The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

JAG1  -  jagged 1

Homo sapiens

Synonyms: AGS, AHD, AWS, CD339, HJ1, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of JAG1


Psychiatry related information on JAG1

  • Patients with "recently" diagnosed Huntington's Disease (RHD) were compared on a neuropsychological test battery to patients who have had the disease three to 15 years (AHD) and to intact controls [6].
  • The present study was designed to assess effects of aversive stimuli on learning and memory in wild-caught Arctic ground squirrels (AGS, Spermophilus parryii) using an active avoidance learning paradigm [7].
  • With its emphasis on friendship, the saliency of health, reinforcement of self-efficacy and control over one's health, health education, the ecological nature of health, and the need to preserve the quality of the future for children and grandchildren, the AHDP model has national and international implications [8].
  • Eighty-one Shia Imami Nizari Ismaili Muslims living in Ontario, Canada, provided demographic data and completed the Bem Sex-Role Inventory (BSRI; Bem, 1981) and the Attitudes Toward Women Scale (AWS; Spence, Helmreich, & Stapp, 1973) [9].

High impact information on JAG1

  • Mutations in JAG1, encoding a Notch ligand, cause the Alagille syndrome in humans, characterized by poor development of the biliary system, suggesting that the Notch pathway is also involved in normal biliary development [10].
  • Increasing evidence suggests that, in addition to the inhibitory Jagged1/Notch1 signaling cascade, other pathways act via Notch to mediate oligodendrocyte differentiation [11].
  • Determining the complete exon-intron structure of JAG1 allowed detailed mutational analysis of DNA samples from non-deletion AGS patients, revealing three frame-shift mutations, two splice donor mutations and one mutation abolishing RNA expression from the altered allele [12].
  • During mammalian central nervous system (CNS) development, contact-mediated activation of Notch1 receptors on oligodendrocyte precursors by the ligand Jagged1 induces Hes5, which inhibits maturation of these cells [13].
  • Experiments in vitro showed that Jagged1 signaling inhibited process outgrowth from primary human oligodendrocytes [13].

Chemical compound and disease context of JAG1


Biological context of JAG1

  • 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 [2].
  • JAG1 mutations in AGS include gene deletions and protein truncating, splicing, and missense mutations, suggesting that haploinsufficiency is the mechanism of disease causation [2].
  • Of the remaining 51 patients, 35 (69%) had mutations within JAG1, identified by SSCP analysis [18].
  • Evaluation of candidate loci in a large kindred segregating autosomal dominant ToF with reduced penetrance culminated in identification of a missense mutation (G274D) in JAG1, the gene encoding jagged1, a Notch ligand expressed in the developing right heart [19].
  • We have isolated the human homolog of the rat Jagged1 gene, JAG1, from a CpG island in a YAC clone covering the Alagille syndrome critical region at chromosome 20p12 (tel-SNAP-D20S186-cen) [20].

Anatomical context of JAG1


Associations of JAG1 with chemical compounds

  • A candidate-gene approach was undertaken and culminated in the identification of a novel Jagged 1 (JAG1) missense mutation (C234Y) in the first cysteine of the first epidermal-growth-factor-like repeat domain of the protein [3].
  • Finally, coculture of Dl-1-expressing cells with myogenic C2 cells suppresses differentiation of C2 cells into myotubes, as previously demonstrated for Jagged-1 and Jagged-2, and also leads to an increased level of endogenous HES-1 mRNA [24].
  • BACKGROUND: Aspartyl (asparaginyl)-beta-hydroxylase (AAH) hydroxylates Asp and Asn residues within EGF-like domains of Notch and Jagged, which mediate cell motility and differentiation [25].
  • Interestingly, addition of a beta1,4 galactose by beta4GalT-1 to the GlcNAc added by fringe is required for Jagged1-induced Notch signaling to be inhibited in a co-culture assay [26].
  • Since PTH(1-34) activates both Adenylate Cyclase/Protein Kinase A (AC/PKA) and Protein Kinase C (PKC) downstream of the PTH1R in osteoblastic cells, we independently determined the effect of either pathway on Jagged1 [27].

Physical interactions of JAG1

  • JAG1 then binds to the Notch receptor on adjacent stem cells to induce Notch receptor proteolyses for the release of Notch intracellular domain (NICD) [28].

