InterPro : IPR022355

Name  Neurogenic locus Notch 4 Short Name  Notch_4
Type  Family Description  Notch cell surface receptors are large, single-pass type-1 transmembrane proteins found in a diverse range of metazoan species, from human to Caenorhabditis species. The fruit fly, Drosophila melanogaster, possesses only one Notch protein, whereas in C.elegans, two receptors have been found; by contrast, four Notch paralogues (designated N1-4) have been identified in mammals, playing both unique and redundant roles. The hetero-oligomer Notch comprises a large extracellular domain (ECD), containing 10-36 tandem Epidermal Growth Factor (EFG)-like repeats, which are involved in ligand interactions; a negative regulatory region, including three cysteine-rich Lin12-Notch Repeats (LNR); a single trans-membrane domain (TM); a small intracellular domain (ICD), which includes a RAM (RBPjk-association module) domain; six ankyrin repeats (ANK), which are involved in protein-protein interactions; and a PEST domain. Drosophila Notch also contains an OPA domain []. Notch signalling is an evolutionarily conserved pathway involved in a wide variety of developmental processes, including adult homeostasis and stem cell maintenance, cell proliferation and apoptosis []. Notch is activated by a range of ligands -the so-called DSL ligands (Delta/Seratte/LAG-2). Activation is also mediated by a sequence of proteolytic events: ligand binding leads to cleavage of Notch by ADAM proteases []at site 2 (S2) and presenilin-1/g-secretase at sites 3 (S3)and 4 (S4) [].The last cleavage releases the Notch intracellular part of the protein (NICD) from the membrane and, upon release, the NICD translocates to the nucleus where it associates with a CBF1/RBJk/Su(H)/Lag1 (CSL) family of DNA-binding proteins. The subsequent recruitment of a co-activator mastermind like (MAML1) protein []promotes transcriptional activation of Notch target genes: well established Notch targets are the Hes and Hey gene families. Aberrant Notch function and signalling has been associated with a number of human disorders, including Allagile syndrome, spondylocostal dysostosis, aortic valve disease, CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), and T-cell Acute Lympho-blastic Leukemia (T-ALL); it has also been implicated in various human carcinomas [, ]. Notch 4 is selectively expressed in vascular endothelium, and regulates vascular remodelling [].

Sequence Features

GO Displayer


InterPro protein domain ID --> Contigs



0 Child Features

7 Contains

Id Name Short Name Type
IPR020683 Ankyrin repeat-containing domain Ankyrin_rpt-contain_dom Domain
IPR002110 Ankyrin repeat Ankyrin_rpt Repeat
IPR013032 EGF-like, conserved site EGF-like_CS Conserved_site
IPR000742 Epidermal growth factor-like domain EG-like_dom Domain
IPR000800 Notch domain Notch_dom Domain
IPR011656 Notch, NODP domain Notch_NODP_dom Domain
IPR010660 Notch, NOD domain Notch_NOD_dom Domain

0 Found In

1 Parent Features

Id Name Short Name Type
IPR008297 Notch Notch Family

8 Publications

First Author Title Year Journal Volume Pages
Artavanis-Tsakonas S Notch signaling: cell fate control and signal integration in development. 1999 Science 284 770-6
Kopan R The canonical Notch signaling pathway: unfolding the activation mechanism. 2009 Cell 137 216-33
Hartmann D The disintegrin/metalloprotease ADAM 10 is essential for Notch signalling but not for alpha-secretase activity in fibroblasts. 2002 Hum Mol Genet 11 2615-24
Wu L MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors. 2000 Nat Genet 26 484-9
Gridley T Notch signaling and inherited disease syndromes. 2003 Hum Mol Genet 12 Spec No 1 R9-13
Louvi A Notch signalling in vertebrate neural development. 2006 Nat Rev Neurosci 7 93-102
De Strooper B A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. 1999 Nature 398 518-22
Shirayoshi Y Proto-oncogene of int-3, a mouse Notch homologue, is expressed in endothelial cells during early embryogenesis. 1997 Genes Cells 2 213-24

To cite PlanMine, please refer to the following publication:

Rozanski, A., Moon, H., Brandl, H., Martín-Durán, J. M., Grohme, M., Hüttner, K., Bartscherer, K., Henry, I., & Rink, J. C.
PlanMine 3.0—improvements to a mineable resource of flatworm biology and biodiversity
Nucleic Acids Research, gky1070. doi:10.1093/nar/gky1070 (2018)