SCNN1D

The first cDNA encoding the delta subunit of ENaC was cloned and sequenced by Waldmann et al. from human kidney mRNA. == Gene structure ==

The sequence of the SCNN1D gene was first revealed by the Human Genome Project. SCNN1D is located in the short arm of chromosome 1 (Ensembl database code: ENSG00000162572) and starts at nucleotide 1,280,436 on the forward strand. Its length is about 11,583 bp. The gene encodes several alternative transcripts with different transcription and translation initiation sites. In mRNA samples from human brain, alternative splicing products have been detected, cloned and characterized. The SCNN1D gene is found in most vertebrates, == Tissue-specific expression ==

The tissue specific expression of the δ-subunit is very different from that of the other three subunits encoded by SCNN1A, SCNN1B, and SCNN1G. While the α, β, and γ subunits are expressed mainly in the kidney tubular epithelia, the respiratory airway, the female reproductive tract, the δ-subunit is expressed mainly in the brain, pancreas, testis and ovary. == Protein structure ==

The primary structures of all four ENaC subunits show strong similarity. Thus, these four proteins represent a family of proteins that share a common ancestor. In global alignment (meaning alignments of sequences along their entire length and not just a partial segment), the human δ subunit shares 34% identity with the α subunit and 23% identity with the β and γ subunits. In the membrane-bound form, the TM segments are embedded in the membrane bilayer, the amino- and carboxy-terminal regions are located inside the cell, and the segment between the two TMs remains outside of the cell as the extracellular region of ENaC. This extracellular region includes about 70% of the residues of each subunit. Thus, in the membrane-bound form, the bulk of each subunit is located outside of the cell. The structure of ENaC has not been yet determined. Yet, the structure of a homologous protein ASIC1 has been resolved. The chicken ASIC1 structure revealed that ASIC1 is assembled as a homotrimer of three identical subunits. The authors of the original study suggested that the ASIC1 trimer resembles a hand holding a ball. == Associated diseases ==

So far mutations in the delta subunit have not been associated with a specific disease. ==Notes==