rbpjb

UniProt ID: A4FTT4
Organism: Danio rerio
Review Status: COMPLETE
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Gene Description

rbpjb encodes Su(H)B, one of two zebrafish paralogs (rbpja and rbpjb, products of the teleost genome duplication) of the CSL (CBF1/RBPJ, Suppressor of Hairless, LAG-1) transcription factor, the DNA-binding effector of canonical Notch signalling. The protein has the conserved CSL architecture: an N-terminal Rel-homology region and beta-trefoil domain that together bind the C(T/A)GTGGGAA-type RBPJ motif, and a C-terminal Ig-like domain. In the nucleus it binds the RAM and ankyrin regions of the Notch intracellular domain (NICD) and recruits Mastermind to form the NICD-CSL-MAML activation complex that induces Notch target genes (e.g. her/hey genes); in the absence of NICD, CSL proteins act with corepressors to repress targets. In zebrafish, Rbpj binds NICD and also physically interacts with Wt1a and Foxc1a to control podocyte formation, and Su(H) knockdown disrupts neurogenic lateral inhibition, the somite segmentation clock and its bilateral symmetry (via tailbud cyp26a1), left-right asymmetry, heart development and arterial/angiogenic behaviour. Many morpholino studies target both paralogs, so paralog-specific roles are not fully resolved.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0000122 negative regulation of transcription by RNA polymerase II
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: ARBA negative regulation of transcription by RNA polymerase II.
Reason: CSL proteins repress targets with corepressors in the absence of NICD; plausible by homology but not tested for zebrafish Rbpjb.
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
IBA
GO_REF:0000033
ACCEPT
Summary: RNA polymerase II cis-regulatory region sequence-specific DNA binding (IBA).
Reason: CSL proteins bind RBPJ motifs in target enhancers; conserved DNA-binding residues.
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
IEA
GO_REF:0000120
ACCEPT
Summary: RNA polymerase II cis-regulatory region sequence-specific DNA binding (IEA).
Reason: CSL proteins bind RBPJ motifs in target enhancers; conserved DNA-binding residues.
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
IBA
GO_REF:0000033
ACCEPT
Summary: IBA from PANTHER:PTN000071433.
Reason: Core molecular function of CSL proteins; ancestral node placement is sound.
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific
IEA
GO_REF:0000120
ACCEPT
Summary: IEA DNA-binding transcription activator activity, RNA polymerase II-specific.
Reason: Activator function in complex with NICD and MAML.
GO:0001756 somitogenesis
IGI
PMID:16545363
her1 and her13.2 are jointly required for somitic border spe...
KEEP AS NON CORE
Summary: somitogenesis (IGI, PMID:16545363): phenotype of Su(H)/rbpj knockdown reflecting loss of canonical Notch transcriptional output in this developmental context.
Reason: Downstream developmental consequence of the core CSL transcription factor activity. Morpholinos in these studies may target both rbpj paralogs; the curator's annotation is not disputed.
Supporting Evidence:
file:DANRE/rbpjb/rbpjb-deep-research-falcon.md
The available literature confirms this paralog pair but rarely distinguishes their individual biochemical or developmental
GO:0001756 somitogenesis
IMP
PMID:17098223
Coordination of symmetric cyclic gene expression during somi...
KEEP AS NON CORE
Summary: Su(H) knockdown disrupts the segmentation oscillator (Echeverri and Oates 2007).
Reason: Developmental context; Notch/CSL drives her1/her7/dlc cyclic transcription.
Supporting Evidence:
PMID:17098223
Combined Su(H) gene knockdown caused defects in visceral left/right asymmetry, neurogenic lateral inhibition, and symmetrical failure of the segmentation oscillator.
GO:0002040 sprouting angiogenesis
IGI
PMID:17259972
Notch signalling limits angiogenic cell behaviour in develop...
KEEP AS NON CORE
Summary: sprouting angiogenesis (IGI, PMID:17259972): phenotype of Su(H)/rbpj knockdown reflecting loss of canonical Notch transcriptional output in this developmental context.
Reason: Downstream developmental consequence of the core CSL transcription factor activity. Morpholinos in these studies may target both rbpj paralogs; the curator's annotation is not disputed.
Supporting Evidence:
file:DANRE/rbpjb/rbpjb-deep-research-falcon.md
The available literature confirms this paralog pair but rarely distinguishes their individual biochemical or developmental
GO:0002193 MAML1-RBP-Jkappa- ICN1 complex
IBA
GO_REF:0000033
ACCEPT
Summary: MAML1-RBP-Jkappa-ICN1 complex (IBA from PANTHER:PTN002580211).
Reason: The NICD-CSL-MAML ternary complex is the conserved activation complex; the term label names human subunits but denotes the orthologous complex.
GO:0003140 determination of left/right asymmetry in lateral mesoderm
IGI
PMID:20876649
Notch signalling regulates left-right asymmetry through cili...
KEEP AS NON CORE
Summary: determination of left/right asymmetry in lateral mesoderm (IGI, PMID:20876649): phenotype of Su(H)/rbpj knockdown reflecting loss of canonical Notch transcriptional output in this developmental context.
