Urea transporter

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]

UT
Identifiers
SymbolUT
PfamPF03253
InterProIPR004937
TCDB1.A.28
OPM superfamily13
OPM protein3k3f
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

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]

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. 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. 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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