Notch Signaling Pathway (Danio rerio)

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1MAPK signaling pathwayS2Ras/Mapg-secretasecomplexco-repressor complexgene expressionDNANICDS3Notch Intracellular DomainDLL1aph1bJAG2mfnglfngSKIPrfngzgc:66440zgc:136929LOC571888JAG1psen2kat2bnumbhdac1DVL1B8A4R6_DANREDVL3ctbp2numblncor2kat2anotch2TNFPTCRAAPH1Advl2HES5DLL3LOC100148345DTX4B8JI71_DANREdll4NCSTNHDAC2zgc:194800LOC568641her6LOC100148437psen1ADAM17wu:fc10f03rbpjbMAML1NOTCH1CREBBP


The Notch signaling pathway is an evolutionarily conserved, intercellular signaling mechanism essential for proper embryonic development in all metazoan organisms in the Animal kingdom. The Notch proteins (Notch1-Notch4 in vertebrates) are single-pass receptors that are activated by the Delta (or Delta-like) and Jagged/Serrate families of membrane-bound ligands. They are transported to the plasma membrane as cleaved, but otherwise intact polypeptides. Interaction with ligand leads to two additional proteolytic cleavages that liberate the Notch intracellular domain (NICD) from the plasma membrane. The NICD translocates to the nucleus, where it forms a complex with the DNA binding protein CSL, displacing a histone deacetylase (HDAc)-co-repressor (CoR) complex from CSL. Components of an activation complex, such as MAML1 and histone acetyltransferases (HATs), are recruited to the NICD-CSL complex, leading to the transcriptional activation of Notch target genes.

Source: KEGG

Adapted from KEGG:


This pathway was inferred from Homo sapiens pathway WP268(r29891) with a 65% conversion rate.

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Ontology Terms



  1. Weinmaster G; ''The ins and outs of notch signaling.''; Mol Cell Neurosci, 1997 PubMed Europe PMC Scholia


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68633view04:46, 6 July 2013MaintBotUpdated to 2013 gpml schema
67522view11:20, 26 June 2013DdiglesOntology Term : 'Notch signaling pathway' added !
58787view22:45, 20 February 2013MaintBotUpdated Ensembl and UniProt data source
40799view22:16, 1 March 2011MaintBotRemoved redundant pathway information and comments
35629view16:12, 12 February 2010Thomasadded literature
35628view16:11, 12 February 2010ThomasModified description
34188view21:24, 9 December 2009MaintBotAutomatic update of empty xrefs
32331view13:29, 15 August 2009MaintBotFixed text labels
31940view12:58, 14 August 2009MaintBotFixed group labels
31370view20:37, 13 August 2009MaintBotFixed text labels
31068view01:28, 30 July 2009MaintBotNew pathway

External references


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NameTypeDatabase referenceComment
B8A4R6_DANREGeneProductENSDARG00000079552 (Ensembl)
B8JI71_DANREGeneProductENSDARG00000079519 (Ensembl)
DVL3GeneProduct80972 (Entrez Gene)
HES5GeneProduct359836 (Entrez Gene)
JAG2GeneProduct140422 (Entrez Gene)
LOC100148345GeneProductENSDARG00000062840 (Ensembl)
LOC100148437GeneProductENSDARG00000075504 (Ensembl)
LOC568641GeneProductENSDARG00000074148 (Ensembl)
LOC571888GeneProduct571888 (Entrez Gene)
MAML1GeneProductENSDARG00000076466 (Ensembl)
NCSTNGeneProductENSDARG00000073668 (Ensembl)
aph1bGeneProductENSDARG00000005612 (Ensembl)
ctbp2GeneProductENSDARG00000044062 (Ensembl)
dll4GeneProductENSDARG00000070425 (Ensembl)
dvl2GeneProductENSDARG00000056184 (Ensembl)
hdac1GeneProductENSDARG00000015427 (Ensembl)
her6GeneProductENSDARG00000006514 (Ensembl)
kat2aGeneProductENSDARG00000006017 (Ensembl)
kat2bGeneProductENSDARG00000062634 (Ensembl)
lfngGeneProductENSDARG00000037879 (Ensembl)
mfngGeneProductENSDARG00000042925 (Ensembl)
ncor2GeneProductENSDARG00000000966 (Ensembl)
notch2GeneProductENSDARG00000043130 (Ensembl)
numbGeneProductENSDARG00000027279 (Ensembl)
numblGeneProductENSDARG00000024043 (Ensembl)
psen1GeneProductENSDARG00000004870 (Ensembl)
psen2GeneProductENSDARG00000015540 (Ensembl)
rbpjbGeneProduct563306 (Entrez Gene) aka RBP-Jkappa aka CBF1. Serves as a co-factor for the processed notch receptor after translocation to the nucleus to activate down-stream notch transcription. PMID: 15187023. In the nucleus, NIC (processed notch) regulates transcription through association with the DNA-binding protein RBP-J (also known as CBF1, KBF2, or CSL). The primary gene targets of RBP-J include members of the hairy and enhancer of split (HES) and hairy related transcription factor (HRT) families of basic-helix-loop-helix transcriptional repressors. In the absence of NIC, RBP-J actively represses transcription by way of recruitment of a corepressor complex.8 Nuclear translocation of NIC leads to dissociation of repressor proteins from RBP-J and formation of a coactivator complex.9-13. PMID: 15194757. RBP-J is a downstream target of the Notch pathway, a conserved signal transduction pathway that is important in development and cell fate determination (43). The intracellular domain (ICD) of activated Notch is released from the membrane through proteolytic cleavage and is translocated to the nucleus, where it is directed to target promoters through interaction with RBP-J (47, 68). RBP-J is a repressor in the ground state; its interaction with Notch ICD relieves this repression and turns on target genes. Interestingly, KSHV is not the only virus that has parasitized this pathway. Several viral transcription factors, e.g., EBNA2 and EBNA3 of Epstein-Barr virus and the 13S isoform of adenovirus E1A, are known to bind and activate target genes via RBP-J interactions (1, 22, 25, 26, 29). In all cases, the viral proteins target the same (central repressive) domain of RBP-J that is targeted by Notch, although KSHV RTA is capable of interactions with an additional region of RBP-J in vitro (33). RBP-J can bind RTA and recruit it to its cognate recognition site; when this happens, the activation function of RTA can relieve RBP-J-mediated repression and upregulate expression of the targeted gene. EMSA studies reveal that both sites A and C can bind to RBP-J; sequence inspection reveals that site A is a novel functional variant of known RBP-J recognition sites. 

rfngGeneProductENSDARG00000019746 (Ensembl)
wu:fc10f03GeneProductENSDARG00000052139 (Ensembl)
zgc:136929GeneProductENSDARG00000019213 (Ensembl)
zgc:194800GeneProductENSDARG00000032933 (Ensembl)
zgc:66440GeneProductENSDARG00000025766 (Ensembl)

Annotated Interactions

No annotated interactions
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