Regulatory relationships of JAG1


Other interactions of JAG1

  • Activation of this signaling pathway by constitutive Notch-1 mutants and by Jagged-1 causes an angiogenic and invasive tumor phenotype [32].
  • Transfection of PaCa cells with the constitutive active Notch-IC mutant and with Jagged-1 revealed increased levels for VEGF [32].
  • Jagged1 increases the number of bipotent colony-forming unit-granulocyte macrophage (CFU-GM) and unipotent progenitors (CFU-granulocytes and CFU-macrophages), without quantitatively affecting terminal cell differentiation, whereas Delta1 reduces the number of CFU-GM and differentiated monocytic cells [33].
  • Four Notch receptors have been identified in vertebrates and different ligands, divided into Delta-like and Serrate-like (Jagged) [34].
  • Further, Jagged1 expression correlates with the rapid induction of PI3K-mediated epithelial-mesenchymal transition in both HaCaT cells and a human cervical tumor-derived cell line, suggestive of Delta1;Serrate/Jagged;Lag2 ligand-specific roles [35].

Analytical, diagnostic and therapeutic context of JAG1

  • The JAG1 gene mutations were generally found in severely ill patients subjected to liver transplantation at less than 5 years of age [4].
  • Notch1 and Notch3 expression overlapped with that of Jagged1, as determined by confocal microscopy [36].
  • The results were correlated with the expression of Notch ligand JAG1 gene and the clinicopathologic features and the full-length p63 protein expression by immunohistochemistry [37].
  • We investigated the JAG1 gene for genetic alterations in eight Japanese AGS patients, using fluorescence in situ hybridization (FISH), single strand conformation polymorphism (SSCP) analysis, and direct sequencing [38].
  • The mRNA transcript levels of AAH, insulin receptor substrate (IRS), insulin and insulin-like growth factor (IGF) receptors and polypeptides, Notch, Jagged, and HES were measured in 15 paired samples of HCC and adjacent HCC-free human liver biopsy specimens using real-time quantitative RT-PCR and Western blot analysis [39].


