BAXA (Danio rerio)
Description [+]
- Synonyms: BAXA, BAXA, BCL2-ASSOCIATED X PROTEIN A, WU:FJ16E01, ZBAX1, BAX, FJ16E01, WU:FC50B10
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Pisces; Danio rerio
- Short gene description: bcl2-associated X protein, a [Source:RefSeq_peptide;Acc:NP_571637]
- Family: Bcl-2 family : multidomain Bcl-2
- Process: apoptosis,
- Pathways: intrinsic pathway, pre-mitochondrial signaling events,
- Criteria: manually curated
- Curator comment: Overexpression of Baxa RNA in early stage zebrafish embryos induces Caspase-3 activation and apoptosis [16888646]. Knockdown of Baxa using antisense morpholino oligonucleotides protects zebrafish embryos from apoptosis in response to gamma-irradiation [16888646]. Baxa transcription is induced by tp53 following gamma-irradiation in zebrafish embryos [15630097].
- Human ortholog(s): BAX
- WIKI: BAXA-D_rerio
References [+]
- 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.
- tp53 mutant zebrafish develop malignant peripheral nerve sheath tumors.
- Berghmans S,Murphey RD,Wienholds E,Neuberg D,Kutok JL,Fletcher CD,Morris JP,Liu TX,Schulte-Merker S,Kanki JP,Plasterk R,Zon LI,Look AT
- TP53 is the most frequently mutated tumor suppressor gene in human cancer, with nearly 50% of all tumors exhibiting a loss-of-function mutation. To further elucidate the genetic pathways involving TP53 and cancer, we have exploited the zebrafish, a powerful vertebrate model system that is amenable to whole-genome forward-genetic analysis and synthetic-lethal screens. Zebrafish lines harboring missense mutations in the tp53 DNA-binding domain were identified by using a target-selected mutagenesis strategy. Homozygous mutant fish from two of these lines were viable and exhibited mutations similar to those found in human cancers (tp53(N168K) and tp53(M214K)). Although homozygous tp53(N168K) mutants were temperature-sensitive and suppressed radiation-induced apoptosis only at 37 degrees C, cells in the tp53(M214K) embryos failed to undergo apoptosis in response to gamma radiation at both 28 and 37 degrees C. Unlike wild-type control embryos, irradiated tp53(M214K) embryos also failed to up-regulate p21 and did not arrest at the G(1)/S checkpoint. Beginning at 8.5 months of age, 28% of tp53(M214K) mutant fish developed malignant peripheral nerve sheath tumors. In addition to providing a model for studying the molecular pathogenic pathways of malignant peripheral nerve sheath tumors, these mutant zebrafish lines provide a unique platform for modifier screens to identify genetic mutations or small molecules that affect tp53-related pathways, including apoptosis, cell-cycle delay, and tumor suppression. Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):407-12. Epub 2005 Jan 3.
- References from Human ortholog(s):
- Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death.
- Oltvai ZN, Milliman CL, Korsmeyer SJ
- Bcl-2 protein is able to repress a number of apoptotic death programs. To investigate the mechanism of Bcl-2's effect, we examined whether Bcl-2 interacted with other proteins. We identified an associated 21 kd protein partner, Bax, that has extensive amino acid homology with Bcl-2, focused within highly conserved domains I and II. Bax is encoded by six exons and demonstrates a complex pattern of alternative RNA splicing that predicts a 21 kd membrane (alpha) and two forms of cytosolic protein (beta and gamma). Bax homodimerizes and forms heterodimers with Bcl-2 in vivo. Overexpressed Bax accelerates apoptotic death induced by cytokine deprivation in an IL-3-dependent cell line. Overexpressed Bax also counters the death repressor activity of Bcl-2. These data suggest a model in which the ratio of Bcl-2 to Bax determines survival or death following an apoptotic stimulus. Cell. 1993 Aug 27;74(4):609-19.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | Bcl-2 | 65 | 160 |
