Atlas of Genetics and Cytogenetics in Oncology and Haematology
BIRC6 (Baculoviral IAP repeat-containing 6)
| Identity |
| Other names | Baculoviral IAP repeat-containing ubiquitin-conjugating enzyme (BRUCE) |
| Baculoviral IAP repeat-containing 6 (Apollon) | |
| FLJ13726 | |
| FLJ13786 | |
| KIAA1289 | |
| HGNC (Hugo) | BIRC6 |
| Location | 2p22 |
| Location_base_pair | Starts at 32435600 and ends at 32697469 bp from pter ( according to hg18-Mar_2006) [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 |
| 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 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 11-2006 | Christian Pohl, Stefan Jentsch |
| Citation |
| This paper should be referenced as such : |
| Pohl C, Jentsch S . BIRC6 (Baculoviral IAP repeat-containing 6). Atlas Genet Cytogenet Oncol Haematol. November 2006 . URL : http://AtlasGeneticsOncology.org/Genes/BIRC6ID798ch2p22.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Sat Feb 27 10:47:56 CET 2010 |
For comments and suggestions or contributions, please contact us