| IED ID | IndEnz0002001078 |
| Enzyme Type ID | protease001078 |
| Protein Name |
Uromodulin Tamm-Horsfall urinary glycoprotein THP Cleaved into: Uromodulin, secreted form |
| Gene Name | UMOD |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MGQPSLTWMLMVVVASWFITTAATDTSEARWCSECHSNATCTEDEAVTTCTCQEGFTGDGLTCVDLDECAIPGAHNCSANSSCVNTPGSFSCVCPEGFRLSPGLGCTDVDECAEPGLSHCHALATCVNVVGSYLCVCPAGYRGDGWHCECSPGSCGPGLDCVPEGDALVCADPCQAHRTLDEYWRSTEYGEGYACDTDLRGWYRFVGQGGARMAETCVPVLRCNTAAPMWLNGTHPSSDEGIVSRKACAHWSGHCCLWDASVQVKACAGGYYVYNLTAPPECHLAYCTDPSSVEGTCEECSIDEDCKSNNGRWHCQCKQDFNITDISLLEHRLECGANDMKVSLGKCQLKSLGFDKVFMYLSDSRCSGFNDRDNRDWVSVVTPARDGPCGTVLTRNETHATYSNTLYLADEIIIRDLNIKINFACSYPLDMKVSLKTALQPMVSALNIRVGGTGMFTVRMALFQTPSYTQPYQGSSVTLSTEAFLYVGTMLDGGDLSRFALLMTNCYATPSSNATDPLKYFIIQDRCPHTRDSTIQVVENGESSQGRFSVQMFRFAGNYDLVYLHCEVYLCDTMNEKCKPTCSGTRFRSGSVIDQSRVLNLGPITRKGVQATVSRAFSSLGLLKVWLPLLLSATLTLTFQ |
| Enzyme Length | 640 |
| Uniprot Accession Number | P07911 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: [Uromodulin]: Functions in biogenesis and organization of the apical membrane of epithelial cells of the thick ascending limb of Henle's loop (TALH), where it promotes formation of complex filamentous gel-like structure that may play a role in the water barrier permeability (Probable). May serve as a receptor for binding and endocytosis of cytokines (IL-1, IL-2) and TNF (PubMed:3498215). Facilitates neutrophil migration across renal epithelia (PubMed:20798515). {ECO:0000269|PubMed:20798515, ECO:0000269|PubMed:3498215, ECO:0000305}.; FUNCTION: [Uromodulin, secreted form]: In the urine, may contribute to colloid osmotic pressure, retards passage of positively charged electrolytes, prevents urinary tract infection and inhibits formation of liquid containing supersaturated salts and subsequent formation of salt crystals. {ECO:0000250|UniProtKB:Q91X17, ECO:0000305}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (4); Beta strand (24); Chain (2); Disulfide bond (17); Domain (4); Glycosylation (8); Helix (5); Lipidation (1); Mutagenesis (11); Natural variant (40); Propeptide (1); Region (6); Sequence conflict (3); Signal peptide (1); Site (1); Turn (2) |
| Keywords | 3D-structure;Alternative splicing;Cell membrane;Cell projection;Ciliopathy;Cilium;Direct protein sequencing;Disease variant;Disulfide bond;EGF-like domain;GPI-anchor;Glycoprotein;Lipoprotein;Membrane;Nephronophthisis;Reference proteome;Repeat;Secreted;Signal |
| Interact With | Q9BWP8 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Apical cell membrane {ECO:0000269|PubMed:22776760, ECO:0000269|PubMed:23988501, ECO:0000269|PubMed:26673890, ECO:0000269|PubMed:7028707}; Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:2249987}. Basolateral cell membrane {ECO:0000269|PubMed:7028707}; Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:2249987}. Cell projection, cilium membrane {ECO:0000269|PubMed:20172860}. Note=Only a small fraction sorts to the basolateral pole of tubular epithelial cells compared to apical localization (PubMed:22776760). Secreted into urine after cleavage (PubMed:18375198, PubMed:26811476). Colocalizes