PROSITE documentation PDOC51051
DSL 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.


Technical section

PROSITE method (with tools and information) covered by this documentation:

DSL, PS51051; DSL domain profile  (MATRIX)


1AuthorsArtavanis-Tsakonas S. Matsuno K. Fortini M.E.
SourceScience 268:225-232(1995).

2AuthorsFitzgerald K. Greenwald I.
TitleInterchangeability of Caenorhabditis elegans DSL proteins and intrinsic signalling activity of their extracellular domains in vivo.
SourceDevelopment 121:4275-4282(1995).
PubMed ID8575327

3AuthorsHenderson S.T. Gao D. Lambie E.J. Kimble J.
Titlelag-2 may encode a signaling ligand for the GLP-1 and LIN-12 receptors of C. elegans.
SourceDevelopment 120:2913-2924(1994).
PubMed ID7607081

4AuthorsCordle 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.
TitleA conserved face of the Jagged/Serrate DSL domain is involved in Notch trans-activation and cis-inhibition.
SourceNat. Struct. Mol. Biol. 15:849-857(2008).
PubMed ID18660822

5AuthorsYuan Z.R. Okaniwa M. Nagata I. Tazawa Y. Ito M. Kawarazaki H. Inomata Y. Okano S. Yoshida T. Kobayashi N. Kohsaka T.
TitleThe DSL domain in mutant JAG1 ligand is essential for the severity of the liver defect in Alagille syndrome.
SourceClin. Genet. 59:330-337(2001).
PubMed ID11359464

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