  1. Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1. Li, L., Krantz, I.D., Deng, Y., Genin, A., Banta, A.B., Collins, C.C., Qi, M., Trask, B.J., Kuo, W.L., Cochran, J., Costa, T., Pierpont, M.E., Rand, E.B., Piccoli, D.A., Hood, L., Spinner, N.B. Nat. Genet. (1997) [Pubmed]
  2. Conditional JAG1 mutation shows the developing heart is more sensitive than developing liver to JAG1 dosage. Lu, F., Morrissette, J.J., Spinner, N.B. Am. J. Hum. Genet. (2003) [Pubmed]
  3. Familial deafness, congenital heart defects, and posterior embryotoxon caused by cysteine substitution in the first epidermal-growth-factor-like domain of jagged 1. Le Caignec, C., Lefevre, M., Schott, J.J., Chaventre, A., Gayet, M., Calais, C., Moisan, J.P. Am. J. Hum. Genet. (2002) [Pubmed]
  4. The significance of human jagged 1 mutations detected in severe cases of extrahepatic biliary atresia. Kohsaka, T., Yuan, Z.R., Guo, S.X., Tagawa, M., Nakamura, A., Nakano, M., Kawasasaki, H., Inomata, Y., Tanaka, K., Miyauchi, J. Hepatology (2002) [Pubmed]
  5. Notch ligand, JAG1, is evolutionarily conserved target of canonical WNT signaling pathway in progenitor cells. Katoh, M., Katoh, M. Int. J. Mol. Med. (2006) [Pubmed]
  6. Comparison of the neuropsychological deficits associated with early and advanced Huntington's disease. Butters, N., Sax, D., Montgomery, K., Tarlow, S. Arch. Neurol. (1978) [Pubmed]
  7. Effects of aversive stimuli on learning and memory in Arctic ground squirrels. Zhao, H., Bucci, D.J., Weltzin, M., Drew, K.L. Behav. Brain Res. (2004) [Pubmed]
  8. Intergenerational Health Education. The Adults Health and Development Programme. Leviton, D. Hygie. (1989) [Pubmed]
  9. Gender role identity and perceptions of Ismaili Muslim men and women. Damji, T., Lee, C.M. The Journal of social psychology. (1995) [Pubmed]
  10. Conversion of biliary system to pancreatic tissue in Hes1-deficient mice. Sumazaki, R., Shiojiri, N., Isoyama, S., Masu, M., Keino-Masu, K., Osawa, M., Nakauchi, H., Kageyama, R., Matsui, A. Nat. Genet. (2004) [Pubmed]
  11. F3/contactin acts as a functional ligand for Notch during oligodendrocyte maturation. Hu, Q.D., Ang, B.T., Karsak, M., Hu, W.P., Cui, X.Y., Duka, T., Takeda, Y., Chia, W., Sankar, N., Ng, Y.K., Ling, E.A., Maciag, T., Small, D., Trifonova, R., Kopan, R., Okano, H., Nakafuku, M., Chiba, S., Hirai, H., Aster, J.C., Schachner, M., Pallen, C.J., Watanabe, K., Xiao, Z.C. Cell (2003) [Pubmed]
  12. Mutations in the human Jagged1 gene are responsible for Alagille syndrome. Oda, T., Elkahloun, A.G., Pike, B.L., Okajima, K., Krantz, I.D., Genin, A., Piccoli, D.A., Meltzer, P.S., Spinner, N.B., Collins, F.S., Chandrasekharappa, S.C. Nat. Genet. (1997) [Pubmed]
  13. Multiple sclerosis: re-expression of a developmental pathway that restricts oligodendrocyte maturation. John, G.R., Shankar, S.L., Shafit-Zagardo, B., Massimi, A., Lee, S.C., Raine, C.S., Brosnan, C.F. Nat. Med. (2002) [Pubmed]
  14. Evidence for the notch signaling pathway on the role of estrogen in angiogenesis. Soares, R., Balogh, G., Guo, S., Gärtner, F., Russo, J., Schmitt, F. Mol. Endocrinol. (2004) [Pubmed]
  15. the selective cyclooxygenase-2 inhibitor nimesulide prevents Helicobacter pylori-associated gastric cancer development in a mouse model. Nam, K.T., Hahm, K.B., Oh, S.Y., Yeo, M., Han, S.U., Ahn, B., Kim, Y.B., Kang, J.S., Jang, D.D., Yang, K.H., Kim, D.Y. Clin. Cancer Res. (2004) [Pubmed]
  16. Analysis of genes upregulated by the demethylating agent 5-aza-2'-deoxycytidine in gastric cancer cell lines. Mikata, R., Yokosuka, O., Fukai, K., Imazeki, F., Arai, M., Tada, M., Kurihara, T., Zhang, K., Kanda, T., Saisho, H. Int. J. Cancer (2006) [Pubmed]
  17. Rebamipide inhibits gastric cancer growth by targeting survivin and Aurora-B. Tarnawski, A., Pai, R., Chiou, S.K., Chai, J., Chu, E.C. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  18. Spectrum and frequency of jagged1 (JAG1) mutations in Alagille syndrome patients and their families. Krantz, I.D., Colliton, R.P., Genin, A., Rand, E.B., Li, L., Piccoli, D.A., Spinner, N.B. Am. J. Hum. Genet. (1998) [Pubmed]
  19. Familial Tetralogy of Fallot caused by mutation in the jagged1 gene. Eldadah, Z.A., Hamosh, A., Biery, N.J., Montgomery, R.A., Duke, M., Elkins, R., Dietz, H.C. Hum. Mol. Genet. (2001) [Pubmed]
  20. Identification and cloning of the human homolog (JAG1) of the rat Jagged1 gene from the Alagille syndrome critical region at 20p12. Oda, T., Elkahloun, A.G., Meltzer, P.S., Chandrasekharappa, S.C. Genomics (1997) [Pubmed]
