POTASSIUM CHANNEL, SUBFAMILY K, MEMBER 17; KCNK17

Alternative titles; symbols

• TWIK-RELATED ACID-SENSITIVE K+ CHANNEL 4; TASK4
• TWIK-RELATED ALKALINE pH-ACTIVATED K+ CHANNEL 2; TALK2

HGNC Approved Gene Symbol: KCNK17

Cytogenetic location: 6p21.2 Genomic coordinates (GRCh38): 6:39,299,000-39,314,418 (from NCBI)

▼ Description
KCNK17 is a member of the 2-pore domain superfamily of background K(+) channels, which are open at all membrane potentials and contribute to cellular resting membrane potential.

▼ Cloning and Expression
Using homology with KCNK4 (605720) in a database search, followed by PCR amplification of an adrenal cDNA library, Decher et al. (2001) cloned a full-length cDNA encoding KCNK17, which they called TASK4. The deduced 343-amino acid KCNK17 protein has a calculated molecular mass of about 38 kD. It contains 4 transmembrane (M) domains and 2 intervening pore (P) domains. The extracellular M1P1 interdomain is extended and has 2 N-linked glycosylation sites and a conserved cysteine (residue 68) that, in KCNK1 (601745), is involved in homodimer formation. KCNK17 also has phosphorylation sites for casein kinase II (see 115440), protein kinase A (see 601639), and protein kinase C (see 176960). Within the transmembrane domains, KCNK17 shares 38% identity with KCNK5 (603493). RT-PCR revealed wide expression of KCNK17. Highest expression was in liver, lung, placenta, pancreas, small intestine, and aorta. Intermediate levels were detected in heart, colon, ovary, peripheral blood leukocytes, prostate, spleen, testis, and thymus. Expression was also detected in brain, but not in skeletal muscle. Within heart, KCNK17 was expressed in both atria, each auricle, and in the atrioventricular node. A faint signal was detected in the interventricular septum, but no signal was detected in the ventricles, apex, or in fetal heart.

Using 2-pore domain K(+) channel sequences as queries in a database search, followed by PCR-RACE of a pancreas cDNA library, Girard et al. (2001) cloned KCNK17, which they called TALK2. The deduced protein contains 332 amino acids and shares 37% sequence identity with KCNK16 (607369). Northern blot analysis revealed a 1.9-kb transcript in pancreas and liver, with weaker expression in placenta, heart, and lung.

▼ Gene Function
Decher et al. (2001) and Girard et al. (2001) studied the channel properties of KCNK17 expressed in Xenopus oocytes. KCNK17 generated K(+) currents that were outward rectifying and lost by elevation of extracellular K(+). Alkaline extracellular pH caused a near instantaneous and noninactivating current. Currents were blocked by barium and at least partially inhibited by quinine and most volatile anesthetics. Tetraethylammonium had little effect, and KCNK17 was not sensitive to protein kinase A or C activation. Girard et al. (2001) found that KCNK17 expressed in COS cells had similar channel properties.

▼ Gene Structure
Girard et al. (2001) determined that the KCNK17 gene contains 5 exons.

▼ Mapping
By genomic sequence analysis, Decher et al. (2001) mapped the KCNK17 gene to chromosome 6p21.2-p21.1. By genomic sequence analysis, Girard et al. (2001) determined that the KCNK16, KCNK17, and KCNK5 genes form a tight cluster of 25 kb on chromosome 6p21.2-p21.1. The 3-prime end of KCNK16 is separated from the 5-prime end of KCNK17 by less than 1 kb.

▼ Gene Family
Girard et al. (2001) developed a dendrogram that suggested that KCNK5, KCNK16, KCNK17, KCNK2 (603219), KCNK10 (605873), and KCNK4 (605720) arose from a single common ancestral gene that underwent several duplication events.