UROM_RAT
ID UROM_RAT Reviewed; 644 AA.
AC P27590; Q642D6;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 25-MAY-2022, entry version 155.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
RX PubMed=1531535; DOI=10.1073/pnas.89.4.1189;
RA Fukuoka S., Freedman S.D., Yu H., Sukhatme V.P., Scheele G.A.;
RT "GP-2/THP gene family encodes self-binding glycosylphosphatidylinositol-
RT anchored proteins in apical secretory compartments of pancreas and
RT kidney.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:1189-1193(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7531049;
RA Yu H., Papa F., Sukhatme V.P.;
RT "Bovine and rodent Tamm-Horsfall protein (THP) genes: cloning, structural
RT analysis, and promoter identification.";
RL Gene Expr. 4:63-75(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=379435;
RA Hoyer J.R., Sisson S.P., Vernier R.L.;
RT "Tamm-Horsfall glycoprotein: ultrastructural immunoperoxidase localization
RT in rat kidney.";
RL Lab. Invest. 41:168-173(1979).
CC -!- FUNCTION: [Uromodulin]: Functions in biogenesis and organization of the
CC apical membrane of epithelial cells of the thick ascending limb of
CC Henle's loop (TALH), where it promotes formation of complex filamentous
CC gel-like structure that may play a role in the water barrier
CC permeability. May serve as a receptor for binding and endocytosis of
CC cytokines (IL-1, IL-2) and TNF. Facilitates neutrophil migration across
CC renal epithelia. {ECO:0000250|UniProtKB:P07911}.
CC -!- FUNCTION: [Uromodulin, secreted form]: In the urine, may contribute to
CC colloid osmotic pressure, retards passage of positively charged
CC electrolytes, prevents urinary tract infection and inhibits formation
CC of liquid containing supersaturated salts and subsequent formation of
CC salt crystals. {ECO:0000250|UniProtKB:Q91X17}.
CC -!- SUBUNIT: [Uromodulin, secreted form]: Homodimer that then polymerizes
CC into long filaments. The filaments can additionally assemble laterally
CC to form a sheet. {ECO:0000250|UniProtKB:P07911}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane {ECO:0000269|PubMed:379435};
CC Lipid-anchor, GPI-anchor {ECO:0000250|UniProtKB:P07911}. Basolateral
CC cell membrane {ECO:0000250|UniProtKB:P07911}; Lipid-anchor, GPI-anchor
CC {ECO:0000250|UniProtKB:P07911}. Cell projection, cilium membrane
CC {ECO:0000250|UniProtKB:P07911}. Note=Only a small fraction sorts to the
CC basolateral pole of tubular epithelial cells compared to apical
CC localization. Secreted into urine after cleavage. Colocalizes with
CC NPHP1 and KIF3A. {ECO:0000250|UniProtKB:P07911}.
CC -!- SUBCELLULAR LOCATION: [Uromodulin, secreted form]: Secreted
CC {ECO:0000250|UniProtKB:P07911}. Note=Detected in urine.
CC {ECO:0000250|UniProtKB:P07911}.
CC -!- TISSUE SPECIFICITY: Expression restricted to the thick ascending limb
CC of the loop of Henle (TALH). {ECO:0000269|PubMed:379435}.
CC -!- DOMAIN: The ZP domain mediates polymerization, leading to the formation
CC of long filaments. The core of the filament consists of stacked ZP
CC domains which assemble into a helical structure. Each ZP domain
CC consists of an N-terminal (ZP-N) and C-terminal (ZP-C) region connected
CC by a flexible linker; the linker allows the ZP domain to wrap around
CC the ZP-C subdomain of the preceding subunit. The heavily glycosylated
CC N-terminal part of the protein (containing several EGF-like domains)
CC forms branches which protrude from the core and may be involved in
CC pathogen capture. {ECO:0000250|UniProtKB:P07911}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:P07911}.
CC -!- PTM: Proteolytically cleaved at a conserved C-terminal proteolytic
CC cleavage site to generate the secreted form found in urine. This
CC cleavage is catalyzed by HPN. {ECO:0000250|UniProtKB:P07911}.
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DR EMBL; M63510; AAA42319.1; -; mRNA.
DR EMBL; S75960; AAB33313.1; -; mRNA.
DR EMBL; BC081814; AAH81814.1; -; mRNA.
DR PIR; A40212; A40212.
DR RefSeq; NP_058778.1; NM_017082.1.
DR RefSeq; XP_006230169.1; XM_006230107.2.
DR AlphaFoldDB; P27590; -.
DR SMR; P27590; -.
DR STRING; 10116.ENSRNOP00000021027; -.
DR GlyGen; P27590; 8 sites.
