ID UROM_HUMAN Reviewed; 640 AA. AC P07911; B3KP48; B3KRN9; E9PEA4; Q540J6; Q6ZS84; Q8IYG0; DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1988, sequence version 1. DT 09-DEC-2015, entry version 161. DE RecName: Full=Uromodulin; DE AltName: Full=Tamm-Horsfall urinary glycoprotein; DE Short=THP; DE Contains: DE RecName: Full=Uromodulin, secreted form; DE Flags: Precursor; GN Name=UMOD; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=3453112; DOI=10.1126/science.3453112; RA Pennica D., Kohr W.J., Kuang W.-J., Glaister D., Aggarwal B.B., RA Chen E.Y., Goeddel D.V.; RT "Identification of human uromodulin as the Tamm-Horsfall urinary RT glycoprotein."; RL Science 236:83-88(1987). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE. RX PubMed=3498215; DOI=10.1126/science.3498215; RA Hession C., Decker J.M., Sherblom A.P., Kumar S., Yue C.C., RA Mattaliano R.J., Tizard R., Kawashima E., Schmeissner U., Heletky S., RA Chow E.P., Burne C.A., Shaw A., Muchmore A.V.; RT "Uromodulin (Tamm-Horsfall glycoprotein): a renal ligand for RT lymphokines."; RL Science 237:1479-1484(1987). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HNFJ1 TYR-148 AND ARG-217, RP AND VARIANT MCKD2 CYS-103. RX PubMed=12471200; DOI=10.1136/jmg.39.12.882; RA Hart T.C., Gorry M.C., Hart P.S., Woodard A.S., Shihabi Z., Sandhu J., RA Shirts B., Xu L., Zhu H., Barmada M.M., Bleyer A.J.; RT "Mutations of the UMOD gene are responsible for medullary cystic RT kidney disease 2 and familial juvenile hyperuricaemic nephropathy."; RL J. Med. Genet. 39:882-892(2002). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 4 AND 5). RC TISSUE=Kidney; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., RA Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., RA Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Kidney; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP PROTEIN SEQUENCE OF 578-587, PROTEOLYTIC CLEAVAGE, AND IDENTIFICATION RP BY MASS SPECTROMETRY. RX PubMed=18375198; DOI=10.1016/j.bbrc.2008.03.099; RA Santambrogio S., Cattaneo A., Bernascone I., Schwend T., Jovine L., RA Bachi A., Rampoldi L.; RT "Urinary uromodulin carries an intact ZP domain generated by a RT conserved C-terminal proteolytic cleavage."; RL Biochem. Biophys. Res. Commun. 370:410-413(2008). RN [8] RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. RX PubMed=7028707; RA Sikri K.L., Foster C.L., MacHugh N., Marshall R.D.; RT "Localization of Tamm-Horsfall glycoprotein in the human kidney using RT immuno-fluorescence and immuno-electron microscopical techniques."; RL J. Anat. 132:597-605(1981). RN [9] RP GPI-ANCHOR. RX PubMed=2249987; RA Rindler M.J., Naik S.S., Li N., Hoops T.C., Peraldi M.-N.; RT "Uromodulin (Tamm-Horsfall glycoprotein/uromucoid) is a RT phosphatidylinositol-linked membrane protein."; RL J. Biol. Chem. 265:20784-20789(1990). RN [10] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=20798515; DOI=10.1159/000320554; RA Schmid M., Prajczer S., Gruber L.N., Bertocchi C., Gandini R., RA Pfaller W., Jennings P., Joannidis M.; RT "Uromodulin facilitates neutrophil migration across renal epithelial RT monolayers."; RL Cell. Physiol. Biochem. 26:311-318(2010). RN [11] RP SUBCELLULAR LOCATION. RX PubMed=20172860; DOI=10.1093/hmg/ddq077; RA Zaucke F., Boehnlein J.M., Steffens S., Polishchuk R.S., Rampoldi L., RA Fischer A., Pasch A., Boehm C.W., Baasner A., Attanasio M., Hoppe B., RA Hopfer H., Beck B.B., Sayer J.A., Hildebrandt F., Wolf M.T.; RT "Uromodulin is expressed in renal primary cilia and UMOD mutations RT result in decreased ciliary uromodulin expression."; RL Hum. Mol. Genet. 