PXD072059-1

PXD072059 is an original dataset announced via ProteomeXchange.

Title	Deep Red Blood Cell Proteome Defines the Band 3 N-Terminus Interactome as a Regulator of Hypoxic Adaptation via BLVRB-Dependent S-Nitroso Transfer
Description	Red blood cells (RBCs) are transcriptionally silent yet dynamically remodel metabolism in response to oxygen tension. Using ultra-pure human RBCs, we generated the deepest contamination-free proteome to date (3,775 proteins) and mapped the oxygen-dependent interactome. These datasets reveal an oxygen-responsive metabolon centered on the Band 3 (SLC4A1) N-terminus. We identify biliverdin reductase B (BLVRB) as a previously unrecognized Band 3 interactor that dissociates under hypoxia, coincident with increased Band 3–deoxyhemoglobin contacts. This reversible assembly functions as an oxygen-sensitive switch coordinating redox and glycolytic remodeling. Humanized mice lacking Band 3 N-terminal segments exhibit impaired glycolytic activation, reduced 2,3-bisphosphoglycerate synthesis, and diminished exercise tolerance, demonstrating physiological relevance. Population-scale cis-pQTLs for SLC4A1 and BLVRB suggest functions beyond canonical heme catabolism. Mechanistically, BLVRB serves as a nitric-oxide relay that trans-nitrosates the glycolytic enzyme GAPDH at C152, transiently inhibiting glycolysis. Together, these findings define a Band 3–BLVRB–hemoglobin axis integrating oxygen sensing and metabolic control.
HostingRepository	PRIDE
AnnounceDate	2026-06-29
AnnouncementXML	Submission_2026-06-28_16:42:27.551.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD072059
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Shaun Bevers
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-16 15:03:50	ID requested
⏵ 1	2026-06-28 16:42:28	announced

10.1182/blood.2025032915;

10.6019/PXD072059;

Issaian AV, Dzieciatkowska M, Bevers S, Safari Z, Hay AM, Cendali FI, Argabright A, Rogers SC, Saviola AJ, Redzic JS, Wartchow E, Reisz Haines J, Keele GR, Haiman ZB, Nemkov T, Stephenson D, Lisk C, Vallese F, Palsson BO, King SB, Page GP, Doctor A, Hudson KE, Hansen KC, Irwin DC, Mohandas N, Zimring JC, Eisenmesser EZ, D'Alessandro A, The red blood cell proteome and interactome identify a Band 3-BLVRB axis regulating hypoxic metabolic adaptation. Blood, ():(2026) [pubmed]

submitter keyword: Erythrocytes, Hyponia,Red Blood Cells, Nitric Oxide

Angelo D'Alessandro
contact affiliation	University of Colorado - Anschutz Medical Campus Department of Biochemistry and Molecular Genetics
contact email	angelo.dalessandro@cuanschutz.edu
lab head
Shaun Bevers
contact affiliation	University of Colorado - Anschutz Medical Campus
contact email	shaun.bevers@cuanschutz.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD072059

PRIDE project URI

• PRIDE
  1. PXD072059
     1. Label: PRIDE project
     2. Name: Deep Red Blood Cell Proteome Defines the Band 3 N-Terminus Interactome as a Regulator of Hypoxic Adaptation via BLVRB-Dependent S-Nitroso Transfer