Annotated transcripts do not represent all possible combinations of alternative exons and/or alternative promoters.
gene_with_stop_codon_read_through ; SO:0000697
Stop-codon suppression (UGA) postulated; FBrf0216884.
Gene model reviewed during 5.44
Low-frequency RNA-Seq exon junction(s) not annotated.
Gene model reviewed during 5.47
11, 5.8 (northern blot)
None of the polypeptides share 100% sequence identity.
This is the A1/C2/E2/G5/I0 form of the slo protein. See sloA1C2E2G5I0 for a functional analysis of the protein.
PCR analysis has demonstrated that many alternate coding sequences exist for the slo protein. Conserved amino acids 18-326 encode the first five and part of the sixth transmembrane domain and are followed by domains A-J. The variable A, C, E, G, and I domains have alternate forms and the B, D, F, H, and J domains are conserved. The A domains (A1-A3) are 30aa long, B is 37aa, C1 and C2 are 35aa, D is 104aa,E1 and E2 are 37aa, F is 79aa, G1-G6 are 60, 27, 13, 47, 22, and 59 aa long, respectively, H is 65aa, I0 and I1 are 0 and 22 aa, respectively,and J is 440aa. It is not known how many of the 144 potential forms of the protein are actually used in the fly head but evidence for at least 31 has been obtained. Results suggest that the different isoforms are functionally diverse.
This is the A1/C2/E1/G3/I0 form of the slo protein. See sloA1C2E1G3I0 for a functional analysis of the protein.
slo protein has seven hydrophobic domains near
the amino terminus, a structure that is similar to other known
K+-channel polypeptides. Similarities are observed between the slo
protein and other voltage-gated channels in the S4 domain which is thought
to mediate voltage sensitivity. The greatest similarity to other
K+-channel polypeptides is in the H5 domain, an integral part of the ion
conduction pore. Outside of these two regions, the slo protein is
distinct from all known K+ channels. A putative EF-hand domain and an
ATP-binding site were identified. The protein sequence is probably
incomplete at the amino terminus.
Homotetramer; which constitutes the calcium-activated potassium channel (By similarity). Interacts with Slip1. Interacts with Slob, and, indirectly with 14-3-3-zeta via its interaction with Slob. Interacts with Pka-C1 and Src kinases, which can bind simultaneously to it.
Phosphorylated. Phosphorylation may be mediated by both PKA and SRC kinases, which activate the channel activity. Phosphorylation by PKA is however unclear. Indeed, although modulation of channel activity requires Pka-C1, it does not interacts with the whole PKA holoenzyme. Moreover, modulation of activity does not depend upon phosphorylation of Ser-978.
The S4 segment, which is characterized by a series of positively charged amino acids at every third position, is part of the voltage-sensor.
The pore-forming domain (also referred as P region) is imbedded into the membrane, and forms the selectivity filter of the pore. It contains the signature sequence of potassium channels that displays selectivity to potassium (By similarity).
The RCK N-terminal domain mediates the homotetramerization, thereby promoting the assembly of monomers into functional potassium channel. It includes binding sites for Ca(2+) and Mg(2+) (By similarity).
The calcium bowl constitutes one of the Ca(2+) sensors and probably acts as a Ca(2+)-binding site.
Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\slo using the Feature Mapper tool.
GBrowse - Visual display of RNA-Seq signalsView Dmel\slo in GBrowse 2
Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete
Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.
For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.
Slob is identified as a protein that binds to the carboxy-terminal domain of slo in a yeast two-hybrid screen. Slob and slo co-immunoprecipitate from heads and heterologous host cells, suggesting they interact in vivo.
The region downstream of promoter C2 (exon C2 and exon C3) contains elements required for CNS expression, modulates expression in a developmental stage-specific manner and directs expression to the eye.
slo promoters are physically mapped and sequences responsible for the expression in the CNS, muscles and tracheal and midgut cells are functionally mapped.
Cloned slo channels in excised patches from Xenopus oocytes can exhibit large variability in gating properties, both within a single channel and among channels.
Mutation of slo causes a reduction of transmitter release at the neuromuscular junction. The slo mutation partially suppresses the increase in transmitter release caused by Sh mutants. The mutations confers suppression by reducing calcium influx into the nerve terminal.
Protein phosphorylation modulates the activity of slo channels expressed in Xenopus oocytes. Mutant channel protein can block the modulation by ATP-γS demonstrating that phosphorylation of the slo channel protein itself modulates channel activity.
Alternate splicing of a common slo RNA precursor contributes to the functional diversity of the encoded large conductance calcium-activated potassium channel. The variable region of the slo channel subunit comprises modular, yet interactive functional domains which influence the essential features of unit conductance, calcium sensitivity and gating of the channel.
Using PCR with nested primers and cloning from cDNA libraries, alternatively spliced versions predicting up to 144 different coding combinations were found. The existence of 31 of these was directly demonstrated. Excised inside out patch recordings show opening of the channel only when the Ca2+ is on the cytoplasmic side: opening increases both with depolarization and with increasing Ca2+ concentration. Single channel conductance is 126pS. Mean open times are different for different splice variants, proving that slo encodes a large family of functionally diverse Ca2+-activated K+ channels.
Effects of potassium channel blocking drugs on the presynaptic action potential repolarization after electrotonic stimulation was studied. At least four K+ currents contribute to repolarization of the nerve terminal.
Mutation analysis reveals that the slo polypeptide is essential for the expression or function of the channel mediating the fast Ca2+ activated K+ current.
Isolated in screen for third chromosomal temperature-sensitive paralytic mutants (Elkins, Ganetzky and Wu, 1986); this one is uncoordinated and unable to climb when exposed to 38oC but not completely paralyzed; four-minute exposure to that high temperature causes several minutes of motionlessness on return to 22oC. Legs shake when under ether anesthesia, as in Shaker mutants but less extreme. Unconditionally defective in behavior (e.g., diminished flight ability; tends to walk or fly in anomalous short hops when in large open container). Physiologically, the mutation abolishes Ca2+-dependent potassium current (IC), as shown, and analyzed further, in a variety of experiments involving recordings from dorsal longitudinal flight muscles (DLMs) of adults (Elkins, Ganetzky and Wu, 1986; Elkins and Ganetzky, 1988): DLM spikes abnormally broadened after stimulation of giant fiber nerve pathway (one of whose endpoints is DLMs) or of motor neurons synapsing on these muscles. From voltage clamp analyses, a peak of early outward current following a step pulse from -80 to -40 mV, as revealed by a Sh mutation, is absent in slo, though inward Ca2+ currents in same traces are normal; no early outward current seen when slo is treated with 4-aminopyridine (which phenocopies Sh) or combined with Sh14. (This double mutant has very low viability and severe impairment in locomotor activity); charybdotoxin, which blocks IC channels in wild-type DLMs, had no effect on outward currents in slo; delayed excitation of DLMs, observed in response to depolarizing currents delivered to wild-type (or Sh), absent in slo and spike amplitudes increased; these abnormalities phenocopied by reducing IC in normal muscle by injecting EGTA into such cells or using low-Ca2+ saline; the lengthened muscle action potentials in slo indicate importance of IC in effecting repolarization of such potentials.