UMOD Antibodies

Background

UMOD is a glycoprotein secreted by the epithelial cells of the thick segment of the ascending branch of the Heinz loop in the kidney and is mainly present in urine. This protein regulates the reabsorption of water and electrolytes by forming a gel-like structure and participates in the innate immune defense mechanism. Mutations in the UMOD gene are associated with various renal tubular diseases and have been widely studied due to their crucial role in maintaining the hypertonic environment of the renal medulla. In 2002, Hart et al. first analyzed its crystal structure, revealing unique calcium ion-dependent polymerization characteristics. As an important physiological barrier protein of the urinary system, the abnormal expression of UMOD has become a biomarker for chronic kidney disease and urinary tract infection, and the study of its molecular mechanism provides a new perspective for renal physiology and pathology.

Structure Function Application Advantage Our Products

Structure of UMOD

UMOD is a glycoprotein with a molecular weight of approximately 85-95 kDa, and its exact molecular weight varies slightly depending on the degree of glycosylation modification. The following is a comparison of the molecular characteristics of UMOD in different species:

Species	Human	Mice	Rats
Molecular Weight (kDa)	~85-95	~80-90	~82-92
Primary Structural Differences	Highly glycosylated and containing multiple cysteines	The degree of glycosylation is relatively low	Structure similar to person UMOD height

UMOD is composed of 640 amino acids, and its primary structure contains multiple conserved cysteine residues that form disulfide bonds to stabilize protein folding. The secondary structure of this protein is mainly composed of β -folded and disordered regions, enabling it to form a gel-like filament network in urine. The tertiary structure of UMOD relies on calcium ion-mediated polymerization, and the ZF (Zona Pellucida) module in its N-terminal domain is responsible for binding to pathogens and exerting innate immune defense functions. In addition, the C-terminal hydrophobic region of UMOD promotes filament self-assembly in a high-salt urine environment, a characteristic that holds significant research value in renal physiology and diseases.

Fig. 1:Changes in the structure of UMOD. Fig. 1 Uromodulin 3D structure and disulfide bond prediction.WT versus C41R¹

Key structural properties of myoglobin:

Modular architecture composed of ZP domains
Calcium ion-dependent polymerization interface
Conservative cysteine network
C-terminal extension modified by glycosylation
Hydrophobic core and hydrophilic surface

Functions of UMOD

UMOD is a key glycoprotein secreted by the kidneys. Its core functions include electrolyte regulation and innate immune defense, and it is also involved in various physiological and pathological processes of the kidneys.

Function	Description
Regulation of electrolyte balance	By forming a gel-like structure to regulate the reabsorption of Na⁺, K⁺ and Ca²⁺ by renal tubules, the hypertonic environment of the medulla is maintained.
Innate immune defense	Capture urinary tract pathogens (such as Escherichia coli) through the ZP domain, inhibit bacterial adhesion, and prevent urinary tract infections.
Markers of chronic kidney disease	Abnormal expression of UMOD is associated with renal tubulointerstitial fibrosis, and its urine level can reflect the degree of renal function impairment.
Regulation of stone formation	Inhibit the aggregation of calcium salt crystals and reduce the risk of kidney stones; However, some mutants (such as C41R) may promote crystalline deposition.
Inflammatory regulation	Local immune response is regulated through TLR4 receptor pathway, and excessive activation may lead to renal tubular injury.

Applications of UMOD and UMOD Antibody in Literature

1. Gudbjartsson, Daniel F., et al. "Association of variants at UMOD with chronic kidney disease and kidney stones—role of age and comorbid diseases." PLoS genetics 6.7 (2010): e1001039. https://doi.org/10.1371/journal.pgen.1001039

Research has found that the UMOD gene variant rs4293393-T is associated with an increased risk of chronic kidney disease (CKD) (OR=1.25), and simultaneously affects renal function indicators such as creatinine and urea. The effect of this variation increases with age, but it can reduce the risk of kidney stones (OR=0.88). Research has revealed the significant role of UMOD in kidney diseases.

2. Padmanabhan, Sandosh, et al. "Genome-wide association study of blood pressure extremes identifies variant near UMOD associated with hypertension." PLoS genetics 6.10 (2010): e1001177. https://doi.org/10.1371/journal.pgen.1001177

Research has found that the rs13333226-G variant of the UMOD gene can reduce the risk of hypertension (OR=0.87), decrease the secretion of uromodulin and improve renal function. This variation regulates blood pressure by affecting the sodium homeostasis of renal tubules, reducing the risk of cardiovascular events by 7.7% in carriers and providing a new target for the treatment of hypertension.

3. Kemter, Elisabeth, et al. "Mitochondrial dysregulation secondary to endoplasmic reticulum stress in autosomal dominant tubulointerstitial kidney disease–UMOD (ADTKD-UMOD)." Scientific reports 7.1 (2017): 42970. https://doi.org/10.1038/srep42970

Research has found that mutations in the UMOD gene lead to disorders in the secretion of uromodulin, triggering endoplasmic reticulum stress and unfolding protein responses, while also causing mitochondrial dysfunction and energy metabolism disorders, which in turn result in pathological changes of autosomal dominant tubulointerstitial nephropathy (ADTKD-UMOD).

4. Trudu, Matteo, et al. "Early involvement of cellular stress and inflammatory signals in the pathogenesis of tubulointerstitial kidney disease due to UMOD mutations." Scientific reports 7.1 (2017): 7383.https://doi.org/10.1038/s41598-017-07804-6

Research has found that mutations in the UMOD gene lead to abnormal accumulation of uromodulin in the endoplasmic reticulum, triggering early inflammatory responses and lipid metabolism disorders in the kidneys, and eventually developing into autosomal dominant tubulointerstitial disease (ADTKD-UMOD). This disease shows pro-inflammatory signals in young mice, earlier than fibrotic lesions, suggesting that inflammatory pathways can serve as potential therapeutic targets.

5. Yang, Yong, et al. "Elevated UMOD methylation level in peripheral blood is associated with gout risk." Scientific reports 7.1 (2017): 11196. https://doi.org/10.1038/s41598-017-11627-w

The study found that the methylation level of the UMOD gene in the peripheral blood of gout patients was significantly increased (1.45 vs 0.75, P<0.001), and its AUC for predicting gout reached 0.764. UMOD methylation was negatively correlated with blood uric acid levels (r=-0.208), and could up-regulate gene expression (2 times, P=0.004), suggesting that it could be used as a predictive marker for gout.

Creative Biolabs: UMOD Antibodies for Research

Creative Biolabs specializes in the production of high-quality UMOD antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

Custom UMOD Antibody Development: Tailor-made solutions to meet specific research requirements.
Bulk Production: Large-scale antibody manufacturing for industry partners.
Technical Support: Expert consultation for protocol optimization and troubleshooting.
Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our UMOD antibodies, custom preparations, or technical support, contact us at email.

Reference

Chen, Huan-Da, et al. "UMOD mutations in chronic kidney disease in Taiwan." Biomedicines 10.9 (2022): 2265. https://doi.org/10.3390/biomedicines10092265