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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 a) two populations of proteins are produced from this allele b) one population is abnormally glycosylated & is retained intracellularly rather than being transported to the cell surface c) a second population is normally glycosylated & is transported to the cell surface, where it is able to signal to the notch receptor d) the Asp-274 protein is temperature sensitive, with more abnormally glycosylated (& nonfunctional) molecules produced at higher temperatures e) carriers of this mutation therefore have more than 50% but less than 100% of the normal concentration of molecules on the cell surface f) 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

Interactions

molecular events

Related

Alagille syndrome (arteriohepatic dysplasia) JAG1 or jagged 1 gene

General

cluster-of-differentiation antigen; cluster designation antigen; CD antigen glycoprotein jagged protein

Properties

SIZE: entity length = 1218 aa MW = 134 kD COMPARTMENT: plasma membrane MOTIF: N-glycosylation site {N143} DSL {185-229} MOTIF: cysteine residue {C187} MODIFICATION: cysteine residue {C196} cysteine residue {C196} MODIFICATION: cysteine residue {C187} cysteine residue {C200} MODIFICATION: cysteine residue {C212} cysteine residue {C212} MODIFICATION: cysteine residue {C200} N-glycosylation site {N217} cysteine residue {C220} MODIFICATION: cysteine residue {C229} cysteine residue {C229} MODIFICATION: cysteine residue {C220} EGF domain {230-856} (15) N-glycosylation site {N960} N-glycosylation site {N991} N-glycosylation site {N1045} N-glycosylation site {N1064} transmembrane domain {1068-1093}

Database Correlations

OMIM correlations MORBIDMAP 601920 UniProt P78504 PFAM correlations Entrez Gene 182 Kegg hsa:182

References

  1. UniProt :accession P78504
  2. Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/JAG1ID41029ch20p12.html
  3. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=JAG1

Component-of

molecular complex