Potassium inwardly-rectifying channel, subfamily J, member 15, also known as KCNJ15 is a human
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
, which encodes the K
ir4.2
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
.
Function
Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. K
ir4.2 is an integral membrane protein and inward-rectifier type potassium channel. K
ir4.2 has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Three transcript variants encoding the same protein have been found for this gene.
The existing literature describing KCNJ15 and K
ir4.2 is sparse. In spite of some initial channel nomenclature confusion, in which the gene was referred to as Kir1.3
the channel was first cloned from human
kidney
In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...
by Shuck and coworkers in 1997.
Shortly thereafter it was shown that mutation of an extracellular
lysine
Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. Lysine contains an α-amino group (which is in the protonated form when the lysine is dissolved in water at physiological pH), an α-carboxylic acid group ( ...
residue resulted in 6-fold increase in K
+ current.
Two years later, in 1999, voltage clamp measurements in
xenopus
''Xenopus'' () (Gk., ξενος, ''xenos'' = strange, πους, ''pous'' = foot, commonly known as the clawed frog) is a genus of highly aquatic frogs native to sub-Saharan Africa. Twenty species are currently described with ...
oocytes
An oocyte (, oöcyte, or ovocyte) is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The female ger ...
found that intracellular acidification decreased the potassium current of K
ir4.2. Also activation of protein kinase C decreased the current although in a non-reversible fashion. Furthermore, it was found that coexpression with related potassium channel
Kir5.1, changed these results somewhat, which the authors concluded was likely to be a result of heterodimerization.
Further voltage clamp investigations found the exact pH sensitivity (pK
a = 7.1), open probability (high) and conductance of ~25 pS.
In 2007 the channel was found to interact with the
Calcium-sensing receptor
The calcium-sensing receptor (CaSR) is a Class C G-protein coupled receptor which senses extracellular levels of calcium ions. It is primarily expressed in the parathyroid gland, the renal tubules of the kidney, pancreatic islets and the br ...
in human kidney, using a yeast-two-hybrid system. This co-localization was verified at the protein level using both
immunofluorescence
Immunofluorescence (IF) is a light microscopy-based technique that allows detection and localization of a wide variety of target biomolecules within a cell or tissue at a quantitative level. The technique utilizes the binding specificity of anti ...
techniques and
coimmunoprecipitation
Immunoprecipitation (IP) is the technique of precipitating a protein antigen out of solution using an antibody that specifically binds to that particular protein. This process can be used to isolate and concentrate a particular protein from a sam ...
of K
ir4.2 and the
Calcium-sensing receptor
The calcium-sensing receptor (CaSR) is a Class C G-protein coupled receptor which senses extracellular levels of calcium ions. It is primarily expressed in the parathyroid gland, the renal tubules of the kidney, pancreatic islets and the br ...
.
Also a mutational study of K
ir4.2 has demonstrated that removal of a c-terminal
tyrosine
-Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a conditionally essential amino acid with a polar side group. The word "tyrosine" is ...
increased the K
+ current more than 10-fold.
Because the channel has a very high open probability, the authors of this last article conclude that this increase is mediated by increased trafficking of the protein to the membrane and not increased single-channel conductance. This same line of reasoning is applicable to the initial work of Derst and coworkers.
Interactions
KCNJ15 has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...
with
Interleukin 16
Interleukin 16 is a pro-inflammatory pleiotropic cytokine. Its precursor, pro-interleukin-16 is a protein that in humans is encoded by the ''IL16'' gene. This gene was discovered in 1982 at Boston University by Dr. David Center and Dr. William Cru ...
.
See also
*
Inward-rectifier potassium ion channel
Inward-rectifier potassium channels (Kir, IRK) are a specific Lipid-gated_ion_channels, lipid-gated subset of potassium channels. To date, seven subfamilies have been identified in various mammalian cell types, plants, and bacteria. They are acti ...
References
{{Ion channels, g3, date=Feb 1999, vauthors=Pearson WL, Dourado M, Schreiber M, Salkoff L, Nichols CG
Ion channels