protein jagged-1; Jagged1; hJ1; CD339 (JAG1, JAGL1)

Function

• ligand for multiple notch receptors & involved in the mediation of notch signaling
• may be involved in cell-fate decisions during hematopoiesis
• seems to be involved in early & late stages of mammalian cardiovascular development
• inhibits myoblast differentiation (putative)
• enhances fibroblast growth factor-induced angiogenesis (in vitro)
• interacts with NOTCH1, NOTCH2 & NOTCH3 (putative)

Structure

• contains 1 DSL domain
• contains 15 EGF-like domains

Compartment

• membrane; single-pass type 1 membrane protein

Expression

• widely expressed in adult & fetal tissues
• in cervix epithelium, expressed in undifferentiated subcolumnar reserve cells & squamous metaplasia
• expression is up-regulated in cervical squamous cell carcinoma
• expressed in bone marrow cell line HS-27a which supports the long-term maintenance of immature progenitor cells
• expressed in 32-52 days embryos in the distal cardiac outflow tract & pulmonary artery, major arteries, portal vein, optic vesicle, otocyst, branchial arches, metanephros, pancreas, mesocardium, around the major bronchial branches, & in the neural tube

Pathology

• defects in JAG1 are the cause of Alagille syndrome type 1
• defects in JAG1 are a cause of tetralogy of fallot
• mutation Asp-274 is leaky
  • two populations of proteins are produced from this allele
  • one population is abnormally glycosylated & is retained intracellularly rather than being transported to the cell surface
  • a second population is normally glycosylated & is transported to the cell surface, where it is able to signal to the notch receptor
  • the Asp-274 protein is temperature sensitive, with more abnormally glycosylated (& nonfunctional) molecules produced at higher temperatures
  • carriers of this mutation therefore have more than 50% but less than 100% of the normal concentration of molecules on the cell surface
  • the cardiac-specific phenotype associated with this mutation suggests that the developing heart is more sensitive than the developing liver to decreased dosage of JAG1 protein

More general terms

• jagged protein
• CD antigen
• glycoprotein

Additional terms

• Alagille syndrome (arteriohepatic dysplasia)

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=182
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:182
• OMIM: https://mirror.omim.org/entry/118450
• OMIM: https://mirror.omim.org/entry/187500
• OMIM: https://mirror.omim.org/entry/601920
• UniProt: http://www.uniprot.org/uniprot/P78504.html