Molecular cloning and biochemical characterization of a truncated, secreted member of the human family of Ca2+-activated Cl- channels.
A novel family of chloride channel proteins has recently been discovered including two bovine (Lu-ECAM-1, bCLCA1), one murine (mCLCA1), and two human (hCLCA1 and hCLCA2) members. Here, we describe the cloning, expression, and molecular characterization of a truncated human homolog, tentatively named hCLCA3. It was cloned from a human spleen cDNA library and is expressed in numerous tissues including lung, trachea, spleen, thymus, and mammary gland as determined by reverse transcriptase-polymerase chain reaction. Unlike all previously known CLCA family members which consistently encode an approximately 125-kDa transmembrane protein that is cleaved to form a heterodimer of two proteins of approximately 90 and 35 kDa, the 3.6-kb hCLCA3 mRNA encodes a 37-kDa glycoprotein that corresponds to the N-terminal extracellular domain of its homologs. Moreover, when expressed in human embryonic kidney 293 or Chinese hamster ovary cells, this 37-kDa glycoprotein is secreted into the culture supernatant. These observations suggest that hCLCA3 is a structurally divergent member of the CLCA family of proteins and that it does not act as a channel protein but has distinct, yet unidentified functions.
Gruber
A D
AD
Department of Molecular Medicine, Cancer Biology Laboratories, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Pauli
B U
BU
D000595:Amino Acid Sequence; D018118:Chloride Channels; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D016415:Sequence Alignment
C118655:CLCA3P protein, human; D018118:Chloride Channels; D018076:DNA, Complementary; D008562:Membrane Glycoproteins