Protein sequence [+]
baxa | Danio rerio | 7955 | length:192
MAAPSGGGDTGSGNDQILDLGAALLNNFVYERVRRHGDRDAEVTRSQLGGVELCDPSHKR
LAQCLQQIGDELDGNAQLQSMLNNSNLQPTQDVFIRVAREIFSDGKFNWGRVVALFYFAC
RLVIKAISTRVPDIIRTIISWTMSYIQEHVINWIREQGGWDGIRSYFGTPTWQTVGVFLA
GVITTALVIRKM
LAQCLQQIGDELDGNAQLQSMLNNSNLQPTQDVFIRVAREIFSDGKFNWGRVVALFYFAC
RLVIKAISTRVPDIIRTIISWTMSYIQEHVINWIREQGGWDGIRSYFGTPTWQTVGVFLA
GVITTALVIRKM
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 |
|---|---|---|
| BAX | orthology | Chimpanzee |
| C_intestinalis_ENSCINP00000024813 | orthology | Ciona |
| BAX_BOVIN | orthology | Cow |
| NP_001003011.1 | orthology | Dog |
| BAX | orthology | Fugu |
| BAX | orthology | Gasterosteus |
| BAX | orthology | Gorilla |
| BAX | orthology | Horse |
| BAX | orthology | Human |
| BAX | orthology | Lyzard |
| BAX | orthology | Macaca |
| BAX | orthology | Medaka |
| BAX | orthology | Monodelphis |
| Bax | orthology | Mouse |
| A0EJI1_PONPY | orthology | Orangutan |
| BAX | orthology | Rabbit |
| Bax | orthology | Rat |
| R_norvegicus_ENSRNOP00000052069 | orthology | Rat |
| RGD1561847_predicted | orthology | Rat |
| bax | orthology | Xenopus |
| BAX | orthology | Zebra finch |
| A_aegypti_AAEL001521-PA | paralogy | Aedes |
| Q2PHG8_ANOGA | paralogy | Anopheles |
| BOK_CHICK | paralogy | Chicken |
| BCL2_CHICK | paralogy | Chicken |
| NP_001026091.1 | paralogy | Chicken |
| BCLX_CHICK | paralogy | Chicken |
| BCL2L1 | paralogy | Chimpanzee |
| XR_024448.1 | paralogy | Chimpanzee |
| BCL2A1 | paralogy | Chimpanzee |
| BCL2 | paralogy | Chimpanzee |
| MCL1 | paralogy | Chimpanzee |
| BCL2L2 | paralogy | Chimpanzee |
| C_intestinalis_ENSCINP00000000654 | paralogy | Ciona |
| NP_001092676.1 | paralogy | Cow |
| NP_001070954.1 | paralogy | Cow |
| BCLW_BOVIN | paralogy | Cow |
| NP_001092338.1 | paralogy | Cow |
| Q462R3_BOVIN | paralogy | Cow |
| B2LA1_BOVIN | paralogy | Cow |
| NP_001071386.1 | paralogy | Cow |
| NP_001003072.1 | paralogy | Dog |
| NP_001018644.1 | paralogy | Dog |
| BCL2 | paralogy | Dog |
| MCL1_CANFA | paralogy | Dog |
| BCL2A1 | paralogy | Dog |
| BCL2L1 (2 of 6) | paralogy | Fugu |
| T_rubripes_ENSTRUP00000006891 | paralogy | Fugu |
| BCL2L1 (3 of 6) | paralogy | Fugu |
| BCL2 | paralogy | Fugu |
| BCL2L1 (4 of 6) | paralogy | Fugu |
| BOK (1 of 2) | paralogy | Fugu |
| BCL2L1 (5 of 6) | paralogy | Fugu |
| BCL2L1 (6 of 6) | paralogy | Fugu |
| BCL2L1 (1 of 6) | paralogy | Fugu |
| BOK (2 of 2) | paralogy | Gasterosteus |
| BCL2 | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000018978 | paralogy | Gasterosteus |
| BCL2L1 (2 of 2) | paralogy | Gasterosteus |
| BOK (1 of 2) | paralogy | Gasterosteus |
| MCL1 | paralogy | Gorilla |
| BOK | paralogy | Gorilla |
| BAK1 | paralogy | Gorilla |
| BCL2L2 | paralogy | Gorilla |
| BCL2A1 | paralogy | Gorilla |
| BCL2 | paralogy | Gorilla |
| BCL2 | paralogy | Horse |
| BAK1 | paralogy | Horse |
| BCL2L1 | paralogy | Horse |
| BCL2L2 | paralogy | Horse |
| BCL2A1 | paralogy | Horse |
| BOK | paralogy | Horse |
