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Protein

Uromodulin

Gene

Umod

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Uromodulin: Functions in biogenesis and organization of the apical membrane of epithelial cells of the thick ascending limb of Henle's loop (TALH), where it promotes formation of complex filamentous gel-like structure that may play a role in the water barrier permeability. May serve as a receptor for binding and endocytosis of cytokines (IL-1, IL-2) and TNF. Facilitates neutrophil migration across renal epithelia.By similarity
Uromodulin, secreted form: In the urine, may contribute to colloid osmotic pressure, retards passage of positively charged electrolytes, prevents urinary tract infection and inhibits formation of liquid containing supersaturated salts and subsequent formation of salt crystals.2 Publications

GO - Molecular functioni

GO - Biological processi

  • chemical homeostasis Source: MGI
  • excretion Source: MGI
  • heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules Source: MGI
  • leukocyte cell-cell adhesion Source: MGI
  • metanephric ascending thin limb development Source: UniProtKB
  • metanephric distal convoluted tubule development Source: UniProtKB
  • metanephric thick ascending limb development Source: UniProtKB
  • neutrophil migration Source: MGI
  • regulation of ion homeostasis Source: UniProtKB
Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-MMU-446203. Asparagine N-linked glycosylation.

Names & Taxonomyi

Protein namesi
Recommended name:
Uromodulin
Alternative name(s):
Tamm-Horsfall urinary glycoprotein
Short name:
THP
Cleaved into the following chain:
Gene namesi
Name:Umod
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:102674. Umod.

Subcellular locationi

Uromodulin, secreted form :

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane, Secreted

Pathology & Biotechi

Disruption phenotypei

Mice suffer significantly more frequently from urinary tract infections. They shown also spontaneous formation of calcium crystals in adult kidneys, and excessive intake of calcium and oxalate dramatically increases both the frequency and the severity of renal calcium crystal formation in mutant mice, but not in wild-type mice.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24By similarityAdd BLAST24
ChainiPRO_000004167325 – 618UromodulinAdd BLAST594
ChainiPRO_000040791025 – 588Uromodulin, secreted formAdd BLAST564
PropeptideiPRO_0000041674619 – 642Removed in mature formSequence analysisAdd BLAST24

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi25N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi32 ↔ 41PROSITE-ProRule annotation
Disulfide bondi35 ↔ 50PROSITE-ProRule annotation
Glycosylationi38N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi52 ↔ 63PROSITE-ProRule annotation
Disulfide bondi69 ↔ 82PROSITE-ProRule annotation
Glycosylationi76N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi77 ↔ 91PROSITE-ProRule annotation
Glycosylationi79N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi93 ↔ 105PROSITE-ProRule annotation
Disulfide bondi111 ↔ 125PROSITE-ProRule annotation
Disulfide bondi119 ↔ 134PROSITE-ProRule annotation
Disulfide bondi136 ↔ 147PROSITE-ProRule annotation
Glycosylationi233N-linked (GlcNAc...)Sequence analysis1
Glycosylationi276N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi298 ↔ 307By similarity
Disulfide bondi301 ↔ 316By similarity
Disulfide bondi318 ↔ 348By similarity
Glycosylationi323N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi336 ↔ 426By similarity
Disulfide bondi367 ↔ 390By similarity
Glycosylationi397N-linked (GlcNAc...)Sequence analysis1
Glycosylationi448N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi507 ↔ 567PROSITE-ProRule annotation
Glycosylationi514N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi528 ↔ 583By similarity
Disulfide bondi572 ↔ 579By similarity
Lipidationi618GPI-anchor amidated alanineSequence analysis1

Post-translational modificationi

N-glycosylated.2 Publications
Proteolytically cleaved at a conserved C-terminal proteolytic cleavage site to generate the secreted form found in urine (PubMed:18375198). This cleavage is catalyzed by HPN (PubMed:26673890).2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei588 – 589Cleavage2 Publications2

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

Proteomic databases

PaxDbiQ91X17.
PRIDEiQ91X17.

Expressioni

Tissue specificityi

Detected in urine (secreted form). Detected in kidney thick ascending limb epithelial cells (at protein level).1 Publication

Gene expression databases

BgeeiENSMUSG00000030963.
CleanExiMM_UMOD.
ExpressionAtlasiQ91X17. baseline and differential.
GenevisibleiQ91X17. MM.

Interactioni

Subunit structurei

Uromodulin, secreted form: homodimer that then polymerizes into long filaments.1 Publication

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000033263.

