尿调理素
尿调理素(uromodulin),又称Tamm–Horsfall蛋白(Tamm–Horsfall glycoprotein,THP),为一种糖蛋白。该蛋白由 UMOD 基因翻译而成[6][7]。尿调理素为人类正常尿液中最主要的蛋白质[8]。
基因
人类的 UMOD 基因位于第16对染色体,该基因可能存在许多不同种变异,但目前已报导的全蛋白序列仅有两种。大多数人属于这两种蛋白[7]。
蛋白质
尿调理素属于多糖磷脂肌醇锚定物糖蛋白,在哺乳动物中主要由肾脏的亨耳氏套粗上升支产生。尿调理素的单体约为85 kDa,在尿液中则常聚合成数百万 Da 的大分子[8]。该蛋白在低pH值时会形成胶状型态,为正常人类尿液中最主要的蛋白质[9]。尿调理素为尿液管型的主要成分。
功能
尿调理素被翻译完成后,会借由外结构域中的糖磷脂肌醇键与膜相接,剩下的部分会暴露于亨耳氏套的管腔中。当糖磷脂肌醇键被打断后,尿调理素便会进入尿液中。尿调理素可能可以抑制尿钙造成结石,或是防止细菌造成的泌尿道感染[7]。
目前有关尿调理素的功能尚不清楚。有研究发现,尿调理素可能扮演运输的角色[10]。另外一份研究则显示该蛋白可能具有抗菌的功能:大肠杆菌的MS 性菌毛或菌毛对于甘露糖相当敏感,而尿调理素侧链中的甘露糖结构则可以抓住大肠杆菌的菌毛[8]。该蛋白也可能在急性肾损伤时具有抑制发炎的功能[11]。
临床意义
尿调理素、尿桥蛋白,以及肾钙蛋白为目前已知三种可能影响肾钙结石的糖蛋白。尿调理素虽然为肾结石的成分之一,但其对于肾结石的角色目前仍未有定论。但目前已知尿调理素过低是预测肾结石的良好指标[8]。
历史
参考文献
- ^ 與家族性少年高血尿酸癥腎病相關的疾病;在維基數據上查看/編輯參考.
- ^ 2.0 2.1 2.2 GRCh38: Ensembl release 89: ENSG00000169344 - Ensembl, May 2017
- ^ 3.0 3.1 3.2 GRCm38: Ensembl release 89: ENSMUSG00000030963 - Ensembl, May 2017
- ^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Jeanpierre C, Whitmore SA, Austruy E, Cohen-Salmon M, Callen DF, Junien C. Chromosomal assignment of the uromodulin gene (UMOD) to 16p13.11. Cytogenet Cell Genet. Mar 1993, 62 (4): 185–7. PMID 8382593. doi:10.1159/000133470.
- ^ 7.0 7.1 7.2 Entrez Gene: UMOD uromodulin (uromucoid, Tamm–Horsfall glycoprotein). [2016-12-20]. (原始内容存档于2010-03-07).
- ^ 8.0 8.1 8.2 8.3 Lau WH, Leong WS, Ismail Z, Gam LH. Qualification and application of an ELISA for the determination of Tamm Horsfall protein (THP) in human urine and its use for screening of kidney stone disease. Int. J. Biol. Sci. 2008, 4 (4): 215–22. PMC 2500153 . PMID 18695745. doi:10.7150/ijbs.4.215.
- ^ Nagaraj N, Mann M. Quantitative analysis of the intra- and inter-individual variability of the normal urinary proteome. J. Proteome Res. February 2011, 10 (2): 637–45. PMID 21126025. doi:10.1021/pr100835s.
- ^ Bachmann S, Mutig K, Bates J, Welker P, Geist B, Gross V, Luft FC, Alenina N, Bader M, Thiele BJ, Prasadan K, Raffi HS, Kumar S. Renal effects of Tamm-Horsfall protein (uromodulin) deficiency in mice. Am. J. Physiol. Renal Physiol. 2005, 288 (3): F559–67. PMID 15522986. doi:10.1152/ajprenal.00143.2004.
- ^ El-Achkar TM, Wu XR, Rauchman M, McCracken R, Kiefer S, Dagher PC. Tamm-Horsfall protein protects the kidney from ischemic injury by decreasing inflammation and altering TLR4 expression. Am J Physiol Renal Physiol. 2008 Aug;295(2):F534-44. doi: 10.1152/ajprenal.00083.2008. Epub 2008 May 21. PMID 18495803
延伸阅读
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- Rindler MJ, Naik SS, Li N, et al. Uromodulin (Tamm-Horsfall glycoprotein/uromucoid) is a phosphatidylinositol-linked membrane protein.. J. Biol. Chem. 1991, 265 (34): 20784–9. PMID 2249987.
- Muchmore AV, Decker JM. Uromodulin: a unique 85-kilodalton immunosuppressive glycoprotein isolated from urine of pregnant women.. Science. 1985, 229 (4712): 479–81. PMID 2409603. doi:10.1126/science.2409603.
- Pennica D, Kohr WJ, Kuang WJ, et al. Identification of human uromodulin as the Tamm-Horsfall urinary glycoprotein.. Science. 1987, 236 (4797): 83–8. PMID 3453112. doi:10.1126/science.3453112.
- Hession C, Decker JM, Sherblom AP, et al. Uromodulin (Tamm-Horsfall glycoprotein): a renal ligand for lymphokines.. Science. 1987, 237 (4821): 1479–84. PMID 3498215. doi:10.1126/science.3498215.
- Prasadan K, Bates J, Badgett A, et al. Nucleotide sequence and peptide motifs of mouse uromodulin (Tamm-Horsfall protein)--the most abundant protein in mammalian urine.. Biochim. Biophys. Acta. 1995, 1260 (3): 328–32. PMID 7873609. doi:10.1016/0167-4781(94)00240-4.
- Huang ZQ, Kirk KA, Connelly KG, Sanders PW. Bence Jones proteins bind to a common peptide segment of Tamm-Horsfall glycoprotein to promote heterotypic aggregation.. J. Clin. Invest. 1994, 92 (6): 2975–83. PMC 288501 . PMID 8254051. doi:10.1172/JCI116920.
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- Thomas DB, Davies M, Peters JR, Williams JD. Tamm Horsfall protein binds to a single class of carbohydrate specific receptors on human neutrophils.. Kidney Int. 1993, 44 (2): 423–9. PMID 8397318. doi:10.1038/ki.1993.260.
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- Scolari F, Puzzer D, Amoroso A, et al. Identification of a new locus for medullary cystic disease, on chromosome 16p12.. Am. J. Hum. Genet. 1999, 64 (6): 1655–60. PMC 1377908 . PMID 10330352. doi:10.1086/302414.
- Kamatani N, Moritani M, Yamanaka H, et al. Localization of a gene for familial juvenile hyperuricemic nephropathy causing underexcretion-type gout to 16p12 by genome-wide linkage analysis of a large family.. Arthritis Rheum. 2000, 43 (4): 925–9. PMID 10765940. doi:10.1002/1529-0131(200004)43:4<925::AID-ANR26>3.0.CO;2-B.
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外部链接
- GeneReviews/NCBI/NIH/UW entry on UMOD-Related Kidney Disease Includes: Familial Juvenile Hyperuricemic Nephropathy, Medullary Cystic Kidney Disease 2 (页面存档备份,存于互联网档案馆)
- OMIM entries on UMOD-Related Kidney Disease Includes: Familial Juvenile Hyperuricemic Nephropathy, Medullary Cystic Kidney Disease 2
- Tamm–Horsfall protein deposition Archive.is的存档,存档日期2007-06-24