BCL2L (Danio rerio)
Description [+]
- Synonyms: BCL2L, ZFBLP1, BCL-XL, CB1021, BCL2-LIKE
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Pisces; Danio rerio
- Short gene description: bcl2-like [Source:RefSeq_peptide;Acc:NP_571882]
- Family: Bcl-2 family : multidomain Bcl-2
- Process: apoptosis,
- Pathways: intrinsic pathway, pre-mitochondrial signaling events,
- Criteria: manually curated
- Curator comment: Ectopic expression of Bcl2l in zebrafish embryos inhibits apoptosis induced by multiple stimuli including death receptor signaling [16888647], ectopic expression of several pro-apoptotic Bcl2 family members [16888646], and gamma-irradiation [16888646].
- Human ortholog(s): BCL2L1
- WIKI: BCL2L-D_rerio
References [+]
- Delineation of the cell-extrinsic apoptosis pathway in the zebrafish.
- Eimon PM, Kratz E, Varfolomeev E, Hymowitz SG, Stern H, Zha J, Ashkenazi A
- The mammalian extrinsic apoptosis pathway is triggered by Fas ligand (FasL) and Apo2 ligand/tumor necrosis factor (TNF)-related apoptosis-inducing ligand (Apo2L/TRAIL). Ligand binding to cognate receptors activates initiator caspases directly in a death-inducing signaling complex. In Drosophila, TNF ligand binding activates initiator caspases indirectly, through JNK. We characterized the extrinsic pathway in zebrafish to determine how it operates in a nonmammalian vertebrate. We identified homologs of FasL and Apo2L/TRAIL, their receptors, and other components of the cell death machinery. Studies with three Apo2L/TRAIL homologs demonstrated that they bind the receptors zHDR (previously linked to hematopoiesis) and ovarian TNFR (zOTR). Ectopic expression of these ligands during embryogenesis induced apoptosis in erythroblasts and notochord cells. Inhibition of zHDR, zOTR, the adaptor zFADD, or caspase-8-like proteases blocked ligand-induced apoptosis, as did antiapoptotic Bcl-2 family members. Thus, the extrinsic apoptosis pathway in zebrafish closely resembles its mammalian counterpart and cooperates with the intrinsic pathway to trigger tissue-specific apoptosis during embryogenesis in response to ectopic Apo2L/TRAIL expression. Cell Death Differ. 2006 Oct;13(10):1619-30. Epub 2006 Aug 4.
- Cloning and characterization of zfBLP1, a Bcl-XL homologue from the zebrafish, Danio rerio.
- Chen MC, Gong HY, Cheng CY, Wang JP, Hong JR, Wu JL
- The importance of the Bcl-2 family proteins in normal vertebrate embryogenesis is being recognized; however, their regulatory mechanism is poorly understood. We report here the cloning and characterization of a novel zebrafish Bcl-2 family protein, zfBLP1. The zfBLP1 cDNA is 1942 nucleotides long, encoding a polypeptide of 238 amino acids. The primary sequence of zfBLP1 shares 50% identity to human Bcl-XL, and contains all four conserved BH domains of the Bcl-2 family proteins. Primary sequence analysis identified a consensus ER retention signal at the C-terminal end of zfBLP1. Northern blot analysis indicated that there were two major and two minor zfBLP1 mRNA species expressed during embryonic development. Among the two major mRNA species, the short one, approx. 3 kb in size, was expressed throughout embryonic development, while the long one, approx. 7 kb long, was not detectable until the gastrula stage. These results suggest that zfBLP1 is a novel Bcl-2 family protein under complicated regulations, and is likely to play an important role in zebrafish oogenesis and embryogenesis. Biochim Biophys Acta. 2001 May 28;1519(1-2):127-33.
- Functional characterization of the Bcl-2 gene family in the zebrafish.
