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Protein

Uromodulin

Gene

Umod

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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.By similarity

GO - Molecular functioni

GO - Biological processi

  • response to organic substance Source: RGD
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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3940. Umod.

Subcellular locationi

  • Apical cell membrane 1 Publication; 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. Secreted into urine after cleavage. Colocalizes with NPHP1 and KIF3A.By similarity
Uromodulin, secreted form :
  • Secreted By similarity

  • Note: Detected in urine.By similarity

GO - Cellular componenti

  • anchored component of membrane Source: UniProtKB
  • apical part of cell Source: RGD
  • apical plasma membrane Source: UniProtKB
  • basolateral plasma membrane Source: UniProtKB
  • ciliary membrane Source: UniProtKB-SubCell
  • cilium Source: UniProtKB
  • cytoplasmic, membrane-bounded vesicle Source: RGD
  • cytoplasmic vesicle Source: RGD
  • extracellular space Source: RGD
  • Golgi apparatus Source: RGD
  • membrane raft Source: RGD
  • spindle pole Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 26By similarityAdd BLAST26
ChainiPRO_000004167527 – 615UromodulinAdd BLAST589
ChainiPRO_000040791227 – 590Uromodulin, secreted formAdd BLAST564
PropeptideiPRO_0000041676616 – 644Removed in mature formSequence analysisAdd BLAST29

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi34 ↔ 43PROSITE-ProRule annotation
Disulfide bondi37 ↔ 52PROSITE-ProRule annotation
Glycosylationi40N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi54 ↔ 65PROSITE-ProRule annotation
Disulfide bondi71 ↔ 84PROSITE-ProRule annotation
Glycosylationi78N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi79 ↔ 93PROSITE-ProRule annotation
Disulfide bondi95 ↔ 107PROSITE-ProRule annotation
Disulfide bondi113 ↔ 127PROSITE-ProRule annotation
Disulfide bondi121 ↔ 136PROSITE-ProRule annotation
Disulfide bondi138 ↔ 149PROSITE-ProRule annotation
Glycosylationi235N-linked (GlcNAc...)Sequence analysis1
Glycosylationi278N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi300 ↔ 309By similarity
Disulfide bondi303 ↔ 318By similarity
Disulfide bondi320 ↔ 350By similarity
Glycosylationi325N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi338 ↔ 428By similarity
Disulfide bondi369 ↔ 392By similarity
Glycosylationi399N-linked (GlcNAc...)Sequence analysis1
Glycosylationi450N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi509 ↔ 569PROSITE-ProRule annotation
Glycosylationi516N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi530 ↔ 585By similarity
Disulfide bondi574 ↔ 581By similarity
Lipidationi615GPI-anchor amidated serineSequence analysis1

Post-translational modificationi

N-glycosylated.By similarity
Proteolytically cleaved at a conserved C-terminal proteolytic cleavage site to generate the secreted form found in urine. This cleavage is catalyzed by HPN.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei590 – 591CleavageBy similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

Proteomic databases

PaxDbiP27590.
PRIDEiP27590.

Expressioni

Tissue specificityi

Expression restricted to the thick ascending limb of the loop of Henle (TALH).1 Publication

Gene expression databases

BgeeiENSRNOG00000015557.

Interactioni

Subunit structurei

Uromodulin, secreted form: homodimer that then polymerizes into long filaments.By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000021027.

Structurei

3D structure databases

ProteinModelPortaliP27590.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini30 – 66EGF-like 1PROSITE-ProRule annotationAdd BLAST37
Domaini67 – 108EGF-like 2; calcium-bindingPROSITE-ProRule annotationAdd BLAST42
Domaini109 – 150EGF-like 3; calcium-bindingPROSITE-ProRule annotationAdd BLAST42
Domaini337 – 592ZPPROSITE-ProRule annotationAdd BLAST256

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni433 – 456Important for secretion and polymerization into filamentsBy similarityAdd BLAST24
Regioni589 – 592Essential for cleavage by HPNBy similarity4
Regioni601 – 610Regulates polymerization into filamentsBy similarity10

Domaini

The ZP domain mediates polymerization, leading to the formation of long filaments.By similarity

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.
HOGENOMiHOG000293303.
HOVERGENiHBG004349.
InParanoidiP27590.
KOiK18274.
PhylomeDBiP27590.
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. 4 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.