Structurei

3D structure databases

ProteinModelPortaliQ91X17.
SMRiQ91X17.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini28 – 64EGF-like 1PROSITE-ProRule annotationAdd BLAST37
Domaini65 – 106EGF-like 2; calcium-bindingPROSITE-ProRule annotationAdd BLAST42
Domaini107 – 148EGF-like 3; calcium-bindingPROSITE-ProRule annotationAdd BLAST42
Domaini335 – 590ZPPROSITE-ProRule annotationAdd BLAST256

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni431 – 454Important for secretion and polymerization into filamentsBy similarityAdd BLAST24
Regioni587 – 590Essential for cleavage by HPNBy similarity4
Regioni599 – 608Regulates polymerization into filamentsBy similarity10

Domaini

The ZP domain mediates polymerization, leading to the formation of long filaments.2 Publications

Sequence similaritiesi

Contains 3 EGF-like domains.PROSITE-ProRule annotation
Contains 1 ZP domain.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IVSV. Eukaryota.
ENOG410YDU6. LUCA.
GeneTreeiENSGT00530000063244.
HOGENOMiHOG000293303.
HOVERGENiHBG004349.
InParanoidiQ91X17.
KOiK18274.
OMAiVFMYLRD.
OrthoDBiEOG091G06RJ.
PhylomeDBiQ91X17.
TreeFamiTF330284.

Family and domain databases

Gene3Di2.40.155.10. 1 hit.
InterProiIPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR024731. EGF_dom.
IPR023413. GFP-like.
IPR009030. Growth_fac_rcpt_.
IPR001507. ZP_dom.
IPR017977. ZP_dom_CS.
[Graphical view]
PfamiPF12947. EGF_3. 1 hit.
PF07645. EGF_CA. 1 hit.
PF00100. Zona_pellucida. 1 hit.
[Graphical view]
PRINTSiPR00023. ZPELLUCIDA.
SMARTiSM00181. EGF. 3 hits.
SM00179. EGF_CA. 2 hits.
SM00241. ZP. 1 hit.
[Graphical view]
SUPFAMiSSF57184. SSF57184. 1 hit.
PROSITEiPS00010. ASX_HYDROXYL. 2 hits.
PS01186. EGF_2. 3 hits.
PS50026. EGF_3. 3 hits.
PS01187. EGF_CA. 2 hits.
PS00682. ZP_1. 1 hit.
PS51034. ZP_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q91X17-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGIPLTWMLL VMMVTSWFTL AEASNSTEAR RCSECHNNAT CTVDGVVTTC
60 70 80 90 100
SCQTGFTGDG LVCEDMDECA TPWTHNCSNS SCVNTPGSFK CSCQDGFRLT
110 120 130 140 150
PELSCTDVDE CSEQGLSNCH ALATCVNTEG DYLCVCPEGF TGDGWYCECS
160 170 180 190 200
PGSCEPGLDC LPQGPDGKLV CQDPCNTYET LTEYWRSTEY GVGYSCDAGL
210 220 230 240 250
HGWYRFTGQG GVRMAETCVP VLRCNTAAPM WLNGSHPSSS EGIVSRTACA
260 270 280 290 300
HWSDQCCRWS TEIQVKACPG GFYIYNLTAP PECNLAYCTD PSSVEGTCEE
310 320 330 340 350
CRVDEDCISD NGRWRCQCKQ DSNITDVSQL EYRLECGAND IKMSLRKCQL
360 370 380 390 400
QSLGFMNVFM YLNDRQCSGF SESDERDWMS IVTPARNGPC GTVLRRNETH
410 420 430 440 450
ATYSNTLYLA NAIIIRDIII RMNFECSYPL DMKVSLKTSL QPMVSALNIS
460 470 480 490 500
LGGTGKFTVR MALFQSPTYT QPHQGPSVML STEAFLYVGT MLDGGDLSRF
510 520 530 540 550
VLLMTNCYAT PSSNSTDPVK YFIIQDSCPR TEDTTIQVTE NGESSQARFS
560 570 580 590 600
VQMFRFAGNY DLVYLHCEVY LCDSTSEQCK PTCSGTRFRS GNFIDQTRVL
610 620 630 640
NLGPITRQGV QASVSKAASS NLRLLSIWLL LFPSATLIFM VQ
Length:642
Mass (Da):70,845
Last modified:December 1, 2001 - v1
Checksum:i31B1461B4DCAE927
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti22E → G in AAA73896 (PubMed:7873609).Curated1
Sequence conflicti102 – 104ELS → GLG in AAA73896 (PubMed:7873609).Curated3
Sequence conflicti138E → K in AAA73896 (PubMed:7873609).Curated1
Sequence conflicti152G → S in AAA73896 (PubMed:7873609).Curated1
Sequence conflicti200L → Q in AAA73896 (PubMed:7873609).Curated1
Sequence conflicti223R → A in AAA73896 (PubMed:7873609).Curated1
Sequence conflicti255Q → H in AAA73896 (PubMed:7873609).Curated1
Sequence conflicti279A → E in AAA73896 (PubMed:7873609).Curated1
Sequence conflicti340D → G in BAE38225 (PubMed:16141072).Curated1
Sequence conflicti473H → Y in AAA73896 (PubMed:7873609).Curated1
Sequence conflicti590S → C in AAA73896 (PubMed:7873609).Curated1
Sequence conflicti606T → TRQ in AAA73896 (PubMed:7873609).Curated1
Sequence conflicti616 – 617Missing in AAA73896 (PubMed:7873609).Curated2
Sequence conflicti633P → L in AAA73896 (PubMed:7873609).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L33406 mRNA. Translation: AAA73896.1.
AK085460 mRNA. Translation: BAC39452.1.
AK144065 mRNA. Translation: BAE25681.1.
AK164688 mRNA. Translation: BAE37877.1.
AK165507 mRNA. Translation: BAE38225.1.
BC012973 mRNA. Translation: AAH12973.1.
CCDSiCCDS21780.1.
PIRiS52111.
RefSeqiNP_001265534.1. NM_001278605.1.
NP_033496.1. NM_009470.5.
UniGeneiMm.10826.