Reason: Downstream developmental consequence of the core CSL transcription factor activity. Morpholinos in these studies may target both rbpj paralogs; the curator's annotation is not disputed.
Supporting Evidence:
file:DANRE/rbpjb/rbpjb-deep-research-falcon.md
The available literature confirms this paralog pair but rarely distinguishes their individual biochemical or developmental
GO:0003677 DNA binding
IEA
GO_REF:0000002
ACCEPT
Summary: InterPro DNA binding.
Reason: Correct, general.
GO:0003700 DNA-binding transcription factor activity
IEA
GO_REF:0000002
ACCEPT
Summary: InterPro DNA-binding transcription factor activity.
Reason: Correct, general parent of the RNA polymerase II-specific term.
GO:0005634 nucleus
IBA
GO_REF:0000033
ACCEPT
Summary: Nucleus (IBA; IBA from PANTHER:PTN000071433).
Reason: CSL factors are nuclear DNA-binding transcription factors.
GO:0005634 nucleus
IEA
GO_REF:0000120
ACCEPT
Summary: Nucleus (IEA; IBA from PANTHER:PTN000071433).
Reason: CSL factors are nuclear DNA-binding transcription factors.
GO:0005667 transcription regulator complex
IEA
GO_REF:0000117
ACCEPT
Summary: ARBA transcription regulator complex.
Reason: Rbpj functions within NICD/MAML activator and corepressor complexes.
GO:0006355 regulation of DNA-templated transcription
IEA
GO_REF:0000002
ACCEPT
Summary: InterPro regulation of DNA-templated transcription.
Reason: Correct, general.
GO:0006357 regulation of transcription by RNA polymerase II
IEA
GO_REF:0000002
ACCEPT
Summary: InterPro regulation of transcription by RNA polymerase II.
Reason: Correct, general.
GO:0007219 Notch signaling pathway
IBA
GO_REF:0000033
ACCEPT
Summary: Notch signaling pathway (IBA from PANTHER:PTN002580211).
Reason: Core process; Rbpj is the DNA-binding effector of canonical Notch signalling.
Supporting Evidence:
PMID:21871448
Wt1a, Foxc1a, and Rbpj can physically interact with each other, whereas only Rbpj binds to the Notch intracellular domain (NICD)
GO:0007221 positive regulation of transcription of Notch receptor target
IEA
GO_REF:0000117
ACCEPT
Summary: ARBA positive regulation of transcription of Notch receptor target.
Reason: Defining process of CSL factors.
GO:0007368 determination of left/right symmetry
IGI
PMID:17098223
Coordination of symmetric cyclic gene expression during somi...
KEEP AS NON CORE
Summary: determination of left/right symmetry (IGI, PMID:17098223): phenotype of Su(H)/rbpj knockdown reflecting loss of canonical Notch transcriptional output in this developmental context.
Reason: Downstream developmental consequence of the core CSL transcription factor activity. Morpholinos in these studies may target both rbpj paralogs; the curator's annotation is not disputed.
Supporting Evidence:
file:DANRE/rbpjb/rbpjb-deep-research-falcon.md
The available literature confirms this paralog pair but rarely distinguishes their individual biochemical or developmental
GO:0007507 heart development
IGI
PMID:17098223
Coordination of symmetric cyclic gene expression during somi...
KEEP AS NON CORE
Summary: heart development (IGI, PMID:17098223): phenotype of Su(H)/rbpj knockdown reflecting loss of canonical Notch transcriptional output in this developmental context.
Reason: Downstream developmental consequence of the core CSL transcription factor activity. Morpholinos in these studies may target both rbpj paralogs; the curator's annotation is not disputed.
Supporting Evidence:
file:DANRE/rbpjb/rbpjb-deep-research-falcon.md
The available literature confirms this paralog pair but rarely distinguishes their individual biochemical or developmental
GO:0007507 heart development
IMP
PMID:17098223
Coordination of symmetric cyclic gene expression during somi...
KEEP AS NON CORE
Summary: heart development (IMP, PMID:17098223): phenotype of Su(H)/rbpj knockdown reflecting loss of canonical Notch transcriptional output in this developmental context.
Reason: Downstream developmental consequence of the core CSL transcription factor activity. Morpholinos in these studies may target both rbpj paralogs; the curator's annotation is not disputed.
Supporting Evidence:
file:DANRE/rbpjb/rbpjb-deep-research-falcon.md
The available literature confirms this paralog pair but rarely distinguishes their individual biochemical or developmental
GO:0009653 anatomical structure morphogenesis
IEA
GO_REF:0000117
MARK AS OVER ANNOTATED
Summary: ARBA anatomical structure morphogenesis.
Reason: Uninformative high-level developmental term.
GO:0022008 neurogenesis
IGI
PMID:17098223
Coordination of symmetric cyclic gene expression during somi...
KEEP AS NON CORE
Summary: neurogenesis (IGI, PMID:17098223): phenotype of Su(H)/rbpj knockdown reflecting loss of canonical Notch transcriptional output in this developmental context.
Reason: Downstream developmental consequence of the core CSL transcription factor activity. Morpholinos in these studies may target both rbpj paralogs; the curator's annotation is not disputed.
Supporting Evidence:
file:DANRE/rbpjb/rbpjb-deep-research-falcon.md
The available literature confirms this paralog pair but rarely distinguishes their individual biochemical or developmental
GO:0022008 neurogenesis
IMP
PMID:17098223
Coordination of symmetric cyclic gene expression during somi...
KEEP AS NON CORE
Summary: neurogenesis (IMP, PMID:17098223): phenotype of Su(H)/rbpj knockdown reflecting loss of canonical Notch transcriptional output in this developmental context.
