ID UROM_BOVIN Reviewed; 643 AA.
AC P48733;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 24-JAN-2024, entry version 140.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
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).
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, and inhibits formation of liquid containing
CC supersaturated salts and subsequent formation of salt crystals.
CC Protects against urinary tract infections by binding to type 1
CC fimbriated E.coli. Binds to bacterial adhesin fimH which mediates the
CC stable formation of bacterial aggregates, prevents the binding of
CC E.coli to uroplakins UPK1A and UPK1B which act as urothelial receptors
CC for type I fimbriae, and allows for pathogen clearance through
CC micturation. Also promotes aggregation of other bacteria including
CC K.pneumoniae, P.aeruginosa and S.mitis and so may also protect against
CC other uropathogens. {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. The filaments consist of a zigzag-shaped backbone with
CC laterally protruding arms which interact with bacterial adhesin fimH.
CC Two fimH molecules can bind to a single UMOD monomer.
CC {ECO:0000250|UniProtKB:P07911}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000250|UniProtKB:P07911}; Lipid-anchor, GPI-anchor
CC {ECO:0000250|UniProtKB:P07911}. Basolateral cell membrane
CC {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 -!- DOMAIN: The ZP domain mediates polymerization, leading to the formation
CC of long filaments. The core of the filament consists of interlocked 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 are 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; S75958; AAB33312.1; -; mRNA.
DR RefSeq; NP_776638.1; NM_174213.2.
DR AlphaFoldDB; P48733; -.
DR SMR; P48733; -.
DR STRING; 9913.ENSBTAP00000061186; -.
DR GlyCosmos; P48733; 9 sites, No reported glycans.
DR PaxDb; 9913-ENSBTAP00000043345; -.
DR GeneID; 281567; -.
DR KEGG; bta:281567; -.
DR CTD; 7369; -.
DR eggNOG; ENOG502QT6B; Eukaryota.
DR InParanoid; P48733; -.
DR OrthoDB; 5293157at2759; -.
DR Proteomes; UP000009136; Unplaced.
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:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0098552; C:side of membrane; IEA:UniProtKB-KW.
DR GO; GO:0000922; C:spindle pole; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0140367; P:antibacterial innate immune response; ISS:UniProtKB.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; ISS:UniProtKB.
DR GO; GO:1990266; P:neutrophil migration; IBA:GO_Central.
DR CDD; cd00054; EGF_CA; 2.
DR Gene3D; 2.10.25.10; Laminin; 3.
DR Gene3D; 2.60.40.4100; Zona pellucida, ZP-C domain; 1.
DR Gene3D; 2.60.40.3210; Zona pellucida, ZP-N domain; 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; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR042235; ZP-C.
DR InterPro; IPR048290; ZP_chr.
DR InterPro; IPR001507; ZP_dom.
DR InterPro; IPR017977; ZP_dom_CS.
DR PANTHER; PTHR14002; ENDOGLIN/TGF-BETA RECEPTOR TYPE III; 1.
DR PANTHER; PTHR14002:SF40; UROMODULIN; 1.
DR Pfam; PF07645; EGF_CA; 2.
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; Growth factor receptor domain; 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 2: Evidence at transcript level;
KW Cell membrane; Cell projection; Disulfide bond; EGF-like domain;
KW Glycoprotein; GPI-anchor; Immunity; Innate immunity; Lipoprotein; Membrane;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..26
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT CHAIN 27..621
FT /note="Uromodulin"
FT /id="PRO_0000041667"
FT CHAIN 27..589
FT /note="Uromodulin, secreted form"
FT /id="PRO_0000407907"
FT PROPEP 622..643
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000041668"
FT DOMAIN 32..66
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 67..109
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 110..151
FT /note="EGF-like 3; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 294..325
FT /note="EGF-like 4"
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DOMAIN 336..587
FT /note="ZP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00375"
FT REGION 152..173
FT /note="Beta hairpin"
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT REGION 174..293
FT /note="D10C"
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT REGION 336..431
FT /note="ZP-N"
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT REGION 432..455
FT /note="Flexible ZP-N/ZP-C linker; important for secretion
FT and polymerization into filaments"
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT REGION 456..587
FT /note="ZP-C"
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT REGION 456..466
FT /note="Internal hydrophobic patch (IHP)"
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT REGION 588..591
FT /note="Essential for cleavage by HPN"
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT REGION 600..608
FT /note="External hydrophobic patch (EHP); regulates
FT polymerization into filaments"
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT SITE 589..590
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT LIPID 621
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 134
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 234
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 277
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 324
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 398
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 449
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 515
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..85
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 79..94
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 96..108
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 114..128
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 122..137
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 139..150
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 152..163
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 157..172
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 176..269
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 197..284
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 219..257
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 225..289
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 250..258
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 299..308
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 302..317
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 319..349
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 337..427
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 368..391
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 508..568
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 529..584
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 573..580
FT /evidence="ECO:0000250|UniProtKB:P07911"
SQ SEQUENCE 643 AA; 69898 MW; 448984AB01DFA477 CRC64;
MKCLFSPNFM WMAAVVTSWV IIPAATDTSS AKSCSECHSN ATCTVDGAAT TCACQEGFTG
DGLECVDLDE CAVLGAHNCS ATKSCVNTLG SYTCVCPEGF LLSSELGCED VDECAEPGLS
RCHALATCIN GEGNYSCVCP AGYLGDGRHC ECSPGSCGPG LDCVREGDAL VCVDPCQVHR
ILDEYWRSTE YGSGYICDVS LGGWYRFVGQ AGVRLPETCV PVLHCNTAAP MWLNGTHPSS
DEGIVNRVAC AHWSGDCCLW DAPIQVKACA GGYYVYNLTA PPECHLAYCT DPSSVEGTCE
ECRVDEDCKS DNGEWHCQCK QDFNVTDLSL LERRLECGVD DIKLSLSKCQ LKSLGFEKVF
MYLHDSQCSG FTERGDRDWM SVVTPARDGP CGTVMTRNET HATYSNTLYL ADEIIIRDLN
IRINFACSYP LDMKVSLKTS LQPMVSALNI SMGGTGTFTV RMALFQSPAY TQPYQGSSVT
LSTEAFLYVG TMLDGGDLSR FVLLMTNCYA TPSSNATDPL KYFIIQDRCP RAADSTIQVE
ENGESPQGRF SVQMFRFAGN YDLVYLHCEV YLCDTVNEKC RPTCPETRFR SGSIIDQTRV
LNLGPITRKG GQAAMSRAAP SSLGLLQVWL PLLLSATLTL MSP
//
