Canonical and Non-canonical Notch signaling (Homo sapiens)

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1CytoplasmSignal sending cellLigandsCanonical target genesSignal receiving cellNOTCH non-canonical targetsNucleusNOTCH extra-cellular domainNOTCH intra-cellular domainDLL1MAML3NOTCH2RBPJDLL4MAML1NF-kB PathwayPSEN1DLK1LEF1NOTCH1HEY1IKKaNOTCH3JAG2NICDHES1JAG1UnknownADAM10Cell AdhesionPSEN2NB3RRASDLK2DNERMAGP2NOTCH4MAML2MAGP1DLL3NECDNECDNICDNICDNICDNICDNICDNICD


This pathway is based on figure 1 of "Alteration of Notch signaling in skeletal development and disease" (see bibliography). In the NOTCH signaling pathway, mammals have 11 ligands (JAG, DLL, DLK, etc.) and 4 NOTCH receptors (NOTCH1,2,3,4). The pathway is activated by the interaction between a ligand in a ligand expressing cell and a NOTCH receptor in an adjacent, receptor expressing cell. At this point, proteases (ADAM10 and PSEN1/2) cleave the intracellular domain (NICD) of the NOTCH protein from the extracellular domain (NECD). In the canonical pathway, NICD travels into the nucleus where it forms a transcription complex with other proteins (RBPJ and MAML1,2,3). This transcriptional complex regulates the transcription of downstream canonical target genes, such as HES1 and HEY1. In the non-canonical pathway, otherwise known as RBPJ-independent NOTCH signaling, NOTCH can activate through R-Ras to promote cell adhesion. Alternatively, NOTCH may interact with IKKa in the NF-kB pathway, or LEF1 in the Wnt pathway.While the role that the canonical NOTCH pathway plays in skeletal biology is well understood, our understanding of the role of the non-canonical pathway remains primitive.

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Ontology Terms



  1. Tao J, Chen S, Lee B; ''Alteration of Notch signaling in skeletal development and disease.''; Ann N Y Acad Sci, 2010 PubMed Europe PMC Scholia


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110756view15:31, 2 June 2020EgonwAdded missing @Type annotation
110724view14:37, 29 May 2020EveloFixed unknonw datanodes, we should still look at the fact that NICD is actually a subpeptide
90027view19:36, 8 October 2016AlexanderPicoModified description
89632view22:58, 21 September 2016Khanspersupdating PMID for ref
89631view22:46, 21 September 2016Khanspersadded label for nucleus and adjusted interactions
88837view14:59, 15 August 2016AAR&CoEdited Aesthetics and Added Label
88378view00:44, 2 August 2016AAR&CoOntology Term : 'Notch signaling pathway' added !
88377view00:44, 2 August 2016AAR&CoOntology Term : 'signaling pathway' added !
88376view00:40, 2 August 2016AAR&CoFixed Labels
88375view00:36, 2 August 2016AAR&CoEdited Labels
88372view21:34, 1 August 2016AAR&CoModify Datanode
88371view21:33, 1 August 2016AAR&CoPeriodical save, work in progress
88370view21:25, 1 August 2016AAR&CoModify Datanode
88368view21:14, 1 August 2016AAR&CoModify Datanode
88215view17:59, 31 July 2016AAR&CoModify Datanode
88214view17:53, 31 July 2016AAR&CoModify Datanode
87102view17:20, 18 July 2016AAR&CoFixed Unconnected Lines
86823view23:26, 11 July 2016AAR&CoModified description
86822view23:25, 11 July 2016AAR&CoNew pathway

External references


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NameTypeDatabase referenceComment
ADAM10GeneProductENSG00000137845 (Ensembl)
Cell AdhesionPathwayIdentifier Not Found
DLK1GeneProductENSG00000185559 (Ensembl)
DLK2GeneProductENSG00000171462 (Ensembl)
DLL1GeneProductENSG00000198719 (Ensembl)
DLL3GeneProductENSG00000090932 (Ensembl)
DLL4GeneProductENSG00000128917 (Ensembl)
DNERGeneProductENSG00000187957 (Ensembl)
HES1GeneProductENSG00000114315 (Ensembl)
HEY1GeneProductENSG00000164683 (Ensembl)
IKKaGeneProductENSG00000213341 (Ensembl)
JAG1GeneProductENSG00000101384 (Ensembl)
JAG2GeneProductENSG00000184916 (Ensembl)
LEF1GeneProductENSG00000138795 (Ensembl)
MAGP1GeneProductENSG00000140259 (Ensembl)
MAGP2 GeneProductENSG00000117122 (Ensembl)
MAML1GeneProductENSG00000161021 (Ensembl)
MAML2GeneProductENSG00000184384 (Ensembl)
MAML3GeneProductENSG00000196782 (Ensembl)
NB3GeneProductENSG00000134115 (Ensembl)
NECDProteinO00548 (Uniprot-TrEMBL)
NF-kB PathwayPathwayWP3545 (WikiPathways)
NICDProteinP46531 (Uniprot-TrEMBL)
NOTCH1GeneProductENSG00000148400 (Ensembl)
NOTCH2GeneProductENSG00000134250 (Ensembl)
NOTCH3GeneProductENSG00000074181 (Ensembl)
NOTCH4GeneProductENSG00000204301 (Ensembl)
PSEN1GeneProductENSG00000080815 (Ensembl)
PSEN2GeneProductENSG00000143801 (Ensembl)
RBPJGeneProductENSG00000168214 (Ensembl)
RRASGeneProductENSG00000126458 (Ensembl)
UnknownPathwayIdentifier Not Found

Annotated Interactions

No annotated interactions

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