尿調理素
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尿調理素(uromodulin),又稱Tamm–Horsfall蛋白(Tamm–Horsfall glycoprotein,THP),為一種醣蛋白。該蛋白由 UMOD 基因轉譯而成[6][7]。尿調理素為人類正常尿液中最主要的蛋白質[8]。
基因
人類的 UMOD 基因位於第16對染色體,該基因可能存在許多不同種變異,但目前已報導的全蛋白序列僅有兩種。大多數人屬於這兩種蛋白[7]。
蛋白質
尿調理素屬於多糖磷脂肌醇錨定物醣蛋白,在哺乳動物中主要由腎臟的亨耳氏套粗上升支產生。尿調理素的單體約為85 kDa,在尿液中則常聚合成數百萬 Da 的大分子[8]。該蛋白在低pH值時會形成膠狀型態,為正常人類尿液中最主要的蛋白質[9]。尿調理素為尿液管型的主要成分。
功能
尿調理素被轉譯完成後,會藉由外結構域中的醣磷脂肌醇鍵與膜相接,剩下的部分會暴露於亨耳氏套的管腔中。當醣磷脂肌醇鍵被打斷後,尿調理素便會進入尿液中。尿調理素可能可以抑制尿鈣造成結石,或是防止細菌造成的泌尿道感染[7]。
目前有關尿調理素的功能尚不清楚。有研究發現,尿調理素可能扮演運輸的角色[10]。另外一份研究則顯示該蛋白可能具有抗菌的功能:大腸桿菌的MS 性菌毛或菌毛對於甘露糖相當敏感,而尿調理素側鏈中的甘露糖結構則可以抓住大腸桿菌的菌毛[8]。該蛋白也可能在急性腎損傷時具有抑制發炎的功能[11]。
臨床意義
尿調理素、尿橋蛋白,以及腎鈣蛋白為目前已知三種可能影響腎鈣結石的醣蛋白。尿調理素雖然為腎結石的成分之一,但其對於腎結石的角色目前仍未有定論。但目前已知尿調理素過低是預測腎結石的良好指標[8]。
歷史
參考文獻
- ^ 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]. (原始內容存檔於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
延伸閱讀
- Scolari F, Viola BF, Ghiggeri GM, et al. Towards the identification of (a) gene(s) for autosomal dominant medullary cystic kidney disease.. J. Nephrol. 2003, 16 (3): 321–8. PMID 12832729.
- 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
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- Rhodes DC, Hinsman EJ, Rhodes JA. Tamm-Horsfall glycoprotein binds IgG with high affinity.. Kidney Int. 1994, 44 (5): 1014–21. PMID 8264130. doi:10.1038/ki.1993.343.
- Fukushima K, Watanabe H, Takeo K, et al. N-linked sugar chain structure of recombinant human lymphotoxin produced by CHO cells: the functional role of carbohydrate as to its lectin-like character and clearance velocity.. Arch. Biochem. Biophys. 1993, 304 (1): 144–53. PMID 8323280. doi:10.1006/abbi.1993.1332.
- 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.
- Badgett A, Kumar S. Phylogeny of Tamm-Horsfall protein.. Urol. Int. 1999, 61 (2): 72–5. PMID 9873244. doi:10.1159/000030292.
- van Rooijen JJ, Voskamp AF, Kamerling JP, Vliegenthart JF. Glycosylation sites and site-specific glycosylation in human Tamm-Horsfall glycoprotein.. Glycobiology. 1999, 9 (1): 21–30. PMID 9884403. doi:10.1093/glycob/9.1.21.
- 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.
- Pirulli D, Puzzer D, De Fusco M, et al. Molecular analysis of uromodulin and SAH genes, positional candidates for autosomal dominant medullary cystic kidney disease linked to 16p12.. J. Nephrol. 2002, 14 (5): 392–6. PMID 11730273.
- Menozzi FD, Debrie AS, Tissier JP, et al. Interaction of human Tamm-Horsfall glycoprotein with Bordetella pertussis toxin.. Microbiology (Reading, Engl.). 2002, 148 (Pt 4): 1193–201. PMID 11932463. doi:10.1099/00221287-148-4-1193.
- Zbikowska HM, Soukhareva N, Behnam R, et al. Uromodulin promoter directs high-level expression of biologically active human alpha1-antitrypsin into mouse urine.. Biochem. J. 2002, 365 (Pt 1): 7–11. PMC 1222653
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- Hart TC, Gorry MC, Hart PS, et al. Mutations of the UMOD gene are responsible for medullary cystic kidney disease 2 and familial juvenile hyperuricaemic nephropathy.. J. Med. Genet. 2003, 39 (12): 882–92. PMC 1757206
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外部連結
- GeneReviews/NCBI/NIH/UW entry on UMOD-Related Kidney Disease Includes: Familial Juvenile Hyperuricemic Nephropathy, Medullary Cystic Kidney Disease 2 (頁面存檔備份,存於互聯網檔案館)
- OMIM entries on UMOD-Related Kidney Disease Includes: Familial Juvenile Hyperuricemic Nephropathy, Medullary Cystic Kidney Disease 2
- Tamm–Horsfall protein deposition Archive.is的存檔,存檔日期2007-06-24