Evolutionarily conserved, "acatalytic" carbonic anhydrase-related protein XI contains a sequence motif present in the neuropeptide sauvagine: The human CA-RP XI gene (CA11) is embedded between the secretor gene cluster and the DBP gene at 19q13.3

Conserved amino acid motifs are found in numerous expressed genes. Proteins and peptides with functional relationships may be identified using probes designed to hybridize with these motifs. An oligonucleotide probe was prepa red to match the sequence of the expected active region of a frog corticotr opin-releasing factor-like peptide sauvagine and used to screen a sheep bra in cDNA library. A novel 1331-bp cDNA encoding a putative 328-residue prote in with a theoretical mass of 36 kDa was identified. The presence of a stro ng signal sequence indicates that it is a secreted protein. The amino- and carboxy-terminal regions are characterized by several potential phosphoryla tion sites and binding motifs, suggesting a role in intracellular signal tr ansduction, Although the protein possesses a 7-residue sequence identical t o that found in sauvagine, its overall primary structure most closely resem bles those of the cu-carbonic anhydrases (alpha-CAs). Moreover, the detecti on of the human and mouse orthologues in the EST databases, together with a n evolutionary analysis, indicates that the protein represents a new member of the alpha-CA gene family, which we designate carbonic anhydrase-related protein XI (CA-RP XI), encoded by CA11 (human) and Car11 (mouse, rat). The human CA11 gene appears to be located between the secretor type alpha(1,2) -fucosyltransferase gene cluster (FUT1-FUT2-FUT2P) and the D-site binding p rotein gene (DBP) on chromosome 19q13.3. Despite potentially inactivating c hanges in the active-site residues, CA-RP XI is evolving very slowly in mam mals, a property indicative of an important function, which has also been o bserved in the two other "acatalytic" CA isoforms, CA-RP VIII and CA-RP X, whose functions are unknown. (C) 1998 Academic Press.