ROMK

Last updated
KCNJ1
Identifiers
Aliases KCNJ1 , KIR1.1, ROMK, ROMK1, potassium voltage-gated channel subfamily J member 1, potassium inwardly rectifying channel subfamily J member 1
External IDs OMIM: 600359 MGI: 1927248 HomoloGene: 56764 GeneCards: KCNJ1
Orthologs
SpeciesHumanMouse
Entrez

3758

56379

Ensembl

ENSG00000151704

ENSMUSG00000041248

UniProt

P48048

O88335

RefSeq (mRNA)

NM_153767
NM_000220
NM_153764
NM_153765
NM_153766

NM_001168354
NM_019659

RefSeq (protein)

NP_000211
NP_722448
NP_722449
NP_722450
NP_722451

NP_001161826
NP_062633

Location (UCSC) Chr 11: 128.84 – 128.87 Mb Chr 9: 32.28 – 32.31 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

The renal outer medullary potassium channel (ROMK) is an ATP-dependent potassium channel (Kir1.1) that transports potassium out of cells. It plays an important role in potassium recycling in the thick ascending limb (TAL) and potassium secretion in the cortical collecting duct (CCD) of the nephron. In humans, ROMK is encoded by the KCNJ1 (potassium inwardly-rectifying channel, subfamily J, member 1) gene. [5] [6] [7] Multiple transcript variants encoding different isoforms have been found for this gene. [8]

Contents

Function

Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. It is inhibited by internal ATP and probably plays an important role in potassium homeostasis. The encoded protein has a greater tendency to allow potassium to flow into a cell rather than out of a cell, which has (hence the term "inwardly rectifying" referring to corresponding currents in electrophysiology, but has limited physiological relevance). [8] ROMK was identified as the pore-forming component of the mitochondrial ATP-sensitive potassium (mitoKATP) channel, known to play a critical role in cardioprotection against ischemic-reperfusion injury in the heart [9] as well as in the protection against hypoxia-induced brain injury from stroke or other ischemic attacks.

Klotho is a beta-glucuronidase-like enzyme that activates ROMK by removal of sialic acid. [10] [11]

Clinical significance

Mutations in this gene have been associated with antenatal Bartter syndrome, which is characterized by salt wasting, hypokalemic alkalosis, hypercalciuria, and low blood pressure. [8]

Role in hypokalemia and magnesium deficiency

The ROMK channels are inhibited by magnesium in the nephron's normal physiologic state. In states of hypokalemia (a state of potassium deficiency), concurrent magnesium deficiency results in a state of hypokalemia that may be more difficult to correct with potassium replacement alone. This may be directly due to decreased inhibition of the outward potassium current in states where magnesium is low. Conversely, magnesium deficiency alone is not likely to cause a state of hypokalemia. [12] Sgk1 kinase has also been reported to phosphorylate ROMK, resulting in an increase of channels on the apical surface of the distal tubule. [13] Sgk1 is in turn regulated by the mineralocorticoid receptor such an effect may contribute to the kaliuretic action of aldosterone.

Related Research Articles

<span class="mw-page-title-main">Potassium channel</span> Ion channel that selectively passes K+

Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of cell functions.

<span class="mw-page-title-main">Inward-rectifier potassium channel</span> Group of transmembrane proteins that passively transport potassium ions

Inward-rectifier potassium channels (Kir, IRK) are a specific lipid-gated subset of potassium channels. To date, seven subfamilies have been identified in various mammalian cell types, plants, and bacteria. They are activated by phosphatidylinositol 4,5-bisphosphate (PIP2). The malfunction of the channels has been implicated in several diseases. IRK channels possess a pore domain, homologous to that of voltage-gated ion channels, and flanking transmembrane segments (TMSs). They may exist in the membrane as homo- or heterooligomers and each monomer possesses between 2 and 4 TMSs. In terms of function, these proteins transport potassium (K+), with a greater tendency for K+ uptake than K+ export. The process of inward-rectification was discovered by Denis Noble in cardiac muscle cells in 1960s and by Richard Adrian and Alan Hodgkin in 1970 in skeletal muscle cells.

