UROM_BOVIN
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 03-AUG-2022, entry version 134.
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, 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
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 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}.
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; S75958; AAB33312.1; -; mRNA.
DR RefSeq; NP_776638.1; NM_174213.2.
DR AlphaFoldDB; P48733; -.
DR SMR; P48733; -.
DR STRING; 9913.ENSBTAP00000043345; -.
DR PaxDb; P48733; -.
DR GeneID; 281567; -.
DR KEGG; bta:281567; -.
DR CTD; 7369; -.
DR eggNOG; ENOG502QT6B; Eukaryota.
DR InParanoid; P48733; -.
DR OrthoDB; 665331at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0031225; C:anchored component of membrane; ISS:UniProtKB.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0060170; C:ciliary membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005929; C:cilium; ISS:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
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 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; 1.
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; 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; Lipoprotein; Membrane; Reference proteome;
KW 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 336..587
FT /note="ZP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00375"
FT REGION 336..431
FT /note="ZP-N"
FT /evidence="ECO:0000255"
FT REGION 432..455
FT /note="Flexible linker; important for secretion and
FT polymerization into filaments"
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT REGION 456..466
FT /note="Internal hydrophobic patch (IHP)"
FT /evidence="ECO:0000255"
FT REGION 467..591
FT /note="ZP-C"
FT /evidence="ECO:0000255"
FT REGION 588..591
FT /note="Essential for cleavage by HPN"
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT REGION 600..609
FT /note="Regulates 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 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
