Ch. Huang et Pz. Liu, New insights into the Rh superfamily of genes and proteins in erythroid cells and nonerythroid tissues, BL CELL M D, 27(1), 2001, pp. 90-101
The past decade has seen extensive studies of the erythrocyte Rh30 polypept
ides and Rh-associated glycoprotein, which specify the clinically important
Rh blood group system. Here we consider recent advances on these and other
Rh homologues in the context of gene organization, molecular evolution, ti
ssue-specific expression, protein structure, and potential biological funct
ions. The Rh family is now known to contain a large number of homologues th
at form a unique branch in the eucarya life domain. The ancient origin and
broad distribution imply central roles for the various Rh proteins in maint
aining normal cellular and organismal homeostatic conditions. Rh homologues
occur in the form of multiple chromosomal loci in mice and humans, but as
single-copy genes in unicellular organisms (e.g., green alga and slime mold
). While primitive Rh genes vary largely in exon/intron design, the mammali
an Rh homologues bear a similar genomic organization. Sequence comparisons
have revealed the signatures and a consensus 12-transmembrane fold characte
ristic of the Rh family. Phylogenetic analysis has placed all Rh homologues
as a related cluster that intercepts ammonium transporter (Amt) clusters,
indicating an intimate evolutionary and structural relationship between the
Rh and Amt families. The biochemical identification and epithelial express
ion of RhBG and RhCG orthologues in mammalian kidney, liver, skin, testis,
and brain suggest that they serve as transporters likely participating in a
mmonia homeostasis. Further inquires into the structure, function, biosynth
esis, and interaction of Rh proteins will shed new light on ammonia homeost
asis in a wide range of human physiological and pathological states. (C) 20
01 Academic Press.