MCL1B (Danio rerio)
Description [+]
- Synonyms: MCL1B, MYELOID CELL LEUKEMIA SEQUENCE 1B, ZGC:109763
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Pisces; Danio rerio
- Short gene description: myeloid cell leukemia sequence 1b [Source:RefSeq_peptide;Acc:NP_919375]
- Family: Bcl-2 family : multidomain Bcl-2
- Process: apoptosis,
- Pathways: intrinsic pathway, pre-mitochondrial signaling events,
- Criteria: manually curated
- Curator comment: Ectopic expression of Mcl1b in zebrafish embryos inhibits apoptosis induced by several pro-apoptotic Bcl2 family members [ Ref: 16888646 "> Ref: Ref: 16888646 "> Ref: Ref: 16888646 "> Ref: Ref: 16888646 ] and gamma-irradiation [ Ref: 16888646 "> Ref: Ref: 16888646 "> Ref: Ref: 16888646 "> Ref: Ref: 16888646 ]. Simultaneous knockdown of both Mcl1a and Mcl1b in zebrafish embryos using antisense morpholino oligonucleotides significantly decreases viability and increases sensitivity to apoptosis induced by the Apo2L/TRAIL ortholog Tnfsf10l3 [ Ref: 16888646 "> Ref: Ref: 16888646 "> Ref: Ref: 16888646 "> Ref: Ref: 16888646 ].
- Human ortholog(s): MCL1
- WIKI: MCL1B-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.
- References from Human ortholog(s):
- MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2.
- Kozopas KM, Yang T, Buchan HL, Zhou P, Craig RW
- During their lifespan, immature cells normally pass through sequential transitions to a differentiated state and eventually undergo cell death. This progression is aberrant in cancer, although the transition to differentiation can be reestablished in inducible leukemia cell lines. This report describes a gene, MCL1, that we isolated from the ML-1 human myeloid leukemia cell line during phorbol ester-induced differentiation along the monocyte/macrophage pathway. Our results demonstrate that expression of MCL1 increases early in the induction, or "programming," of differentiation in ML-1 (at 1-3 hr), before the appearance of differentiation markers and mature morphology (at 1-3 days). They further show that MCL1 has sequence similarity to BCL2, a gene involved in normal lymphoid development and in lymphomas with the t(14;18) chromosome translocation. MCL1 and BCL2 do not fall into previously known gene families. BCL2 differs from many oncogenes in that it inhibits programmed cell death, promoting viability rather than proliferation; this parallels the association of MCL1 with the programming of differentiation and concomitant maintenance of viability but not proliferation. Thus, in contrast to proliferation-associated genes, expression of MCL1 and BCL2 relates to the programming of differentiation and cell viability/death. The discovery of MCL1 broadens our perspective on an emerging MCL1/BCL2 gene family and will allow further comparison with oncogene families. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3516-20.
- MCL-1S, a splicing variant of the antiapoptotic BCL-2 family member MCL-1, encodes a proapoptotic protein possessing only the BH3 domain.
- Bae J, Leo CP, Hsu SY, Hsueh AJ
- MCL-1 (myeloid cell leukemia-1) is an antiapoptotic BCL-2 family protein discovered as an early induction gene during myeloblastic leukemia cell differentiation. This survival protein has the BCL-2 homology (BH) domains 1, 2, and 3 and a C-terminal transmembrane region. We identified a short splicing variant of the MCL-1 mRNA in the human placenta encoding a protein, termed MCL-1 short (MCL-1S), with an altered C terminus as compared with the full-length MCL-1 long (MCL-1L), leading to the loss of BH1, BH2, and the transmembrane domains. Analysis of the human MCL-1 gene indicated that MCL-1S results from the splicing out of exon 2 during mRNA processing. MCL-1S, unlike MCL-1L, does not interact with diverse proapoptotic BCL-2-related proteins in the yeast two-hybrid system. In contrast, MCL-1S dimerizes with MCL-1L in the yeast assay and coprecipitates with MCL-1L in transfected mammalian cells. Overexpression of MCL-1S induces apoptosis in transfected Chinese hamster ovary cells, and the MCL-1S action was antagonized by the antiapoptotic MCL-1L. Thus, the naturally occurring MCL-1S variant represents a new proapoptotic BH3 domain-only protein capable of dimerizing with the antiapoptotic MCL-1L. The fate of MCL-1-expressing cells could be regulated through alternative splicing mechanisms and interactions of the resulting anti- and proapoptotic gene products. J Biol Chem. 2000 Aug 18;275(33):25255-61.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | Bcl-2 | 90 | 190 |
