Shaye and Greenwald
Supplementary Information 1
The downregulation targeting signal (DTS) is conserved in other nematode LIN-12/Notch proteins

Alignment of RAM domains from different nematode LIN-12/Notch proteins.
DTS
C. elegans LIN-12
C. elegans GLP-1
C. briggsae LIN-12
C. briggsae GLP-1
C. remanei GLP-1
M
M
I
I
I
.
I
V
I
I
I
I
N
N
N
H
H
.
A
A
A
A
A
A
S
T
P
P
P
V
V
V
V
V
V
WM
WM
W T
WM
W T
W
P
P
P
P
P
P
P
P
P
P
P
P
M
M
M
P
M
M
E
E
E
M
E
E
N
S
N
T
E
T
E
P
E
N
D
I
K
E
K
D
N
K
N
K
N
-
R
Q
R
G
R
T
K
R
M
P
N
R
H
Q
H
N
N
N
.
Q
Q
Q
E
P
.
S
S
S
S
S
S
I
N
M
L
I
.
T
H
N
L
Y
S
S
S
C
S
S
S
S
S
S
S
Q
Q
Q
Q
Q
Q
H
C
H
S
V
S
S
S
S
S
S
L
L
L
L
L
L
L
L
L
L
L
L
E
D
D
E
N
.
A
N
P
H
D
S
S
T
S
S
S
Y
A
G
M
N
D
Y
Y
H
M
G
Y
F
H
Y
Y
H
D
V
L
P
N
N
N
A
A
I
T
S
A
P
K
K
K
K
K
K
R
R
R
K
R
R
Q
H
H
P
V
R
C
R
R
R
R
N
S
T
V
R
E
D
D
D
E
.
L
Y
Y
Y
F
.
Q
S
E
S
Y
H
T
N
D
L
Y
G
G
G
P
S
Y
H
G
G
L
N
M
L
P
Y
G
M
Y
E
P
E
T
Q
E
N
Q
T
E
Q
H
I
-
- - - - - P Q G
- - - - Y S Q I
Y N Q F F P Q S
- - - - Y Q E I
.
The RAM domain is the amino-terminal part of the intracellular domain (see ref. 1 and Fig. 2e in main text). LIN-12 and GLP1 are the two C. elegans Notch proteins. The lin-12 and glp-1 genes appear to have arisen from a duplication event2, and GLP1 can substitute for LIN-12 in VPC specification3. C. elegans, C. briggsae and C. remanei are estimated to have diverged
between 404 and 100 (http://www.sanger.ac.uk/Projects/C_briggsae/) million years ago. See ref. 2 for C. elegans sequences. C.
briggsae LIN-12 was obtained from the Sanger Institute (Cambridge, UK) and the Genome Sequencing Center (Washington
University, St Louis) C. briggsae sequencing projects. C. briggsae and C. remanei GLP-1 sequences are from ref. 4
Alignments were obtained with the ClustalW program5.
1.
Tamura, K. et al. Physical interaction between a novel domain of the receptor Notch and the transcription factor RBP-J kappa/Su(H). Curr Biol
5, 1416-23. (1995).
2.
Yochem, J. & Greenwald, I. glp-1 and lin-12, genes implicated in distinct cell-cell interactions in C. elegans, encode similar transmembrane
proteins. Cell 58, 553-63. (1989).
3.
Fitzgerald, K., Wilkinson, H. A. & Greenwald, I. glp-1 can substitute for lin-12 in specifying cell fate decisions in Caenorhabditis elegans.
Development 119, 1019-27. (1993).
4.
Rudel, D. & Kimble, J. Conservation of glp-1 regulation and function in nematodes. Genetics 157, 639-54. (2001).
5.
Thompson, J. D., Higgins, D. G. & Gibson, T. J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through
sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22, 4673-80. (1994).