{PDOC51051}
{PS51051; DSL}
{BEGIN}
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* DSL domain profile *
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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     beta-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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: November 2011 / Text revised.

[ 1] Artavanis-Tsakonas S., Matsuno K., Fortini M.E.
     Science 268:225-232(1995).
[ 2] Fitzgerald K., Greenwald I.
     "Interchangeability of Caenorhabditis elegans DSL proteins and
     intrinsic signalling activity of their extracellular domains in
     vivo."
     Development 121:4275-4282(1995).
     PubMed=8575327
[ 3] Henderson S.T., Gao D., Lambie E.J., Kimble J.
     "lag-2 may encode a signaling ligand for the GLP-1 and LIN-12
     receptors of C. elegans."
     Development 120:2913-2924(1994).
     PubMed=7607081
[ 4] 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.
     "A conserved face of the Jagged/Serrate DSL domain is involved in
     Notch trans-activation and cis-inhibition."
     Nat. Struct. Mol. Biol. 15:849-857(2008).
     PubMed=18660822; DOI=10.1038/nsmb.1457
[ 5] Yuan Z.R., Okaniwa M., Nagata I., Tazawa Y., Ito M., Kawarazaki H.,
     Inomata Y., Okano S., Yoshida T., Kobayashi N., Kohsaka T.
     "The DSL domain in mutant JAG1 ligand is essential for the severity of
     the liver defect in Alagille syndrome."
     Clin. Genet. 59:330-337(2001).
     PubMed=11359464

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