19:1985-1997(2010). RN [12] RP GLYCOSYLATION AT ASN-232; ASN-322 AND ASN-396, STRUCTURE OF RP CARBOHYDRATES, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=22171320; DOI=10.1074/mcp.M111.013649; RA Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.; RT "Human urinary glycoproteomics; attachment site specific analysis of RT N-and O-linked glycosylations by CID and ECD."; RL Mol. Cell. Proteomics 0:0-0(2011). RN [13] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INVOLVEMENT IN HNFJ1. RX PubMed=22776760; DOI=10.1159/000339752; RA Wei X., Xu R., Yang Z., Li Z., Liao Y., Johnson R.J., Yu X., Chen W.; RT "Novel uromodulin mutation in familial juvenile hyperuricemic RT nephropathy."; RL Am. J. Nephrol. 36:114-120(2012). RN [14] RP VARIANT HNFJ1 TYR-223. RX PubMed=12900848; DOI=10.1016/S0272-6386(03)00670-X; RA Bleyer A.J., Trachtman H., Sandhu J., Gorry M.C., Hart T.C.; RT "Renal manifestations of a mutation in the uromodulin (Tamm Horsfall RT protein) gene."; RL Am. J. Kidney Dis. 42:E20-E26(2003). RN [15] RP INVOLVEMENT IN MCKD2, VARIANTS HNFJ1 TRP-148; SER-150 AND TYR-317, RP VARIANT GCKDHI ARG-315, CHARACTERIZATION OF VARIANTS HNFJ1 TRP-148; RP SER-150 AND TYR-317, AND CHARACTERIZATION OF VARIANT GCKDHI ARG-315. RX PubMed=14570709; DOI=10.1093/hmg/ddg353; RA Rampoldi L., Caridi G., Santon D., Boaretto F., Bernascone I., RA Lamorte G., Tardanico R., Dagnino M., Colussi G., Scolari F., RA Ghiggeri G.M., Amoroso A., Casari G.; RT "Allelism of MCKD, FJHN and GCKD caused by impairment of uromodulin RT export dynamics."; RL Hum. Mol. Genet. 12:3369-3384(2003). RN [16] RP INVOLVEMENT IN HNFJ1, AND VARIANTS HNFJ1 ALA-59; ARG-112; ARG-126; RP TYR-170; SER-185; GLY-204; GLY-217; PRO-222; MET-225 AND ARG-282. RX PubMed=14569098; DOI=10.1097/01.ASN.0000092147.83480.B5; RA Dahan K., Devuyst O., Smaers M., Vertommen D., Loute G., Poux J.M., RA Viron B., Jacquot C., Gagnadoux M.F., Chauveau D., Buchler M., RA Cochat P., Cosyns J.P., Mougenot B., Rider M.H., Antignac C., RA Verellen-Dumoulin C., Pirson Y.; RT "A cluster of mutations in the UMOD gene causes familial juvenile RT hyperuricemic nephropathy with abnormal expression of uromodulin."; RL J. Am. Soc. Nephrol. 14:2883-2893(2003). RN [17] RP VARIANTS HNFJ1 TYR-77; ARG-126; SER-128; TYR-255 AND GLY-300. RX PubMed=12629136; DOI=10.1210/jc.2002-021973; RA Turner J.J.O., Stacey J.M., Harding B., Kotanko P., Lhotta K., RA Puig J.G., Roberts I., Torres R.J., Thakker R.V.; RT "UROMODULIN mutations cause familial juvenile hyperuricemic RT nephropathy."; RL J. Clin. Endocrinol. Metab. 88:1398-1401(2003). RN [18] RP VARIANTS MCKD2 93-VAL--GLY-97 DELINS ALA-ALA-SER-CYS; LYS-225 AND RP TRP-248. RX PubMed=14531790; DOI=10.1046/j.1523-1755.2003.00269.x; RA Wolf M.T.F., Mucha B.E., Attanasio M., Zalewski I., Karle S.M., RA Neumann H.P.H., Rahman N., Bader B., Baldamus C.A., Otto E., RA Witzgall R., Fuchshuber A., Hildebrandt F.; RT "Mutations of the Uromodulin gene in MCKD type 2 patients cluster in RT exon 4, which encodes three EGF-like domains."; RL Kidney Int. 64:1580-1587(2003). RN [19] RP INVOLVEMENT IN HNFJ1, AND VARIANTS HNFJ1 TRP-52; SER-135; PHE-195; RP SER-202 AND LEU-236. RX PubMed=15086896; DOI=10.1111/j.1523-1755.2004.00559.x; RA Kudo E., Kamatani N., Tezuka O., Taniguchi A., Yamanaka H., Yabe S., RA Osabe D., Shinohara S., Nomura K., Segawa M., Miyamoto T., RA Moritani M., Kunika K., Itakura M.; RT "Familial juvenile hyperuricemic nephropathy: detection of mutations RT in the uromodulin gene in five Japanese families."; RL Kidney Int. 65:1589-1597(2004). RN [20] RP VARIANT HNFJ1 GLY-347, AND CHARACTERIZATION OF VARIANT HNFJ1 GLY-347. RX PubMed=15575003; DOI=10.1093/ndt/gfh524; RA Tinschert S., Ruf N., Bernascone I., Sacherer K., Lamorte G., RA Neumayer H.H., Nurnberg P., Luft F.C., Rampoldi L.; RT "Functional consequences of a novel uromodulin mutation in a family RT with familial juvenile hyperuricaemic nephropathy."; RL Nephrol. Dial. Transplant. 