Genomic and cDNA clones encoding a novel Shaw-related potassium channel gene have been isolated from mice and humans. The mouse-Kv3.3 gene encodes a protein of 679 amino acids. Unlike the vertebrate Shaker-related genes that have intronless coding regions, mouse Kv3.3 is encoded by at least two exons separated by 3 kb of intervening sequence. The amino-terminal 212 amino acids are encoded by a single exon, and the hydrophobic core of the protein beginning at the S1 transmembrane segment is contained in a separate exon. Multiple Kv3.3-hybridizing transcripts are visible in the mouse brain, liver, thymus, and heart. Using probes derived from a human genomic clone containing the 3' exon of human Kv3.3 (KCNC3), we have localized the gene to human chromosome 19. The related gene, human Kv3.4 (KCNC4), was localized to human chromosome 1.

Four related genes, Shaker, Shab, Shaw, and Shal, encode voltage-gated K+ channels in Drosophila. Multigene subfamilies corresponding to each of these Drosophila genes have been identified in rodents and primates; this suggests that the four genes are older than the common ancestor of present-day insects and mammals and that the expansion of each into a family occurred before the divergence of rodents and primates. In order to define these evolutionary relationships more precisely and to facilitate the search for mammalian candidate K+ channel gene mutations, we have mapped members of the Shaw-homologous gene family in humans and mice. Fluorescence in situ hybridization analysis of human metaphase chromosomes mapped KCNC2 (KShIIIA, KV3.2) and KCNC3 (KShIIID, KV3.3) to Chromosome (Chr) 19q13.3-q13.4. Inheritance patterns of DNA restriction fragment length variants in recombinant inbred strains of mice placed the homologous mouse genes on distal Chr 10 near Ms15-8 and Mdm-1. The mouse Kcnc1 (KShIIIB, NGK2-KV4, KV3.1) gene mapped to Chr7 near Tam-1. These results are consistent with the hypothesis that the generation of the mammalian KCNC gene family included both duplication events to generate family members in tandem arrays (KCNC2, KCNC3) and dispersion of family members to unlinked chromosomal sites (KCNC1). The KNCN2 and KCNC3 genes define a new synteny group between humans and mice.

>sp|Q14003|KCNC3_HUMAN Potassium voltage-gated channel subfamily C member 3 OS=Homo sapiens GN=KCNC3 PE=1 SV=3
MLSSVCVSSFRGRQGASKQQPAPPPQPPESPPPPPLPPQQQQPAQPGPAASPAGPPAPRGPGDRRAEPCPGLPAAAMGRH
GGGGGDSGKIVINVGGVRHETYRSTLRTLPGTRLAGLTEPEAAARFDYDPGADEFFFDRHPGVFAYVLNYYRTGKLHCPA
DVCGPLFEEELGFWGIDETDVEACCWMTYRQHRDAEEALDSFEAPDPAGAANAANAAGAHDGGLDDEAGAGGGGLDGAGG
ELKRLCFQDAGGGAGGPPGGAGGAGGTWWRRWQPRVWALFEDPYSSRAARYVAFASLFFILISITTFCLETHEGFIHISN
KTVTQASPIPGAPPENITNVEVETEPFLTYVEGVCVVWFTFEFLMRITFCPDKVEFLKSSLNIIDCVAILPFYLEVGLSG
LSSKAAKDVLGFLRVVRFVRILRIFKLTRHFVGLRVLGHTLRASTNEFLLLIIFLALGVLIFATMIYYAERIGADPDDIL
GSNHTYFKNIPIGFWWAVVTMTTLGYGDMYPKTWSGMLVGALCALAGVLTIAMPVPVIVNNFGMYYSLAMAKQKLPKKKN
KHIPRPPQPGSPNYCKPDPPPPPPPHPHHGSGGISPPPPITPPSMGVTVAGAYPAGPHTHPGLLRGGAGGLGIMGLPPLP
APGEPCPLAQEEVIEINRADPRPNGDPAAAALAHEDCPAIDQPAMSPEDKSPITPGSRGRYSRDRACFLLTDYAPSPDGS
IRKATGAPPLPPQDWRKPGPPSFLPDLNANAAAWISP