| MCL1 | paralogy | Horse |
| BCL2L1 | paralogy | Human |
| BOK | paralogy | Human |
| BAK1 | paralogy | Human |
| BCL2 | paralogy | Human |
| BCL2L2 | paralogy | Human |
| BCL2A1 | paralogy | Human |
| MCL1 | paralogy | Human |
| BAK1 | paralogy | Lyzard |
| BCL2L1 | paralogy | Lyzard |
| BCL2 | paralogy | Lyzard |
| BOK | paralogy | Lyzard |
| BCL2A1 | paralogy | Lyzard |
| A_carolinensis_ENSACAP00000004550 | paralogy | Lyzard |
| BCL2A1 | paralogy | Macaca |
| BOK | paralogy | Macaca |
| BCL2L2 | paralogy | Macaca |
| BAK1 | paralogy | Macaca |
| BCL2 | paralogy | Macaca |
| BCL2L1 | paralogy | Macaca |
| MCL1 | paralogy | Macaca |
| BCL2L1 | paralogy | Medaka |
| BCL2 | paralogy | Medaka |
| BCL2L1 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000005598 | paralogy | Monodelphis |
| BOK | paralogy | Monodelphis |
| BCL2 | paralogy | Monodelphis |
| MCL1 | paralogy | Monodelphis |
| BCL2A1 | paralogy | Monodelphis |
| Bak1 | paralogy | Mouse |
| Bcl2l1 | paralogy | Mouse |
| Bcl2 | paralogy | Mouse |
| Bok | paralogy | Mouse |
| Bcl2l2 | paralogy | Mouse |
| Mcl1 | paralogy | Mouse |
| P_pygmaeus_ENSPPYP00000018457 | paralogy | Orangutan |
| MCL1 | paralogy | Orangutan |
| BCL2A1 | paralogy | Orangutan |
| BOK | paralogy | Orangutan |
| P_pygmaeus_ENSPPYP00000006150 | paralogy | Orangutan |
| BCL2L1 | paralogy | Orangutan |
| BCL2 | paralogy | Orangutan |
| BCL2L2 | paralogy | Ornithorhynchus |
| BOK | paralogy | Ornithorhynchus |
| Q9MYW4_RABIT | paralogy | Rabbit |
| MCL1 | paralogy | Rabbit |
| BAK1 | paralogy | Rabbit |
| BCL2A1 | paralogy | Rabbit |
| BCLX_RAT | paralogy | Rat |
| Bak1 | paralogy | Rat |
| Bcl2a1 | paralogy | Rat |
| Bcl2 | paralogy | Rat |
| Bok | paralogy | Rat |
| RGD1562809_predicted | paralogy | Rat |
| RGD1565822_predicted | paralogy | Rat |
| BCL2L1 (1 of 3) | paralogy | Tetraodon |
| BOK (2 of 2) | paralogy | Tetraodon |
| BCL2L1 (3 of 3) | paralogy | Tetraodon |
| BCL2L1 (2 of 3) | paralogy | Tetraodon |
| BOK (1 of 2) | paralogy | Tetraodon |
| BCL2 | paralogy | Tetraodon |
| T_nigroviridis_ENSTNIP00000002209 | paralogy | Tetraodon |
| T_nigroviridis_ENSTNIP00000017211 | paralogy | Tetraodon |
| bcl2l2 | paralogy | Xenopus |
| BCL2L1 | paralogy | Xenopus |
| BAK1 | paralogy | Xenopus |
| BCL2 | paralogy | Xenopus |
| BCL2 | paralogy | Zebra finch |
| BCL2L1 | paralogy | Zebra finch |
| BOK | paralogy | Zebra finch |
| D_rerio_ENSDARP00000037180 | paralogy | Zebrafish |
| zgc:153993 | paralogy | Zebrafish |
| BAXB | paralogy | Zebrafish |
| boka | paralogy | Zebrafish |
| bcl2 | paralogy | Zebrafish |
| mcl1b | paralogy | Zebrafish |
| bcl2l | paralogy | Zebrafish |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0042981 | regulation of apoptosis | biological_proccess | IEA |
| GO:0046686 | response to cadmium ion | biological_proccess | IDA |
| GO:0051597 | response to methylmercury | biological_proccess | IDA |
| GO:0043065 | positive regulation of apoptosis | biological_proccess | IDA |
| GO:0043280 | positive regulation of caspase activity | biological_proccess | IMP |
Check GO Evidence Codes here
KEGG Pathways [+]
Information from other databases [+]
- Gene info from ZFIN [?] ZDB-GENE-000511-6
- Ensembl genome browser [?] : ENSDARG00000020623
- Expression info from Arrayexpress [?] : ENSDARG00000020623
- Protein expression from Protein Atlas: [?] ENSDARG00000020623
- Community gene edition from Wikigenes: [?] 58081
Click on [?] for more information.