P27590-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGQLLSLTWL LLVMVVTPWF TVAGANDSPE ARRCSECHDN ATCVLDGVVT
60 70 80 90 100
TCSCQAGFTG DGLVCEDIDE CATPWTHNCS NSICMNTLGS YECSCQDGFR
110 120 130 140 150
LTPGLGCIDV NECTEQGLSN CHSLATCVNT EGSYSCVCPK GYRGDGWYCE
160 170 180 190 200
CSPGFCEPGL DCLPQGPSGK LVCQDPCNVY ETLTEYWRST DYGAGYSCDS
210 220 230 240 250
DMHGWYRFTG QGGVRMAETC VPVLRCNTAA PMWLNGSHPS SREGIVSRTA
260 270 280 290 300
CAHWSDHCCL WSTEIQVKAC PGGFYVYNLT EPPECNLAYC TDPSSVEGTC
310 320 330 340 350
EECGVDEDCV SDNGRWRCQC KQDFNVTDVS LLEHRLECEA NEIKISLSKC
360 370 380 390 400
QLQSLGFMKV FMYLNDRQCS GFSERGERDW MSIVTPARDG PCGTVLRRNE
410 420 430 440 450
THATYSNTLY LASEIIIRDI NIRINFECSY PLDMKVSLKT SLQPMVSALN
460 470 480 490 500
ISLGGTGKFT VQMALFQNPT YTQPYQGPSV MLSTEAFLYV GTMLDGGDLS
510 520 530 540 550
RFVLLMTNCY ATPSSNSTDP VKYFIIQDRC PHTEDTTIQV TENGESSQAR
560 570 580 590 600
FSIQMFRFAG NSDLVYLHCE VYLCDTMSEQ CKPTCSGTRY RSGNFIDQTR
610 620 630 640
VLNLGPITRQ GVQASVSKAA SSNLGFLSIW LLLFLSATLT LMVH
Length:644
Mass (Da):71,062
Last modified:August 1, 1992 - v1
Checksum:iD26DB419C669826A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti155F → S in AAH81814 (PubMed:15489334).Curated1
Sequence conflicti326V → I in AAH81814 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M63510 mRNA. Translation: AAA42319.1.
S75960 mRNA. Translation: AAB33313.1.
BC081814 mRNA. Translation: AAH81814.1.
PIRiA40212.
RefSeqiNP_058778.1. NM_017082.1.
XP_006230169.1. XM_006230107.2.
UniGeneiRn.31982.

Genome annotation databases

GeneIDi25128.
KEGGirno:25128.
UCSCiRGD:3940. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M63510 mRNA. Translation: AAA42319.1.
S75960 mRNA. Translation: AAB33313.1.
BC081814 mRNA. Translation: AAH81814.1.
PIRiA40212.
RefSeqiNP_058778.1. NM_017082.1.
XP_006230169.1. XM_006230107.2.
UniGeneiRn.31982.

3D structure databases

ProteinModelPortaliP27590.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000021027.

Proteomic databases

PaxDbiP27590.
PRIDEiP27590.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi25128.
KEGGirno:25128.
UCSCiRGD:3940. rat.

Organism-specific databases

CTDi7369.
RGDi3940. Umod.

Phylogenomic databases

eggNOGiENOG410IVSV. Eukaryota.
ENOG410YDU6. LUCA.
HOGENOMiHOG000293303.
HOVERGENiHBG004349.
InParanoidiP27590.
KOiK18274.
PhylomeDBiP27590.
TreeFamiTF330284.

Miscellaneous databases

PROiP27590.

Gene expression databases

BgeeiENSRNOG00000015557.

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. 4 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_RAT
AccessioniPrimary (citable) accession number: P27590
Secondary accession number(s): Q642D6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: November 30, 2016
This is version 135 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, Reference proteome

Documents

  1. 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.