Notch4

Function

Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs. May regulate branching morphogenesis in the developing vascular system (By similarity).

Post-translational modifications

Synthesized in the endoplasmic reticulum as an inactive form which is proteolytically cleaved by a furin-like convertase in the trans-Golgi network before it reaches the plasma membrane to yield an active, ligand-accessible form. Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC). Following ligand binding, it is cleaved by TNF-alpha converting enzyme (TACE) to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT). This fragment is then cleaved by presenilin dependent gamma-secretase to release a notch-derived peptide containing the intracellular domain (NICD) from the membrane (By similarity).

Phosphorylated.

Sequence similarities

Belongs to the NOTCH family.

Tissue specificity

Highly expressed in the heart, moderately in the lung and placenta and at low levels in the liver, skeletal muscle, kidney, pancreas, spleen, lymph node, thymus, bone marrow and fetal liver. No expression was seen in adult brain or peripheral blood leukocytes.

Cellular localization

• Cell membrane
• Single-pass type I membrane protein
• Notch 4 intracellular domain
• Nucleus
• Following proteolytical processing NICD is translocated to the nucleus.

Alternative names

• Neurogenic locus notch homolog protein 4
• Notch 4
• hNotch4
• INT3
• NOTCH4

Database links

• entrezGene:4855
• omim:164951
• swissprot:Q99466

Target type

Proteins

Primary research area

Oncology

Molecular weight

209622Da