19:3150-3154(2004). RN [21] RP VARIANT HNFJ1 PRO-316. RX PubMed=15983957; DOI=10.1053/j.ajkd.2005.04.003; RA Lens X.M., Banet J.F., Outeda P., Barrio-Lucia V.; RT "A novel pattern of mutation in uromodulin disorders: autosomal RT dominant medullary cystic kidney disease type 2, familial juvenile RT hyperuricemic nephropathy, and autosomal dominant glomerulocystic RT kidney disease."; RL Am. J. Kidney Dis. 46:52-57(2005). RN [22] RP VARIANT HNFJ1 ARG-236, CHARACTERIZATION OF VARIANTS HNFJ1 ALA-59; RP SER-128; TRP-148; SER-150; GLY-204; ARG-217 AND ARG-236, RP CHARACTERIZATION OF VARIANT MCKD2 LYS-225, AND CHARACTERIZATION OF RP VARIANT GCKDHI ARG-315. RX PubMed=17010121; DOI=10.1111/j.1600-0854.2006.00481.x; RA Bernascone I., Vavassori S., Di Pentima A., Santambrogio S., RA Lamorte G., Amoroso A., Scolari F., Ghiggeri G.M., Casari G., RA Polishchuk R., Rampoldi L.; RT "Defective intracellular trafficking of uromodulin mutant isoforms."; RL Traffic 7:1567-1579(2006). RN [23] RP VARIANT HNFJ1 GLU-461. RX PubMed=21060763; DOI=10.3346/jkms.2010.25.11.1680; RA Lee D.H., Kim J.K., Oh S.E., Noh J.W., Lee Y.K.; RT "A case of familial juvenile hyperuricemic nephropathy with novel RT uromodulin gene mutation, a novel heterozygous missense mutation in RT Korea."; RL J. Korean Med. Sci. 25:1680-1682(2010). RN [24] RP VARIANT HNFJ1 ARG-230. RX PubMed=23197950; DOI=10.1159/000337343; RA Nakayama M., Mori Y., Ota N., Ishida M., Shiotsu Y., Matsuoka E., RA Kado H., Ishida R., Nakata M., Kitani T., Tamagaki K., Sekita C., RA Taniguchi A.; RT "A Japanese family suffering from familial juvenile hyperuricemic RT nephropathy due to a rare mutation of the uromodulin gene."; RL Case Rep. Nephrol. Urol. 2:15-19(2012). RN [25] RP VARIANTS HNFJ1 GLU-109; GLN-236 AND TRP-248, CHARACTERIZATION OF RP VARIANTS HNFJ1 GLU-109; GLN-236 AND TRP-248, SUBCELLULAR LOCATION, AND RP TISSUE SPECIFICITY. RX PubMed=23988501; DOI=10.1016/j.gene.2013.08.041; RA Liu M., Chen Y., Liang Y., Liu Y., Wang S., Hou P., Zhang H., Zhao M.; RT "Novel UMOD mutations in familial juvenile hyperuricemic nephropathy RT lead to abnormal uromodulin intracellular trafficking."; RL Gene 531:363-369(2013). RN [26] RP VARIANT ARG-155, CHARACTERIZATION OF VARIANT MCKD2 93-VAL--GLY-97 RP DELINS ALA-ALA-SER-CYS, CHARACTERIZATION OF VARIANTS HNFJ1 SER-150, RP AND CHARACTERIZATION OF VARIANT ARG-155. RX PubMed=25436415; DOI=10.1016/j.febslet.2014.11.029; RA Stewart A.P., Sandford R.N., Karet Frankl F.E., Edwardson J.M.; RT "Pathogenic uromodulin mutations result in premature intracellular RT polymerization."; RL FEBS Lett. 589:89-93(2015). CC -!- FUNCTION: Uromodulin: Functions in biogenesis and organization of CC the apical membrane of epithelial cells of the thick ascending CC limb of Henle's loop (TALH), where it promotes formation of CC complex filamentous gel-like structure providing the water barrier CC permeability. May serve as a receptor for binding and endocytosis CC for cytokines (IL-1, IL-2) and TNF. Facilitates neutrophil CC migration across renal epithelial. {ECO:0000269|PubMed:20798515}. CC -!- FUNCTION: Uromodulin, secreted form: Secreted into urine after CC proteolytically cleaveage. Into the urine, may contribute to CC colloid osmotic pressure, retards passage of positively charged CC electrolytes, prevents urinary tract infection and modulates CC formation of supersaturated salts and their crystals. CC {ECO:0000269|PubMed:20798515}. CC -!