BUFFY (Drosophila melanogaster)
Description [+]
- Synonyms: BUFFY
- Species: Metazoa;Bilateria;Ecdysozoa;Arthropoda;Hexapoda; Drosophila melanogaster
- Short gene description: NA
- Family: Bcl-2 family : multidomain Bcl-2
- Process: apoptosis,
- Pathways:
- Criteria: manually curated
- Curator comment:
- Human ortholog(s): BOK
- WIKI: BUFFY-D_melanogaster
References [+]
- Buffy, a Drosophila Bcl-2 protein, has anti-apoptotic and cell cycle inhibitory functions.
- Quinn L, Coombe M, Mills K, Daish T, Colussi P, Kumar S, Richardson H
- Bcl-2 family proteins are key regulators of apoptosis. Both pro-apoptotic and anti-apoptotic members of this family are found in mammalian cells, but only the pro-apoptotic protein Debcl has been characterized in Drosophila: Here we report that Buffy, the second Drosophila Bcl-2-like protein, is a pro-survival protein. Ablation of Buffy by RNA interference leads to ectopic apoptosis, whereas overexpression of buffy results in the inhibition of developmental programmed cell death and gamma irradiation-induced apoptosis. Buffy interacts genetically and physically with Debcl to suppress Debcl-induced cell death. Genetic interactions suggest that Buffy acts downstream of Rpr, Grim and Hid, and upstream of the apical caspase Dronc. Furthermore, overexpression of buffy inhibits ectopic cell death in diap1 (th(5)) mutants. Taken together these data suggest that Buffy can act downstream of Rpr, Grim and Hid to block caspase-dependent cell death. Overexpression of Buffy in the embryo results in inhibition of the cell cycle, consistent with a G(1)/early-S phase arrest. Our data suggest that Buffy is functionally similar to the mammalian pro-survival Bcl-2 family of proteins. EMBO J. 2003 Jul 15;22(14):3568-79.
- References from Human ortholog(s):
- Nuclear translocation of the pro-apoptotic Bcl-2 family member Bok induces apoptosis.
- Bartholomeusz G, Wu Y, Ali Seyed M, Xia W, Kwong KY, Hortobagyi G, Hung MC
- The anti-apoptotic members of the Bcl-2 family, such as Bcl-2 and Bcl-XL, play a central role in preventing the induction of apoptosis via the intrinsic apoptotic pathway. It has been previously shown that induction of apoptosis by the pro-apoptotic Bcl-2 family member Bok is not antagonized by either Bcl-2 or Bcl-xL, suggesting that Bok might have a unique role in the apoptotic cascade. We showed here that human Bok is the only member of the Bcl-2 family to have a leucine-rich sequence indicative of a nuclear export signal within its BH3 domain. Western blot analysis of nuclear and cytoplasmic fractions identified Bok in both the nucleus and the cytoplasm of HEK 293T cells, HeLa cells, and breast cancer cells, and its nuclear concentration increased after treatment of those cells with leptomycin B, an inhibitor of the exportin Crm1. Immunocytochemistry of flag-tagged Bok confirmed its nuclear localization. Mutating the nuclear export signal of Bok by site-directed mutagenesis resulted in an increase in its nuclear localization and apoptotic activity. We also found that Crm1 interacted with wild-type Bok but not with the mutated form. These results suggest that nuclear export of Bok is a regulated process mediated by Crm1, and constitutes the first report of a link between the apoptotic activity and nuclear localization of a pro-apoptotic member of the Bcl-2 family. Mol Carcinog. 2006 Feb;45(2):73-83.
- Mtd, a novel Bcl-2 family member activates apoptosis in the absence of heterodimerization with Bcl-2 and Bcl-XL.
- Inohara N, Ekhterae D, Garcia I, Carrio R, Merino J, Merry A, Chen S, Nunez G
- We have identified and characterized Mtd, a novel regulator of apoptosis. Sequence analysis revealed that Mtd is a member of the Bcl-2 family of proteins containing conserved BH1, BH2, BH3, and BH4 regions and a carboxyl-terminal hydrophobic domain. In adult tissues, Mtd mRNA was predominantly detected in the brain, liver, and lymphoid tissues, while in the embryo Mtd mRNA was detected in the liver, thymus, lung, and intestinal epithelium. Expression of Mtd promoted the death of primary sensory neurons, 293T cells and HeLa cells, indicating that Mtd is a proapoptotic protein. Unlike all other known death agonists of the Bcl-2 family, Mtd did not bind significantly to the survival-promoting proteins Bcl-2 or Bcl-XL. Furthermore, apoptosis induced by Mtd was not inhibited by Bcl-2 or Bcl-XL. A Mtd mutant with glutamine substitutions of highly conserved amino acids in the BH3 domain retained its ability to promote apoptosis, further indicating that Mtd does not promote apoptosis by heterodimerizing with Bcl-2 or Bcl-XL. Mtd-induced apoptosis was not blocked by broad range synthetic caspase inhibitors z-VAD-fmk or a viral protein CrmA. Mtd is the first example of a naturally occurring Bcl-2 family member that can activate apoptosis independently of heterodimerization with survival-promoting Bcl-2 and Bcl-XL. J Biol Chem. 1998 Apr 10;273(15):8705-10.