UROM_CANLF
ID UROM_CANLF Reviewed; 642 AA.
AC Q862Z3;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 25-MAY-2022, entry version 110.
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 Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=12751332; DOI=10.1080/1042517021000056943;
RA Cox M.L., Quignon P., Galibert F., Lees G.E., Murphy K.E.;
RT "Sequencing and radiation hybrid mapping of canine uromodulin.";
RL DNA Seq. 14:61-69(2003).
RN [2]
RP TISSUE SPECIFICITY.
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).
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 -!- TISSUE SPECIFICITY: Detected in kidney and pancreas.
CC {ECO:0000269|PubMed:1531535}.
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; AF498324; AAO33163.1; -; mRNA.
DR AlphaFoldDB; Q862Z3; -.
DR SMR; Q862Z3; -.
DR STRING; 9612.ENSCAFP00000026625; -.
DR PaxDb; Q862Z3; -.
DR PRIDE; Q862Z3; -.
DR eggNOG; ENOG502QT6B; Eukaryota.
DR InParanoid; Q862Z3; -.
DR Proteomes; UP000002254; 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: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: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:1990266; P:neutrophil migration; 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..620
FT /note="Uromodulin"
FT /id="PRO_0000041669"
FT CHAIN 27..588
FT /note="Uromodulin, secreted form"
FT /id="PRO_0000407908"
FT PROPEP 621..642
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000041670"
FT DOMAIN 32..64
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 335..590
FT /note="ZP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00375"
FT REGION 335..430
FT /note="ZP-N"
FT /evidence="ECO:0000255"
FT REGION 431..454
FT /note="Flexible linker; important for secretion and
FT polymerization into filaments"
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT REGION 455..465
FT /note="Internal hydrophobic patch (IHP)"
FT /evidence="ECO:0000255"
FT REGION 466..590
FT /note="ZP-C"
FT /evidence="ECO:0000255"
FT REGION 587..590
FT /note="Essential for cleavage by HPN"
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT REGION 599..608
FT /note="Regulates polymerization into filaments"
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT SITE 588..589
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT LIPID 620
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 246
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 397
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 448
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 514
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..348
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 336..426
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 367..390
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 507..567
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 528..583
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 572..579
FT /evidence="ECO:0000250|UniProtKB:P07911"
SQ SEQUENCE 642 AA; 70178 MW; 608ACCF13A667E64 CRC64;
MGQLSSLTSV WMVVVVTSWV IIAANIDTVE ARSCSECHSN ATCMEDGMVT TCSCLVGFTG
SGFECVDLDE CAIPGAHNCS EGSSCMNTLG SYLCTCPDGF RLTPGLGCID VDECSEPGLS
RCHALATCIN NKGNYSCVCP AGYRGDGQHC ECSPGSCGPG LDCVPVGDAL VCADPCQEHR
ILDEYWRSTE YGAGYTCDVG LNGWYRFTGP GGVRLAETCV PVLHCNTAAP MWLNGTHPTR
DQGIVNRTAC AHWRGHCCLW DASIQVKACA GGYYVYNLTE TPECYLAYCT DPTSVLGTCE
ECSVEEDCKS HDGMWSCQCK QDFNVTDLFL LDRLECRPND IKVSLSKCQL KSLGFEKVFM
YLRDSQCSGF NERGDRDWVS VVTPARDGPC GTVMVRNETH ATYSNTLYLA DEIVIRDRNI
KINFECSYPL DMKVSLETSL QPIVSSLNIS VGGTGMFTVR MALFQTPDYT QPYQGSSVTL
TTEAFLYVGT MLDGGDLSRF ALLMTNCYAT PSSNATDPLK YFIIQDRCPR TTDSTIQVVE
NGESPQGRFS VQMFRFAGNY DLVYLHCEVY LCDIINEKCK PTCSGTRFRS GGIIDQSRVL
NLGPITRKNV QAVVSRAASS SLGFLKVCLP LLLSATLTLM FQ