- SUBCELLULAR LOCATION: Apical cell membrane CC {ECO:0000269|PubMed:22776760, ECO:0000269|PubMed:23988501}; Lipid- CC anchor, GPI-anchor. Basolateral cell membrane; Lipid-anchor, GPI- CC anchor. Cell projection, cilium membrane. Note=Only a small CC fraction sorts to the basolateral pole of tubular epithelial cells CC compared to apical localization. Secreted into urine after CC cleavage. Colocalized with NPHP1 and KIF3A. CC -!- SUBCELLULAR LOCATION: Uromodulin, secreted form: Secreted. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=P07911-1; Sequence=Displayed; CC Name=2; CC IsoId=P07911-2; Sequence=VSP_017565; CC Note=No experimental confirmation available.; CC Name=3; CC IsoId=P07911-3; Sequence=VSP_017566; CC Note=No experimental confirmation available.; CC Name=4; CC IsoId=P07911-4; Sequence=VSP_040973; CC Name=5; CC IsoId=P07911-5; Sequence=VSP_054828; CC -!- TISSUE SPECIFICITY: Expressed in the tubular cells of the kidney CC (at protein level). Synthesized exclusively in the kidney. CC Expressed exclusively by epithelial cells of the thick ascending CC limb of Henle's loop (TALH) and of distal convoluted tubule lumen. CC Most abundant protein in normal urine. CC {ECO:0000269|PubMed:22776760, ECO:0000269|PubMed:23988501, CC ECO:0000269|PubMed:7028707}. CC -!- DOMAIN: The ZP domain is involved in the polymerization of the CC protein to promote the formation of complex gel-like structure. CC -!- PTM: N-glycosylated. N-glycan heterogeneity at Asn-232: CC Hex7HexNAc6 (major) and dHex1Hex7HexNAc6 (minor); at Asn-322: CC dHex1Hex6HexNAc5 (minor), dHex1Hex7HexNAc6 (major) and CC dHex1Hex8HexNAc7 (minor); at Asn-396: Hex6HexNAc5 (major), CC dHex1Hex6HexNAc5 (minor) and Hex7HexNAc6 (minor). CC {ECO:0000269|PubMed:22171320}. CC -!- PTM: Proteolytically cleaved at a conserved C-terminal proteolytic CC cleavage site to generate the secreted form found into urine. CC {ECO:0000269|PubMed:18375198}. CC -!- DISEASE: Familial juvenile hyperuricemic nephropathy 1 (HNFJ1) CC [MIM:162000]: A renal disease characterized by juvenile onset of CC hyperuricemia, polyuria, progressive renal failure, and gout. The CC disease is associated with interstitial pathological changes CC resulting in fibrosis. {ECO:0000269|PubMed:12471200, CC ECO:0000269|PubMed:12629136, ECO:0000269|PubMed:12900848, CC ECO:0000269|PubMed:14569098, ECO:0000269|PubMed:14570709, CC ECO:0000269|PubMed:15086896, ECO:0000269|PubMed:15575003, CC ECO:0000269|PubMed:15983957, ECO:0000269|PubMed:17010121, CC ECO:0000269|PubMed:21060763, ECO:0000269|PubMed:22776760, CC ECO:0000269|PubMed:23197950, ECO:0000269|PubMed:23988501}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- DISEASE: Medullary cystic kidney disease 2 (MCKD2) [MIM:603860]: A CC form of tubulointerstitial nephropathy characterized by formation CC of renal cysts at the corticomedullary junction. It is CC characterized by adult onset of impaired renal function and salt CC wasting resulting in end-stage renal failure by the sixth decade. CC {ECO:0000269|PubMed:12471200, ECO:0000269|PubMed:14531790, CC ECO:0000269|PubMed:17010121, ECO:0000269|PubMed:25436415}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- DISEASE: Glomerulocystic kidney disease with hyperuricemia and CC isosthenuria (GCKDHI) [MIM:609886]: A renal disorder characterized CC by a cystic dilation of Bowman space, a collapse of glomerular CC tuft, and hyperuricemia due to low fractional excretion of uric CC acid and severe impairment of urine concentrating ability. CC {ECO:0000269|PubMed:14570709, ECO:0000269|PubMed:17010121}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- MISCELLANEOUS: A specific, but as yet unidentified, protease(s) CC cleaves off and releases UMOD into urine. CC -!