DR PaxDb; P27590; -.
DR PRIDE; P27590; -.
DR GeneID; 25128; -.
DR KEGG; rno:25128; -.
DR UCSC; RGD:3940; rat.
DR CTD; 7369; -.
DR RGD; 3940; Umod.
DR eggNOG; ENOG502QT6B; Eukaryota.
DR InParanoid; P27590; -.
DR OrthoDB; 665331at2759; -.
DR PhylomeDB; P27590; -.
DR TreeFam; TF330284; -.
DR PRO; PR:P27590; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0031225; C:anchored component of membrane; ISS:UniProtKB.
DR GO; GO:0045177; C:apical part of cell; IDA:RGD.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0060170; C:ciliary membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005929; C:cilium; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005794; C:Golgi apparatus; IDA:RGD.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0000922; C:spindle pole; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005201; F:extracellular matrix structural constituent; IBA:GO_Central.
DR GO; GO:0019864; F:IgG binding; ISO:RGD.
DR GO; GO:0006915; P:apoptotic process; ISO:RGD.
DR GO; GO:0097190; P:apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0006914; P:autophagy; ISO:RGD.
DR GO; GO:0055074; P:calcium ion homeostasis; ISO:RGD.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISO:RGD.
DR GO; GO:0030644; P:cellular chloride ion homeostasis; ISO:RGD.
DR GO; GO:0030643; P:cellular phosphate ion homeostasis; ISO:RGD.
DR GO; GO:0034620; P:cellular response to unfolded protein; ISO:RGD.
DR GO; GO:0006883; P:cellular sodium ion homeostasis; ISO:RGD.
DR GO; GO:0061077; P:chaperone-mediated protein folding; ISO:RGD.
DR GO; GO:0048878; P:chemical homeostasis; ISO:RGD.
DR GO; GO:0055064; P:chloride ion homeostasis; ISO:RGD.
DR GO; GO:0046720; P:citric acid secretion; ISO:RGD.
DR GO; GO:0072044; P:collecting duct development; ISO:RGD.
DR GO; GO:0097709; P:connective tissue replacement; ISO:RGD.
DR GO; GO:0097273; P:creatinine homeostasis; ISO:RGD.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; ISO:RGD.
DR GO; GO:0007029; P:endoplasmic reticulum organization; ISO:RGD.
DR GO; GO:0010467; P:gene expression; ISO:RGD.
DR GO; GO:0003094; P:glomerular filtration; ISO:RGD.
DR GO; GO:0007157; P:heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; ISO:RGD.
DR GO; GO:0006954; P:inflammatory response; ISO:RGD.
DR GO; GO:0050801; P:ion homeostasis; ISO:RGD.
DR GO; GO:0072051; P:juxtaglomerular apparatus development; ISO:RGD.
DR GO; GO:0001822; P:kidney development; ISO:RGD.
DR GO; GO:0007159; P:leukocyte cell-cell adhesion; ISO:RGD.
DR GO; GO:0006629; P:lipid metabolic process; ISO:RGD.
DR GO; GO:0072070; P:loop of Henle development; ISO:RGD.
DR GO; GO:0072218; P:metanephric ascending thin limb development; ISO:RGD.
DR GO; GO:0072221; P:metanephric distal convoluted tubule development; ISO:RGD.
DR GO; GO:0072233; P:metanephric thick ascending limb development; ISO:RGD.
DR GO; GO:0060073; P:micturition; ISO:RGD.
DR GO; GO:0048871; P:multicellular organismal homeostasis; ISO:RGD.
DR GO; GO:0033555; P:multicellular organismal response to stress; ISO:RGD.
DR GO; GO:1990266; P:neutrophil migration; ISO:RGD.
DR GO; GO:0002251; P:organ or tissue specific immune response; ISO:RGD.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISO:RGD.
DR GO; GO:0055062; P:phosphate ion homeostasis; ISO:RGD.
DR GO; GO:0055075; P:potassium ion homeostasis; ISO:RGD.
DR GO; GO:0072665; P:protein localization to vacuole; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD.
DR GO; GO:0044861; P:protein transport into plasma membrane raft; ISO:RGD.
DR GO; GO:0008217; P:regulation of blood pressure; ISO:RGD.
DR GO; GO:0051223; P:regulation of protein transport; ISO:RGD.
DR GO; GO:0035809; P:regulation of urine volume; ISO:RGD.
DR GO; GO:0070294; P:renal sodium ion absorption; ISO:RGD.
DR GO; GO:0097744; P:renal urate salt excretion; ISO:RGD.
DR GO; GO:0003091; P:renal water homeostasis; ISO:RGD.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISO:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISO:RGD.
