KEGG   PATHWAY: hsa04330Help
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
BRITE hierarchy
Pathway map
Notch signaling pathway
hsa04330

All organismsOrtholog table
Module
Notch signaling [PATH:hsa04330]
Disease
H00078  
Frontotemporal lobar degeneration (FTLD)
H00409  
Type II diabetes mellitus
H00517  
Spondylocostal dysostosis (SCD)
H00536  
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL)
H00549  
Tetralogy of Fallot
H00551  
Alagille syndrome
H00554  
Bicuspid aortic valve
H00623  
Hajdu-Cheney syndrome
H00681  
Acne inversa
H01508  
Salivary gland cancer
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 (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)
D10353  
Demcizumab (USAN/INN)
D10460  
Enoticumab (USAN/INN)
Other DBs
BSID: 
GO: 
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 1 [KO:K06052]
3714  
JAG2; jagged 2 [KO:K06052]
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 1 [KO:K02599]
4853  
NOTCH2; notch 2 [KO:K02599]
4854  
NOTCH3; notch 3 [KO:K02599]
4855  
NOTCH4; notch 4 [KO:K02599]
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]
171558  
PTCRA; pre T-cell antigen receptor alpha [KO:K06056]
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]
113878  
DTX2; deltex 2, E3 ubiquitin ligase [KO:K06058] [EC:2.3.2.27]
151636  
DTX3L; deltex 3 like, E3 ubiquitin ligase [KO:K06058] [EC:2.3.2.27]
1840  
DTX1; deltex 1 [KO:K06058] [EC:2.3.2.27]
196403  
DTX3; deltex 3, E3 ubiquitin ligase [KO:K06058] [EC:2.3.2.27]
23220  
DTX4; deltex 4, E3 ubiquitin ligase [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]
1488  
CTBP2; C-terminal binding protein 2 [KO:K04496]
9612  
NCOR2; nuclear receptor corepressor 2 [KO:K06065]
9541  
CIR1; corepressor interacting with RBPJ, 1 [KO:K06066]
3065  
HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
3066  
HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
Reference
  Authors
Hansson EM, Lendahl U, Chapman G.
  Title
Notch signaling in development and disease.
  Journal
Semin Cancer Biol 14:320-8 (2004)
Reference
  Authors
Callahan R, Egan SE.
  Title
Notch signaling in mammary development and oncogenesis.
  Journal
J Mammary Gland Biol Neoplasia 9:145-63 (2004)
Reference
  Authors
Zweidler-McKay PA, Pear WS.
  Title
Notch and T cell malignancy.
  Journal
Semin Cancer Biol 14:329-40 (2004)
Reference
  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)
Reference
  Authors
Tsukumo S, Yasutomo K.
  Title
Notch governing mature T cell differentiation.
  Journal
J Immunol 173:7109-13 (2004)
Reference
  Authors
Haltiwanger RS.
  Title
Regulation of signal transduction pathways in development by glycosylation.
  Journal
Curr Opin Struct Biol 12:593-8 (2002)
Reference
  Authors
Koo EH, Kopan R.
  Title
Potential role of presenilin-regulated signaling pathways in sporadic neurodegeneration.
  Journal
Nat Med 10 Suppl:S26-33 (2004)
Reference
  Authors
Okano H, Imai T, Okabe M.
  Title
Musashi: a translational regulator of cell fate.
  Journal
J Cell Sci 115:1355-9 (2002)
Reference
  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)
Reference
  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)
Reference
  Authors
Cooper MT, Bray SJ.
  Title
Frizzled regulation of Notch signalling polarizes cell fate in the Drosophila eye.
  Journal
Nature 397:526-30 (1999)
Reference
  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)
KO pathway
 

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