- SIMILARITY: Contains 3 EGF-like domains. {ECO:0000255|PROSITE- CC ProRule:PRU00076}. CC -!- SIMILARITY: Contains 1 ZP domain. {ECO:0000255|PROSITE- CC ProRule:PRU00375}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M15881; AAA36798.1; -; mRNA. DR EMBL; M17778; AAA36799.1; -; mRNA. DR EMBL; AY162970; AAO64446.1; -; Genomic_DNA. DR EMBL; AY162963; AAO64446.1; JOINED; Genomic_DNA. DR EMBL; AY162964; AAO64446.1; JOINED; Genomic_DNA. DR EMBL; AY162965; AAO64446.1; JOINED; Genomic_DNA. DR EMBL; AY162967; AAO64446.1; JOINED; Genomic_DNA. DR EMBL; AY162968; AAO64446.1; JOINED; Genomic_DNA. DR EMBL; AY162969; AAO64446.1; JOINED; Genomic_DNA. DR EMBL; AK127643; BAC87070.1; -; mRNA. DR EMBL; AK055722; BAG51560.1; -; mRNA. DR EMBL; AK091961; BAG52451.1; -; mRNA. DR EMBL; AC106796; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC035975; AAH35975.1; -; mRNA. DR CCDS; CCDS10583.1; -. [P07911-1] DR CCDS; CCDS61876.1; -. [P07911-5] DR PIR; A30452; A30452. DR RefSeq; NP_001008390.1; NM_001008389.2. [P07911-1] DR RefSeq; NP_001265543.1; NM_001278614.1. [P07911-5] DR RefSeq; NP_003352.2; NM_003361.3. [P07911-1] DR UniGene; Hs.654425; -. DR ProteinModelPortal; P07911; -. DR SMR; P07911; 29-174. DR BioGrid; 113216; 1. DR IntAct; P07911; 2. DR STRING; 9606.ENSP00000306279; -. DR UniCarbKB; P07911; -. DR BioMuta; UMOD; -. DR DMDM; 137116; -. DR PaxDb; P07911; -. DR PRIDE; P07911; -. DR Ensembl; ENST00000302509; ENSP00000306279; ENSG00000169344. [P07911-1] DR Ensembl; ENST00000396134; ENSP00000379438; ENSG00000169344. [P07911-5] DR Ensembl; ENST00000570689; ENSP00000460548; ENSG00000169344. [P07911-1] DR GeneID; 7369; -. DR KEGG; hsa:7369; -. DR UCSC; uc002dgz.3; human. [P07911-1] DR UCSC; uc002dhb.3; human. DR CTD; 7369; -. DR GeneCards; UMOD; -. DR GeneReviews; UMOD; -. DR H-InvDB; HIX0012858; -. DR HGNC; HGNC:12559; UMOD. DR HPA; CAB009446; -. DR HPA; HPA043420; -. DR HPA; HPA054721; -. DR MalaCards; UMOD; -. DR MIM; 162000; phenotype. DR MIM; 191845; gene. DR MIM; 603860; phenotype. DR MIM; 609886; phenotype. DR neXtProt; NX_P07911; -. DR Orphanet; 34149; Autosomal dominant medullary cystic kidney disease with or without hyperuricemia. DR Orphanet; 209886; Familial juvenile hyperuricemic nephropathy type 1. DR PharmGKB; PA37199; -. DR eggNOG; ENOG410IVSV; Eukaryota. DR eggNOG; ENOG410YDU6; LUCA. DR GeneTree; ENSGT00530000063244; -. DR HOGENOM; HOG000293303; -. DR HOVERGEN; HBG004349; -. DR InParanoid; P07911; -. DR KO; K18274; -. DR OrthoDB; EOG7SFHWJ; -. DR PhylomeDB; P07911; -. DR TreeFam; TF330284; -. DR GeneWiki; Tamm%E2%80%93Horsfall_protein; -. DR GenomeRNAi; 7369; -. DR NextBio; 28856; -. DR PRO; PR:P07911; -. DR Proteomes; UP000005640; Chromosome 16. DR Bgee; P07911; -. DR CleanEx; HS_UMOD; -. DR ExpressionAtlas; P07911; baseline and differential. DR Genevisible; P07911; HS. DR GO; GO:0031225; C:anchored component of membrane; IDA:UniProtKB. DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB. DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB. DR GO; GO:0060170; C:ciliary membrane; IEA:UniProtKB-SubCell. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0019898; C:extrinsic component of membrane; TAS:ProtInc. DR GO; GO:0072372; C:primary cilium; IDA:UniProtKB. DR GO; GO:0000922; C:spindle pole; IDA:UniProtKB. