Notch Signaling Pathway (Mus musculus)

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1NICDDNAgene expressionNotch Intracellular DomainRas/MapMAPK signaling pathwayS2co-repressor complexS3Jag1Adam17Ctbp1Hdac1Dvl1Notch2Dvl2Aph1aHdac2PCAFPsen1Psen2Notch3NcstnMfngSKIPTnfLOC330129GCN5L2RBP-JRBPSUHLCIRAph1bHes5Ctbp2Dvl3Maml1Jag2Dtx4Notch1Dll3Dtx2Hes1Dll1Ncor2Notch4LfngNumbRfngMaml3Dtx1Dll4Dtx3lDtx3PtcraCrebbpNumbl


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.

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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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104994view04:24, 28 June 2019KhanspersModified description
79679view12:38, 4 April 2015EgonwThe 'LOC330129' identifier is not found in BridgeDb and not in Entrez.
78440view10:26, 7 January 2015MaintBotadded missing graphIds
74445view07:33, 20 April 2014EgonwAdded the PubMed 9245493 from scratch, hoping it will now show up in the publist properly.
74444view07:30, 20 April 2014EgonwFixed a PubMed ID.
71312view17:14, 17 October 2013MaintBotAutomated update of data sources
69810view14:29, 11 July 2013Mkutmonfixing unconnected lines
69070view18:08, 8 July 2013MaintBotUpdated to 2013 gpml schema
67524view11:20, 26 June 2013DdiglesOntology Term : 'Notch signaling pathway' added !
41252view00:20, 2 March 2011MaintBotRemoved redundant pathway information and comments
40101view11:08, 8 February 2011Thomasfixed several gene annotations
35611view15:58, 12 February 2010Thomasconnected lines
35610view15:56, 12 February 2010Thomasadded literature
35609view15:56, 12 February 2010ThomasModified description
33382view14:39, 30 November 2009MaintBotRemoved group label
32984view00:06, 30 September 2009MaintBotadded xrefs and connectors
32983view23:59, 29 September 2009MaintBotPeriodical save, work in progress
29892view11:18, 9 June 2009Thomasupdated ensembl references
20739view11:29, 14 November 2008MaintBot[[Pathway:Mus musculus:Notch signaling KEGG]] moved to [[Pathway:WP29]]: Moved to stable identifier
8280view13:46, 7 January 2008MaintBot[[Pathway:Mouse:Notch signaling KEGG]] moved to [[Pathway:Mus musculus:Notch signaling KEGG]]: Renaming species
7760view16:16, 18 December 2007MaintBotfixed category names
7281view12:41, 4 November 2007MaintBotAdded categories to GPML
6478view22:19, 22 May 2007169.230.77.174gpml file for [[Mouse:Notch_signaling_KEGG]]

External references


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NameTypeDatabase referenceComment
Adam17GeneProduct11491 (Entrez Gene)
Aph1aGeneProduct226548 (Entrez Gene)
Aph1bGeneProduct208117 (Entrez Gene)
CIRGeneProduct66935 (Entrez Gene)
CrebbpGeneProduct12914 (Entrez Gene)
Ctbp1GeneProduct13016 (Entrez Gene)
Ctbp2GeneProduct13017 (Entrez Gene)
Dll1GeneProduct13388 (Entrez Gene)
Dll3GeneProduct13389 (Entrez Gene)
Dll4GeneProduct54485 (Entrez Gene)
Dtx1GeneProduct14357 (Entrez Gene)
Dtx2GeneProduct74198 (Entrez Gene)
Dtx3GeneProduct80904 (Entrez Gene)
Dtx3lGeneProduct209200 (Entrez Gene)
Dtx4GeneProduct207521 (Entrez Gene)
Dvl1GeneProduct13542 (Entrez Gene)
Dvl2GeneProduct13543 (Entrez Gene)
Dvl3GeneProduct13544 (Entrez Gene)
GCN5L2GeneProduct14534 (Entrez Gene)
Hdac1GeneProduct433759 (Entrez Gene)
Hdac2GeneProduct15182 (Entrez Gene)
Hes1GeneProduct15205 (Entrez Gene)
Hes5GeneProduct15208 (Entrez Gene)
Jag1GeneProduct16449 (Entrez Gene)
Jag2GeneProduct16450 (Entrez Gene)
LfngGeneProduct16848 (Entrez Gene)
Maml1GeneProduct103806 (Entrez Gene)
Maml3GeneProduct433586 (Entrez Gene)
MfngGeneProduct17305 (Entrez Gene)
Ncor2GeneProduct20602 (Entrez Gene)
NcstnGeneProduct59287 (Entrez Gene)
Notch1GeneProduct18128 (Entrez Gene)
Notch2GeneProduct18129 (Entrez Gene)
Notch3GeneProduct18131 (Entrez Gene)
Notch4GeneProduct18132 (Entrez Gene)
NumbGeneProduct18222 (Entrez Gene)
NumblGeneProduct18223 (Entrez Gene)
PCAFGeneProductQ9JHD1 (Uniprot-TrEMBL)
Psen1GeneProduct19164 (Entrez Gene)
Psen2GeneProduct19165 (Entrez Gene)
PtcraGeneProduct19208 (Entrez Gene)
RBP-JGeneProduct19664 (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.
RBPSUHLGeneProduct19668 (Entrez Gene)
RfngGeneProduct19719 (Entrez Gene)
SKIPGeneProduct66354 (Entrez Gene)
TnfGeneProduct21926 (Entrez Gene)

Annotated Interactions

No annotated interactions

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