  21. Human jagged 1 mutants cause liver defect in Alagille syndrome by overexpression of hepatocyte growth factor. Yuan, Z.R., Kobayashi, N., Kohsaka, T. J. Mol. Biol. (2006) [Pubmed]
  22. Characterization of Notch receptor expression in the developing mammalian heart and liver. Loomes, K.M., Taichman, D.B., Glover, C.L., Williams, P.T., Markowitz, J.E., Piccoli, D.A., Baldwin, H.S., Oakey, R.J. Am. J. Med. Genet. (2002) [Pubmed]
  23. JAGGED1 expression in human embryos: correlation with the Alagille syndrome phenotype. Jones, E.A., Clement-Jones, M., Wilson, D.I. J. Med. Genet. (2000) [Pubmed]
  24. Delta-1 activation of notch-1 signaling results in HES-1 transactivation. Jarriault, S., Le Bail, O., Hirsinger, E., Pourquié, O., Logeat, F., Strong, C.F., Brou, C., Seidah, N.G., Isra l, A. Mol. Cell. Biol. (1998) [Pubmed]
  25. Differential growth factor regulation of aspartyl-(asparaginyl)-beta-hydroxylase family genes in SH-Sy5y human neuroblastoma cells. Lahousse, S.A., Carter, J.J., Xu, X.J., Wands, J.R., de la Monte, S.M. BMC Cell Biol. (2006) [Pubmed]
  26. Modulation of receptor signaling by glycosylation: fringe is an O-fucose-beta1,3-N-acetylglucosaminyltransferase. Haltiwanger, R.S., Stanley, P. Biochim. Biophys. Acta (2002) [Pubmed]
  27. Parathyroid hormone stimulates expression of the Notch ligand Jagged1 in osteoblastic cells. Weber, J.M., Forsythe, S.R., Christianson, C.A., Frisch, B.J., Gigliotti, B.J., Jordan, C.T., Milner, L.A., Guzman, M.L., Calvi, L.M. Bone (2006) [Pubmed]
  28. WNT antagonist, DKK2, is a Notch signaling target in intestinal stem cells: Augmentation of a negative regulation system for canonical WNT signaling pathway by the Notch-DKK2 signaling loop in primates. Katoh, M., Katoh, M. Int. J. Mol. Med. (2007) [Pubmed]
  29. Manic fringe and lunatic fringe modify different sites of the Notch2 extracellular region, resulting in different signaling modulation. Shimizu, K., Chiba, S., Saito, T., Kumano, K., Takahashi, T., Hirai, H. J. Biol. Chem. (2001) [Pubmed]
  30. The soluble Notch ligand, Jagged-1, inhibits proliferation of CD34+ macrophage progenitors. Masuya, M., Katayama, N., Hoshino, N., Nishikawa, H., Sakano, S., Araki, H., Mitani, H., Suzuki, H., Miyashita, H., Kobayashi, K., Nishii, K., Minami, N., Shiku, H. Int. J. Hematol. (2002) [Pubmed]
  31. Down-regulation of Jagged-1 induces cell growth inhibition and S phase arrest in prostate cancer cells. Zhang, Y., Wang, Z., Ahmed, F., Banerjee, S., Li, Y., Sarkar, F.H. Int. J. Cancer (2006) [Pubmed]
  32. The Notch signaling pathway is related to neurovascular progression of pancreatic cancer. Büchler, P., Gazdhar, A., Schubert, M., Giese, N., Reber, H.A., Hines, O.J., Giese, T., Ceyhan, G.O., Müller, M., Büchler, M.W., Friess, H. Ann. Surg. (2005) [Pubmed]
  33. Effects of Delta1 and Jagged1 on early human hematopoiesis: correlation with expression of notch signaling-related genes in CD34+ cells. Neves, H., Weerkamp, F., Gomes, A.C., Naber, B.A., Gameiro, P., Becker, J.D., Lúcio, P., Clode, N., van Dongen, J.J., Staal, F.J., Parreira, L. Stem Cells (2006) [Pubmed]
  34. Expression and distribution of notch protein members in human placenta throughout pregnancy. De Falco, M., Cobellis, L., Giraldi, D., Mastrogiacomo, A., Perna, A., Colacurci, N., Miele, L., De Luca, A. Placenta (2007) [Pubmed]
  35. Complementation of human papillomavirus type 16 E6 and E7 by Jagged1-specific Notch1-phosphatidylinositol 3-kinase signaling involves pleiotropic oncogenic functions independent of CBF1;Su(H);Lag-1 activation. Veeraraghavalu, K., Subbaiah, V.K., Srivastava, S., Chakrabarti, O., Syal, R., Krishna, S. J. Virol. (2005) [Pubmed]
  36. Immunohistological localization of Notch receptors and their ligands Delta and Jagged in synovial tissues of rheumatoid arthritis. Yabe, Y., Matsumoto, T., Tsurumoto, T., Shindo, H. Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association. (2005) [Pubmed]
  37. Differential expression of p63 isotypes (DeltaN and TA) in salivary gland neoplasms: biological and diagnostic implications. Maruya, S., Kies, M.S., Williams, M., Myers, J.N., Weber, R.S., Batsakis, J.G., El-Naggar, A.K. Hum. Pathol. (2005) [Pubmed]
  38. Genetic alterations in the JAG1 gene in Japanese patients with Alagille syndrome. Onouchi, Y., Kurahashi, H., Tajiri, H., Ida, S., Okada, S., Nakamura, Y. J. Hum. Genet. (1999) [Pubmed]
  39. Aspartyl-asparagyl beta hydroxylase over-expression in human hepatoma is linked to activation of insulin-like growth factor and notch signaling mechanisms. Cantarini, M.C., de la Monte, S.M., Pang, M., Tong, M., D'Errico, A., Trevisani, F., Wands, J.R. Hepatology (2006) [Pubmed]
WikiGenes - Universities