, Hay BA
Current biology : CB. 2002 ; 12 (13) : 1164-1168.
PMID 12121627
 
Dual role of BRUCE as an antiapoptotic IAP and a chimeric E2/E3 ubiquitin ligase.
Bartke T, Pohl C, Pyrowolakis G, Jentsch S
Molecular cell. 2004 ; 14 (6) : 801-811.
PMID 15200957
 
Apollon ubiquitinates SMAC and caspase-9, and has an essential cytoprotection function.
Hao Y, Sekine K, Kawabata A, Nakamura H, Ishioka T, Ohata H, Katayama R, Hashimoto C, Zhang X, Noda T, Tsuruo T, Naito M
Nature cell biology. 2004 ; 6 (9) : 849-860.
PMID 15300255
 
BRUCE, a giant E2/E3 ubiquitin ligase and inhibitor of apoptosis protein of the trans-Golgi network, is required for normal placenta development and mouse survival.
Lotz K, Pyrowolakis G, Jentsch S
Molecular and cellular biology. 2004 ; 24 (21) : 9339-9350.
PMID 15485903
 
An Apollon vista of death and destruction.
Martin SJ
Nature cell biology. 2004 ; 6 (9) : 804-806.
PMID 15340445
 
Nrdp1-mediated degradation of the gigantic IAP, BRUCE, is a novel pathway for triggering apoptosis.
Qiu XB, Markant SL, Yuan J, Goldberg AL
The EMBO journal. 2004 ; 23 (4) : 800-810.
PMID 14765125
 
Bone marrow cells of myelodysplastic syndromes exhibit significant expression of apollon, livin and ILP-2 with reduction after transformation to overt leukemia.
Abe S, Yamamoto K, Hasegawa M, Inoue M, Kurata M, Hirokawa K, Kitagawa M, Nakagawa Y, Suzuki K
Leukemia research. 2005 ; 29 (9) : 1095-1096.
PMID 16038738
 
Progressive loss of the spongiotrophoblast layer of Birc6/Bruce mutants results in embryonic lethality.
Hitz C, Vogt-Weisenhorn D, Ruiz P, Wurst W, Floss T
Genesis (New York, N.Y. : 2000). 2005 ; 42 (2) : 91-103.
PMID 15887267
 
The membrane-associated inhibitor of apoptosis protein, BRUCE/Apollon, antagonizes both the precursor and mature forms of Smac and caspase-9.
Qiu XB, Goldberg AL
The Journal of biological chemistry. 2005 ; 280 (1) : 174-182.
PMID 15507451
 
The Birc6 (Bruce) gene regulates p53 and the mitochondrial pathway of apoptosis and is essential for mouse embryonic development.
Ren J, Shi M, Liu R, Yang QH, Johnson T, Skarnes WC, Du C
Proceedings of the National Academy of Sciences of the United States of America. 2005 ; 102 (3) : 565-570.
PMID 15640352
 
HtrA2 cleaves Apollon and induces cell death by IAP-binding motif in Apollon-deficient cells.
Sekine K, Hao Y, Suzuki Y, Takahashi R, Tsuruo T, Naito M
Biochemical and biophysical research communications. 2005 ; 330 (1) : 279-285.
PMID 15781261
 
Bruce/apollon promotes hippocampal neuron survival and is downregulated by kainic acid.
Sokka AL, Mudo G, Aaltonen J, Belluardo N, Lindholm D, Korhonen L
Biochemical and biophysical research communications. 2005 ; 338 (2) : 729-735.
PMID 16236253
 
Comparative study of gene expression by cDNA microarray in human colorectal cancer tissues and normal mucosa.
Bianchini M, Levy E, Zucchini C, Pinski V, Macagno C, De Sanctis P, Valvassori L, Carinci P, Mordoh J
International journal of oncology. 2006 ; 29 (1) : 83-94.
PMID 16773188
 
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Contributor(s)

Written11-2006Christian Pohl, Stefan Jentsch

Citation

This paper should be referenced as such :
Jentsch, S ; Pohl, C
BIRC6 (baculoviral IAP repeat-containing 6)
Atlas Genet Cytogenet Oncol Haematol. 2007;11(2):84-85.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/BIRC6ID798ch2p22.html

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indexed on : Sat Nov 8 16:29:44 CET 2014

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