PROSITE documentation PDOC51051DSL domain profile
The about 50 amino acids DSL (Delta / Serrate / Lag-2) domain is an extracellular domain essential to activate members of the Lin-12/Notch receptors family. The DSL domain may mediates oligomerization of DSL proteins to form an active ligand and mediates interaction with the extracellular domain of Lin-12/Notch proteins involved in cell-cell signaling interactions [1,2,3]. The DSL domain is found followed by a variable number of tandemly repeated copies of EGF motifs (see <PDOC00021>). Like EGF motifs this domain contains six conserved cysteines spanning different sequence lengths. Furthermore, the DSL domain contains a conserved YYG motif not present in the EGF motifs.
The DSL domain has clear structural similarities to an EGF domain, with a double-stranded antiparallel β-sheet immediately preceding the characteristic loop between the final disulfide-bonded cysteines residues (see <PDB:2VJ2>). However, the DSL domain adopts a fold with a different disulfide-bonded pattern (C1-C2, C3-C4, C5-C6). On the basis of the structure, it has been proposed that the DSL domain may have evolved from a truncation of two tandem short EGF domains [4].
Proteins currently known to contain a DSL domain are:
- The mammalian Serrate proteins, which are ligands for Notch receptors essential for the differenciation of certain tissues.
- The human JAG1 and the Drosophila Delta proteins. They are ligands for multiple Notch receptors and are involved in the mediation of Notch signaling [5].
- The Caenorhabditis elegans lag-2/Apx1 proteins which are signaling ligands for the glp-1 and lin-12 receptors [3].
The profile we developed covers the entire DSL domain.
Last update:November 2011 / Text revised.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Artavanis-Tsakonas S. Matsuno K. Fortini M.E. |
| Source | Science 268:225-232(1995). |
| 2 | Authors | Fitzgerald K. Greenwald I. |
| Title | Interchangeability of Caenorhabditis elegans DSL proteins and intrinsic signalling activity of their extracellular domains in vivo. | |
| Source | Development 121:4275-4282(1995). | |
| PubMed ID | 8575327 |
| 3 | Authors | Henderson S.T. Gao D. Lambie E.J. Kimble J. |
| Title | lag-2 may encode a signaling ligand for the GLP-1 and LIN-12 receptors of C. elegans. | |
| Source | Development 120:2913-2924(1994). | |
| PubMed ID | 7607081 |
| 4 | Authors | Cordle J. Johnson S. Tay J.Z.Y. Roversi P. Wilkin M.B. Hernandez de Madrid B. Shimizu H. Jensen S. Whiteman P. Jin B. Redfield C. Baron M. Lea S.M. Handford P.A. |
| Title | A conserved face of the Jagged/Serrate DSL domain is involved in Notch trans-activation and cis-inhibition. | |
| Source | Nat. Struct. Mol. Biol. 15:849-857(2008). | |
| PubMed ID | 18660822 | |
| DOI | 10.1038/nsmb.1457 |
| 5 | Authors | Yuan Z.R. Okaniwa M. Nagata I. Tazawa Y. Ito M. Kawarazaki H. Inomata Y. Okano S. Yoshida T. Kobayashi N. Kohsaka T. |
| Title | The DSL domain in mutant JAG1 ligand is essential for the severity of the liver defect in Alagille syndrome. | |
| Source | Clin. Genet. 59:330-337(2001). | |
| PubMed ID | 11359464 |
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