Notch signaling pathway (WP912)

Pan troglodytes

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:


Thomas Kelder , Daniela Digles , Andra Waagmeester , and Eric Weitz


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Pan troglodytes



Pathway Ontology

Notch signaling pathway


Label Type Compact URI Comment
RBPSUHL GeneProduct ensembl:ENSPTRG00000013542
PTCRA GeneProduct ensembl:ENSPTRG00000018176
HDAC2 GeneProduct ensembl:ENSPTRG00000018519
XR_020433.1 GeneProduct ensembl:ENSPTRG00000015827
XR_021983.1 GeneProduct ensembl:ENSPTRG00000003035
CREBBP GeneProduct ensembl:ENSPTRG00000007710
KAT2A GeneProduct ensembl:ENSPTRG00000009192
KAT2B GeneProduct ensembl:ENSPTRG00000014685
DLL1 GeneProduct ensembl:ENSPTRG00000018824
XR_020078.1 GeneProduct ensembl:ENSPTRG00000010975
DLL4 GeneProduct ensembl:ENSPTRG00000006937
JAG1 GeneProduct ensembl:ENSPTRG00000013250
JAG2 GeneProduct ensembl:ENSPTRG00000006784
LFNG GeneProduct ensembl:ENSPTRG00000018864
MFNG GeneProduct ensembl:ENSPTRG00000014335
RFNG GeneProduct ensembl:ENSPTRG00000009787
NOTCH2 GeneProduct ensembl:ENSPTRG00000001182
XR_024606.1 GeneProduct ensembl:ENSPTRG00000010617
NOTCH4 GeneProduct ensembl:ENSPTRG00000034379
ADAM17 GeneProduct ensembl:ENSPTRG00000011640
APH1A GeneProduct ensembl:ENSPTRG00000001250
APH1B GeneProduct ensembl:ENSPTRG00000007146
TNFA_PANTR GeneProduct ensembl:ENSPTRG00000017965
PSEN1 GeneProduct ensembl:ENSPTRG00000006510
PSEN2 GeneProduct ensembl:ENSPTRG00000002052
NCSTN GeneProduct ensembl:ENSPTRG00000001550
DVL1_PANTR GeneProduct ensembl:ENSPTRG00000000025
DVL2 GeneProduct ensembl:ENSPTRG00000008665
DVL3 GeneProduct ensembl:ENSPTRG00000015681
NUMB GeneProduct ensembl:ENSPTRG00000006513
NUMBL GeneProduct ensembl:ENSPTRG00000011003
DTX1 GeneProduct ensembl:ENSPTRG00000005480
DTX2 GeneProduct ensembl:ENSPTRG00000019326
DTX3 GeneProduct ensembl:ENSPTRG00000005141
DTX4 GeneProduct ensembl:ENSPTRG00000003688
DTX3L GeneProduct ensembl:ENSPTRG00000015295
RBPJ GeneProduct ncbigene:461152 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. 
MAML1 GeneProduct ensembl:ENSPTRG00000033932
NCOR2 GeneProduct ensembl:ENSPTRG00000005613
HES1 GeneProduct ensembl:ENSPTRG00000015753
HES5 GeneProduct ensembl:ENSPTRG00000024233
NOTCH1 GeneProduct ensembl:ENSPTRG00000021561
MAML3 GeneProduct ensembl:ENSPTRG00000016459
HDAC1 GeneProduct ensembl:ENSPTRG00000000480
KCNJ5 GeneProduct ncbigene:451660
SKIP GeneProduct ensembl:ENSPTRG00000008525


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