Notch signaling pathway (Bos taurus)

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1S2DNAgene expressionS3g-secretasecomplexco-repressor complexRas/MapNICDNotch Intracellular DomainNOTCH3DVL1DLL1PCAFDTX3PSEN1CTBP1DTX4DVL2KAT2ALFNGNUMBLHDAC2DTX1PSEN2DTX2APH1AKCNJ5NUMBDLL4JAG2HDAC1PTCRACREBBPDVL3DLL3DTX3LMAPK signaling pathwayNOTCH4NOTCH1TNFRFNGHES1MFNGNCSTNADAM17RBPJAPH1BINPP5KNCOR2NOTCH2MAML3HES5CTBP2JAG1RBPJLMAML1


Description

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: http://www.genome.jp/kegg-bin/show_pathway?org_name=hsa&mapno=04330

Comments

HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP268(70096) with a 97.0% conversion rate.

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Ontology Terms

 

Bibliography

  1. Weinmaster G; ''The ins and outs of notch signaling.''; Mol Cell Neurosci, 1997 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
122565view10:31, 16 April 2022EgonwMade a pathway clickable
117568view11:21, 21 May 2021EweitzModified title
80806view15:26, 30 June 2015Mkutmonhomology conversion
67518view11:20, 26 June 2013DdiglesOntology Term : 'Notch signaling pathway' added !
63352view22:22, 9 May 2013MaintBotUpdated to 2013 gpml schema
58815view23:18, 20 February 2013MaintBotUpdated Ensembl and UniProt data source
40526view19:30, 1 March 2011MaintBotRemoved redundant pathway information and comments
35622view16:06, 12 February 2010Thomasadded literature
35620view16:04, 12 February 2010ThomasModified description
33768view00:05, 9 December 2009MaintBotAutomatic update of empty xrefs
32502view12:49, 17 August 2009MaintBotFixed text labels
32193view12:35, 15 August 2009MaintBotFixed text labels
31668view11:41, 14 August 2009MaintBotFixed group labels
31200view19:33, 13 August 2009MaintBotFixed text labels
30598view22:15, 29 July 2009MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ADAM17GeneProductENSBTAG00000001141 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000151694
APH1AGeneProductENSBTAG00000021482 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000117362
APH1BGeneProductENSBTAG00000010641 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000138613
CREBBPGeneProductENSBTAG00000026403 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000005339
CTBP1GeneProductENSBTAG00000008480 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000159692
CTBP2GeneProductENSBTAG00000003397 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000175029
DLL1GeneProductENSBTAG00000031476 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000198719
DLL3GeneProductENSBTAG00000010483 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000090932
DLL4GeneProductENSBTAG00000010361 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000128917
DTX1GeneProductENSBTAG00000016738 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000135144
DTX2GeneProductENSBTAG00000001470 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000091073
DTX3GeneProductENSBTAG00000018002 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000178498
DTX3LGeneProductENSBTAG00000009933 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000163840
DTX4GeneProductENSBTAG00000004046 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000110042
DVL1GeneProductENSBTAG00000010696 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000107404
DVL2GeneProductENSBTAG00000003075 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000004975
DVL3GeneProductENSBTAG00000019336 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000161202
HDAC1GeneProductENSBTAG00000012698 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000116478
HDAC2GeneProductENSBTAG00000011849 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000196591
HES1GeneProductENSBTAG00000000569 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000114315
HES5GeneProductENSBTAG00000002483 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000197921
INPP5KGeneProductENSBTAG00000011479 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000132376
JAG1GeneProductENSBTAG00000012817 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000101384
JAG2GeneProductENSBTAG00000007319 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000184916
KAT2AGeneProductENSBTAG00000044019 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000108773
KCNJ5GeneProductENSBTAG00000006902 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3762
LFNGGeneProductENSBTAG00000040361 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000106003
MAML1GeneProductENSBTAG00000047633 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000161021
MAML3GeneProductENSBTAG00000011373 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000196782
MAPK signaling pathwayPathwayWP382 (WikiPathways)
MFNGGeneProductENSBTAG00000015043 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000100060
NCOR2GeneProductENSBTAG00000024603 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000196498
NCSTNGeneProductENSBTAG00000004334 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000162736
NOTCH1GeneProductENSBTAG00000022799 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000148400
NOTCH2GeneProductENSBTAG00000007909 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000134250
NOTCH3GeneProductENSBTAG00000043971 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000074181
NOTCH4GeneProductENSBTAG00000025424 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000204301
NUMBGeneProductENSBTAG00000011683 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000133961
NUMBLGeneProductENSBTAG00000019461 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000105245
PCAFGeneProductENSBTAG00000000746 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000114166
PSEN1GeneProductENSBTAG00000011757 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000080815
PSEN2GeneProductENSBTAG00000013197 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000143801
PTCRAGeneProductENSBTAG00000017097 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000171611
RBPJGeneProductENSBTAG00000003602 (Ensembl)
  • 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
RBPJLGeneProductENSBTAG00000011283 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000124232
RFNGGeneProductENSBTAG00000011575 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000169733
TNFGeneProduct

Annotated Interactions

No annotated interactions
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