NOTCH4

NOTCH4

Target · Notch receptor

NOTCH4 Notch receptor 4 · Neurogenic locus notch homolog protein 4

NOTCH4 (notch receptor 4, also known as INT3) is a type I transmembrane receptor of the NOTCH family. It binds membrane-bound ligands to regulate cell-fate determination and may influence branching morphogenesis in the developing vascular system. Browse Assay Genie's current range of NOTCH4 research reagents below, or read on for the biology behind the target.

Cell membrane and nucleusNotch family receptorRegulates cell-fate decisions
2003 aa
Protein length
~210 kDa
Molecular weight
6p21.32
Gene locus
Notch receptor
Protein family
Target information

What is NOTCH4 (notch receptor 4)?

NOTCH4 functions as a receptor for the membrane-bound ligands Jagged1, Jagged2 and Delta1, and through them regulates cell-fate determination. Following ligand activation, the released Notch intracellular domain (NICD) forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. In this way NOTCH4 affects the implementation of differentiation, proliferation and apoptotic programmes. It may also regulate branching morphogenesis in the developing vascular system.

The NOTCH4 gene encodes a member of the NOTCH family, a group of type I transmembrane proteins. Family members share an extracellular domain made up of multiple epidermal growth factor-like (EGF) repeats and an intracellular domain composed of several different domain types. The encoded preproprotein is proteolytically processed in the trans-Golgi network into two polypeptide chains, which heterodimerize to form the mature cell-surface receptor. UniProt lists the protein at the cell membrane and in the nucleus, consistent with the movement of the intracellular domain after activation. Alternative splicing produces multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed.

Notch signalling is an evolutionarily conserved intercellular pathway that regulates interactions between physically adjacent cells, through binding of Notch receptors to their cognate ligands. NCBI Gene notes that NOTCH4 may play a role in vascular, renal and hepatic development, and that mutations in the gene may be associated with schizophrenia. The gene was previously named notch 4 and Notch homolog 4 (Drosophila), and is classed by HGNC among the Notch receptors. The mouse ortholog is Notch4.

Notch signalling pathway studies

NOTCH4 is a ligand-activated receptor whose intracellular domain partners with RBPJ to drive enhancer of split genes, making it a model for Notch signal transduction.

Vascular development

NOTCH4 may regulate branching morphogenesis in the developing vascular system, and NCBI Gene links it to vascular development.

Cell-fate and differentiation

The receptor regulates cell-fate determination and affects differentiation, proliferation and apoptotic programmes, so it is relevant to developmental and cell biology.

Renal, hepatic and neuropsychiatric research

NOTCH4 may contribute to renal and hepatic development, and mutations in the gene may be associated with schizophrenia.

Background

NOTCH4 frequently asked questions

What does NOTCH4 do?

NOTCH4 is a cell-surface receptor for the ligands Jagged1, Jagged2 and Delta1. After ligand activation, its released intracellular domain forms a complex with RBPJ/RBPSUH and activates enhancer of split genes, regulating cell fate, differentiation, proliferation and apoptosis. It may also regulate vascular branching morphogenesis.

What other names and forms does NOTCH4 have?

NOTCH4 is also called INT3, and its UniProt name is neurogenic locus notch homolog protein 4. Earlier names include notch 4 and Notch homolog 4 (Drosophila). The preproprotein is cleaved in the trans-Golgi network into two chains that heterodimerize, and alternative splicing gives multiple transcript variants.

Is NOTCH4 conserved, and is it linked to disease?

Notch signalling is an evolutionarily conserved pathway, and NOTCH4 has a mouse ortholog, Notch4. NCBI Gene reports that mutations in the human gene may be associated with schizophrenia. Check the datasheet of any product for its validated reactivity.

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Related targets

Other Notch family receptors and related Notch signalling targets with products at Assay Genie.

Gene and protein annotations from HGNC, NCBI Gene and UniProt Q99466; product specifications from Assay Genie datasheets.

NOTCH4 Product listing