Reason: Downstream developmental consequence of the core CSL transcription factor activity. Morpholinos in these studies may target both rbpj paralogs; the curator's annotation is not disputed.
Supporting Evidence:
file:DANRE/rbpjb/rbpjb-deep-research-falcon.md
The available literature confirms this paralog pair but rarely distinguishes their individual biochemical or developmental
GO:0030325 adrenal gland development
IGI
PMID:21871448
Wt1a, Foxc1a, and the Notch mediator Rbpj physically interac...
KEEP AS NON CORE
Summary: adrenal gland development (IGI, PMID:21871448): phenotype of Su(H)/rbpj knockdown reflecting loss of canonical Notch transcriptional output in this developmental context.
Reason: Downstream developmental consequence of the core CSL transcription factor activity. Morpholinos in these studies may target both rbpj paralogs; the curator's annotation is not disputed.
Supporting Evidence:
file:DANRE/rbpjb/rbpjb-deep-research-falcon.md
The available literature confirms this paralog pair but rarely distinguishes their individual biochemical or developmental
GO:0039021 pronephric glomerulus development
IGI
PMID:21871448
Wt1a, Foxc1a, and the Notch mediator Rbpj physically interac...
KEEP AS NON CORE
Summary: pronephric glomerulus development (IGI, PMID:21871448): phenotype of Su(H)/rbpj knockdown reflecting loss of canonical Notch transcriptional output in this developmental context.
Reason: Downstream developmental consequence of the core CSL transcription factor activity. Morpholinos in these studies may target both rbpj paralogs; the curator's annotation is not disputed.
Supporting Evidence:
file:DANRE/rbpjb/rbpjb-deep-research-falcon.md
The available literature confirms this paralog pair but rarely distinguishes their individual biochemical or developmental
GO:0039021 pronephric glomerulus development
IGI
PMID:21871448
Wt1a, Foxc1a, and the Notch mediator Rbpj physically interac...
KEEP AS NON CORE
Summary: pronephric glomerulus development (IGI, PMID:21871448): phenotype of Su(H)/rbpj knockdown reflecting loss of canonical Notch transcriptional output in this developmental context.
Reason: Downstream developmental consequence of the core CSL transcription factor activity. Morpholinos in these studies may target both rbpj paralogs; the curator's annotation is not disputed.
Supporting Evidence:
file:DANRE/rbpjb/rbpjb-deep-research-falcon.md
The available literature confirms this paralog pair but rarely distinguishes their individual biochemical or developmental
GO:0039022 pronephric duct development
IGI
PMID:21871448
Wt1a, Foxc1a, and the Notch mediator Rbpj physically interac...
KEEP AS NON CORE
Summary: pronephric duct development (IGI, PMID:21871448): phenotype of Su(H)/rbpj knockdown reflecting loss of canonical Notch transcriptional output in this developmental context.
Reason: Downstream developmental consequence of the core CSL transcription factor activity. Morpholinos in these studies may target both rbpj paralogs; the curator's annotation is not disputed.
Supporting Evidence:
file:DANRE/rbpjb/rbpjb-deep-research-falcon.md
The available literature confirms this paralog pair but rarely distinguishes their individual biochemical or developmental
GO:0048513 animal organ development
IEA
GO_REF:0000117
MARK AS OVER ANNOTATED
Summary: ARBA animal organ development.
Reason: Uninformative high-level developmental term.
GO:0060429 epithelium development
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: ARBA epithelium development.
Reason: General developmental context (e.g. pronephric podocytes and duct).
GO:0060840 artery development
IGI
PMID:23818617
Analysis of Dll4 regulation reveals a combinatorial role for...
KEEP AS NON CORE
Summary: artery development (IGI, PMID:23818617): phenotype of Su(H)/rbpj knockdown reflecting loss of canonical Notch transcriptional output in this developmental context.
Reason: Downstream developmental consequence of the core CSL transcription factor activity. Morpholinos in these studies may target both rbpj paralogs; the curator's annotation is not disputed.
Supporting Evidence:
file:DANRE/rbpjb/rbpjb-deep-research-falcon.md
The available literature confirms this paralog pair but rarely distinguishes their individual biochemical or developmental
GO:0072149 podocyte cell fate commitment
IGI
PMID:21871448
Wt1a, Foxc1a, and the Notch mediator Rbpj physically interac...
KEEP AS NON CORE
Summary: Podocyte cell fate commitment (IGI with wt1a/foxc1a; O'Brien et al. 2011).
Reason: Developmental context of Notch/Rbpj transcriptional activity.
Supporting Evidence:
PMID:21871448
Wt1a, Foxc1a, and Rbpj can physically interact with each other, whereas only Rbpj binds to the Notch intracellular domain (NICD)
GO:0072149 podocyte cell fate commitment
IGI
PMID:21871448
Wt1a, Foxc1a, and the Notch mediator Rbpj physically interac...
KEEP AS NON CORE
Summary: Podocyte cell fate commitment (IGI with wt1a/foxc1a; O'Brien et al. 2011).
Reason: Developmental context of Notch/Rbpj transcriptional activity.
Supporting Evidence:
PMID:21871448
Wt1a, Foxc1a, and Rbpj can physically interact with each other, whereas only Rbpj binds to the Notch intracellular domain (NICD)

