Structure and complex transcription pattern of the mouse SK1 K(Ca) channel gene, KCNN1.
Small conductance calcium-gated K(+) channels (SK channels) are encoded by the three SK genes, SK1, SK2, and SK3. These channels likely contribute to slow synaptic afterhyperpolarizations of apamin-sensitive and apamin-insensitive types. SK channels are also widely expressed outside the nervous system. The mouse SK1 gene comprises at least 12 exons extending across 19.8 kb of genomic DNA. This gene encodes a complex pattern of alternatively spliced SK1 transcripts widely expressed among mouse tissues. These transcripts exhibit at least four distinct 5'-nucleotide sequence variants encoding at least two N-terminal amino acid sequences. Optional inclusion of exons 7 and 9, together with two alternate splice donor sites in exon 8, yields transcripts encoding eight variant C-terminal amino acid sequences for SK1. These include an altered putative S6 transmembrane span, modification of the C-terminal cytoplasmic domain binding site for calmodulin, and generation of two alternate predicted binding sites for PDZ domain-containing proteins. 20 of the 32 predicted mouse SK1 transcripts are expressed in brain at levels sufficient to allow consistent detection, and encode 16 SK1 polypeptide variants. Only four of these 16 polypeptides preserve the ability to bind calmodulin in a Ca(2+)-independent manner. Mouse SK1 also exhibits novel, strain-specific, length polymorphism of a polyglutamate repeat in the N-terminal cytoplasmic domain. The evolutionary conservation of this complex transcription pattern suggests a possible role in the tuning of SK1 channel function.
Molecular Medicine Unit, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA.
B E
BE
Shmukler
C T
CT
Bond
S
S
Wilhelm
A
A
Bruening-Wright
J
J
Maylie
J P
JP
Adelman
S L
SL
Alper
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002147:Calmodulin / Q000378:metabolism; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics; D011099:Polyglutamic Acid; D011110:Polymorphism, Genetic; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated; D012333:RNA, Messenger; D051381:Rats; D020449:Repetitive Sequences, Amino Acid; D017386:Sequence Homology, Amino Acid; D051640:Small-Conductance Calcium-Activated Potassium Channels; D014158:Transcription, Genetic
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D002147:Calmodulin; D018076:DNA, Complementary; C496895:Kcnn1 protein, mouse; C496896:Kcnn1 protein, rat; C496898:Kcnn2 protein, mouse; C496899:Kcnn2 protein, rat; C496900:Kcnn3 protein, mouse; C496901:Kcnn3 protein, rat; D010455:Peptides; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D012333:RNA, Messenger; D051640:Small-Conductance Calcium-Activated Potassium Channels; D011099:Polyglutamic Acid