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Urea transporter

From Wikipedia, the free encyclopedia
Membrane transport protein
Protein family
UT
Identifiers
SymbolUT
PfamPF03253
InterProIPR004937
TCDB1.A.28
OPM superfamily13
OPM protein3k3f
Available protein structures:
Pfam  structures /ECOD  
PDBRCSB PDB;PDBe;PDBj
PDBsumstructure summary

Aurea transporter is amembrane transport protein, transportingurea. Humans and other mammals have two types of urea transport proteins, UT-A and UT-B. The UT-A proteins are important forrenal urea handling and are produced by alternative splicing of theSLC14A2 gene.[1] Urea transport in the kidney is regulated byvasopressin.[2]

The structure of a urea transport family protein fromDesulfovibrio vulgaris was determined byx-ray crystallography.[3] The structure has a pathway through the membrane that is similar to that ofion 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 likethiourea and glycosides likephloretin.[4] Their inhibition results in increased diuresis due to urea induced osmosis in the collecting ducts of thekidney.[5]

Types

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In mammals, there are two urea transportergenes: UT-A (SLC14A2) and UT-B (SLC14A1). Multipleprotein isoforms derived from each gene are produced byalternative splicing and alternativepromoters.[5]

UT-A1

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Urea transporter A1 transports urea across theapical membrane into theintracellular space of luminal cells in theinner medullary collecting duct of thekidneys. UT-1 is activated byADH, but is a passive transporter. It reabsorbs up to 70% of the original filtered load of urea.[5]

UT-A2

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Urea Transporter 2 transports urea across theapical membrane into the luminal space of cells in thethin descending loop of Henle of thekidneys.[5]

UT-A3

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

UT-A4

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

UT-A5

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

UT-B

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UT-B is widely expressed and has been studied inerythrocytes,[7]kidney,intestine,[8] and at theblood–brain barrier.[9] TheSLC14A1 gene codes for the UT-B protein. UT-B is expressed at the basolateral and apical regions of the descendingVasa recta.[5]

References

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  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. ^abcdeFenton 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. ^abcFenton 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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