PAP IB, a new member of the Reg gene family: cloning, expression, structural properties, and evolution by gene duplication.
Reg proteins are expressed in various organs and are involved in cancers and neurodegenerative diseases. They display a typical C-type lectin-like domain but possess additional highly conserved amino acids. By studying human databases and Expressed Sequence Tags library, we identified a new member called PAP IB. Using probabilistic approaches, we established a phylogenetic tree of eighteen Reg proteins. The dendogram showed that they constitute a superfamily composed of three distinct families (FI to FIII) of paralogues that resulted from duplication. We therefore focused on two proteins, REG Ialpha and PAP IB, belonging to the more closely related FI and FII families, respectively. REG Ialpha and PAP IB share 50% sequence identity. After cloning PAP IB, however, we found that it was expressed almost only in pancreas, unlike REG Ialpha, whose expression is ubiquitous. In addition, by building a model of the structure of PAP IB based on the X-ray structure of REG Ialpha, we observed that the two proteins displayed distinctive surface charge distribution, which may lead to different ligands binding. In spite of their common fold that should result in closely related functions, REG Ialpha and PAP IB are a good example of duplication and divergence, probably with the acquisition of new functions, thus participating in the evolution of the protein repertoire.
Laurine
Emmanuelle
E
INSERM U710, Montpellier, France.
Manival
Xavier
X
Montgelard
Claudine
C
Bideau
Chantal
C
Bergé-Lefranc
Jean-Louis
JL
Erard
Monique
M
Verdier
Jean-Michel
JM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001499:Bayes Theorem; D016466:CHO Cells; D003001:Cloning, Molecular; D016384:Consensus Sequence; D006224:Cricetinae; D017931:DNA Primers; D019143:Evolution, Molecular; D020440:Gene Duplication; D015894:Genome, Human; D006801:Humans; D037181:Lectins, C-Type / Q000737:chemistry / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D000073718:Pancreatitis-Associated Proteins; D010802:Phylogeny; D011487:Protein Conformation; D011506:Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D017931:DNA Primers; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; C494437:REG3G protein, human