Core Functions

Sequence-specific DNA-binding transcription factor of the CSL family that binds RBPJ motifs in Notch target enhancers and, upon binding the Notch intracellular domain and Mastermind, activates Notch target gene transcription (repressing targets in the absence of NICD).

Supporting Evidence:
  • PMID:21871448
    Wt1a, Foxc1a, and Rbpj can physically interact with each other, whereas only Rbpj binds to the Notch intracellular domain (NICD)

References

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Suggested Questions for Experts

Q: What are the respective contributions of rbpja and rbpjb (Su(H)1/Su(H)2) to Notch target activation in the PSM, neural tube and vasculature, given that rbpja currently lacks an active UniProtKB entry?

Q: Does zebrafish Rbpjb recruit corepressors (e.g. SHARP/Mint homologs) to repress Notch targets in the absence of NICD?

Suggested Experiments

Experiment: Paralog-specific CRISPR mutants of rbpja and rbpjb with a Tp1/12xCSL Notch reporter to quantify each paralog's contribution to Notch target activation.

Experiment: ChIP-seq of tagged Rbpjb in somitogenesis-stage embryos to map direct targets (her1, her7, dlc, cyp26a1).

Deep Research

Falcon

(rbpjb-deep-research-falcon.md)

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πŸ“š Additional Documentation

Notes

(rbpjb-notes.md)

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