K<sub>ir</sub>2.1 Protein-coding gene in the species Homo sapiens

The Kir2.1 inward-rectifier potassium channel is a lipid-gated ion channel encoded by the KCNJ2 gene.

<span class="mw-page-title-main">WNK1</span> Protein-coding gene in the species Homo sapiens

WNK , also known as WNK1, is an enzyme that is encoded by the WNK1 gene. WNK1 is serine-threonine protein kinase and part of the "with no lysine/K" kinase WNK family. The predominant role of WNK1 is the regulation of cation-Cl− cotransporters (CCCs) such as the sodium chloride cotransporter (NCC), basolateral Na-K-Cl symporter (NKCC1), and potassium chloride cotransporter (KCC1) located within the kidney. CCCs mediate ion homeostasis and modulate blood pressure by transporting ions in and out of the cell. WNK1 mutations as a result have been implicated in blood pressure disorders/diseases; a prime example being familial hyperkalemic hypertension (FHHt).

<span class="mw-page-title-main">KCNJ6</span> Protein-coding gene in the species Homo sapiens

G protein-activated inward rectifier potassium channel 2 is a protein that in humans is encoded by the KCNJ6 gene. Mutation in KCNJ6 gene has been proposed to be the cause of Keppen-Lubinsky Syndrome (KPLBS).

<span class="mw-page-title-main">KCNJ4</span> Protein-coding gene in the species Homo sapiens

Potassium inwardly-rectifying channel, subfamily J, member 4, also known as KCNJ4 or Kir2.3, is a human gene.

<span class="mw-page-title-main">KCNJ8</span>

Potassium inwardly-rectifying channel, subfamily J, member 8, also known as KCNJ8, is a human gene encoding the Kir6.1 protein. A mutation in KCNJ8 has been associated with cardiac arrest in the early repolarization syndrome.

<span class="mw-page-title-main">KCNJ5</span> Protein-coding gene in the species Homo sapiens

G protein-activated inward rectifier potassium channel 4(GIRK-4) is a protein that in humans is encoded by the KCNJ5 gene and is a type of G protein-gated ion channel.

<span class="mw-page-title-main">KCNJ12</span> Protein-coding gene in the species Homo sapiens

ATP-sensitive inward rectifier potassium channel 12 is a lipid-gated ion channel that in humans is encoded by the KCNJ12 gene.

<span class="mw-page-title-main">KCNJ3</span> Protein-coding gene in the species Homo sapiens

G protein-activated inward rectifier potassium channel 1(GIRK-1) is encoded in the human by the gene KCNJ3.

<span class="mw-page-title-main">KCNJ10</span> Protein-coding gene in the species Homo sapiens

ATP-sensitive inward rectifier potassium channel 10 is a protein that in humans is encoded by the KCNJ10 gene.

<span class="mw-page-title-main">KCNJ15</span> Protein-coding gene in the species Homo sapiens

Potassium inwardly-rectifying channel, subfamily J, member 15, also known as KCNJ15 is a human gene, which encodes the Kir4.2 protein.

<span class="mw-page-title-main">WNK4</span> Protein-coding gene in the species Homo sapiens

Serine/threonine protein kinase WNK4 also known as WNK lysine deficient protein kinase 4 or WNK4, is an enzyme that in humans is encoded by the WNK4 gene. Missense mutations cause a genetic form of pseudohypoaldosteronism type 2, also called Gordon syndrome.

<span class="mw-page-title-main">KCNJ16</span> Protein-coding gene in the species Homo sapiens

Potassium inwardly-rectifying channel, subfamily J, member 16 (KCNJ16) is a human gene encoding the Kir5.1 protein.

<span class="mw-page-title-main">KCNJ14</span> Protein-coding gene in the species Homo sapiens

Potassium inwardly-rectifying channel, subfamily J, member 14 (KCNJ14), also known as Kir2.4, is a human gene.

<span class="mw-page-title-main">KCNJ9</span> Protein-coding gene in the species Homo sapiens

G protein-activated inward rectifier potassium channel 3 is a protein that in humans is encoded by the KCNJ9 gene.

