Q91X17 (UROM_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Uromodulin

Alternative name(s):
Tamm-Horsfall urinary glycoprotein
Short name=THP

Cleaved into the following chain:

1. Uromodulin, secreted form

Gene names

Name:

Umod

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	642 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.5 Ref.6 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. Ref.5 Ref.6
Subcellular location	Apical cell membrane; Lipid-anchor › GPI-anchor By similarity. Basolateral cell membrane; Lipid-anchor › GPI-anchor By similarity. Cell projection › cilium membrane By similarity. Note: Only a small fraction is sorts to the basolateral pole of tubular epithelial cells compared to apical localization By similarity. Uromodulin, secreted form: Secreted By similarity.
Domain	The ZP domain is involved in the polymerization of the protein to promote the formation of complex gel-like structure. Ref.4
Post-translational modification	N-glycosylated. Ref.4
Disruption phenotype	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. Ref.5 Ref.6
Sequence similarities	Contains 3 EGF-like domains. Contains 1 ZP domain.

Ontologies

Keywords
Cellular component	Cell membrane Cell projection Membrane Secreted
Domain	EGF-like domain Repeat Signal
PTM	Disulfide bond GPI-anchor Glycoprotein Lipoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	chemical homeostasis Inferred from mutant phenotype PubMed 17264314. Source: MGI excretion Inferred from mutant phenotype PubMed 17264314. Source: MGI metanephric ascending thin limb development Inferred from expression pattern PubMed 18618131. Source: UniProtKB metanephric distal convoluted tubule development Inferred from expression pattern PubMed 18618131. Source: UniProtKB metanephric thick ascending limb development Inferred from expression pattern PubMed 18618131. Source: UniProtKB regulation of ion homeostasis Inferred from mutant phenotype Ref.6. Source: UniProtKB response to organic substance Inferred from electronic annotation. Source: Compara
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: Compara anchored to membrane Inferred from sequence or structural similarity. Source: UniProtKB apical plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB basolateral plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB cilium membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasmic vesicle Inferred from electronic annotation. Source: Compara extracellular space Inferred from electronic annotation. Source: Compara membrane raft Inferred from electronic annotation. Source: Compara primary cilium Inferred from sequence or structural similarity. Source: UniProtKB spindle pole Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Potential
	Chain	24 – 618	595	Uromodulin		PRO_0000041673
	Chain	25 – 588	564	Uromodulin, secreted form By similarity		PRO_0000407910
	Propeptide	619 – 642	24	Removed in mature form Potential		PRO_0000041674
Regions
	Domain	28 – 64	37	EGF-like 1
	Domain	65 – 106	42	EGF-like 2; calcium-binding Potential
	Domain	107 – 148	42	EGF-like 3; calcium-binding Potential
	Domain	335 – 590	256	ZP
Sites
	Site	588 – 589	2	Cleavage
Amino acid modifications
	Lipidation	618	1	GPI-anchor amidated alanine Potential
	Glycosylation	25	1	N-linked (GlcNAc...) Potential
	Glycosylation	38	1	N-linked (GlcNAc...) Potential
	Glycosylation	76	1	N-linked (GlcNAc...) Potential
	Glycosylation	79	1	N-linked (GlcNAc...) Potential
	Glycosylation	233	1	N-linked (GlcNAc...) Potential
	Glycosylation	276	1	N-linked (GlcNAc...) Potential
	Glycosylation	323	1	N-linked (GlcNAc...) Potential
	Glycosylation	397	1	N-linked (GlcNAc...) Potential
	Glycosylation	448	1	N-linked (GlcNAc...) Potential
	Glycosylation	514	1	N-linked (GlcNAc...) Potential
	Disulfide bond	32 ↔ 41		By similarity
	Disulfide bond	35 ↔ 50		By similarity
	Disulfide bond	52 ↔ 63		By similarity
	Disulfide bond	69 ↔ 82		By similarity
	Disulfide bond	77 ↔ 91		By similarity
	Disulfide bond	93 ↔ 105		By similarity
	Disulfide bond	111 ↔ 125		By similarity
	Disulfide bond	119 ↔ 134		By similarity
	Disulfide bond	136 ↔ 147		By similarity
	Disulfide bond	507 ↔ 567		By similarity
Experimental info
	Sequence conflict	22	1	E → G in AAA73896. Ref.1
