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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 providing the water barrier permeability. May serve as a receptor for binding and endocytosis for cytokines (IL-1, IL-2) and TNF. Facilitates neutrophil migration across renal epithelial (By similarity).By similarity
Uromodulin, secreted form: Secreted into urine after proteolytically cleaveage. Into the urine, may contribute to colloid osmotic pressure, retards passage of positively charged electrolytes, prevents urinary tract infection and modulates formation of supersaturated salts and their crystals.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei588 – 5892Cleavage

GO - Molecular functioni

  1. calcium ion binding Source: InterPro
  2. IgG binding Source: MGI

GO - Biological processi

  1. chemical homeostasis Source: MGI
  2. excretion Source: MGI
  3. heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules Source: MGI
  4. leukocyte cell-cell adhesion Source: MGI
  5. metanephric ascending thin limb development Source: UniProtKB
  6. metanephric distal convoluted tubule development Source: UniProtKB
  7. metanephric thick ascending limb development Source: UniProtKB
  8. neutrophil migration Source: MGI
  9. regulation of ion homeostasis Source: UniProtKB
  10. response to organic substance Source: Ensembl
Complete GO annotation...

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
ProteomesiUP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:102674. Umod.

Subcellular locationi

Apical cell membrane By similarity; Lipid-anchorGPI-anchor By similarity. Basolateral cell membrane By similarity; Lipid-anchorGPI-anchor By similarity. Cell projectioncilium membrane By similarity
Note: Only a small fraction sorts to the basolateral pole of tubular epithelial cells compared to apical localization.By similarity

GO - Cellular componenti

  1. anchored component of membrane Source: UniProtKB
  2. apical plasma membrane Source: UniProtKB
  3. basolateral plasma membrane Source: UniProtKB
  4. ciliary membrane Source: UniProtKB-SubCell
  5. cytoplasmic vesicle Source: Ensembl
  6. extracellular space Source: Ensembl
  7. extracellular vesicular exosome Source: MGI
  8. Golgi apparatus Source: Ensembl
  9. membrane raft Source: Ensembl
  10. primary cilium Source: UniProtKB
  11. spindle pole Source: UniProtKB
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 deficient-mice but not in wild-type mice.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2323Sequence AnalysisAdd
BLAST
Chaini24 – 618595UromodulinPRO_0000041673Add
BLAST
Chaini25 – 588564Uromodulin, secreted formBy similarityPRO_0000407910Add
BLAST
Propeptidei619 – 64224Removed in mature formSequence AnalysisPRO_0000041674Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi25 – 251N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi32 ↔ 41PROSITE-ProRule annotation
Disulfide bondi35 ↔ 50PROSITE-ProRule annotation
Glycosylationi38 – 381N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi52 ↔ 63PROSITE-ProRule annotation
Disulfide bondi69 ↔ 82PROSITE-ProRule annotation
Glycosylationi76 – 761N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi77 ↔ 91PROSITE-ProRule annotation
Glycosylationi79 – 791N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi93 ↔ 105PROSITE-ProRule annotation
Disulfide bondi111 ↔ 125PROSITE-ProRule annotation
Disulfide bondi119 ↔ 134PROSITE-ProRule annotation
Disulfide bondi136 ↔ 147PROSITE-ProRule annotation
Glycosylationi233 – 2331N-linked (GlcNAc...)Sequence Analysis
Glycosylationi276 – 2761N-linked (GlcNAc...)Sequence Analysis
Glycosylationi323 – 3231N-linked (GlcNAc...)Sequence Analysis
Glycosylationi397 – 3971N-linked (GlcNAc...)Sequence Analysis
Glycosylationi448 – 4481N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi507 ↔ 567PROSITE-ProRule annotation
Glycosylationi514 – 5141N-linked (GlcNAc...)Sequence Analysis
Lipidationi618 – 6181GPI-anchor amidated alanineSequence Analysis

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

Proteomic databases

PaxDbiQ91X17.
PRIDEiQ91X17.

Expressioni

Gene expression databases

BgeeiQ91X17.
CleanExiMM_UMOD.
ExpressionAtlasiQ91X17. baseline and differential.
GenevestigatoriQ91X17.

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000033263.

Structurei

3D structure databases

ProteinModelPortaliQ91X17.
SMRiQ91X17. Positions 48-143.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini28 – 6437EGF-like 1PROSITE-ProRule annotationAdd
BLAST
Domaini65 – 10642EGF-like 2; calcium-bindingPROSITE-ProRule annotationAdd
BLAST
Domaini107 – 14842EGF-like 3; calcium-bindingPROSITE-ProRule annotationAdd
BLAST
Domaini335 – 590256ZPPROSITE-ProRule annotationAdd
BLAST

Domaini

The ZP domain is involved in the polymerization of the protein to promote the formation of complex gel-like structure.1 Publication

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

eggNOGiNOG44010.
GeneTreeiENSGT00530000063244.
HOGENOMiHOG000293303.
HOVERGENiHBG004349.
InParanoidiQ91X17.
KOiK18274.
OMAiNCHALAT.
OrthoDBiEOG7SFHWJ.
PhylomeDBiQ91X17.
TreeFamiTF330284.

