UROM_PONAB
ID UROM_PONAB Reviewed; 641 AA.
AC Q5R5C1;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 97.
DE RecName: Full=Uromodulin;
DE Contains:
DE RecName: Full=Uromodulin, secreted form;
DE Flags: Precursor;
GN Name=UMOD;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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}.
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DR EMBL; CR860941; CAH93045.1; -; mRNA.
DR RefSeq; NP_001126801.1; NM_001133329.1.
DR AlphaFoldDB; Q5R5C1; -.
DR SMR; Q5R5C1; -.
DR STRING; 9601.ENSPPYP00000008090; -.
DR PRIDE; Q5R5C1; -.
DR GeneID; 100173805; -.
DR KEGG; pon:100173805; -.
DR CTD; 7369; -.
DR eggNOG; ENOG502QT6B; Eukaryota.
DR HOGENOM; CLU_028679_1_0_1; -.
DR InParanoid; Q5R5C1; -.
DR OMA; LECGVND; -.
DR OrthoDB; 665331at2759; -.
DR TreeFam; TF330284; -.
DR Proteomes; UP000001595; 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: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 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; 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 Calcium; Cell membrane; Cell projection; Disulfide bond; EGF-like domain;
KW Glycoprotein; GPI-anchor; Lipoprotein; Membrane; Reference proteome;
KW Repeat; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT CHAIN 25..614
FT /note="Uromodulin"
FT /id="PRO_0000228125"
FT CHAIN 25..587
FT /note="Uromodulin, secreted form"
FT /id="PRO_0000407911"
FT PROPEP 615..641
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000228126"
FT DOMAIN 28..64
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 65..107
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 108..149
FT /note="EGF-like 3; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 334..589
FT /note="ZP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00375"
FT REGION 334..429
FT /note="ZP-N"
FT /evidence="ECO:0000255"
FT REGION 430..453
FT /note="Flexible linker; important for secretion and
FT polymerization into filaments"
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT REGION 454..464
FT /note="Internal hydrophobic patch (IHP)"
FT /evidence="ECO:0000255"
FT REGION 465..589
FT /note="ZP-C"
FT /evidence="ECO:0000255"
FT REGION 586..589
FT /note="Essential for cleavage by HPN"
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT REGION 598..607
FT /note="Regulates polymerization into filaments"
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT SITE 587..588
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT LIPID 614
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 25
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 76
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 232
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 275
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 322
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 447
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 32..41
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 35..50
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 52..63
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 69..83
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 77..92
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 94..106
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 112..126
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 120..135
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 137..148
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 297..306
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 300..315
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 317..347
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 335..425
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 366..389
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 506..566
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 527..582
FT /evidence="ECO:0000250|UniProtKB:P07911"
FT DISULFID 571..578
FT /evidence="ECO:0000250|UniProtKB:P07911"
SQ SEQUENCE 641 AA; 69806 MW; 81AE37CB04FFDA0E CRC64;
MGQPPLTWML MVVVASWFIT TAATNTSEAR WCSECHSNAT CTEDEAVTTC TCQEGFTGDG
LTCVDLDECA IPGAHNCSAN SSCVNTPGSF SCVCPEGFRL SPGLGCTDVD ECAEPGLSHC
HALATCVNVV GNYLCVCPAG YRGDGWHCEC SPGSCGPGLD CVPEGDALVC ADPCQAHRTL
DEYWRSTEYG EGYACDTDLR GWYRFVGQGG ARLAETCVPV LRCNTAAPMW LNGTHPSSDE
GIVSRKACAH WSGHCCLWDA SVQVKACAGG YYVYNLTAPP ECHLAYCTDP SSVEGTCEEC
SIDEDCKSDN GRWHCQCKQD FNITDISLLE HRLECGANDM KVSLGKCQLK SLGFDKVFMY
LSDSRCSGFN DRDNRDWVSV VTPARDGPCG TVLTRNETHA TYSNTLYLAD EIIIRDRNIK
INFACSYPLD MKVSLKTSLQ PVVSALNITV GGTGMFTVRM ALFQNPSYTQ PYQGSSVTLS
TEAFLYVGTM LDGGDLSRFA LLMTNCYATP SGNATDPLKY FIIQDRCPHT RDSTIQVVEN
GESSQGRFSV QMFRFAGNYD LVYLHCEVYL CDTMNEKCKP TCSGTRFRSG SVIDQSRVLN
LGPITRKGVQ ATVSRAAFSS LGLLKVWLPL LLSATLTLTF Q