with NPHP1 and KIF3A (PubMed:20172860). {ECO:0000269|PubMed:18375198, ECO:0000269|PubMed:20172860, ECO:0000269|PubMed:26811476, ECO:0000269|PubMed:3453112, ECO:0000269|PubMed:7028707}.; SUBCELLULAR LOCATION: [Uromodulin, secreted form]: Secreted {ECO:0000269|PubMed:18375198, ECO:0000269|PubMed:19005207, ECO:0000269|PubMed:26673890, ECO:0000269|PubMed:26811476, ECO:0000269|PubMed:3453112, ECO:0000269|PubMed:7028707}. Note=Detected in urine. {ECO:0000269|PubMed:18375198, ECO:0000269|PubMed:26811476, ECO:0000269|PubMed:3453112, ECO:0000269|PubMed:7028707}. |
| Modified Residue | |
| Post Translational Modification | PTM: N-glycosylated (PubMed:19005207, PubMed:26673890, PubMed:26811476, PubMed:32815518, PubMed:33196145). N-glycan heterogeneity at Asn-232: Hex7HexNAc6 (major) and dHex1Hex7HexNAc6 (minor); at Asn-322: dHex1Hex6HexNAc5 (minor), dHex1Hex7HexNAc6 (major) and dHex1Hex8HexNAc7 (minor); at Asn-396: Hex6HexNAc5 (major), dHex1Hex6HexNAc5 (minor) and Hex7HexNAc6 (minor) (PubMed:22171320). {ECO:0000269|PubMed:19005207, ECO:0000269|PubMed:22171320, ECO:0000269|PubMed:26673890, ECO:0000269|PubMed:26811476, ECO:0000269|PubMed:32815518, ECO:0000269|PubMed:33196145}.; PTM: Proteolytically cleaved at a conserved C-terminal proteolytic cleavage site to generate the secreted form found in urine (PubMed:18375198, PubMed:19005207). This cleavage is catalyzed by HPN (PubMed:26673890). {ECO:0000269|PubMed:18375198, ECO:0000269|PubMed:19005207, ECO:0000269|PubMed:26673890}. |
| Signal Peptide | SIGNAL 1..24 |
| Structure 3D | Electron microscopy (4); X-ray crystallography (1) |
| Cross Reference PDB | 4WRN; 6TQK; 6TQL; 6ZS5; 6ZYA; |
| Mapped Pubmed ID | 11730273; 11932463; 11982485; 12021773; 12624657; 12678917; 12832729; 14520616; 14570881; 14688233; 15033942; 15079052; 15253706; 15266028; 15327389; 15430405; 15589826; 15785410; 15952882; 16164624; 16982955; 17065110; 17151335; 17245395; 18047931; 18351395; 18409515; 18409531; 18455532; 18600511; 18651238; 18830570; 18846391; 18950917; 19203555; 19430482; 19465746; 19959715; 1999417; 20075439; 20151160; 20222955; 20237496; 20624112; 20686651; 20711500; 20948228; 20970175; 21067798; 21081491; 21082022; 21109754; 21332338; 21358122; 21546974; 21654721; 21738052; 21868615; 22034507; 22117067; 22132988; 22237754; 22538938; 22592667; 22693617; 22947327; 22997256; 23009031; 23344472; 23586973; 23826568; 24112972; 24185693; 24577984; 24628133; 24648000; 24667016; 24697042; 24849497; 25163389; 25493955; 25671765; 25840631; 25935139; 26040415; 26617860; 26966016; 27045027; 27113631; 27315129; 27448670; 27938332; 27958261; 28182086; 28206617; 28598953; 28605509; 28609449; 28613246; 28742158; 28829050; 28858977; 28914853; 28954491; 29180395; 29511113; 29513881; 29578190; 29698955; 29779026; 29853186; 30454063; 30903163; 31253490; 31411505; 31422399; 32011449; 32045104; 32058862; 32113667; 32291270; 32450155; 32616672; 32764816; 32769629; 32815518; 32847529; 33196145; 33414784; 34071541; 34145125; 34187999; 34824175; 6156677; 7072193; 9590290; |
| Motif | |
| Gene Encoded By | |
| Mass | 69,761 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |