Urea transporter

Last updated
UT
Identifiers
SymbolUT
Pfam PF03253
InterPro IPR004937
TCDB 1.A.28
OPM superfamily 13
OPM protein 3k3f
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

A urea transporter is a membrane transport protein, transporting urea. Humans and other mammals have two types of urea transport proteins, UT-A and UT-B. The UT-A proteins are important for renal urea handling and are produced by alternative splicing of the SLC14A2 gene. [1] Urea transport in the kidney is regulated by vasopressin. [2]

Contents

The structure of a urea transport family protein from Desulfovibrio vulgaris was determined by x-ray crystallography. [3] The structure has a pathway through the membrane that is similar to that of ion channel proteins, accounting for the ability of urea transport proteins to move up to one million urea molecules per second across the membrane.

Urea transporters can be inhibited by the action of urea analogues like thiourea and glycosides like phloretin. [4] Their inhibition results in increased diuresis due to urea induced osmosis in the collecting ducts of the kidney. [5]

Types

In mammals, there are two urea transporter genes: UT-A ( SLC14A2 ) and UT-B ( SLC14A1 ). Multiple protein isoforms derived from each gene are produced by alternative splicing and alternative promoters. [5]

UT-A1

Urea transporter A1 transports urea across the apical membrane into the intracellular space of luminal cells in the inner medullary collecting duct of the kidneys. UT-1 is activated by ADH, but is a passive transporter. It reabsorbs up to 70% of the original filtered load of urea. [5]

UT-A2

Urea Transporter 2 transports urea across the apical membrane into the luminal space of cells in the thin descending loop of Henle of the kidneys. [5]

UT-A3

Urea transporter 3 transports urea into the interstitium of the Inner Medullary Collecting Duct. [6]

UT-A4

Urea transporter 4 has been detected in rat but not mouse kidney medulla. [6]

UT-A5

Urea transporter 5 is not expressed in the kidney but in the testis. [6]

UT-B

UT-B is widely expressed and has been studied in erythrocytes, [7] kidney, intestine, [8] and at the blood–brain barrier. [9] The SLC14A1 gene codes for the UT-B protein. UT-B is expressed at the basolateral and apical regions of the descending Vasa recta. [5]

Related Research Articles

<span class="mw-page-title-main">Vasopressin</span> Mammalian hormone released from the pituitary gland

Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then travels down the axon terminating in the posterior pituitary, and is released from vesicles into the circulation in response to extracellular fluid hypertonicity (hyperosmolality). AVP has two primary functions. First, it increases the amount of solute-free water reabsorbed back into the circulation from the filtrate in the kidney tubules of the nephrons. Second, AVP constricts arterioles, which increases peripheral vascular resistance and raises arterial blood pressure.

<span class="mw-page-title-main">Collecting duct system</span> Kidney system

The collecting duct system of the kidney consists of a series of tubules and ducts that physically connect nephrons to a minor calyx or directly to the renal pelvis. The collecting duct system is the last part of nephron and participates in electrolyte and fluid balance through reabsorption and excretion, processes regulated by the hormones aldosterone and vasopressin.

The actions of vasopressin are mediated by stimulation of tissue-specific G protein-coupled receptors (GPCRs) called vasopressin receptors that are classified into the V1 (V1A), V2, and V3 (V1B) receptor subtypes. These three subtypes differ in localization, function and signal transduction mechanisms.

<span class="mw-page-title-main">Aquaporin-2</span> Protein-coding gene in the species Homo sapiens

Aquaporin-2 (AQP-2) is found in the apical cell membranes of the kidney's collecting duct principal cells and in intracellular vesicles located throughout the cell. It is encoded by the AQP2 gene.

The Na–K–Cl cotransporter (NKCC) is a transport protein that aids in the secondary active transport of sodium, potassium, and chloride into cells. In humans there are two isoforms of this membrane transport protein, NKCC1 and NKCC2, encoded by two different genes. Two isoforms of the NKCC1/Slc12a2 gene result from keeping or skipping exon 21 in the final gene product.

Pendrin is an anion exchange protein that in humans is encoded by the SLC26A4 gene . Pendrin was initially identified as a sodium-independent chloride-iodide exchanger with subsequent studies showing that it also accepts formate and bicarbonate as substrates. Pendrin is similar to the Band 3 transport protein found in red blood cells. Pendrin is the protein which is mutated in Pendred syndrome, which is an autosomal recessive disorder characterized by sensorineural hearing loss, goiter and a partial organification problem detectable by a positive perchlorate test.

<span class="mw-page-title-main">Neutral and basic amino acid transport protein rBAT</span> Protein-coding gene in the species Homo sapiens

Neutral and basic amino acid transport protein rBAT is a protein that in humans is encoded by the SLC3A1 gene.

<span class="mw-page-title-main">Multidrug resistance-associated protein 2</span> Protein-coding gene in the species Homo sapiens

Multidrug resistance-associated protein 2 (MRP2) also called canalicular multispecific organic anion transporter 1 (cMOAT) or ATP-binding cassette sub-family C member 2 (ABCC2) is a protein that in humans is encoded by the ABCC2 gene.

<span class="mw-page-title-main">Electrogenic sodium bicarbonate cotransporter 1</span> Protein-coding gene in the species Homo sapiens

Electrogenic sodium bicarbonate cotransporter 1, sodium bicarbonate cotransporter is a membrane transport protein that in humans is encoded by the SLC4A4 gene.

<span class="mw-page-title-main">SLC22A2</span> Protein-coding gene

Solute carrier family 22 member 2 is a protein that in humans is encoded by the SLC22A2 gene.