	Sequence conflict	102 – 104	3	ELS → GLG in AAA73896. Ref.1
	Sequence conflict	138	1	E → K in AAA73896. Ref.1
	Sequence conflict	152	1	G → S in AAA73896. Ref.1
	Sequence conflict	200	1	L → Q in AAA73896. Ref.1
	Sequence conflict	223	1	R → A in AAA73896. Ref.1
	Sequence conflict	255	1	Q → H in AAA73896. Ref.1
	Sequence conflict	279	1	A → E in AAA73896. Ref.1
	Sequence conflict	340	1	D → G in BAE38225. Ref.2
	Sequence conflict	473	1	H → Y in AAA73896. Ref.1
	Sequence conflict	590	1	S → C in AAA73896. Ref.1
	Sequence conflict	606	1	T → TRQ in AAA73896. Ref.1
	Sequence conflict	616 – 617	2	Missing in AAA73896. Ref.1
	Sequence conflict	633	1	P → L in AAA73896. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q91X17 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 31B1461B4DCAE927	FASTA	642	70,845
	10 20 30 40 50 60 MGIPLTWMLL VMMVTSWFTL AEASNSTEAR RCSECHNNAT CTVDGVVTTC SCQTGFTGDG 70 80 90 100 110 120 LVCEDMDECA TPWTHNCSNS SCVNTPGSFK CSCQDGFRLT PELSCTDVDE CSEQGLSNCH 130 140 150 160 170 180 ALATCVNTEG DYLCVCPEGF TGDGWYCECS PGSCEPGLDC LPQGPDGKLV CQDPCNTYET 190 200 210 220 230 240 LTEYWRSTEY GVGYSCDAGL HGWYRFTGQG GVRMAETCVP VLRCNTAAPM WLNGSHPSSS 250 260 270 280 290 300 EGIVSRTACA HWSDQCCRWS TEIQVKACPG GFYIYNLTAP PECNLAYCTD PSSVEGTCEE 310 320 330 340 350 360 CRVDEDCISD NGRWRCQCKQ DSNITDVSQL EYRLECGAND IKMSLRKCQL QSLGFMNVFM 370 380 390 400 410 420 YLNDRQCSGF SESDERDWMS IVTPARNGPC GTVLRRNETH ATYSNTLYLA NAIIIRDIII 430 440 450 460 470 480 RMNFECSYPL DMKVSLKTSL QPMVSALNIS LGGTGKFTVR MALFQSPTYT QPHQGPSVML 490 500 510 520 530 540 STEAFLYVGT MLDGGDLSRF VLLMTNCYAT PSSNSTDPVK YFIIQDSCPR TEDTTIQVTE 550 560 570 580 590 600 NGESSQARFS VQMFRFAGNY DLVYLHCEVY LCDSTSEQCK PTCSGTRFRS GNFIDQTRVL 610 620 630 640 NLGPITRQGV QASVSKAASS NLRLLSIWLL LFPSATLIFM VQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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(1995) [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(2005) [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(2004) [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(2002) [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(2004) [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(2004) [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(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 573-587, PROTEOLYTIC CLEAVAGE, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00128334.
PIR	S52111.
RefSeq	NP_033496.1. NM_009470.4.
UniGene	Mm.10826.
3D structure databases
ProteinModelPortal	Q91X17.
SMR	Q91X17. Positions 48-143.
ModBase	Search...
Protein-protein interaction databases
STRING	10090.ENSMUSP00000033263.
Proteomic databases
PaxDb	Q91X17.
PRIDE	Q91X17.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000033263; ENSMUSP00000033263; ENSMUSG00000030963.
GeneID	22242.
KEGG	mmu:22242.
UCSC	uc009jlb.1. mouse.
Organism-specific databases
CTD	7369.
MGI	MGI:102674. Umod.
Phylogenomic databases
eggNOG	NOG44010.
GeneTree	ENSGT00530000063244.
HOGENOM	HOG000293303.
HOVERGEN	HBG004349.
InParanoid	Q91X17.
OMA	VLRCNTA.
OrthoDB	EOG498V0G.
Gene expression databases
ArrayExpress	Q91X17.
Bgee	Q91X17.
CleanEx	MM_UMOD.
Genevestigator	Q91X17.
GermOnline	ENSMUSG00000030963. Mus musculus.
Family and domain databases
Gene3D	2.40.155.10. 1 hit.
InterPro	IPR000742. EG-like_dom. IPR001881. EGF-like_Ca-bd. IPR013032. EGF-like_CS. IPR000152. EGF-type_Asp/Asn_hydroxyl_site. IPR018097. EGF_Ca-bd_CS. IPR024731. EGF_dom_MSP1-like. IPR023413. GFP_like. IPR001507. ZP_dom. IPR017977. ZP_dom_CS. [Graphical view]
Pfam	PF12947. EGF_3. 1 hit. PF07645. EGF_CA. 1 hit. PF00100. Zona_pellucida. 1 hit. [Graphical view]
PRINTS	PR00023. ZPELLUCIDA.
SMART	SM00181. EGF. 1 hit. SM00179. EGF_CA. 2 hits. SM00241. ZP. 1 hit. [Graphical view]
PROSITE	PS00010. ASX_HYDROXYL. 2 hits. PS00022. EGF_1. False negative. 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]
ProtoNet	Search...
Other
ChiTaRS	UMOD. mouse.
NextBio	302309.
SOURCE	Search...

Entry information

Entry name

UROM_MOUSE

Accession

Primary (citable) accession number: Q91X17
Secondary accession number(s): Q3TN64, Q3TP60, Q62285

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 26, 2005
Last sequence update:	December 1, 2001
Last modified:	May 1, 2013
This is version 100 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program