- Kratz E, Eimon PM, Mukhyala K, Stern H, Zha J, Strasser A, Hart R, Ashkenazi A
- Members of the Bcl-2 protein family control the intrinsic apoptosis pathway. To evaluate the importance of this family in vertebrate development, we investigated it in the zebrafish (Danio rerio). We found that the zebrafish genome encodes structural and functional homologs of most mammalian Bcl-2 family members, including multi-Bcl-2-homology (BH) domain proteins and BH3-only proteins. Apoptosis induction by gamma-irradiation required zBax1 and zPuma, and could be prevented by overexpression of homologs of prosurvival Bcl-2 family members. Surprisingly, zebrafish Bax2 (zBax2) was homologous to mammalian Bax by sequence and synteny, yet demonstrated functional conservation with human Bak. Morpholino knockdown of both zMcl-1a and zMcl-1b revealed their critical role in early embryonic zebrafish development, and in the modulation of apoptosis activation through the extrinsic pathway. These data indicate substantial functional similarity between zebrafish and mammalian Bcl-2 family members, and establish the zebrafish as a relevant model for studying the intrinsic apoptosis pathway. Cell Death Differ. 2006 Oct;13(10):1631-40. Epub 2006 Aug 4.
- References from Human ortholog(s):
- bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death.
- Boise LH, Gonzalez-Garcia M, Postema CE, Ding L, Lindsten T, Turka LA, Mao X, Nunez G, Thompson CB
- We report the isolation of bcl-x, a bcl-2-related gene that can function as a bcl-2-independent regulator of programmed cell death (apoptosis). Alternative splicing results in two distinct bcl-x mRNAs. The protein product of the larger mRNA, bcl-xL, is similar in size and predicted structure to Bcl-2. When stably transfected into an IL-3-dependent cell line, bcl-xL inhibits cell death upon growth factor withdrawal at least as well as bcl-2. Surprisingly, the second mRNA species, bcl-xS, encodes a protein that inhibits the ability of bcl-2 to enhance the survival of growth factor-deprived cells. In vivo, bcl-xS mRNA is expressed at high levels in cells that undergo a high rate of turnover, such as developing lymphocytes. In contrast, bcl-xL is found in tissues containing long-lived postmitotic cells, such as adult brain. Together these data suggest that bcl-x plays an important role in both positive and negative regulation of programmed cell death. Cell. 1993 Aug 27;74(4):597-608.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | BH4 | 1 | 27 |
| PFAM A | Bcl-2 | 93 | 191 |
Protein sequence [+]
bcl2l | Danio rerio | 7955 | length:238
MSYYNRELVVFFIKYKLSQRNYPCNHIGLTEDTNRTDGAEENGEGAAGATTLVNGTMNRT
NASSTGTPPQSPASSPQRQTNGSGGLDAVKEALRDSANEFELRYSRAFNDLSSQLHITPA
TAYQSFESVMDEVFRDGVNWGRIVGLFAFGGALCVECVEKEMSPLVGRIAEWMTVYLDNH
IQPWIQSQGGWERFAEIFGKDAAAESRKSQESFKKWLFAGMTLLTGVVVGGLIAQKRL
NASSTGTPPQSPASSPQRQTNGSGGLDAVKEALRDSANEFELRYSRAFNDLSSQLHITPA
TAYQSFESVMDEVFRDGVNWGRIVGLFAFGGALCVECVEKEMSPLVGRIAEWMTVYLDNH
IQPWIQSQGGWERFAEIFGKDAAAESRKSQESFKKWLFAGMTLLTGVVVGGLIAQKRL
