Table S1: Published information about select Drosophila serine proteases found after
extensive literature searches
S. No. Drosophila
SP accession
1.
CG15002
(masquerade)
2.
CG1505
(gastrulation
defective)
3.
CG6367 (psh;
Persephone)
4.
CG10129
(nudel)
Brief Functional description (if any)
References
Somatic muscle attachment during
Drosophila embryogenesis. Mutations in
masquerade affect axonal guidance and
taste behavior in Drosophila
The gastrulation defective (gd) locus
encodes a novel serine protease that is
involved in specifying the dorsal-ventral
axis during embryonic development.
At least three of the dorsal group genes
(snake, easter and gastrulation defective)
encode secreted serine proteases, which
probably function during early
development in the perivitelline
compartment of the embryo. The results
indicate that the three proteases function
in a sequential activation cascade, which
the genetic studies suggest is activated
locally in response to a ventral cue
Mutations in the persephone gene, which
encodes a serine protease, block
induction of the Toll pathway by fungi
and resistance to fungal and Grampositive bacterial infection.
The nudel gene, which is expressed in
follicle cells covering the oocyte encodes
an unusual mosaic protein resembling an
extracellular matrix protein with a
central serine protease domain and has
been proposed to function in locally
triggering a protease cascade that
produces the ventral signal. The serine
protease activity of the Nudel protein is
essential for embryonic dorsoventral
polarity and that the active Nudel
protease is generated by autoproteolytic
cleavage of a zymogen form. Threedimensional models of the catalytic
domains of Nudel (Ndl) Gastrulation
Defective (Gd), Snake (Snk), and Easter
(Ea), and their complexes with substrate
(see section 3.1);
(Murugasu-Oei et
al., 1996)
(see section 3.6);
(Ponomareff et al.,
2001)
(Ligoxygakis et al.,
2002)
(Hong and
Hashimoto, 1995;
LeMosy et al.,
1998); (see section
3.6)
5.
CG8867
(Ser4;
Jon25Bi)
6.
CG9564
(Try29F)
7.
CG7996
(Snake; snk)
8.
CG4920
(Easter; ea)
9.
CG4316
(Stubblestubbloid)
suggest a possible organization of the
enzyme cascade controlling the
dorsoventral fate of the fruit fly embryo
Ser4, a gene encoding a trypsin-like
serine protease was isolated and cloned
in Drosophila melanogaster. Northern
blot analysis reveals that the mRNA for
the gene is expressed abundantly in the
larval gut, suggesting a role in digestion
for this protein
Experimental evidence for the
association between Ser4 and CG13045
from Y2H.
The Drosophila melanogaster try29F
gene encodes a protein that shares all
known features of serine proteases like
residues known to be involved in
substrate specificity, catalysis and
disulfide bond formation. In situ
hybridization to mRNA in whole mount
embryos shows that the expression of
try29F is restricted to the posterior
midgut during late embryogenesis.
Experimental evidence for the
association between Try29F and
CG6866 (double-stranded RNA binding;
cytokine and chemokine mediated
signaling pathway; defense response)
Three serine protease zymogens
Gastrulation defective (GD), Snake
(Snk) and Easter (Ea), and a nerve
growth factor-like growth factor ligand
precursor, Spaetzle, are required for
specification of dorsal- ventral cell fate
during Drosophila embryogenesis.
(Refer to gd for more details)
1. Experimental evidence for the
association between ea and CG11581
from Y2H.
2. Experimental evidence for the
association between ea and ng1
(CG10781; structural molecule activity;
puparial adhesion) from IntAct & Y2H.
Stubble-stubbloid (Sb-sbd) locus that
encodes an unusual type II
transmembrane serine protease required
(Ahrens and
Mahoney, 1998)
(Paululat, 1996)
(see section 3.6)
(see section 3.6);
(Chen et al., 2004)
(see section 3.6)
10.
CG31039
(Ser99Dc;
Jon99Ci;
SER3)
11.
CG11313
12.