<span class="mw-page-title-main">Urea transporter 1</span> Protein-coding gene in the species Homo sapiens

Urea transporter 1 is a protein that in humans is encoded by the SLC14A1 gene.

<span class="mw-page-title-main">SLC26A6</span> Protein-coding gene in the species Homo sapiens

Solute carrier family 26 member 6 is a protein that in humans is encoded by the SLC26A6 gene. It is an anion-exchanger expressed in the apical membrane of the kidney proximal tubule, the apical membranes of the duct cells in the pancreas, and the villi of the duodenum.

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

Anion exchange transporter is a protein that in humans is encoded by the SLC26A7 gene.

<span class="mw-page-title-main">Urea transporter 2</span> Protein-coding gene in the species Homo sapiens

Urea transporter 2 is a protein that in humans is encoded by the SLC14A2 gene.

<span class="mw-page-title-main">Sodium-dependent phosphate transport protein 1</span> Protein-coding gene in the species Homo sapiens

Sodium-dependent phosphate transport protein 1 is a protein that in humans is encoded by the SLC17A1 gene.

<span class="mw-page-title-main">SLC13A3</span> Protein-coding gene in the species Homo sapiens

Solute carrier family 13 member 3 also called sodium-dependent dicarboxylate transporter (NaDC3) is a protein that in humans is encoded by the SLC13A3 gene.

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

Organic solute transporter beta, also known as OST-beta, is a protein which in humans is encoded by the OSTB gene.

<span class="mw-page-title-main">KCNA10</span> Protein-coding gene in the species Homo sapiens

Potassium voltage-gated channel subfamily A member 10 also known as Kv1.8 is a protein that in humans is encoded by the KCNA10 gene. The protein encoded by this gene is a voltage-gated potassium channel subunit.

<span class="mw-page-title-main">Phloretin</span> Chemical compound

Phloretin is a dihydrochalcone, a type of natural phenol. It can be found in apple tree leaves and the Manchurian apricot.

<span class="mw-page-title-main">Organic anion transporter 1</span> Protein-coding gene in the species Homo sapiens

The organic anion transporter 1 (OAT1) also known as solute carrier family 22 member 6 (SLC22A6) is a protein that in humans is encoded by the SLC22A6 gene. It is a member of the organic anion transporter (OAT) family of proteins. OAT1 is a transmembrane protein that is expressed in the brain, the placenta, the eyes, smooth muscles, and the basolateral membrane of proximal tubular cells of the kidneys. It plays a central role in renal organic anion transport. Along with OAT3, OAT1 mediates the uptake of a wide range of relatively small and hydrophilic organic anions from plasma into the cytoplasm of the proximal tubular cells of the kidneys. From there, these substrates are transported into the lumen of the nephrons of the kidneys for excretion. OAT1 homologs have been identified in rats, mice, rabbits, pigs, flounders, and nematodes.

References

  1. ↑ Maciver B, Smith CP, Hill WG, Zeidel ML (April 2008). "Functional characterization of mouse urea transporters UT-A2 and UT-A3 expressed in purified Xenopus laevis oocyte plasma membranes". Am. J. Physiol. Renal Physiol. 294 (4): F956–64. doi:10.1152/ajprenal.00229.2007. PMID   18256317.
  2. ↑ Sands JM, Blount MA, Klein JD (2011). "Regulation of renal urea transport by vasopressin". Trans. Am. Clin. Climatol. Assoc. 122: 82–92. PMC   3116377 . PMID   21686211.
  3. ↑ Levin EJ, Quick M, Zhou M (December 2009). "Crystal structure of a bacterial homologue of the kidney urea transporter". Nature. 462 (7274): 757–61. Bibcode:2009Natur.462..757L. doi:10.1038/nature08558. PMC   2871279 . PMID   19865084.
  4. ↑ Chou CL, Knepper MA (September 1989). "Inhibition of urea transport in inner medullary collecting duct by phloretin and urea analogues". Am. J. Physiol. 257 (3 Pt 2): F359–65. doi:10.1152/ajprenal.1989.257.3.F359. PMID   2506765.
  5. 1 2 3 4 5 Fenton RA, Knepper MA (March 2007). "Urea and renal function in the 21st century: insights from knockout mice". J. Am. Soc. Nephrol. 18 (3): 679–88. doi: 10.1681/ASN.2006101108 . PMID   17251384.
  6. 1 2 3 Fenton RA (2005). "Urea transporter UT-A". UCSD Nature Molecule Pages. 18: 679. doi:10.1038/mp.a002589.01.
  7. ↑ Yang B, Verkman AS (September 2002). "Analysis of double knockout mice lacking aquaporin-1 and urea transporter UT-B. Evidence for UT-B-facilitated water transport in erythrocytes". J. Biol. Chem. 277 (39): 36782–6. doi: 10.1074/jbc.M206948200 . PMID   12133842.
  8. ↑ Collins D, Winter DC, Hogan AM, Schirmer L, Baird AW, Stewart GS (March 2010). "Differential protein abundance and function of UT-B urea transporters in human colon". Am. J. Physiol. Gastrointest. Liver Physiol. 298 (3): G345–51. doi:10.1152/ajpgi.00405.2009. PMC   3774180 . PMID   19926813.
  9. ↑ Dahlin A, Royall J, Hohmann JG, Wang J (May 2009). "Expression profiling of the solute carrier gene family in the mouse brain". J. Pharmacol. Exp. Ther. 329 (2): 558–70. doi:10.1124/jpet.108.149831. PMC   2672879 . PMID   19179540.
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