Target intelligence / Profile preview

Jagged-1 protein (JAG1)

Target
JAG1
Molecular classification
Ligand, Cell surface protein, Notch pathway ligand, Cluster of differentiation (CD antigen), Signaling protein
01

Overview

Jagged-1 protein (JAG1) is a single-pass transmembrane cell surface ligand that interacts with Notch receptors to regulate critical cell fate decisions through the Notch signaling pathway. It plays a vital role during embryonic development by controlling differentiation and proliferation in many organs (e.g., heart, liver, skeletal system), and continues to have roles in adult tissue maintenance such as hematopoiesis and angiogenesis. Pathogenic mutations in the JAG1 gene are the major cause of Alagille syndrome, a multisystem developmental disorder. Alterations in JAG1 expression are linked to cancer progression and other diseases by affecting Notch pathway output[1][2][5].

Other names
Jagged1JAG1CD339CD339 antigenHJ1JAG1_HUMANjagged 1 (Alagille syndrome)jagged 1 precursorJAGL1AGSAHDAWS
02

Mechanism of action

Modulators of the Notch pathway may act by inhibiting the interaction between Jagged-1 and Notch receptors or by altering downstream signaling. Mechanisms include ligand-receptor blockade, antibody-mediated inhibition of ligand binding, or small molecule inhibitors of pathway components[2].

03

Biological functions

Signal transductionCell fate determinationEmbryonic developmentCell differentiationCell proliferationHematopoiesisAngiogenesis
04

Disease associations

CancerAlagille syndromeTetralogy of FallotCardiovascular diseaseDevelopmental disorder
05

Safety considerations

Targeting the Notch-Jagged pathway has potential safety concerns due to its vital role in normal development, cell differentiation, and tissue homeostasis; possible toxicities include effects on hematopoiesis and immune response[2].Germline mutations in JAG1 cause Alagille syndrome, highlighting risks of loss-of-function.
06

Interacting drugs

No approved drugs are known to directly target Jagged-1 protein specifically. However, inhibitors and modulators of the Notch signaling pathway, which target Notch-Jagged interaction, are under investigation in preclinical and clinical studies[2][5]. Most are not selective for Jagged-1 itself.
07

Biomarkers

JAG1 mutation analysis is used as a biomarker for Alagille syndrome diagnosis[5].Overexpression of JAG1 has been explored as a biomarker in certain cancers[5].

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