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | Bcl-2 | 139 | 244 |
Protein sequence [+]
Buffy | Drosophila melanogaster | 7227 | length:299
MPGTSYPTNNDNFSNGFPMATTQSERLLQAQNRRKFSFPATLHSASLLEVGGGPKETTRR
RLSNVSDAVTRKLSYTIGWKAAQIPAQDIISQGRCLCGHYIKRRLRRSGLFNKKLGLQRI
RSILGSTSMGIVRDVFPAVQVLGDELERMHPRIYNGVARQICRNPGGEFHTPDAVSLLLG
AVGRELFRVEITWSKVISLFAIAGGLSVDCVRQGHPEYLPKLMESVSEVIEDELVPWINE
NGGWSGINTHVLPTTNSLNPLEWTTLVIGVVFGLILVFMILRFIFNLIVPKIYQRFTNS
RLSNVSDAVTRKLSYTIGWKAAQIPAQDIISQGRCLCGHYIKRRLRRSGLFNKKLGLQRI
RSILGSTSMGIVRDVFPAVQVLGDELERMHPRIYNGVARQICRNPGGEFHTPDAVSLLLG
AVGRELFRVEITWSKVISLFAIAGGLSVDCVRQGHPEYLPKLMESVSEVIEDELVPWINE
NGGWSGINTHVLPTTNSLNPLEWTTLVIGVVFGLILVFMILRFIFNLIVPKIYQRFTNS
Structure links:
- Smartdomain prediction information: SM00337
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| A_aegypti_AAEL001521-PA | orthology | Aedes |
| BOK_CHICK | orthology | Chicken |
| C_intestinalis_ENSCINP00000016140 | orthology | Ciona |
| C_intestinalis_ENSCINP00000019812 | orthology | Ciona |
| NP_001092338.1 | orthology | Cow |
| BOK (2 of 2) | orthology | Fugu |
| BOK (1 of 2) | orthology | Fugu |
| BOK (1 of 2) | orthology | Gasterosteus |
| BOK (2 of 2) | orthology | Gasterosteus |
| BOK | orthology | Gorilla |
| BOK | orthology | Horse |
| BOK | orthology | Human |
| BOK | orthology | Lyzard |
| BOK | orthology | Macaca |
| BOK (1 of 2) | orthology | Medaka |
| BOK (2 of 2) | orthology | Medaka |
| BOK | orthology | Monodelphis |
| Bok | orthology | Mouse |
| BOK | orthology | Orangutan |
| BOK | orthology | Ornithorhynchus |
| Bok | orthology | Rat |
| BOK (1 of 2) | orthology | Tetraodon |
| BOK (2 of 2) | orthology | Tetraodon |
| BOK | orthology | Zebra finch |
| boka | orthology | Zebrafish |
| bokb | orthology | Zebrafish |
| A_aegypti_AAEL001515-PA | paralogy | Aedes |
| Q2PHG8_ANOGA | paralogy | Anopheles |
| BCLX_CHICK | paralogy | Chicken |
| BCL2_CHICK | paralogy | Chicken |
| BCL2 | paralogy | Chimpanzee |
| BCL2L1 | paralogy | Chimpanzee |
| NP_001070954.1 | paralogy | Cow |
| NP_001003072.1 | paralogy | Dog |
| debcl | paralogy | Fly |
| BCL2 | paralogy | Fugu |
| BCL2L1 (1 of 6) | paralogy | Fugu |
| BCL2L1 (2 of 6) | paralogy | Fugu |
| BCL2L1 (1 of 2) | paralogy | Gasterosteus |
| BCL2L1 (2 of 2) | paralogy | Gasterosteus |
| BCL2L1 | paralogy | Horse |
| BCL2L1 | paralogy | Human |
| BCL2 | paralogy | Human |
| BCL2L1 | paralogy | Lyzard |
| BCL2L1 | paralogy | Macaca |
| BCL2 | paralogy | Macaca |
| BCL2 | paralogy | Medaka |
| BCL2 | paralogy | Monodelphis |
| BCL2L1 | paralogy | Monodelphis |
| Bcl2l1 | paralogy | Mouse |
| Bcl2 | paralogy | Mouse |
| BCL2 | paralogy | Orangutan |
| BCL2L1 | paralogy | Orangutan |
| Q9MYW4_RABIT | paralogy | Rabbit |
| Bcl2 | paralogy | Rat |
| BCLX_RAT | paralogy | Rat |
| BCL2L1 (1 of 3) | paralogy | Tetraodon |
| BCL2L1 (2 of 3) | paralogy | Tetraodon |
| BCL2 | paralogy | Xenopus |
| BCL2L1 | paralogy | Xenopus |
| bcl2l2 | paralogy | Xenopus |
| BCL2 | paralogy | Zebra finch |
| BCL2L1 | paralogy | Zebra finch |
| bcl2l | paralogy | Zebrafish |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0006511 | ubiquitin-dependent protein catabolic process | biological_proccess | IEA |
| GO:0004298 | threonine-type endopeptidase activity | mollecular_function | IEA |
| GO:0016787 | hydrolase activity | mollecular_function | IEA |
| GO:0005839 | proteasome core complex | cell_component | IEA |
Check GO Evidence Codes here
Information from other databases [+]
- Gene info from FyBase [?] FBgn0040491
- Ensembl genome browser [?] : FBgn0040491
- Expression info from Arrayexpress [?] : FBgn0040491
- Protein expression from Protein Atlas: [?] FBgn0040491
Click on [?] for more information.