DR GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR GO; GO:0006986; P:response to unfolded protein; ISO:RGD.
DR GO; GO:0009414; P:response to water deprivation; ISO:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:RGD.
DR GO; GO:0008380; P:RNA splicing; ISO:RGD.
DR GO; GO:0055078; P:sodium ion homeostasis; ISO:RGD.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; ISO:RGD.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; ISO:RGD.
DR GO; GO:0015747; P:urate transport; ISO:RGD.
DR GO; GO:0071918; P:urea transmembrane transport; ISO:RGD.
DR GO; GO:0030104; P:water homeostasis; ISO:RGD.
DR Gene3D; 2.60.40.4100; -; 1.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR024731; EGF_dom.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR042235; ZP-C.
DR InterPro; IPR001507; ZP_dom.
DR InterPro; IPR017977; ZP_dom_CS.
DR Pfam; PF12947; EGF_3; 2.
DR Pfam; PF07645; EGF_CA; 1.
DR Pfam; PF00100; Zona_pellucida; 1.
DR PRINTS; PR00023; ZPELLUCIDA.
DR SMART; SM00181; EGF; 3.
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; 4.
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 2: Evidence at transcript level;
KW Cell membrane; Cell projection; Disulfide bond; EGF-like domain;
KW Glycoprotein; GPI-anchor; Lipoprotein; Membrane; Reference proteome;
KW Repeat; Secreted; Signal.
FT SIGNAL 1..26
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT CHAIN 27..615
FT /note="Uromodulin"
FT /id="PRO_0000041675"
FT CHAIN 27..590
FT /note="Uromodulin, secreted form"
FT /id="PRO_0000407912"
FT PROPEP 616..644
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000041676"
FT DOMAIN 30..66
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 67..108
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 109..150
FT /note="EGF-like 3; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 337..592
FT /note="ZP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00375"
FT REGION 337..432
FT /note="ZP-N"
FT /evidence="ECO:0000255"
FT REGION 433..456
FT /note="Flexible linker; important for secretion and
FT polymerization into filaments"
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT REGION 457..467
FT /note="Internal hydrophobic patch (IHP)"
FT /evidence="ECO:0000255"
FT REGION 468..592
FT /note="ZP-C"
FT /evidence="ECO:0000255"
FT REGION 589..592
FT /note="Essential for cleavage by HPN"
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT REGION 601..610
FT /note="Regulates polymerization into filaments"
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT SITE 590..591
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT LIPID 615
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 40
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 78
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 235
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 278
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 325
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 399
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 450
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 516
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 34..43
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 37..52
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 54..65
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 71..84
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 79..93
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 95..107
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 113..127
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 121..136
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 138..149
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 300..309
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 303..318
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 320..350
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 338..428
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 369..392
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 509..569
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 530..585
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 574..581
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT CONFLICT 155
FT /note="F -> S (in Ref. 3; AAH81814)"
FT /evidence="ECO:0000305"
FT CONFLICT 326
FT /note="V -> I (in Ref. 3; AAH81814)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 644 AA; 71062 MW; D26DB419C669826A CRC64;
MGQLLSLTWL LLVMVVTPWF TVAGANDSPE ARRCSECHDN ATCVLDGVVT TCSCQAGFTG
DGLVCEDIDE CATPWTHNCS NSICMNTLGS YECSCQDGFR LTPGLGCIDV NECTEQGLSN
CHSLATCVNT EGSYSCVCPK GYRGDGWYCE CSPGFCEPGL DCLPQGPSGK LVCQDPCNVY
ETLTEYWRST DYGAGYSCDS DMHGWYRFTG QGGVRMAETC VPVLRCNTAA PMWLNGSHPS
SREGIVSRTA CAHWSDHCCL WSTEIQVKAC PGGFYVYNLT EPPECNLAYC TDPSSVEGTC
EECGVDEDCV SDNGRWRCQC KQDFNVTDVS LLEHRLECEA NEIKISLSKC QLQSLGFMKV
FMYLNDRQCS GFSERGERDW MSIVTPARDG PCGTVLRRNE THATYSNTLY LASEIIIRDI
NIRINFECSY PLDMKVSLKT SLQPMVSALN ISLGGTGKFT VQMALFQNPT YTQPYQGPSV
MLSTEAFLYV GTMLDGGDLS RFVLLMTNCY ATPSSNSTDP VKYFIIQDRC PHTEDTTIQV
TENGESSQAR FSIQMFRFAG NSDLVYLHCE VYLCDTMSEQ CKPTCSGTRY RSGNFIDQTR
VLNLGPITRQ GVQASVSKAA SSNLGFLSIW LLLFLSATLT LMVH