Genome annotation databases

EnsembliENSMUST00000033263; ENSMUSP00000033263; ENSMUSG00000030963.
ENSMUST00000209095; ENSMUSP00000146652; ENSMUSG00000030963.
GeneIDi22242.
KEGGimmu:22242.
UCSCiuc009jlb.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L33406 mRNA. Translation: AAA73896.1.
AK085460 mRNA. Translation: BAC39452.1.
AK144065 mRNA. Translation: BAE25681.1.
AK164688 mRNA. Translation: BAE37877.1.
AK165507 mRNA. Translation: BAE38225.1.
BC012973 mRNA. Translation: AAH12973.1.
CCDSiCCDS21780.1.
PIRiS52111.
RefSeqiNP_001265534.1. NM_001278605.1.
NP_033496.1. NM_009470.5.
UniGeneiMm.10826.

3D structure databases

ProteinModelPortaliQ91X17.
SMRiQ91X17.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000033263.

Proteomic databases

PaxDbiQ91X17.
PRIDEiQ91X17.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000033263; ENSMUSP00000033263; ENSMUSG00000030963.
ENSMUST00000209095; ENSMUSP00000146652; ENSMUSG00000030963.
GeneIDi22242.
KEGGimmu:22242.
UCSCiuc009jlb.2. mouse.

Organism-specific databases

CTDi7369.
MGIiMGI:102674. Umod.

Phylogenomic databases

eggNOGiENOG410IVSV. Eukaryota.
ENOG410YDU6. LUCA.
GeneTreeiENSGT00530000063244.
HOGENOMiHOG000293303.
HOVERGENiHBG004349.
InParanoidiQ91X17.
KOiK18274.
OMAiVFMYLRD.
OrthoDBiEOG091G06RJ.
PhylomeDBiQ91X17.
TreeFamiTF330284.

Enzyme and pathway databases

ReactomeiR-MMU-446203. Asparagine N-linked glycosylation.

Miscellaneous databases

ChiTaRSiUmod. mouse.
PROiQ91X17.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000030963.
CleanExiMM_UMOD.
ExpressionAtlasiQ91X17. baseline and differential.
GenevisibleiQ91X17. MM.

Family and domain databases

Gene3Di2.40.155.10. 1 hit.
InterProiIPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR024731. EGF_dom.
IPR023413. GFP-like.
IPR009030. Growth_fac_rcpt_.
IPR001507. ZP_dom.
IPR017977. ZP_dom_CS.
[Graphical view]
PfamiPF12947. EGF_3. 1 hit.
PF07645. EGF_CA. 1 hit.
PF00100. Zona_pellucida. 1 hit.
[Graphical view]
PRINTSiPR00023. ZPELLUCIDA.
SMARTiSM00181. EGF. 3 hits.
SM00179. EGF_CA. 2 hits.
SM00241. ZP. 1 hit.
[Graphical view]
SUPFAMiSSF57184. SSF57184. 1 hit.
PROSITEiPS00010. ASX_HYDROXYL. 2 hits.
PS01186. EGF_2. 3 hits.
PS50026. EGF_3. 3 hits.
PS01187. EGF_CA. 2 hits.
PS00682. ZP_1. 1 hit.
PS51034. ZP_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUROM_MOUSE
AccessioniPrimary (citable) accession number: Q91X17
Secondary accession number(s): Q3TN64, Q3TP60, Q62285
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 26, 2005
Last sequence update: December 1, 2001
Last modified: November 30, 2016
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.