HumanPRENbase is a derivate of PRENbase with
focus on human prenylated proteins. In PRENbase, paralogous proteins are clustered
together in their respective larger family when they are highly similar to each other. This happens, for
example, with the different Ras proteins H-Ras, K-Ras, N-ras, etc. Paralogues can nevertheless have different
functions or often similar but more specialized roles. Especially in the light of the importance of
prenylation of several members of the Ras, Rab and Rho GTPase families, we sought a solution to investigate
the prenylation status of individual human proteins rather than larger families they are part of. Therefore,
we employed a scheme of reciprocal BLASTs in order to identify the true orthologues of a set of prenylated
human proteins (see accompanying publication for details). 238 individual human proteins and their
orthologues form the clusters in HumanPRENbase.
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PRENbase!
This search interface is designed to allow sophisticated queries for the
experimental status of the modification (known/predicted...), exclusive or shared types of modifying enzymes
(FT, GGT1, GGT2) as well as for evolutionary conservation by constraining the taxonomic distribution within
these clusters or for single sequences.
The listed status annotation is taken from the general PRENbase cluster. Therefore, "+" means that at least
one member of the larger protein family has been experimentally verified to be prenylated. This is the case,
for example, for the large Ras, Rab and Rho families of GTPases, where the prenylation of each individual
member has not been shown directly but often can be safely inferred if a valid prenylation motif exists.
To start with, the default settings will give access to the collection of both
known and predicted prenylated proteins clustered around individual human proteins, which can then be
browsed. Below we have listed a series of standard queries that you might find useful or are particularly
biologically important:
- Review of previous knowledge of prenylated proteins:
List the
clusters including KNOWN prenylated proteins.
- LIKELY prenylation candidates for experimental validation (close homologue already
verified):
List the
clusters including LIKELY prenylated proteins.
- Targets for experimental validation of NEW predicted prenylation:
List the
clusters including NEWLY PREDICTED prenylated proteins.
As above
but require conservation between Mammalia and Insecta.
As above
but require conservation between Mammalia and Nematoda.
As above
but require conservation between Mammalia and Fungi.
As above
but require conservation between Mammalia and Plants.
- Possible targets for FTI (FT inhibition, see accompanying publications for details):
List only
proteins that are unique substrates to FT and not GGT1 or GGT2.
List the
clusters of proteins containing unique substrates to FT and not GGT1 or GGT2 and conserved between Human
and Insecta.
List the
clusters of proteins containing unique substrates to FT and not GGT1 or GGT2 and conserved between Human
and Nematoda.
List the
clusters of proteins containing unique substrates to FT and not GGT1 or GGT2 and conserved between Human
and Fungi.
List the
clusters of proteins containing unique substrates to FT and not GGT1 or GGT2 and conserved between Human
and Plants.
- FT substrates less affected by FT inhibition or with altered anchor type under FTI:
List FT
substrates that can be alternatively prenylated by GGT1.
- Predicted prenylation in Viruses:
List the
number of viral proteins with capacity to be prenylated if the biological context would allow processing by
eukaryotic host enzymes.
- Possible importance of specific farnesyl anchor length:
List clusters
that only include FT but not GGT1 or GGT2 substrates.
- Evolutionary exchangeability of different prenyl anchors:
List clusters
that include both FT and GGT1 substrates.
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