urea transporter
{{Short description|Membrane transport protein}}
{{Infobox protein family
| Symbol = UT
| Name = UT
| image =
| width =
| caption = crystal structure of the urea transporter from desulfovibrio vulgaris bound to 1,3-dimethylurea
| Pfam = PF03253
| Pfam_clan =
| InterPro = IPR004937
| SMART =
| PROSITE =
| MEROPS =
| SCOP =
| TCDB = 1.A.28
| OPM family = 13
| OPM protein = 3k3f
| CAZy =
| CDD =
}}
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.{{cite journal |vauthors=Maciver B, Smith CP, Hill WG, Zeidel ML | title = Functional characterization of mouse urea transporters UT-A2 and UT-A3 expressed in purified Xenopus laevis oocyte plasma membranes | journal = Am. J. Physiol. Renal Physiol. | volume = 294 | issue = 4 | pages = F956–64 |date=April 2008 | pmid = 18256317 | doi = 10.1152/ajprenal.00229.2007 | url = http://ajprenal.physiology.org/cgi/reprint/294/4/F956 | url-access = subscription }} Urea transport in the kidney is regulated by vasopressin.{{cite journal |vauthors=Sands JM, Blount MA, Klein JD | title = Regulation of renal urea transport by vasopressin | journal = Trans. Am. Clin. Climatol. Assoc. | volume = 122 | pages = 82–92 | year = 2011 | pmid = 21686211 | pmc = 3116377 }}
The structure of a urea transport family protein from Desulfovibrio vulgaris was determined by x-ray crystallography.{{cite journal |vauthors=Levin EJ, Quick M, Zhou M | title = Crystal structure of a bacterial homologue of the kidney urea transporter | journal = Nature | volume = 462 | issue = 7274 | pages = 757–61 |date=December 2009 | pmid = 19865084 | pmc = 2871279 | doi = 10.1038/nature08558 | bibcode = 2009Natur.462..757L }} 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.{{cite journal |vauthors=Chou CL, Knepper MA | title = Inhibition of urea transport in inner medullary collecting duct by phloretin and urea analogues | journal = Am. J. Physiol. | volume = 257 | issue = 3 Pt 2 | pages = F359–65 |date=September 1989 | doi = 10.1152/ajprenal.1989.257.3.F359 | pmid = 2506765 }} Their inhibition results in increased diuresis due to urea induced osmosis in the collecting ducts of the kidney.
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.
=== 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.{{cite journal |vauthors=Fenton RA, Knepper MA | title = Urea and renal function in the 21st century: insights from knockout mice | journal = J. Am. Soc. Nephrol. | volume = 18 | issue = 3 | pages = 679–88 |date=March 2007 | pmid = 17251384 | doi = 10.1681/ASN.2006101108 | doi-access = free }}
=== 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.
=== UT-A3 ===
Urea transporter 3 transports urea into the interstitium of the Inner Medullary Collecting Duct.{{cite journal | title = Urea transporter UT-A | journal = UCSD Nature Molecule Pages | year = 2005 | doi = 10.1038/mp.a002589.01 | author = Fenton RA | volume = 18 | pages = 679 }}
=== UT-A4 ===
Urea transporter 4 has been detected in rat but not mouse kidney medulla.
= UT-A5 =
= UT-B =
UT-B is widely expressed and has been studied in erythrocytes,{{cite journal |vauthors=Yang B, Verkman AS | title = Analysis of double knockout mice lacking aquaporin-1 and urea transporter UT-B. Evidence for UT-B-facilitated water transport in erythrocytes | journal = J. Biol. Chem. | volume = 277 | issue = 39 | pages = 36782–6 |date=September 2002 | pmid = 12133842 | doi = 10.1074/jbc.M206948200 | doi-access =free }} kidney, intestine,{{cite journal |vauthors=Collins D, Winter DC, Hogan AM, Schirmer L, Baird AW, Stewart GS | title = Differential protein abundance and function of UT-B urea transporters in human colon | journal = Am. J. Physiol. Gastrointest. Liver Physiol. | volume = 298 | issue = 3 | pages = G345–51 |date=March 2010 | pmid = 19926813 | doi = 10.1152/ajpgi.00405.2009 | pmc = 3774180 }} and at the blood–brain barrier.{{cite journal |vauthors=Dahlin A, Royall J, Hohmann JG, Wang J | title = Expression profiling of the solute carrier gene family in the mouse brain | journal = J. Pharmacol. Exp. Ther. | volume = 329 | issue = 2 | pages = 558–70 |date=May 2009 | pmid = 19179540 | pmc = 2672879 | doi = 10.1124/jpet.108.149831 }} The SLC14A1 gene codes for the UT-B protein. UT-B is expressed at the basolateral and apical regions of the descending Vasa recta.