尿调理素

家族性少年高血尿酸症肾病
已知的结构
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	4WRN
识别号
别名	UMOD；, ADMCKD2, FJHN, HNFJ, HNFJ1, MCKD2, THGP, THP, uromodulin, ADTKD1
外部ID	OMIM：191845 MGI：102674 HomoloGene：2522 GeneCards：UMOD
相关疾病
	高血压、肾病变、autosomal dominant medullary cystic kidney disease with hyperuricemia
基因位置（人类）
染色体	16号染色体
终止	20,356,301 bp
基因位置（小鼠）
染色体	小鼠7号染色体
终止	119,078,505 bp
RNA表达模式
	查阅更多表达数据
基因本体
分子功能	• calcium ion binding; • IgG binding;
细胞组分	• cell projection; • spindle pole; • 膜; • 细胞膜; • 细胞外区域; • basolateral plasma membrane; • apical plasma membrane; • ciliary membrane; • anchored component of membrane; • 外排体; • extrinsic component of membrane; • Golgi lumen; • 纤毛;
生物学过程	• leukocyte cell-cell adhesion; • chemical homeostasis; • heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; • 排泄作用; • metanephric distal convoluted tubule development; • metanephric ascending thin limb development; • cellular defense response; • neutrophil migration; • metanephric thick ascending limb development; • negative regulation of cell population proliferation; • protein N-linked glycosylation via asparagine; • ion homeostasis;
	Sources:Amigo / QuickGO
直系同源
	7369
	22242
	ENSG00000169344
	ENSMUSG00000030963
	P07911
	Q91X17
NM_001008389; NM_001278614; NM_003361; NM_001378232; NM_001378233;
	NM_001378234; NM_001378235; NM_001378237
	NM_001278605; NM_009470
NP_001008390; NP_001265543; NP_003352; NP_001365161; NP_001365162;
	NP_001365163; NP_001365164; NP_001365166
	NP_001265534; NP_033496
	维基数据
查看/编辑人类	查看/编辑小鼠

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 基因转译而成^[6]^[7]。尿调理素为人类正常尿液中最主要的蛋白质^[8]。

基因[编辑]

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[编辑]

尿调理素属于多糖磷脂肌醇锚定物（英语：glycophosphatidylinositol）糖蛋白，在哺乳动物中主要由肾脏的亨耳氏套粗上升支（英语：thick ascending limb of the loop of Henle）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[编辑]

尿调理素被转译完成后，会借由外结构域（英语：ectodomain）中的糖磷脂肌醇（英语：glycophosphatidylinositol）键与膜相接，剩下的部分会暴露于亨耳氏套（英语：loop of Henle）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[编辑]

尿调理素、尿桥蛋白（英语：Uropontin），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[编辑]

参考文献[编辑]

^ 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[编辑]

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 . PMID 8254051. doi:10.1172/JCI116920.
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 . PMID 11982485. doi:10.1042/BJ20020643.
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 . PMID 12471200. doi:10.1136/jmg.39.12.882.
Strausberg RL, Feingold EA, Grouse LH, et al. Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.. Proc. Natl. Acad. Sci. U.S.A. 2003, 99 (26): 16899–903. PMC 139241 . PMID 12477932. doi:10.1073/pnas.242603899.

外部链接[编辑]

[1] 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.

[refGRCh38Ensembl-2] 2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000169344 - Ensembl, May 2017

[refGRCm38Ensembl-3] 3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000030963 - Ensembl, May 2017

[4] Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid8382593-6] 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.

[entrez-7] 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）.

[Lau_2008-8] 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_Mann_2011-9] 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.

[pmid15522986-10] 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.

[11] 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

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