Structure links:
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| BCLX_CHICK | orthology | Chicken |
| BCL2L1 | orthology | Chimpanzee |
| NP_001070954.1 | orthology | Cow |
| NP_001003072.1 | orthology | Dog |
| BCL2L1 (1 of 6) | orthology | Fugu |
| BCL2L1 (1 of 2) | orthology | Gasterosteus |
| BCL2L1 | orthology | Horse |
| BCL2L1 | orthology | Human |
| BCL2L1 | orthology | Lyzard |
| BCL2L1 | orthology | Macaca |
| BCL2L1 | orthology | Monodelphis |
| Bcl2l1 | orthology | Mouse |
| BCL2L1 | orthology | Orangutan |
| Q9MYW4_RABIT | orthology | Rabbit |
| LOC684140 | orthology | Rat |
| BCLX_RAT | orthology | Rat |
| BCL2L1 (1 of 3) | orthology | Tetraodon |
| BCL2L1 | orthology | Xenopus |
| BCL2L1 | orthology | Zebra finch |
| A_aegypti_AAEL001521-PA | paralogy | Aedes |
| A_aegypti_AAEL001515-PA | paralogy | Aedes |
| Q2PHG8_ANOGA | paralogy | Anopheles |
| Q9W6F1_CHICK | paralogy | Chicken |
| BOK_CHICK | paralogy | Chicken |
| BCL2_CHICK | paralogy | Chicken |
| NP_001026091.1 | paralogy | Chicken |
| NP_990197.1 | paralogy | Chicken |
| BCL2 | paralogy | Chimpanzee |
| BCL2L2 | paralogy | Chimpanzee |
| MCL1 | paralogy | Chimpanzee |
| XR_024448.1 | paralogy | Chimpanzee |
| C_intestinalis_ENSCINP00000000654 | paralogy | Ciona |
| NP_001092338.1 | paralogy | Cow |
| Q462R3_BOVIN | paralogy | Cow |
| B2LA1_BOVIN | paralogy | Cow |
| IPI00908204.1 | paralogy | Cow |
| NP_001092676.1 | paralogy | Cow |
| NP_001071386.1 | paralogy | Cow |
| BCLW_BOVIN | paralogy | Cow |
| BCL2 | paralogy | Dog |
| NP_001018644.1 | paralogy | Dog |
| MCL1_CANFA | paralogy | Dog |
| Buffy | paralogy | Fly |
| debcl | paralogy | Fly |
| BCL2L1 (4 of 6) | paralogy | Fugu |
| BCL2L1 (5 of 6) | paralogy | Fugu |
| MCL1 | paralogy | Fugu |
| BCL2 | paralogy | Fugu |
| BOK (1 of 2) | paralogy | Fugu |
| BCL2L1 (6 of 6) | paralogy | Fugu |
| BOK (2 of 2) | paralogy | Fugu |
| BCL2L1 (2 of 6) | paralogy | Fugu |
| BCL2L1 (3 of 6) | paralogy | Fugu |
| BOK (1 of 2) | paralogy | Gasterosteus |
| BCL2 | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000018978 | paralogy | Gasterosteus |
| BCL2L1 (2 of 2) | paralogy | Gasterosteus |
| BOK (2 of 2) | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000021797 | paralogy | Gasterosteus |
| BCL2 | paralogy | Gorilla |
| MCL1 | paralogy | Gorilla |
| BOK | paralogy | Gorilla |
| BAK1 | paralogy | Gorilla |
| BCL2L2 | paralogy | Gorilla |
| BOK | paralogy | Horse |
| BCL2A1 | paralogy | Horse |
| MCL1 | paralogy | Horse |
| BAK1 | paralogy | Horse |
| BCL2L2 | paralogy | Horse |
| BCL2 | paralogy | Horse |
| BOK | paralogy | Human |
| BCL2L2 | paralogy | Human |
| MCL1 | paralogy | Human |
| BCL2 | paralogy | Human |
| BAK1 | paralogy | Human |
| MCL1 | paralogy | Lyzard |
| A_carolinensis_ENSACAP00000004550 | paralogy | Lyzard |
| BCL2 | paralogy | Lyzard |
| BOK | paralogy | Lyzard |
| BAX | paralogy | Lyzard |
| BAK1 | paralogy | Lyzard |
| BAK1 | paralogy | Macaca |
| BCL2 | paralogy | Macaca |