Protein sequence [+]
mcl1b | Danio rerio | 7955 | length:228
MFAGRNNDNGFWPCTGLQSKPLVIPELKAHNQFAVDSLQGSVPSSPSDETGDYPPTALDM
DTREIIDTFLKIFTGLPHSKSGRKQVLSTMRRVVDNLAVKHELAYKGMIARLNLEQKGED
VSFIKQVATELFSDGTTNWGRIASLLTFGAMLCKYQNDRGHSKYVRLVGEEISSYLLTEQ
RDWILRNKAWDGFVEFFHVPDTEAAVRNTLLTIGGVATLSAALAYWIR
DTREIIDTFLKIFTGLPHSKSGRKQVLSTMRRVVDNLAVKHELAYKGMIARLNLEQKGED
VSFIKQVATELFSDGTTNWGRIASLLTFGAMLCKYQNDRGHSKYVRLVGEEISSYLLTEQ
RDWILRNKAWDGFVEFFHVPDTEAAVRNTLLTIGGVATLSAALAYWIR
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 |
|---|---|---|
| Q9W6F1_CHICK | orthology | Chicken |
| MCL1 | orthology | Chimpanzee |
| NP_001092676.1 | orthology | Cow |
| IPI00908204.1 | orthology | Cow |
| MCL1_CANFA | orthology | Dog |
| MCL1 | orthology | Fugu |
| MCL1 | orthology | Gasterosteus |
| MCL1 | orthology | Gorilla |
| MCL1 | orthology | Horse |
| MCL1 | orthology | Human |
| MCL1 | orthology | Lyzard |
| MCL1 | orthology | Macaca |
| MCL1 | orthology | Medaka |
| MCL1 | orthology | Monodelphis |
| Mcl1 | orthology | Mouse |
| MCL1 | orthology | Orangutan |
| MCL1 | orthology | Rabbit |
| RGD1562809_predicted | orthology | Rat |
| MCL1 | orthology | Tetraodon |
| MCL1 | orthology | Xenopus |
| NP_990197.1 | paralogy | Chicken |
| BCL2_CHICK | paralogy | Chicken |
| BCLX_CHICK | paralogy | Chicken |
| BAX | paralogy | Chimpanzee |
| BCL2L2 | paralogy | Chimpanzee |
| BCL2L1 | paralogy | Chimpanzee |
| BCL2 | paralogy | Chimpanzee |
| NP_001070954.1 | paralogy | Cow |
| Q462R3_BOVIN | paralogy | Cow |
| IPI00824520.1 | paralogy | Cow |
| BCLW_BOVIN | paralogy | Cow |
| BAX_BOVIN | paralogy | Cow |
| NP_001003072.1 | paralogy | Dog |
| BCL2L1 (2 of 6) | paralogy | Fugu |
| BCL2L1 (1 of 6) | paralogy | Fugu |
| GNB5 (2 of 2) | paralogy | Fugu |
| BCL2L1 (2 of 2) | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000021797 | paralogy | Gasterosteus |
| BCL2L2 | paralogy | Gorilla |
| BCL2 | paralogy | Gorilla |
| BCL2L2 | paralogy | Horse |
| BCL2 | paralogy | Horse |
| BCL2L1 | paralogy | Horse |
| BCL2L1 | paralogy | Human |
| BCL2 | paralogy | Human |
| BCL2L2 | paralogy | Human |
| BCL2 | paralogy | Lyzard |
| BCL2L1 | paralogy | Lyzard |
| BAX | paralogy | Lyzard |
| BCL2 | paralogy | Macaca |
| BCL2L1 | paralogy | Macaca |
| BCL2L2 | paralogy | Macaca |
| BAX | paralogy | Macaca |
| O_latipes_ENSORLP00000015978 | paralogy | Medaka |
| BCL2L1 | paralogy | Medaka |
| M_domestica_ENSMODP00000005598 | paralogy | Monodelphis |
| BCL2 | paralogy | Monodelphis |
| BCL2L1 | paralogy | Monodelphis |
| Bax | paralogy | Mouse |
| Bcl2a1d | paralogy | Mouse |
| Bcl2 | paralogy | Mouse |
| Bcl2a1a | paralogy | Mouse |
| Bcl2a1a | paralogy | Mouse |
| Bcl2l2 | paralogy | Mouse |
| Bcl2l1 | paralogy | Mouse |
| BCL2L1 | paralogy | Orangutan |
| BCL2 | paralogy | Orangutan |
| BCL2L2 | paralogy | Ornithorhynchus |
| Q9MYW4_RABIT | paralogy | Rabbit |
| RGD1565822_predicted | paralogy | Rat |
| Bcl2a1 | paralogy | Rat |
| Bax | paralogy | Rat |
| BCLX_RAT | paralogy | Rat |
| Bcl2 | paralogy | Rat |
| BCL2L1 (1 of 3) | paralogy | Tetraodon |
| T_nigroviridis_ENSTNIP00000002209 | paralogy | Tetraodon |
| bax | paralogy | Xenopus |
| bcl2l2 | paralogy | Xenopus |
| BCL2L1 | paralogy | Xenopus |
| BCL2 | paralogy | Xenopus |
| BAX | paralogy | Zebra finch |
| BCL2L1 | paralogy | Zebra finch |
| BCL2A1 | paralogy | Zebra finch |
| BCL2 | paralogy | Zebra finch |
| bcl2l | paralogy | Zebrafish |
| mcl1a | paralogy | Zebrafish |
| baxa | paralogy | Zebrafish |
| D_rerio_ENSDARP00000037180 | paralogy | Zebrafish |
| bcl2 | paralogy | Zebrafish |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0042981 | regulation of apoptosis | biological_proccess | IEA |
| GO:0043066 | negative regulation of apoptosis | biological_proccess | IGI |
| GO:0043154 | negative regulation of caspase activity | biological_proccess | IDA |
| GO:0043009 | chordate embryonic development | biological_proccess | IGI |
Check GO Evidence Codes here
Information from other databases [+]
- Gene info from ZFIN [?] ZDB-GENE-030825-1
- Ensembl genome browser [?] : ENSDARG00000008363
- Expression info from Arrayexpress [?] : ENSDARG00000008363
- Protein expression from Protein Atlas: [?] ENSDARG00000008363
- Community gene edition from Wikigenes: [?] 373102
Click on [?] for more information.