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0019864; F:IgG binding; IDA:BHF-UCL. DR GO; GO:0006968; P:cellular defense response; TAS:ProtInc. DR GO; GO:0048878; P:chemical homeostasis; IEA:Ensembl. DR GO; GO:0007588; P:excretion; IEA:Ensembl. DR GO; GO:0007157; P:heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; IDA:BHF-UCL. DR GO; GO:0007159; P:leukocyte cell-cell adhesion; IDA:BHF-UCL. DR GO; GO:0072218; P:metanephric ascending thin limb development; IEA:Ensembl. DR GO; GO:0072221; P:metanephric distal convoluted tubule development; IEA:Ensembl. DR GO; GO:0072233; P:metanephric thick ascending limb development; IEA:Ensembl. DR GO; GO:0008285; P:negative regulation of cell proliferation; TAS:ProtInc. DR GO; GO:1990266; P:neutrophil migration; IDA:BHF-UCL. DR GO; GO:2000021; P:regulation of ion homeostasis; IEA:Ensembl. DR Gene3D; 2.40.155.10; -; 1. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR013032; EGF-like_CS. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site. DR InterPro; IPR018097; EGF_Ca-bd_CS. DR InterPro; IPR023413; GFP-like. DR InterPro; IPR009030; Growth_fac_rcpt_N_dom. DR InterPro; IPR001507; ZP_dom. DR InterPro; IPR017977; ZP_dom_CS. DR PRINTS; PR00023; ZPELLUCIDA. DR SMART; SM00181; EGF; 1. DR SMART; SM00179; EGF_CA; 2. DR SMART; SM00241; ZP; 1. DR SUPFAM; SSF57184; SSF57184; 1. DR PROSITE; PS00010; ASX_HYDROXYL; 2. DR PROSITE; PS01186; EGF_2; 3. DR PROSITE; PS50026; EGF_3; 3. DR PROSITE; PS01187; EGF_CA; 2. DR PROSITE; PS00682; ZP_1; 1. DR PROSITE; PS51034; ZP_2; 1. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Cell projection; Ciliopathy; KW Cilium; Complete proteome; Direct protein sequencing; KW Disease mutation; Disulfide bond; EGF-like domain; Glycoprotein; KW GPI-anchor; Lipoprotein; Membrane; Nephronophthisis; Polymorphism; KW Reference proteome; Repeat; Secreted; Signal. FT SIGNAL 1 24 FT CHAIN 25 614 Uromodulin. FT /FTId=PRO_0000041671. FT CHAIN 25 587 Uromodulin, secreted form. FT /FTId=PRO_0000407909. FT PROPEP 615 640 Removed in mature form. {ECO:0000255}. FT /FTId=PRO_0000041672. FT DOMAIN 28 64 EGF-like 1. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 65 107 EGF-like 2; calcium-binding. FT {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DOMAIN 108 149 EGF-like 3; calcium-binding. FT {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DOMAIN 334 589 ZP. {ECO:0000255|PROSITE- FT ProRule:PRU00375}. FT SITE 587 588 Cleavage. FT LIPID 614 614 GPI-anchor amidated serine. FT {ECO:0000255}. FT CARBOHYD 38 38 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 76 76 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 80 80 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 232 232 N-linked (GlcNAc...) (complex). FT {ECO:0000269|PubMed:22171320}. FT CARBOHYD 275 275 N-linked (GlcNAc...). FT /FTId=CAR_000178. FT CARBOHYD 322 322 N-linked (GlcNAc...) (complex). FT {ECO:0000269|PubMed:22171320}. FT CARBOHYD 396 396 N-linked (GlcNAc...) (complex). FT {ECO:0000269|PubMed:22171320}. FT DISULFID 32 41 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 35 50 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 52 63 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 69 83 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 77 92 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 94 106 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 112 126 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 120 135 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 137 148 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 506 566 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT VAR_SEQ 29 29 A -> ARTKYNCPARWSWRTPQRGGDTEQGPDEDFTSQG FT (in isoform 5). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_054828. FT VAR_SEQ 67 199 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_017565. FT VAR_SEQ 133 154 Missing (in isoform 4). