Notch Signaling Pathway (Rattus norvegicus)

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1NICDMAPK signaling pathwayRas/Mapg-secretasecomplexS2co-repressor complexS3gene expressionNotch Intracellular DomainDNACrebbpRBP-JHDAC1Jag2NOTC1_RATAdam17NP_001102074.1Kcnj5DVL1Dll3NM_001108334.1RFNGAPH1BNcstnNotch2Notch4Aph1aPcafNumblLOC688965LfngCtbp2PSEN2RGD1566181_predictedNP_001101230.1Jag1Ctbp1NP_001102523.1Psen1DTX1PTCRAHes1TnfDll1NP_001100520.1Inpp5kNotch3HDAC2Hes5Dvl2NP_001101145.1Dtx4NP_001100551.1Q2LC87_RATNP_001100467.1Mfng


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.


This pathway was inferred from Homo sapiens pathway WP268(r29891) with a 82% 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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109391view15:59, 16 March 2020L DupuisConverted interactions to graphical lines
104999view04:49, 28 June 2019KhanspersModified description
69408view19:01, 8 July 2013MaintBotUpdated to 2013 gpml schema
67525view11:21, 26 June 2013DdiglesOntology Term : 'Notch signaling pathway' added !
61491view19:24, 11 April 2013MaintBotReverted to version '18:34, 21 February 2013' by MaintBot
61463view03:17, 11 April 2013MushtongPeriodical save, work in progress
58961view18:34, 21 February 2013MaintBotUpdated Ensembl and UniProt data source
41730view02:39, 2 March 2011MaintBotRemoved redundant pathway information and comments
35613view15:59, 12 February 2010Thomasadded literature
35612view15:58, 12 February 2010ThomasModified description
34105view19:21, 9 December 2009MaintBotAutomatic update of empty xrefs
32451view17:22, 15 August 2009MaintBotFixed text labels
32132view13:55, 14 August 2009MaintBotFixed group labels
31469view21:19, 13 August 2009MaintBotFixed text labels
30973view00:50, 30 July 2009MaintBotConverted from Homo sapiens
21766view11:32, 14 November 2008MaintBot[[Pathway:Rattus norvegicus:Notch signaling KEGG]] moved to [[Pathway:WP517]]: Moved to stable identifier
8282view13:46, 7 January 2008MaintBot[[Pathway:Rat:Notch signaling KEGG]] moved to [[Pathway:Rattus norvegicus:Notch signaling KEGG]]: Renaming species
7761view16:16, 18 December 2007MaintBotfixed category names
7282view12:41, 4 November 2007MaintBotAdded categories to GPML
6578view22:20, 22 May 2007169.230.77.174gpml file for [[Rat:Notch_signaling_KEGG]]

External references


View all...
NameTypeDatabase referenceComment
APH1BGeneProduct300802 (Entrez Gene)
Adam17GeneProductENSRNOG00000007503 (Ensembl)
Aph1aGeneProductENSRNOG00000023816 (Ensembl)
CrebbpGeneProductENSRNOG00000005330 (Ensembl)
Ctbp1GeneProductENSRNOG00000005428 (Ensembl)
Ctbp2GeneProductENSRNOG00000017326 (Ensembl)
DVL1GeneProduct83721 (Entrez Gene)
Dll1GeneProductENSRNOG00000014667 (Ensembl)
Dll3GeneProductENSRNOG00000019338 (Ensembl)
Dtx4GeneProductENSRNOG00000021086 (Ensembl)
Dvl2GeneProductENSRNOG00000017915 (Ensembl)
HDAC1GeneProduct297893 (Entrez Gene)
HDAC2GeneProductENSRNOG00000038246 (Ensembl)
Hes1GeneProductENSRNOG00000001720 (Ensembl)
Hes5GeneProductENSRNOG00000013850 (Ensembl)
Inpp5kGeneProductENSRNOG00000004041 (Ensembl)
Jag1GeneProductENSRNOG00000007443 (Ensembl)
Jag2GeneProductENSRNOG00000013927 (Ensembl)
Kcnj5GeneProduct29713 (Entrez Gene)
LOC688965GeneProductENSRNOG00000001432 (Ensembl)
LfngGeneProductENSRNOG00000001250 (Ensembl)
MfngGeneProductENSRNOG00000008133 (Ensembl)
NM_001108334.1GeneProductENSRNOG00000001004 (Ensembl)
NOTC1_RATGeneProductENSRNOG00000019322 (Ensembl)
NP_001100467.1GeneProductENSRNOG00000003268 (Ensembl)
NP_001100520.1GeneProductENSRNOG00000018364 (Ensembl)
NP_001100551.1GeneProductENSRNOG00000001708 (Ensembl)
NP_001101145.1GeneProductENSRNOG00000013333 (Ensembl)
NP_001101230.1GeneProductENSRNOG00000014011 (Ensembl)
NP_001102074.1GeneProductENSRNOG00000026295 (Ensembl)
NP_001102523.1GeneProductENSRNOG00000023400 (Ensembl)
NcstnGeneProductENSRNOG00000005355 (Ensembl)
Notch2GeneProductENSRNOG00000018835 (Ensembl)
Notch3GeneProductENSRNOG00000004346 (Ensembl)
Notch4GeneProductENSRNOG00000000442 (Ensembl)
NumblGeneProductENSRNOG00000020867 (Ensembl)
PSEN2GeneProduct81751 (Entrez Gene)
PTCRAGeneProduct116462 (Entrez Gene)
PcafGeneProductENSRNOG00000011871 (Ensembl)
Psen1GeneProductENSRNOG00000009110 (Ensembl)
Q2LC87_RATGeneProductENSRNOG00000009653 (Ensembl)
RBP-JGeneProductaka 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. 

RFNGGeneProduct60433 (Entrez Gene)
RGD1566181_predictedGeneProductENSRNOG00000005129 (Ensembl)
TnfGeneProductENSRNOG00000000837 (Ensembl)

Annotated Interactions

No annotated interactions
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