Notch signaling pathway (WP1029)

Bos taurus

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: [http://www.genome.jp/kegg-bin/show_pathway?org_name=map&mapno=04330&show_description=show KEGG] Adapted from KEGG: http://www.genome.jp/kegg-bin/show_pathway?org_name=hsa&mapno=04330

Authors

Thomas Kelder , Daniela Digles , Martina Summer-Kutmon , Eric Weitz , and Egon Willighagen

Activity

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Organisms

Bos taurus

Communities

Annotations

Pathway Ontology

Notch signaling pathway

Participants

Label Type Compact URI Comment
RBPJL GeneProduct ensembl:ENSBTAG00000011283 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000124232
PTCRA GeneProduct ensembl:ENSBTAG00000017097 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000171611
HDAC2 GeneProduct ensembl:ENSBTAG00000011849 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000196591
CTBP1 GeneProduct ensembl:ENSBTAG00000008480 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000159692
CTBP2 GeneProduct ensembl:ENSBTAG00000003397 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000175029
CREBBP GeneProduct ensembl:ENSBTAG00000026403 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000005339
KAT2A GeneProduct ensembl:ENSBTAG00000044019 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000108773
PCAF GeneProduct ensembl:ENSBTAG00000000746 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000114166
DLL1 GeneProduct ensembl:ENSBTAG00000031476 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000198719
DLL3 GeneProduct ensembl:ENSBTAG00000010483 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000090932
DLL4 GeneProduct ensembl:ENSBTAG00000010361 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000128917
JAG1 GeneProduct ensembl:ENSBTAG00000012817 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000101384
JAG2 GeneProduct ensembl:ENSBTAG00000007319 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000184916
LFNG GeneProduct ensembl:ENSBTAG00000040361 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000106003
MFNG GeneProduct ensembl:ENSBTAG00000015043 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000100060
RFNG GeneProduct ensembl:ENSBTAG00000011575 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000169733
NOTCH2 GeneProduct ensembl:ENSBTAG00000007909 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000134250
NOTCH3 GeneProduct ensembl:ENSBTAG00000043971 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000074181
NOTCH4 GeneProduct ensembl:ENSBTAG00000025424 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000204301
ADAM17 GeneProduct ensembl:ENSBTAG00000001141 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000151694
APH1A GeneProduct ensembl:ENSBTAG00000021482 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000117362
APH1B GeneProduct ensembl:ENSBTAG00000010641 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000138613
PSEN1 GeneProduct ensembl:ENSBTAG00000011757 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000080815
PSEN2 GeneProduct ensembl:ENSBTAG00000013197 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000143801
NCSTN GeneProduct ensembl:ENSBTAG00000004334 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000162736
DVL1 GeneProduct ensembl:ENSBTAG00000010696 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000107404
DVL2 GeneProduct ensembl:ENSBTAG00000003075 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000004975
DVL3 GeneProduct ensembl:ENSBTAG00000019336 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000161202
NUMB GeneProduct ensembl:ENSBTAG00000011683 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000133961
NUMBL GeneProduct ensembl:ENSBTAG00000019461 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000105245
DTX1 GeneProduct ensembl:ENSBTAG00000016738 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000135144
DTX2 GeneProduct ensembl:ENSBTAG00000001470 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000091073
DTX3 GeneProduct ensembl:ENSBTAG00000018002 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000178498
DTX4 GeneProduct ensembl:ENSBTAG00000004046 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000110042
DTX3L GeneProduct ensembl:ENSBTAG00000009933 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000163840
RBPJ GeneProduct ensembl:ENSBTAG00000003602 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. 
 
HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3516
MAML1 GeneProduct ensembl:ENSBTAG00000047633 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000161021
NCOR2 GeneProduct ensembl:ENSBTAG00000024603 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000196498
HES1 GeneProduct ensembl:ENSBTAG00000000569 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000114315
HES5 GeneProduct ensembl:ENSBTAG00000002483 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000197921
NOTCH1 GeneProduct ensembl:ENSBTAG00000022799 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000148400
MAML3 GeneProduct ensembl:ENSBTAG00000011373 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000196782
HDAC1 GeneProduct ensembl:ENSBTAG00000012698 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000116478
KCNJ5 GeneProduct ensembl:ENSBTAG00000006902 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3762
INPP5K GeneProduct ensembl:ENSBTAG00000011479 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000132376

References

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