GENOMIC ORGANIZATION, NUCLEOTIDE-SEQUENCE, BIOPHYSICAL PROPERTIES, AND LOCALIZATION OF THE VOLTAGE-GATED K+ CHANNEL GENE KCNA4 KV1.4 TO MOUSE CHROMOSOME-2 HUMAN-11P14 AND MAPPING OF KCNC1 KV3.1 TO MOUSE-7 HUMAN-11P14.3-P15.2 AND KCNA1 KV1.1 TO HUMAN-12P13/

A genomic clone encoding the Shaker-related potassium channel gene, Kc na4/mKv1.4, was isolated from mice. Its coding region is contained in a single exon, encodes a protein of 654 amino acids, and shares approx imately 91% nucleotide sequence identity with human KCNA4/hKv1.4. We s how that 0.8 kb of the 5' noncoding region (NCR), the entire protein c oding region (approximately 2.0 kb), and all of the known 3' NCR (appr oximately 1.1 kb) are contained within a single exon; the remaining 0. 5 kb of the 5' NCR is separated from this exon by a 3.4-kb intron. The sequenced genomic region thus accounts for essentially all of the lon gest known transcript (4.5 kb), although the precise ends of this tran script have not been defined. The 3' NCR contains several ATTTA and AT TTG motifs that are thought to destabilize mRNAs, and these are also p resent in rat, bovine, and human KcnA4/Kv1.4 cDNAs. It also contains t hree conserved polyadenylation signals, alternate utilization of which could generate mRNAs of differing stabilities. The 5' NCR of Kcna4/mK v1.4 may also serve to regulate channel expression. This region is app roximately 85% identical to KCNA4/hKv1.4 and contains eight consensus translation start sites [(G, A)NNATG] that, based on the 5'-3' scannin g model, would lead to a lowering of translational efficiency. The sho rtest Kcna4/Kv1.4 transcript (2.4 kb) can contain at most 400 bp of NC R and should lack the 3' ATTTAs and most of the 5' ATGs; this transcri pt might therefore exhibit increased stability and translational effic iency. The Kcna4/mKv1.4 channel exhibited biophysical and pharmacologi cal properties indistinguishable from its rat and human homologues. Kc na4/mKv1.4 lies on mouse chromosome 2, near the Fshb locus, and in hum ans on the proximal half of chromosome 11p14 near human FSHB. Another K+, channel gene, Kcnc1/mKv3.1, lies approximately 1.8 cM from the Myo d-1 gene on mouse chromosome 7, and in situ hybridization localizes KC NC1/hKv3.1 to the homologous region on human chromosome 11p14.3-p15.2. A third gene, KCNA1/hKv1.1, was mapped to human 12p13. (C) 1994 Acade mic Press, Inc.