Umod uromodulin [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Umodprovided by MGI
Official Full Name: uromodulinprovided by MGI
Primary source: MGI:MGI:102674
See related: Ensembl:ENSMUSG00000030963 AllianceGenome:MGI:102674
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: THP; Urehd1; urehr4
Summary: This gene encodes a glycoprotein that is the most abundant protein in mammalian urine under physiological conditions. It is synthesized in the kidney as a glycosyl-phosphatidylinositol anchored protein and released into urine as a soluble form by proteolytic cleavage. It is thought to regulate water and salt balance in the thick ascending limb of Henle and to protect against urinary tract infection and calcium oxalate crystal formation. In mouse deficiency of this gene is associated with increased susceptibility to bacterial infections and formation of calcium crystals in kidneys. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
Expression: Restricted expression toward kidney adult (RPKM 1277.7) See more
Orthologs: human all
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Genomic context

Location:: 7 F2; 7 63.88 cM

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	7	NC_000073.7 (119061931..119078485, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	7	NC_000073.6 (119462708..119479262, complement)

Chromosome 7 - NC_000073.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Increased water intake dilutes protective uromodulin levels in urine and results in increased rates of pyelonephritis in a murine model.
Title: Increased water intake dilutes protective uromodulin levels in urine and results in increased rates of pyelonephritis in a murine model.
Allelic effects on uromodulin aggregates drive autosomal dominant tubulointerstitial kidney disease.
Title: Allelic effects on uromodulin aggregates drive autosomal dominant tubulointerstitial kidney disease.
Uromodulin Regulates Murine Aquaporin-2 Activity via Thick Ascending Limb-Collecting Duct Cross-Talk during Water Deprivation.
Title: Uromodulin Regulates Murine Aquaporin-2 Activity via Thick Ascending Limb-Collecting Duct Cross-Talk during Water Deprivation.
Hepsin-mediated Processing of Uromodulin is Crucial for Salt-sensitivity and Thick Ascending Limb Homeostasis.
Title: Hepsin-mediated Processing of Uromodulin is Crucial for Salt-sensitivity and Thick Ascending Limb Homeostasis.
A biological link between salt stress in the loop of Henle and interactions between Umod and heat-shock proteins.
Title: Salt stress in the renal tubules is linked to TAL-specific expression of uromodulin and an upregulation of heat shock genes.
Taken together, our data suggest that interstitial THP positively regulates mononuclear phagocyte number, plasticity, and phagocytic activity. In addition to the effect of THP on the epithelium and granulopoiesis, this new immunomodulatory role could explain the protection conferred by THP during AKI.
Title: Tamm-Horsfall Protein Regulates Mononuclear Phagocytes in the Kidney.
THP deficiency can cause progressive disturbances in renal functions via initially NKCC2 dysfunction and later compensatory responses, resulting in prolonged activation of the renin-angiotensin-aldosterone axis and hyperuricemia.
Title: Tamm-Horsfall protein/uromodulin deficiency elicits tubular compensatory responses leading to hypertension and hyperuricemia.
Our data support a role for uromodulin in the functional heterogeneity along the DCT: Umod-/- mice show less pNCC in DCT1 and increased pNCC in DCT2, paralleled by an expansion of DCT2. When exposed to chronic distal salt loading (furosemide), Umod-/- mice show a severely blunted capacity to increase NCC phosphorylation and lack the capacity to upregulate the DCT1 and DCT2 areas, compared with Umodthorn/thorn mice.
Title: Uromodulin is expressed in the distal convoluted tubule, where it is critical for regulation of the sodium chloride cotransporter NCC.
This work outlines a previously unknown role for Tamm-Horsfall Protein as an essential component for host immune defense against fungal urinary tract infection.
Title: Tamm-Horsfall Protein Protects the Urinary Tract against Candida albicans.
increased urinary UMOD secretion in low-magnesium states reduces TRPM6 endocytosis and thereby up-regulates TRPM6 cell-surface abundance to defend against further urinary magn
Title: Uromodulin regulates renal magnesium homeostasis through the ion channel transient receptor potential melastatin 6 (TRPM6).

Submit: New GeneRIF Correction See all GeneRIFs (45)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Chemically induced (ENU) (2) 1 citation
Endonuclease-mediated (6) 1 citation
Targeted (5) 1 citation