<span class="mw-page-title-main">KCNJ13</span> Protein-coding gene in the species Homo sapiens

Potassium inwardly-rectifying channel, subfamily J, member 13 (KCNJ13) is a human gene encoding the Kir7.1 protein.

<span class="mw-page-title-main">Tertiapin</span>

Tertiapin is a 21-amino acid peptide isolated from venom of the European honey bee. It blocks two different types of potassium channels, inward rectifier potassium channels (Kir) and calcium activated large conductance potassium channels (BK).

<span class="mw-page-title-main">WNK3</span> Protein-coding gene in the species Homo sapiens

Serine/threonine-protein kinase WNK3, also known as protein kinase lysine-deficient 3, is a protein that in humans is encoded by the WNK3 gene.

<span class="mw-page-title-main">SGK1</span> Protein-coding gene in the species Homo sapiens

Serine/threonine-protein kinase Sgk1 also known as serum and glucocorticoid-regulated kinase 1 is an enzyme that in humans is encoded by the SGK1 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000151704 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000041248 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Ho K, Nichols CG, Lederer WJ, Lytton J, Vassilev PM, Kanazirska MV, Hebert SC (March 1993). "Cloning and expression of an inwardly rectifying ATP-regulated potassium channel". Nature. 362 (6415): 31–8. Bibcode:1993Natur.362...31H. doi:10.1038/362031a0. PMID   7680431. S2CID   4332298.
  6. ↑ Yano H, Philipson LH, Kugler JL, Tokuyama Y, Davis EM, Le Beau MM, Nelson DJ, Bell GI, Takeda J (May 1994). "Alternative splicing of human inwardly rectifying K+ channel ROMK1 mRNA". Molecular Pharmacology. 45 (5): 854–60. PMID   8190102.
  7. ↑ Kubo Y, Adelman JP, Clapham DE, Jan LY, Karschin A, Kurachi Y, Lazdunski M, Nichols CG, Seino S, Vandenberg CA (December 2005). "International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels". Pharmacological Reviews. 57 (4): 509–26. doi:10.1124/pr.57.4.11. PMID   16382105. S2CID   11588492.
  8. 1 2 3 "Entrez Gene: potassium inwardly-rectifying channel".
  9. ↑ Foster DB, Ho AS, Rucker J, Garlid AO, Chen L, Sidor A, Garlid KD, O'Rourke B (August 2012). "Mitochondrial ROMK channel is a molecular component of mitoK(ATP)". Circulation Research. 111 (4): 446–54. doi:10.1161/circresaha.112.266445. PMC   3560389 . PMID   22811560.
  10. ↑ Cha SK, Ortega B, Kurosu H, Rosenblatt KP, Kuro-O M, Huang CL (2008). "Removal of sialic acid involving Klotho causes cell-surface retention of TRPV5 channel via binding to galectin-1". Proceedings of the National Academy of Sciences of the United States of America . 105 (28): 9805–9810. Bibcode:2008PNAS..105.9805C. doi: 10.1073/pnas.0803223105 . PMC   2474477 . PMID   18606998.
  11. ↑ Huang CL (2010). "Regulation of ion channels by secreted Klotho: mechanisms and implications". Kidney International . 77 (10): 855–860. doi: 10.1038/ki.2010.73 . PMID   20375979.
  12. ↑ Huang CL, Kuo E (October 2007). "Mechanism of hypokalemia in magnesium deficiency". Journal of the American Society of Nephrology. 18 (10): 2649–2652. doi: 10.1681/asn.2007070792 . PMID   17804670.
  13. ↑ Yoo D, Kim BY, Campo C, Nance L, King A, Maouyo D, Welling PA (June 2003). "Cell surface expression of the ROMK (Kir 1.1) channel is regulated by the aldosterone-induced kinase, SGK-1, and protein kinase A". The Journal of Biological Chemistry. 278 (25): 23066–23075. doi: 10.1074/jbc.M212301200 . PMID   12684516.

Further reading


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