Notch signaling pathway (WP798)

Gallus gallus

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:
last edited


Thomas Kelder , Daniela Digles , Lauren J. Dupuis , and Eric Weitz

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Gallus gallus



Pathway Ontology: Notch signaling pathway


Label Type Compact Identifier Comment
MAML1 GeneProduct ensembl:ENSGALG00000005929
PSN2_CHICK GeneProduct ensembl:ENSGALG00000009073
APH1B GeneProduct ensembl:ENSGALG00000002578
RBPSUHL GeneProduct ensembl:ENSGALG00000003952
DVL3 GeneProduct ensembl:ENSGALG00000008414
O42347_CHICK GeneProduct ensembl:ENSGALG00000011696
HDAC1_CHICK GeneProduct ensembl:ENSGALG00000003297
JAG1 GeneProduct ensembl:ENSGALG00000009020
DTX2 GeneProduct ensembl:ENSGALG00000001905
NP_990166.1 GeneProduct ensembl:ENSGALG00000009300
LFNG_CHICK GeneProduct ensembl:ENSGALG00000004284
NCOR2 GeneProduct ensembl:ENSGALG00000003120
CREBBP GeneProduct ensembl:ENSGALG00000007762
DTX3L GeneProduct ensembl:ENSGALG00000012075
NP_989660.1 GeneProduct ensembl:ENSGALG00000003369
APH1A GeneProduct ncbigene:769986
NP_001008682.1 GeneProduct ensembl:ENSGALG00000016427
Q9DEC9_CHICK GeneProduct ensembl:ENSGALG00000002922
NP_990304.1 GeneProduct ensembl:ENSGALG00000011182
RBPJ GeneProduct ncbigene:422802 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. 
NP_001026044.1 GeneProduct ensembl:ENSGALG00000001600
DLL4 GeneProduct ensembl:ENSGALG00000008514
RFNG_CHICK GeneProduct ensembl:ENSGALG00000002841
NP_001004413.2 GeneProduct ensembl:ENSGALG00000009147
NOTCH1 GeneProduct ensembl:ENSGALG00000002375
KCNJ5 GeneProduct ncbigene:395925
NP_001012908.1 GeneProduct ensembl:ENSGALG00000015718
Q5ZLZ2_CHICK GeneProduct ensembl:ENSGALG00000002739
MFNG GeneProduct ensembl:ENSGALG00000012442
NP_001012713.1 GeneProduct ensembl:ENSGALG00000001141
HES1 GeneProduct ncbigene:395128
Q9IAK2_CHICK GeneProduct ensembl:ENSGALG00000010835
PSN1_CHICK GeneProduct ensembl:ENSGALG00000009320
MAML3 GeneProduct ensembl:ENSGALG00000009809
CTBP2 GeneProduct ensembl:ENSGALG00000013465
Q90ZI1_CHICK GeneProduct ensembl:ENSGALG00000011278
HDAC2_CHICK GeneProduct ensembl:ENSGALG00000014991


  1. The ins and outs of notch signaling. Weinmaster G. Mol Cell Neurosci. 1997;9(2):91–102. PubMed Europe PMC Scholia