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KEGG   PATHWAY: hsa04330
Entry
hsa04330                    Pathway                                
Name
Notch signaling pathway - Homo sapiens (human)
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.
Class
Environmental Information Processing; Signal transduction
Pathway map
hsa04330  Notch signaling pathway
hsa04330

Network
  Element
N00086  Notch signaling pathway
N01478  Notch proteolytic activation
Drug
D06320  Vorinostat (JAN/USAN)
D06637  Romidepsin (JAN/USAN/INN)
D08859  Apratastat (USAN/INN)
D08869  Begacestat (USAN/INN)
D08870  Belinostat (USAN/INN)
D09010  Tarenflurbil (USAN/INN)
D09320  Aderbasib (USAN/INN)
D09338  Entinostat (JAN/USAN/INN)
D09357  Mocetinostat dihydrobromide (USAN)
D09377  Semagacestat (USAN/INN)
D09641  Mocetinostat (USAN/INN)
D09869  Avagacestat (USAN)
D10019  Panobinostat lactate (JAN)
D10060  Abexinostat (USAN)
D10084  Abexinostat hydrochloride (USAN)
D10319  Panobinostat (USAN/INN)
D10321  Quisinostat (USAN/INN)
D10322  Quisinostat hydrochloride (USAN)
D10460  Enoticumab (USAN/INN)
D10960  Nirogacestat (USAN/INN)
D10977  Remetinostat (USAN/INN)
D10981  Rovalpituzumab tesirine (USAN/INN)
D10993  Tucidinostat (JAN/USAN/INN)
D11117  Rovalpituzumab (USAN)
D11126  Navicixizumab (USAN/INN)
D11151  Crenigacestat (USAN/INN)
D11182  Tinostamustine (USAN/INN)
D11229  Brontictuzumab (USAN/INN)
D11442  Nanatinostat (USAN)
D11453  Nirogacestat hydrobromide (USAN)
D11642  Dilpacimab (USAN/INN)
D11775  Tarextumab (USAN/INN)
D12235  Osugacestat (USAN/INN)
D12551  Bocodepsin (USAN)
D12552  Bocodepsin besylate (USAN)
Other DBs
GO: 0007219
Organism
Homo sapiens (human) [GN:hsa]
Gene
10683  DLL3; delta like canonical Notch ligand 3 [KO:K06051]
28514  DLL1; delta like canonical Notch ligand 1 [KO:K06051]
54567  DLL4; delta like canonical Notch ligand 4 [KO:K06051]
182  JAG1; jagged canonical Notch ligand 1 [KO:K06052]
3714  JAG2; jagged canonical Notch ligand 2 [KO:K21635]
4242  MFNG; MFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase [KO:K05948] [EC:2.4.1.222]
3955  LFNG; LFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase [KO:K05948] [EC:2.4.1.222]
5986  RFNG; RFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase [KO:K05948] [EC:2.4.1.222]
4851  NOTCH1; notch receptor 1 [KO:K02599]
4853  NOTCH2; notch receptor 2 [KO:K20994]
4854  NOTCH3; notch receptor 3 [KO:K20995]
4855  NOTCH4; notch receptor 4 [KO:K20996]
11317  RBPJL; recombination signal binding protein for immunoglobulin kappa J region like [KO:K06053]
3516  RBPJ; recombination signal binding protein for immunoglobulin kappa J region [KO:K06053]
3280  HES1; hes family bHLH transcription factor 1 [KO:K06054]
388585  HES5; hes family bHLH transcription factor 5 [KO:K06055]
26508  HEYL; hes related family bHLH transcription factor with YRPW motif like [KO:K09091]
23462  HEY1; hes related family bHLH transcription factor with YRPW motif 1 [KO:K09091]
23493  HEY2; hes related family bHLH transcription factor with YRPW motif 2 [KO:K09091]
171558  PTCRA; pre T cell antigen receptor alpha [KO:K06056]
441478  NRARP; NOTCH regulated ankyrin repeat protein [KO:K26480]
1857  DVL3; dishevelled segment polarity protein 3 [KO:K02353]
1856  DVL2; dishevelled segment polarity protein 2 [KO:K02353]
1855  DVL1; dishevelled segment polarity protein 1 [KO:K02353]
8650  NUMB; NUMB endocytic adaptor protein [KO:K06057]
9253  NUMBL; NUMB like endocytic adaptor protein [KO:K06057]
83737  ITCH; itchy E3 ubiquitin protein ligase [KO:K05632] [EC:2.3.2.26]
113878  DTX2; deltex E3 ubiquitin ligase 2 [KO:K06058] [EC:2.3.2.27]
151636  DTX3L; deltex E3 ubiquitin ligase 3L [KO:K06058] [EC:2.3.2.27]
1840  DTX1; deltex E3 ubiquitin ligase 1 [KO:K06058] [EC:2.3.2.27]
196403  DTX3; deltex E3 ubiquitin ligase 3 [KO:K06058] [EC:2.3.2.27]
23220  DTX4; deltex E3 ubiquitin ligase 4 [KO:K06058] [EC:2.3.2.27]
6868  ADAM17; ADAM metallopeptidase domain 17 [KO:K06059] [EC:3.4.24.86]
5663  PSEN1; presenilin 1 [KO:K04505] [EC:3.4.23.-]
5664  PSEN2; presenilin 2 [KO:K04522] [EC:3.4.23.-]
55851  PSENEN; presenilin enhancer, gamma-secretase subunit [KO:K06170]
23385  NCSTN; nicastrin [KO:K06171]
51107  APH1A; aph-1 homolog A, gamma-secretase subunit [KO:K06172]
83464  APH1B; aph-1 homolog B, gamma-secretase subunit [KO:K06172]