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_040973. FT VAR_SEQ 205 234 FVGQGGARMAETCVPVLRCNTAAPMWLNGT -> P (in FT isoform 3). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_017566. FT VARIANT 52 52 C -> W (in HNFJ1). FT {ECO:0000269|PubMed:15086896}. FT /FTId=VAR_073052. FT VARIANT 59 59 D -> A (in HNFJ1; results in defective FT trafficking of mutant protein to the FT plasma membrane; the mutant is retained FT in the ER). {ECO:0000269|PubMed:14569098, FT ECO:0000269|PubMed:17010121}. FT /FTId=VAR_073053. FT VARIANT 77 77 C -> Y (in HNFJ1). FT {ECO:0000269|PubMed:12629136}. FT /FTId=VAR_025950. FT VARIANT 93 97 VCPEG -> AASC (in MCKD2; results in FT mutant retention in the ER; results is FT abnormal intracellular polymerization of FT the mutant protein). FT {ECO:0000269|PubMed:14531790, FT ECO:0000269|PubMed:25436415}. FT /FTId=VAR_025951. FT VARIANT 103 103 G -> C (in MCKD2; dbSNP:rs28934584). FT {ECO:0000269|PubMed:12471200}. FT /FTId=VAR_017666. FT VARIANT 109 109 V -> E (in HNFJ1; causes a delay in FT protein export to the plasma membrane due FT to a longer retention time in the ER). FT {ECO:0000269|PubMed:23988501}. FT /FTId=VAR_071398. FT VARIANT 112 112 C -> R (in HNFJ1). FT {ECO:0000269|PubMed:14569098}. FT /FTId=VAR_073054. FT VARIANT 126 126 C -> R (in HNFJ1). FT {ECO:0000269|PubMed:12629136, FT ECO:0000269|PubMed:14569098}. FT /FTId=VAR_025952. FT VARIANT 128 128 N -> S (in HNFJ1; results in defective FT trafficking of mutant protein to the FT plasma membrane; the mutant is retained FT in the ER). {ECO:0000269|PubMed:12629136, FT ECO:0000269|PubMed:17010121}. FT /FTId=VAR_025953. FT VARIANT 135 135 C -> S (in HNFJ1). FT {ECO:0000269|PubMed:15086896}. FT /FTId=VAR_073055. FT VARIANT 148 148 C -> W (in HNFJ1; phenotype overlapping FT with medullary cystic kidney disease; FT causes a delay in protein export to the FT plasma membrane due to a longer retention FT time in the ER). FT {ECO:0000269|PubMed:14570709, FT ECO:0000269|PubMed:17010121}. FT /FTId=VAR_025954. FT VARIANT 148 148 C -> Y (in HNFJ1; dbSNP:rs28934582). FT {ECO:0000269|PubMed:12471200}. FT /FTId=VAR_017667. FT VARIANT 150 150 C -> S (in HNFJ1; phenotype overlapping FT with medullary cystic kidney disease; FT causes a delay in protein export to the FT plasma membrane due to a longer retention FT time in the ER; results is abnormal FT intracellular polymerization of the FT mutant protein). FT {ECO:0000269|PubMed:14570709, FT ECO:0000269|PubMed:17010121, FT ECO:0000269|PubMed:25436415}. FT /FTId=VAR_025955. FT VARIANT 155 155 C -> R (probable-disease association FT mutation found in a patient with cystic FT kidney disease; results in mutant FT retention in the ER; results is abnormal FT intracellular polymerization of the FT mutant protein). FT {ECO:0000269|PubMed:25436415}. FT /FTId=VAR_073056. FT VARIANT 170 170 C -> Y (in HNFJ1). FT {ECO:0000269|PubMed:14569098}. FT /FTId=VAR_073057. FT VARIANT 185 185 R -> S (in HNFJ1). FT {ECO:0000269|PubMed:14569098}. FT /FTId=VAR_073058. FT VARIANT 195 195 C -> F (in HNFJ1). FT {ECO:0000269|PubMed:15086896}. FT /FTId=VAR_073059. FT VARIANT 202 202 W -> S (in HNFJ1). FT {ECO:0000269|PubMed:15086896}. FT /FTId=VAR_073060. FT VARIANT 204 204 R -> G (in HNFJ1; results in defective FT trafficking of mutant protein to the FT plasma membrane; the mutant is retained FT in the ER). {ECO:0000269|PubMed:14569098, FT ECO:0000269|PubMed:17010121}. FT /FTId=VAR_073061. FT VARIANT 217 217 C -> G (in HNFJ1). FT {ECO:0000269|PubMed:14569098}. FT /FTId=VAR_073062. FT VARIANT 217 217 C -> R (in HNFJ1; results in defective FT trafficking of mutant protein to the FT plasma membrane; the mutant is retained