PXD027914-1

PXD027914 is an original dataset announced via ProteomeXchange.

Title	The kidney releases in the urine and circulation a non-polymerizing form of Uromodulin that retains the external hydrophobic patch domain
Description	Uromodulin (Tamm-Horsfall protein, THP) is a glycoprotein uniquely produced in the kidney. It is released by cells of the thick ascending limbs (TAL) apically in the urine, and basolaterally in the renal interstitium and systemic circulation. Processing of mature urinary THP, which polymerizes into supra-molecular filaments, requires cleavage of an external hydrophobic patch (EHP) at the C terminus. However, THP in the circulation is not polymerized, and it remains unclear if non-aggregated forms of THP exist natively in the urine. We propose that an alternative processing path, which retains the EHP domain, can lead to a non-polymerizing form of THP. We generated an antibody that specifically recognizes THP with retained EHP (THP+EHP) and established its presence in the urine in a non-polymerized native state. Proteomic characterization of urinary THP+EHP revealed its C-terminus to end at F617. In the human kidney, THP+EHP was not only detected in TAL cells, but also diffusely in the renal parenchyma. Using C-terminus proteomic sequencing and immunoblotting, we then demonstrated that serum THP has also retained EHP. In a small cohort of patients at risk for acute kidney injury (AKI), admission urinary THP+EHP was significantly lower in patients who subsequently developed AKI during hospitalization. Our findings uncover novel insights into uromodulin biology by establishing the presence of an alternative path for cellular processing, which could explain the release of non-polymerizing THP in the circulation. Larger studies as needed to establish the utility of urinary THP+EHP as a sensitive biomarker of kidney health and susceptibility to injury.
HostingRepository	PRIDE
AnnounceDate	2024-10-08
AnnouncementXML	Submission_2024-10-08_11:21:18.840.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD027914
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Emma Doud
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-12 15:16:41	ID requested
⏵ 1	2024-10-08 11:21:19	announced

10.1152/AJPRENAL.00322.2021;

submitter keyword: uromodulin, LC-MSMS, AKI, external hydrophobicpatch domain, urine, serum, ELISA,human

Tarek M. El-Achkar
contact affiliation	Division of Nephrology and Hypertension, Indiana University School of Medicine, Indianapolis, IN, USA
contact email	telachka@iu.edu
lab head
Emma Doud
contact affiliation	Indiana University School of Medicine
contact email	edoud@iu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD027914
     1. Label: PRIDE project
     2. Name: The kidney releases in the urine and circulation a non-polymerizing form of Uromodulin that retains the external hydrophobic patch domain