Family and domain databases

Gene3Di2.40.155.10. 1 hit.
InterProiIPR000742. EG-like_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR024731. EGF_dom_MSP1-like.
IPR023413. GFP_like.
IPR009030. Growth_fac_rcpt_N_dom.
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. 1 hit.
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:November 30, 2001 - v1
Checksum:i31B1461B4DCAE927
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti22 – 221E → G in AAA73896 (PubMed:7873609).Curated
Sequence conflicti102 – 1043ELS → GLG in AAA73896 (PubMed:7873609).Curated
Sequence conflicti138 – 1381E → K in AAA73896 (PubMed:7873609).Curated
Sequence conflicti152 – 1521G → S in AAA73896 (PubMed:7873609).Curated
Sequence conflicti200 – 2001L → Q in AAA73896 (PubMed:7873609).Curated
Sequence conflicti223 – 2231R → A in AAA73896 (PubMed:7873609).Curated
Sequence conflicti255 – 2551Q → H in AAA73896 (PubMed:7873609).Curated
Sequence conflicti279 – 2791A → E in AAA73896 (PubMed:7873609).Curated
Sequence conflicti340 – 3401D → G in BAE38225 (PubMed:16141072).Curated
Sequence conflicti473 – 4731H → Y in AAA73896 (PubMed:7873609).Curated
Sequence conflicti590 – 5901S → C in AAA73896 (PubMed:7873609).Curated
Sequence conflicti606 – 6061T → TRQ in AAA73896 (PubMed:7873609).Curated
Sequence conflicti616 – 6172Missing in AAA73896 (PubMed:7873609).Curated
Sequence conflicti633 – 6331P → L in AAA73896 (PubMed:7873609).Curated

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.
GeneIDi22242.
KEGGimmu:22242.
UCSCiuc009jlb.1. 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. Positions 48-143.
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.
GeneIDi22242.
KEGGimmu:22242.
UCSCiuc009jlb.1. mouse.

Organism-specific databases

CTDi7369.
MGIiMGI:102674. Umod.

Phylogenomic databases

eggNOGiNOG44010.
GeneTreeiENSGT00530000063244.
HOGENOMiHOG000293303.
HOVERGENiHBG004349.
InParanoidiQ91X17.
KOiK18274.
OMAiNCHALAT.
OrthoDBiEOG7SFHWJ.
PhylomeDBiQ91X17.
TreeFamiTF330284.

Miscellaneous databases

ChiTaRSiUmod. mouse.
NextBioi302309.
PROiQ91X17.
SOURCEiSearch...

Gene expression databases

BgeeiQ91X17.
CleanExiMM_UMOD.
ExpressionAtlasiQ91X17. baseline and differential.
GenevestigatoriQ91X17.

Family and domain databases

Gene3Di2.40.155.10. 1 hit.
InterProiIPR000742. EG-like_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR024731. EGF_dom_MSP1-like.
IPR023413. GFP_like.
IPR009030. Growth_fac_rcpt_N_dom.
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. 1 hit.
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...

Publicationsi

« Hide 'large scale' publications
  1. "Nucleotide sequence and peptide motifs of mouse uromodulin (Tamm-Horsfall protein) -- the most abundant protein in mammalian urine."
    Prasadan K., Bates J., Badgett A., Dell M., Sukhatme V., Yu H., Kumar S.
    Biochim. Biophys. Acta 1260:328-332(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Kidney.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Liver.
  4. "The ZP domain is a conserved module for polymerization of extracellular proteins."
    Jovine L., Qi H., Williams Z., Litscher E., Wassarman P.M.
    Nat. Cell Biol. 4:457-461(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION, DOMAIN ZP.
  5. "Tamm-Horsfall protein knockout mice are more prone to urinary tract infection: rapid communication."
    Bates J.M., Raffi H.M., Prasadan K., Mascarenhas R., Laszik Z., Maeda N., Hultgren S.J., Kumar S.
    Kidney Int. 65:791-797(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  6. "Tamm-Horsfall protein is a critical renal defense factor protecting against calcium oxalate crystal formation."
    Mo L., Huang H.Y., Zhu X.H., Shapiro E., Hasty D.L., Wu X.R.
    Kidney Int. 66:1159-1166(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  7. "Urinary uromodulin carries an intact ZP domain generated by a conserved C-terminal proteolytic cleavage."
    Santambrogio S., Cattaneo A., Bernascone I., Schwend T., Jovine L., Bachi A., Rampoldi L.
    Biochem. Biophys. Res. Commun. 370:410-413(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 573-587, PROTEOLYTIC CLEAVAGE, IDENTIFICATION BY MASS SPECTROMETRY.

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 25, 2005
Last sequence update: November 30, 2001
Last modified: February 3, 2015
This is version 115 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

External Data

Dasty 3

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 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.