55534  MAML3; mastermind like transcriptional coactivator 3 [KO:K06061]
84441  MAML2; mastermind like transcriptional coactivator 2 [KO:K06061]
9794  MAML1; mastermind like transcriptional coactivator 1 [KO:K06061]
1387  CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
2033  EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
8850  KAT2B; lysine acetyltransferase 2B [KO:K06062] [EC:2.3.1.48]
2648  KAT2A; lysine acetyltransferase 2A [KO:K06062] [EC:2.3.1.48]
22938  SNW1; SNW domain containing 1 [KO:K06063]
1487  CTBP1; C-terminal binding protein 1 [KO:K04496] [EC:1.1.1.428]
1488  CTBP2; C-terminal binding protein 2 [KO:K04496] [EC:1.1.1.428]
102723796  TLE7; TLE family member 7 [KO:K04497]
7088  TLE1; TLE family member 1, transcriptional corepressor [KO:K04497]
7089  TLE2; TLE family member 2, transcriptional corepressor [KO:K04497]
7090  TLE3; TLE family member 3, transcriptional corepressor [KO:K04497]
7091  TLE4; TLE family member 4, transcriptional corepressor [KO:K04497]
79816  TLE6; TLE family member 6, subcortical maternal complex member [KO:K04497]
9612  NCOR2; nuclear receptor corepressor 2 [KO:K06065]
9541  CIR1; corepressor interacting with RBPJ, CIR1 [KO:K06066]
23013  SPEN; spen family transcriptional repressor [KO:K25100]
3065  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
3066  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
342371  ATXN1L; ataxin 1 like [KO:K23616]
6310  ATXN1; ataxin 1 [KO:K23616]
Compound
C22528  Notch intracellular domain
Reference
PMID:15288257
  Authors
Hansson EM, Lendahl U, Chapman G.
  Title
Notch signaling in development and disease.
  Journal
Semin Cancer Biol 14:320-8 (2004)
DOI:10.1016/j.semcancer.2004.04.011
Reference
PMID:15300010
  Authors
Callahan R, Egan SE.
  Title
Notch signaling in mammary development and oncogenesis.
  Journal
J Mammary Gland Biol Neoplasia 9:145-63 (2004)
DOI:10.1023/B:JOMG.0000037159.63644.81
Reference
PMID:15288258
  Authors
Zweidler-McKay PA, Pear WS.
  Title
Notch and T cell malignancy.
  Journal
Semin Cancer Biol 14:329-40 (2004)
DOI:10.1016/j.semcancer.2004.04.012
Reference
PMID:15288260
  Authors
Wu L, Griffin JD.
  Title
Modulation of Notch signaling by mastermind-like (MAML) transcriptional co-activators and their involvement in tumorigenesis.
  Journal
Semin Cancer Biol 14:348-56 (2004)
DOI:10.1016/j.semcancer.2004.04.014
Reference
PMID:15585829
  Authors
Tsukumo S, Yasutomo K.
  Title
Notch governing mature T cell differentiation.
  Journal
J Immunol 173:7109-13 (2004)
DOI:10.4049/jimmunol.173.12.7109
Reference
PMID:12464310
  Authors
Haltiwanger RS.
  Title
Regulation of signal transduction pathways in development by glycosylation.
  Journal
Curr Opin Struct Biol 12:593-8 (2002)
DOI:10.1016/S0959-440X(02)00371-8
Reference
PMID:15272268
  Authors
Koo EH, Kopan R.
  Title
Potential role of presenilin-regulated signaling pathways in sporadic neurodegeneration.
  Journal
Nat Med 10 Suppl:S26-33 (2004)
DOI:10.1038/nm1065
Reference
PMID:11896183
  Authors
Okano H, Imai T, Okabe M.
  Title
Musashi: a translational regulator of cell fate.
  Journal
J Cell Sci 115:1355-9 (2002)
Reference
PMID:12417415
  Authors
Haltiwanger RS, Stanley P.
  Title
Modulation of receptor signaling by glycosylation: fringe is an O-fucose-beta1,3-N-acetylglucosaminyltransferase.
  Journal
Biochim Biophys Acta 1573:328-35 (2002)
DOI:10.1016/S0304-4165(02)00400-2
Reference
PMID:12015972
  Authors
Das G, Reynolds-Kenneally J, Mlodzik M.
  Title
The atypical cadherin Flamingo links Frizzled and Notch signaling in planar polarity establishment in the Drosophila eye.
  Journal
Dev Cell 2:655-66 (2002)
DOI:10.1016/S1534-5807(02)00147-8
Reference
PMID:10028969
  Authors
Cooper MT, Bray SJ.
  Title
Frizzled regulation of Notch signalling polarizes cell fate in the Drosophila eye.
  Journal
Nature 397:526-30 (1999)
DOI:10.1038/17395
Reference
PMID:12681948
  Authors
Tanigaki K, Kuroda K, Han H, Honjo T.
  Title
Regulation of B cell development by Notch/RBP-J signaling.
  Journal
Semin Immunol 15:113-9 (2003)
DOI:10.1016/S1044-5323(03)00008-3
Related
pathway
hsa04010  MAPK signaling pathway
KO pathway
ko04330   

  All links  
Network (2)   
   KEGG NETWORK (2)   
Genome (1)   
   KEGG GENOME (1)   
Gene (62)   
   KEGG GENES (62)   
All databases (65)   

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