title: 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.
abstract: 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 prepared to match the sequence of the expected active region of a frog corticotropin-releasing factor-like peptide sauvagine and used to screen a sheep brain cDNA library. A novel 1331-bp cDNA encoding a putative 328-residue protein with a theoretical mass of 36 kDa was identified. The presence of a strong signal sequence indicates that it is a secreted protein. The amino- and carboxy-terminal regions are characterized by several potential phosphorylation sites and binding motifs, suggesting a role in intracellular signal transduction. Although the protein possesses a 7-residue sequence identical to that found in sauvagine, its overall primary structure most closely resembles those of the alpha-carbonic anhydrases (alpha-CAs). Moreover, the detection of the human and mouse orthologues in the EST databases, together with an 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 protein gene (DBP) on chromosome 19q13.3. Despite potentially inactivating changes in the active-site residues, CA-RP XI is evolving very slowly in mammals, a property indicative of an important function, which has also been observed in the two other "acatalytic" CA isoforms, CA-RP VIII and CA-RP X, whose functions are unknown.
authors.affiliation: The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, California, 92037, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Lovejoy
authors.forename: D
authors.initials: D
authors.lastname: Hewett-Emmett
authors.forename: C A
authors.initials: CA
authors.lastname: Porter
authors.forename: D
authors.initials: D
authors.lastname: Cepoi
authors.forename: A
authors.initials: A
authors.lastname: Sheffield
authors.forename: W W
authors.initials: WW
authors.lastname: Vale
authors.forename: R E
authors.initials: RE
authors.lastname: Tashian
mesh_terms: D000595:Amino Acid Sequence; D029845:Amphibian Proteins; D000818:Animals; D001483:Base Sequence; D014408:Biomarkers, Tumor; D001921:Brain / Q000201:enzymology; D002256:Carbonic Anhydrases / Q000235:genetics*; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D017124:Conserved Sequence; D004268:DNA-Binding Proteins; D020224:Expressed Sequence Tags; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D009419:Nerve Tissue Proteins / Q000235:genetics*; D036361:Peptide Hormones; D010455:Peptides; D010802:Phylogeny; D014176:Protein Biosynthesis; D051381:Rats; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012756:Sheep; D014157:Transcription Factors / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins
chemical_list: D029845:Amphibian Proteins; D014408:Biomarkers, Tumor; D002256:Carbonic Anhydrases; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D036361:Peptide Hormones; D010455:Peptides; D014157:Transcription Factors; C512815:CA10 protein, human; C512817:CA11 protein, human; C512819:Car10 protein, mouse; C512820:Car11 protein, mouse; C512821:Car8 protein, mouse; C063898:DBP protein, human; C485975:DBP protein, rat; C498260:Dbp protein, mouse; C025727:sauvagine; C512818:CA8 protein, human; D047908:Intracellular Signaling Peptides and Proteins