General gene information

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Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables IgG binding	IEA Inferred from Electronic Annotation more info
enables IgG binding	ISO Inferred from Sequence Orthology more info
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of_or_within ERAD pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of RNA splicing	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in antibacterial innate immune response	ISO Inferred from Sequence Orthology more info
involved_in antibacterial innate immune response	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within apoptotic signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within autophagy	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within calcium ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cellular response to stress	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cellular response to unfolded protein	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of chaperone-mediated protein folding	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within chemical homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within chemokine production	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within chloride ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within citric acid secretion	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within collecting duct development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within connective tissue replacement	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within defense response to Gram-negative bacterium	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in defense response to Gram-negative bacterium	ISO Inferred from Sequence Orthology more info
involved_in defense response to Gram-negative bacterium	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within endoplasmic reticulum organization	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within glomerular filtration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules	IEA Inferred from Electronic Annotation more info
involved_in heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within inflammatory response	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within intracellular calcium ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within intracellular chloride ion homeostasis	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within intracellular chloride ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within intracellular phosphate ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within intracellular sodium ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within juxtaglomerular apparatus development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within kidney development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in leukocyte cell-cell adhesion	IEA Inferred from Electronic Annotation more info
involved_in leukocyte cell-cell adhesion	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within lipid metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within loop of Henle development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in metanephric ascending thin limb development	IEP Inferred from Expression Pattern more info	PubMed
involved_in metanephric distal convoluted tubule development	IEP Inferred from Expression Pattern more info	PubMed
involved_in metanephric thick ascending limb development	IEP Inferred from Expression Pattern more info	PubMed
acts_upstream_of_or_within micturition	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in monoatomic ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within multicellular organismal response to stress	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within multicellular organismal-level homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within multicellular organismal-level water homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neutrophil migration	IBA Inferred from Biological aspect of Ancestor more info
involved_in neutrophil migration	IEA Inferred from Electronic Annotation more info
involved_in neutrophil migration	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within organ or tissue specific immune response	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within peptidyl-threonine phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within phosphate ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within potassium ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within protein localization to vacuole	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within_positive_effect protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within_positive_effect protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within protein transport into plasma membrane raft	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of blood pressure	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of protein transport	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of urine volume	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within renal sodium ion absorption	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within renal sodium ion absorption	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within renal urate salt excretion	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within renal water homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to diuretic	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to endoplasmic reticulum stress	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to lipopolysaccharide	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within response to unfolded protein	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to water deprivation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to xenobiotic stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within sodium ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within tumor necrosis factor-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within urate transport	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within urea transmembrane transport	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in apical part of cell	ISO Inferred from Sequence Orthology more info
is_active_in apical plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in apical plasma membrane	ISO Inferred from Sequence Orthology more info
located_in apical plasma membrane	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in basolateral plasma membrane	ISO Inferred from Sequence Orthology more info
located_in basolateral plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
is_active_in cell surface	IBA Inferred from Biological aspect of Ancestor more info
located_in ciliary membrane	IEA Inferred from Electronic Annotation more info
located_in cilium	IDA Inferred from Direct Assay more info	PubMed
located_in cilium	ISO Inferred from Sequence Orthology more info
located_in cilium	ISS Inferred from Sequence or Structural Similarity more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular space	ISO Inferred from Sequence Orthology more info
located_in membrane	ISO Inferred from Sequence Orthology more info
located_in membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in side of membrane	IEA Inferred from Electronic Annotation more info
located_in spindle pole	ISO Inferred from Sequence Orthology more info
located_in spindle pole	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: uromodulin

Names: Tamm-Horsfall urinary glycoprotein; uromucoid

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001278605.1 → NP_001265534.1 uromodulin preproprotein

See identical proteins and their annotated locations for NP_001265534.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode the same protein.

Source sequence(s)

AC125147, AK165507, BB843740

Consensus CDS

CCDS21780.1

UniProtKB/Swiss-Prot

Q3TN64, Q3TP60, Q62285, Q91X17

Related

ENSMUSP00000146652.2, ENSMUST00000209095.2

Conserved Domains (5) summary

smart00179
Location:65 → 98

EGF_CA; Calcium-binding EGF-like domain

smart00241
Location:335 → 584

ZP; Zona pellucida (ZP) domain

pfam00100
Location:464 → 584

Zona_pellucida; Zona pellucida-like domain

pfam12662
Location:88 → 110

cEGF; Complement Clr-like EGF-like

pfam12947
Location:111 → 147

EGF_3; EGF domain
NM_009470.5 → NP_033496.1 uromodulin preproprotein

See identical proteins and their annotated locations for NP_033496.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript. Both variants 1 and 2 encode the same protein.

Source sequence(s)

AC125147, AK085460, AK164688

Consensus CDS

CCDS21780.1

UniProtKB/Swiss-Prot

Q3TN64, Q3TP60, Q62285, Q91X17

Related

ENSMUSP00000033263.5, ENSMUST00000033263.6

Conserved Domains (5) summary

smart00179
Location:65 → 98

EGF_CA; Calcium-binding EGF-like domain

smart00241
Location:335 → 584

ZP; Zona pellucida (ZP) domain

pfam00100
Location:464 → 584

Zona_pellucida; Zona pellucida-like domain

pfam12662
Location:88 → 110

cEGF; Complement Clr-like EGF-like

pfam12947
Location:111 → 147

EGF_3; EGF domain