Molecular cloning, tissue distribution, and chromosomal mapping of the human epithelial Ca2+ channel (ECAC1).
Functional and morphological analyses indicated that the epithelial Ca2+ channel (ECaC), which was recently cloned from rabbit kidney, exhibits the defining properties for being the gatekeeper in transcellular Ca2+ (re)absorption. Its human homologue provides, therefore, a molecular basis for achieving a better understanding of Ca2+ mal(re)absorption. By applying the RACE technique, the full-length cDNA of human ECaC (HGMW-approved symbol ECAC1) was obtained. It consisted of 2,772 bp with an open reading frame of 2,187 bp encoding a protein of 729 amino acids with a predicted molecular mass of 83 kDa. Phylogenetic analysis indicated that this highly selective Ca2+ channel exhibits a low level of homology (<30%) to other Ca2+ channels, suggesting that it belongs to a new family. hECaC was highly expressed in kidney, small intestine, and pancreas, and less intense expression was detected in testis, prostate, placenta, brain, colon, and rectum. These ECaC-positive tissues also expressed the 1,25-dihydroxyvitamin D3-sensitive calcium-binding proteins, calbindin-D9K and/or calbindin-D28K. The human ECaC gene mapped to chromosome 7q31.1-q31.2. Taken together, the conspicuous colocalization of hECaC and calbindins in organs that are not prime regulators of plasma Ca2+ levels could illustrate new pathways in cellular Ca2+ homeostasis.
Müller
D
D
Department of Cell Physiology, University of Nijmegen, The Netherlands.
Hoenderop
J G
JG
Meij
I C
IC
van den Heuvel
L P
LP
Knoers
N V
NV
den Hollander
A I
AI
Eggert
P
P
García-Nieto
V
V
Claverie-Martín
F
F
Bindels
R J
RJ
D000595:Amino Acid Sequence; D000818:Animals; D064092:Calbindin 1; D064026:Calbindins; D015220:Calcium Channels / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D002897:Chromosomes, Human, Pair 7; D003001:Cloning, Molecular; D017931:DNA Primers / Q000737:chemistry; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010802:Phylogeny; D020161:Physical Chromosome Mapping; D012333:RNA, Messenger / Q000032:analysis; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D050916:TRPV Cation Channels; D014018:Tissue Distribution
C576498:CALB1 protein, human; D064092:Calbindin 1; D064026:Calbindins; D015220:Calcium Channels; D017931:DNA Primers; C118497:ECaC protein, Oryctolagus cuniculus; D012333:RNA, Messenger; D064030:S100 Calcium Binding Protein G; C576506:S100G protein, human; D050916:TRPV Cation Channels; C492239:TRPV5 protein, human