JAG1
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| Location (UCSC) | Chr 20: 10.64 – 10.67 Mb | Chr 2: 136.92 – 136.96 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
Jagged1 (JAG1) is one of five cell surface proteins (
autosomal dominant disorder Alagille syndrome (ALGS) resulting from loss of function mutations within the gene. JAG1 has also been designated as CD339 (cluster of differentiation
339).
Structure and function
JAG1 was first identified as a
exons.[7]
The JAG1 protein encoded by JAG1 is the human homolog of the
intracellular domain being trafficked into the nucleus of the cell leading to the activation of different target genes.[8][9][10][11]
Expression profile and mouse studies
otocyst.[12] Generally, JAG1 expression patterns correlate with organ systems affected in ALGS, although it is important to note that not all tissues where JAG1 is expressed are affected in ALGS. More recently JAG1 expression has been found to be altered in breast cancer and adrenocortical carcinoma patients.[13][14]
Mouse models where the Jag1 gene is turned off in certain tissues (conditional knockout mouse models) have been used to study the role of Jag1 in many tissue specific areas. While
haploinsufficient for both Jag1 and Notch2 present with the ALGS phenotype.[15] Conditional gene knockout mouse models with Jag1 mutations targeted to the portal vein mesenchyme, endothelium, and cranial neural crest all exhibit features classic to those in individuals with ALGS, highlighting the role of this tissue type in disease origins[16][17][18][19][20]
Disease phenotype
ALGS is an
pulmonary stenosis that do not show the other clinical signs of the syndrome.[26]
Given the variable expressivity of the disease, there may be other genetic or environmental modifiers present beyond the original JAG1 mutation.
More recently, JAG1 expression changes have been implicated in many types of cancer. Specifically, up regulation of JAG1 has been correlated with both poor overall breast cancer survival rates and an enhancement of tumor proliferation in adrenocortical carcinoma patients.[13][27][28][29]
See also
- Notch signaling
- Alagille syndrome
- Autosomal dominant
- Haploinsufficiency
- Tetralogy of fallot
- In situ hybridization
- Conditional gene knockout
- Cluster of differentiation
Notes
Wikidata Q28606584 . |
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000101384 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027276 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ S2CID 11720367.
- ^ S2CID 5775213.
- S2CID 34651925.
- PMID 11006133.
- PMID 11346656.
- PMID 10551863.
- PMID 10958687.
- ^ PMID 10978356.
- ^ PMID 16166334.
- PMID 22427350.
- PMID 11861489.
- PMID 10556292.
- PMID 23095891.
- PMID 21062863.
- PMID 18245384.
- PMID 22156581.
- ^ PMID 9585603.
- S2CID 45080348.
- PMID 22306179.
- PMID 11157803.
- PMID 10220506.
- PMID 20437614.
- PMID 17507991.
- PMID 25309874.
- PMID 17308118.
Further reading
- Piccoli DA, Spinner NB (2002). "Alagille syndrome and the Jagged1 gene". Semin. Liver Dis. 21 (4): 525–34. S2CID 46554750.
- Lindsell CE, Boulter J, diSibio G, Gossler A, Weinmaster G (1997). "Expression patterns of Jagged, Delta1, Notch1, Notch2, and Notch3 genes identify ligand-receptor pairs that may function in neural development". Mol. Cell. Neurosci. 8 (1): 14–27. S2CID 8058790.
- Zimrin AB, Pepper MS, McMahon GA, Nguyen F, Montesano R, Maciag T (1997). "An antisense oligonucleotide to the notch ligand jagged enhances fibroblast growth factor-induced angiogenesis in vitro". J. Biol. Chem. 271 (51): 32499–502. PMID 8955070.
- Li L, Krantz ID, Deng Y, Genin A, Banta AB, Collins CC, Qi M, Trask BJ, Kuo WL, Cochran J, Costa T, Pierpont ME, Rand EB, Piccoli DA, Hood L, Spinner NB (1997). "Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1". Nat. Genet. 16 (3): 243–51. S2CID 8794354.
- Oda T, Elkahloun AG, Meltzer PS, Chandrasekharappa SC (1997). "Identification and cloning of the human homolog (JAG1) of the rat Jagged1 gene from the Alagille syndrome critical region at 20p12". Genomics. 43 (3): 376–9. PMID 9268641.
- Li L, Milner LA, Deng Y, Iwata M, Banta A, Graf L, Marcovina S, Friedman C, Trask BJ, Hood L, PMID 9462510.
- Hock B, Böhme B, Karn T, Yamamoto T, Kaibuchi K, Holtrich U, Holland S, Pawson T, Rübsamen-Waigmann H, Strebhardt K (1998). "PDZ-domain-mediated interaction of the Eph-related receptor tyrosine kinase EphB3 and the ras-binding protein AF6 depends on the kinase activity of the receptor". Proc. Natl. Acad. Sci. U.S.A. 95 (17): 9779–84. PMID 9707552.
- Gray GE, Mann RS, Mitsiadis E, Henrique D, Carcangiu ML, Banks A, Leiman J, Ward D, Ish-Horowitz D, Artavanis-Tsakonas S (1999). "Human Ligands of the Notch Receptor". Am. J. Pathol. 154 (3): 785–94. PMID 10079256.
- Bash J, Zong WX, Banga S, Rivera A, Ballard DW, Ron Y, Gélinas C (1999). "Rel/NF-kappaB can trigger the Notch signaling pathway by inducing the expression of Jagged1, a ligand for Notch receptors". EMBO J. 18 (10): 2803–11. PMID 10329626.
- Pilia G, Uda M, Macis D, Frau F, Crisponi L, Balli F, Barbera C, Colombo C, Frediani T, Gatti R, Iorio R, Marazzi MG, Marcellini M, Musumeci S, Nebbia G, Vajro P, Ruffa G, Zancan L, Cao A, DeVirgilis S (2000). "Jagged-1 mutation analysis in Italian Alagille syndrome patients". Hum. Mutat. 14 (5): 394–400. S2CID 45123109.
- Wong MK, Prudovsky I, Vary C, Booth C, Liaw L, Mousa S, Small D, Maciag T (2000). "A non-transmembrane form of Jagged-1 regulates the formation of matrix-dependent chord-like structures". Biochem. Biophys. Res. Commun. 268 (3): 853–9. PMID 10679295.
- Heritage ML, MacMillan JC, Colliton RP, Genin A, Spinner NB, Anderson GJ (2000). "Jagged1 (JAG1) mutation detection in an Australian Alagille syndrome population". Hum. Mutat. 16 (5): 408–16. S2CID 22168402.
- Karanu FN, Murdoch B, Gallacher L, Wu DM, Koremoto M, Sakano S, Bhatia M (2000). "The Notch Ligand Jagged-1 Represents a Novel Growth Factor of Human Hematopoietic Stem Cells". J. Exp. Med. 192 (9): 1365–72. PMID 11067884.
External links
- GeneReviews/NCBI/UW/NIH entry on Alagille syndrome
- OMIM entries on Alagille syndrome
- JAG1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Alagille syndrome
This article incorporates text from the United States National Library of Medicine, which is in the public domain.