CG16705
(SPE)
13.
CG1102
(MP1)
14.
CG3066
(MP2)
CG4821
(Tequila)
15.
for normal leg and wing morphogenesis.
mutations affecting the RhoA signaling
pathway also interact genetically with
mutations in the Stubble-stubbloid (Sbsbd) locus, suggesting that RhoA and
Sb-sbd act in a common pathway during
leg morphogenesis
mRNA levels of SER3 appear to be
negatively regulated by cAMP and along
with SER1 and SER2 is abundantly
expressed in larval gut suggesting a
major function in digestion.
Similar to prophenoloxidase-activating
proteases; identified in small quantities
in Drosophila larval hemolymph clot,
suggesting that it may be associated with
clotting and eventually immune response
in Drosophila
Spätzle-processing enzyme, required for
Toll-dependent antimicrobial response in
Drosophila
Involved in activation of melanization in
response to both bacterial and fungal
infection
Involved in activation of melanization
chiefly in response to fungal infection
A neurotrypsin orthologue, regulates
long term memory formation in
Drosophila and is essential for
information processing in Drosophila
(Yun and Davis,
1989)
(Karlsson et al.,
2004)
(Mulinari et al.,
2006)
(Didelot et al.,
2006)
References
Ahrens, J.E., Mahoney, P.A., 1998. Isolation and cloning of Ser4, a gene encoding a
trypsin-like serine protease in Drosophila melanogaster. Biochim. Biophys. Acta
1395 141-4.
Chen, G.C., Gajowniczek, P., Settleman, J., 2004. Rho-LIM kinase signaling regulates
ecdysone-induced gene expression and morphogenesis during Drosophila
metamorphosis. Curr. Biol. 14 309-13.
Didelot, G., Molinari, F., Tchenio, P., Comas, D., Milhiet, E., Munnich, A., Colleaux, L.,
Preat, T., 2006. Tequila, a neurotrypsin ortholog, regulates long-term memory
formation in Drosophila. Science 313 851-3.
Hong, C.C., Hashimoto, C., 1995. An unusual mosaic protein with a protease domain,
encoded by the nudel gene, is involved in defining embryonic dorsoventral
polarity in Drosophila. Cell 82 785-94.
Karlsson, C., Korayem, A.M., Scherfer, C., Loseva, O., Dushay, M.S., Theopold, U.,
2004. Proteomic analysis of the Drosophila larval hemolymph clot. J. Biol. Chem.
279 52033-41.
LeMosy, E.K., Kemler, D., Hashimoto, C., 1998. Role of Nudel protease activation in
triggering dorsoventral polarization of the Drosophila embryo. Development 125
4045-53.
Ligoxygakis, P., Pelte, N., Hoffmann, J.A., Reichhart, J.M., 2002. Activation of
Drosophila Toll during fungal infection by a blood serine protease. Science 297
114-6.
Mulinari, S., Hacker, U., Castillejo-Lopez, C., 2006. Expression and regulation of
Spatzle-processing enzyme in Drosophila. FEBS Lett. 580 5406-10.
Murugasu-Oei, B., Balakrishnan, R., Yang, X., Chia, W., Rodrigues, V., 1996. Mutations
in masquerade, a novel serine-protease-like molecule, affect axonal guidance and
taste behavior in Drosophila. Mech. Dev. 57 91-101.
Paululat, A., 1996. Try29F, a new member of the Drosophila trypsin-like protease gene
family, is specifically expressed in the posterior embryonic midgut. Gene 172
245-7.
Ponomareff, G., Giordano, H., DeLotto, Y., DeLotto, R., 2001. Interallelic
complementation at the Drosophila melanogaster gastrulation defective locus
defines discrete functional domains of the protein. Genetics 159 635-45.
Yun, Y., Davis, R.L., 1989. Levels of RNA from a family of putative serine protease
genes are reduced in Drosophila melanogaster dunce mutants and are regulated by
cyclic AMP. Mol. Cell. Biol. 9 692-700.