The Functionally Unannotated Proteome of Human Male Tissues: A Shared Resource to Uncover New Protein Functions Associated with Reproductive Biology

In the context of the Human Proteome
Project, we built an inventory
of 412 functionally unannotated human proteins for which experimental
evidence at the protein level exists (uPE1) and which are highly expressed
in tissues involved in human male reproduction. We implemented a strategy
combining literature mining, bioinformatics tools to collate annotation
and experimental information from specific molecular public resources,
and efficient visualization tools to put these unknown proteins into
their biological context (protein complexes, tissue and subcellular
location, expression pattern). The gathered knowledge allowed pinpointing
five uPE1 for which a function has recently been proposed and which
should be updated in protein knowledge bases. Furthermore, this bioinformatics
strategy allowed to build new functional hypotheses for five other
uPE1s in link with phenotypic traits that are specific to male reproductive
function such as ciliogenesis/flagellum formation in germ cells (CCDC112
and TEX9), chromatin remodeling (C3orf62) and spermatozoon maturation
(CCDC183). We also discussed the enigmatic case of MAGEB proteins,
a poorly documented cancer/testis antigen subtype. Tools used and
computational outputs produced during this study are freely accessible
via ProteoRE (http://www.proteore.org), a Galaxy-based instance, for reuse purposes. We propose these
five uPE1s should be investigated in priority by expert laboratories
and hope that this inventory and shared resources will stimulate the
interest of the community of reproductive biology.