PXD064788

PXD064788 is an original dataset announced via ProteomeXchange.

Title	Eye opening discoveries: uncovering lacritin glycoforms and the tear fluid glycoproteome
Description	Tear fluid comprises a diverse group of extracellular glycoproteins which are critical for ocular homeostasis. Within the tear fluid glycoproteome, lacritin is highly expressed and plays a key role in immune response, tear secretion, and antimicrobial activity. Importantly, glycosylation constitutes over 50% of lactritin’s molecular weight. However, despite this fact, nothing is known about the specific glycan structures on lacritin and how they influence its protein folding, function, or downstream biological processes. Similarly, it remains completely unknown whether alterations to lacritin glycans are correlated with ocular pathologies. To address this gap in knowledge, we harnessed mass spectrometry (MS) to conduct the first O-glycoproteomic study of tear fluid. Here, we report unprecedented coverage of lacritin glycosylation, detailing 19 O-glycosites bearing a myriad of glycan structures. Further, we leveraged Alphafold 3.0 and GlycoShape to visualize the impact of these glycans on its structure, demonstrating that O-glycosylation renders the protein backbone rigid and extended. Surprisingly, we also detected protein-level evidence of two lacritin spliceoforms, representing the first observation of these isoforms by MS. Simultaneously, we describe the most comprehensive characterization of the tear fluid glycoproteome to date, elucidating the glycosylation profile of Immunoglobulin A (IgA), lactoferrin, and other glycoproteins with demonstrated clinical relevance as diagnostic biomarkers. Overall, this study lays critical groundwork for future biochemical investigation of tear fluid glycoproteins and their application as diagnostic or therapeutic tools for ocular diseases.
HostingRepository	PRIDE
AnnounceDate	2025-08-25
AnnouncementXML	Submission_2025-08-25_11:57:37.944.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Vincent Chang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	complex glycosylation; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-09 12:38:23	ID requested
⏵ 1	2025-08-25 11:57:39	announced

Chang V, Mahoney KE, Lian I, Chen R, Chung N, Paaske Utheim T, Karlsson NG, Malaker SA, In-depth analysis of the tear fluid glycoproteome reveals diverse lacritin glycosylation and spliceoforms. bioRxiv, ():(2025) [pubmed]

10.1101/2025.06.13.659589;

submitter keyword: glycoproteomics, mucin, mucinase, lacritin, mass spectrometry, Immunoglobulin A, tear fluid

Stacy A. Malaker
contact affiliation	Yale University Department of Chemistry
contact email	stacy.malaker@yale.edu
lab head
Vincent Chang
contact affiliation	Yale University
contact email	vincent.chang@yale.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD064788
     1. Label: PRIDE project
     2. Name: Eye opening discoveries: uncovering lacritin glycoforms and the tear fluid glycoproteome