| MCL1 | paralogy | Macaca |
| BCL2L2 | paralogy | Macaca |
| BOK | paralogy | Macaca |
| BCL2 | paralogy | Medaka |
| MCL1 | paralogy | Medaka |
| BCL2L1 | paralogy | Medaka |
| O_latipes_ENSORLP00000015978 | paralogy | Medaka |
| BOK (1 of 2) | paralogy | Medaka |
| MCL1 | paralogy | Monodelphis |
| BCL2A1 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000026730 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000005598 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000037249 | paralogy | Monodelphis |
| BAX | paralogy | Monodelphis |
| BAK1 | paralogy | Monodelphis |
| BOK | paralogy | Monodelphis |
| BCL2 | paralogy | Monodelphis |
| Bax | paralogy | Mouse |
| Bok | paralogy | Mouse |
| Bcl2l2 | paralogy | Mouse |
| Mcl1 | paralogy | Mouse |
| Bak1 | paralogy | Mouse |
| Bcl2 | paralogy | Mouse |
| P_pygmaeus_ENSPPYP00000006150 | paralogy | Orangutan |
| BCL2 | paralogy | Orangutan |
| BOK | paralogy | Orangutan |
| MCL1 | paralogy | Orangutan |
| BCL2L2 | paralogy | Ornithorhynchus |
| BOK | paralogy | Ornithorhynchus |
| BAK1 | paralogy | Rabbit |
| BAX | paralogy | Rabbit |
| BCL2A1 | paralogy | Rabbit |
| MCL1 | paralogy | Rabbit |
| Bcl2 | paralogy | Rat |
| Bok | paralogy | Rat |
| RGD1562809_predicted | paralogy | Rat |
| RGD1565822_predicted | paralogy | Rat |
| Bax | paralogy | Rat |
| Bak1 | paralogy | Rat |
| BCL2 | paralogy | Tetraodon |
| T_nigroviridis_ENSTNIP00000002209 | paralogy | Tetraodon |
| BCL2L1 (2 of 3) | paralogy | Tetraodon |
| T_nigroviridis_ENSTNIP00000017211 | paralogy | Tetraodon |
| BOK (2 of 2) | paralogy | Tetraodon |
| BOK (1 of 2) | paralogy | Tetraodon |
| BCL2L1 (3 of 3) | paralogy | Tetraodon |
| MCL1 | paralogy | Xenopus |
| BCL2 | paralogy | Xenopus |
| BAK1 | paralogy | Xenopus |
| bax | paralogy | Xenopus |
| bcl2l2 | paralogy | Xenopus |
| BCL2 | paralogy | Zebra finch |
| BCL2A1 | paralogy | Zebra finch |
| BOK | paralogy | Zebra finch |
| boka | paralogy | Zebrafish |
| mcl1a | paralogy | Zebrafish |
| bcl2 | paralogy | Zebrafish |
| mcl1b | paralogy | Zebrafish |
| bokb | paralogy | Zebrafish |
| D_rerio_ENSDARP00000037180 | paralogy | Zebrafish |
| BAXB | paralogy | Zebrafish |
| baxa | paralogy | Zebrafish |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0043066 | negative regulation of apoptosis | biological_proccess | IDA |
| GO:0042981 | regulation of apoptosis | biological_proccess | IEA |
| GO:0001894 | tissue homeostasis | biological_proccess | IMP |
| GO:0043154 | negative regulation of caspase activity | biological_proccess | IDA |
| GO:0043027 | caspase inhibitor activity | mollecular_function | IDA |
Check GO Evidence Codes here
KEGG Pathways [+]
Information from other databases [+]
- Gene info from ZFIN [?] ZDB-GENE-010730-1
- Ensembl genome browser [?] : ENSDARG00000008434
- Expression info from Arrayexpress [?] : ENSDARG00000008434
- Protein expression from Protein Atlas: [?] ENSDARG00000008434
- Community gene edition from Wikigenes: [?] 114401
Click on [?] for more information.