FT in the ER; dbSNP:rs28934583). FT {ECO:0000269|PubMed:12471200, FT ECO:0000269|PubMed:17010121}. FT /FTId=VAR_017668. FT VARIANT 222 222 R -> P (in HNFJ1). FT {ECO:0000269|PubMed:14569098}. FT /FTId=VAR_073063. FT VARIANT 223 223 C -> Y (in HNFJ1). FT {ECO:0000269|PubMed:12900848}. FT /FTId=VAR_025956. FT VARIANT 225 225 T -> K (in MCKD2; results in defective FT trafficking of mutant protein to the FT plasma membrane; the mutant is retained FT in the ER). {ECO:0000269|PubMed:14531790, FT ECO:0000269|PubMed:17010121}. FT /FTId=VAR_025957. FT VARIANT 225 225 T -> M (in HNFJ1). FT {ECO:0000269|PubMed:14569098}. FT /FTId=VAR_073064. FT VARIANT 230 230 W -> R (in HNFJ1). FT {ECO:0000269|PubMed:23197950}. FT /FTId=VAR_071399. FT VARIANT 236 236 P -> L (in HNFJ1). FT {ECO:0000269|PubMed:15086896}. FT /FTId=VAR_073065. FT VARIANT 236 236 P -> Q (in HNFJ1; causes a delay in FT protein export to the plasma membrane due FT to a longer retention time in the ER). FT {ECO:0000269|PubMed:23988501}. FT /FTId=VAR_071400. FT VARIANT 236 236 P -> R (in HNFJ1; results in defective FT trafficking of mutant protein to the FT plasma membrane; the mutant is retained FT in the ER). FT {ECO:0000269|PubMed:17010121}. FT /FTId=VAR_073066. FT VARIANT 248 248 C -> W (in MCKD2 and HNFJ1; causes a FT delay in protein export to the plasma FT membrane due to a longer retention time FT in the ER). {ECO:0000269|PubMed:14531790, FT ECO:0000269|PubMed:23988501}. FT /FTId=VAR_025958. FT VARIANT 255 255 C -> Y (in HNFJ1). FT {ECO:0000269|PubMed:12629136}. FT /FTId=VAR_025959. FT VARIANT 282 282 C -> R (in HNFJ1). FT {ECO:0000269|PubMed:14569098}. FT /FTId=VAR_073067. FT VARIANT 300 300 C -> G (in HNFJ1). FT {ECO:0000269|PubMed:12629136}. FT /FTId=VAR_025960. FT VARIANT 315 315 C -> R (in GCKDHI; causes a delay in FT protein export to the plasma membrane due FT to a longer retention time in the ER). FT {ECO:0000269|PubMed:14570709, FT ECO:0000269|PubMed:17010121}. FT /FTId=VAR_025961. FT VARIANT 316 316 Q -> P (in HNFJ1). FT {ECO:0000269|PubMed:15983957}. FT /FTId=VAR_073068. FT VARIANT 317 317 C -> Y (in HNFJ1; phenotype overlapping FT with medullary cystic kidney disease; FT causes a delay in protein export to the FT plasma membrane due to a longer retention FT time in the ER). FT {ECO:0000269|PubMed:14570709}. FT /FTId=VAR_025962. FT VARIANT 347 347 C -> G (in HNFJ1; causes a delay in FT protein export to the plasma membrane due FT to a longer retention time in the ER). FT {ECO:0000269|PubMed:15575003}. FT /FTId=VAR_073069. FT VARIANT 458 458 V -> L (in dbSNP:rs55772253). FT /FTId=VAR_061993. FT VARIANT 461 461 A -> E (in HNFJ1). FT {ECO:0000269|PubMed:21060763}. FT /FTId=VAR_071401. FT CONFLICT 288 288 T -> A (in Ref. 4; BAG51560). FT {ECO:0000305}. FT CONFLICT 503 503 M -> I (in Ref. 4; BAG51560). FT {ECO:0000305}. FT CONFLICT 565 565 H -> D (in Ref. 2; AAA36799). FT {ECO:0000305}. SQ SEQUENCE 640 AA; 69761 MW; D26A07A76353AE48 CRC64; MGQPSLTWML MVVVASWFIT TAATDTSEAR WCSECHSNAT CTEDEAVTTC TCQEGFTGDG LTCVDLDECA IPGAHNCSAN SSCVNTPGSF SCVCPEGFRL SPGLGCTDVD ECAEPGLSHC HALATCVNVV GSYLCVCPAG YRGDGWHCEC SPGSCGPGLD CVPEGDALVC ADPCQAHRTL DEYWRSTEYG EGYACDTDLR GWYRFVGQGG ARMAETCVPV LRCNTAAPMW LNGTHPSSDE GIVSRKACAH WSGHCCLWDA SVQVKACAGG YYVYNLTAPP ECHLAYCTDP SSVEGTCEEC SIDEDCKSNN GRWHCQCKQD FNITDISLLE HRLECGANDM KVSLGKCQLK SLGFDKVFMY LSDSRCSGFN DRDNRDWVSV VTPARDGPCG TVLTRNETHA TYSNTLYLAD EIIIRDLNIK INFACSYPLD MKVSLKTALQ PMVSALNIRV GGTGMFTVRM ALFQTPSYTQ PYQGSSVTLS TEAFLYVGTM LDGGDLSRFA LLMTNCYATP SSNATDPLKY FIIQDRCPHT RDSTIQVVEN GESSQGRFSV QMFRFAGNYD LVYLHCEVYL CDTMNEKCKP TCSGTRFRSG SVIDQSRVLN LGPITRKGVQ ATVSRAFSSL GLLKVWLPLL LSATLTLTFQ //