BACKGROUND: Distantly related proteins adopt and retain similar structural 
scaffolds despite length variations that could be as much as two-fold in some 
protein superfamilies. In this paper, we describe an analysis of indel regions 
that accommodate length variations amongst related proteins. We have developed 
an algorithm CUSP, to examine multi-membered PASS2 superfamily alignments to 
identify indel regions in an automated manner. Further, we have used the method 
to characterize the length, structural type and biochemical features of indels 
in related protein domains.
RESULTS: CUSP, examines protein domain structural alignments to distinguish 
regions of conserved structure common to related proteins from structurally 
unconserved regions that vary in length and type of structure. On a 
non-redundant dataset of 353 domain superfamily alignments from PASS2, we find 
that 'length- deviant' protein superfamilies show > 30% length variation from 
their average domain length. 60% of additional lengths that occur in indels are 
short-length structures (< 5 residues) while 6% of indels are > 15 residues in 
length. Structural types in indels also show class-specific trends.
CONCLUSION: The extent of length variation varies across different superfamilies 
and indels show class-specific trends for preferred lengths and structural 
types. Such indels of different lengths even within a single protein domain 
superfamily could have structural and functional consequences that drive their 
selection, underlying their importance in similarity detection and computational 
modelling. The availability of systematic algorithms, like CUSP, should enable 
decision making in a domain superfamily-specific manner.