PXD020355

PXD020355 is an original dataset announced via ProteomeXchange.

Title	Prothrombin is a binding partner of the human Receptor of Advanced Glycation End products
Description	The receptor for advanced glycation end products (RAGE) plays a key role in mammal physiology and in the etiology and progression of inflammatory and oxidative stress-based diseases. In adults, RAGE expression is high only in the lung where the protein concentrates in the basal membrane of Type I alveolar epithelial cells. In diseases, RAGE levels increase in the affected tissues and sustain chronic inflammation. RAGE exists as a single trans-membrane protein with an ectodomain and a short carboxyl-terminal tail essential for signaling, or also as a soluble ectodomain (sRAGE) that acts as a decoy receptor. The ectodomain is composed of a variable and two constant IgG-like domains (V, C1 and C2). VC1 is a single integrated unit responsible for binding of RAGE to the majority of its ligands including the advanced glycation End products (AGEs), S100 proteins and HMGB-1. Here, we report the identification of 20 new RAGE binding partners captured from human plasma and involved in the coagulation and complement processes and in the extracellular matrix. Four proteins contained a -carboxyl glutamic acid (Gla)-domain. Using MicroScale Thermophoresis, we quantified the interaction of prothrombin (PT) with VC1 and with sRAGE. Calcium competed in the binding of PT to sRAGE and PT devoid of the Gla-domain did not bind to sRAGE, providing evidence that the Gla-domain is critical for the interaction. Finally, the presence of VC1 delayed plasma clotting in a dose-dependent manner. We propose that RAGE is involved in modulating blood coagulation presumably in conditions of lung injury.
HostingRepository	PRIDE
AnnounceDate	2020-07-14
AnnouncementXML	Submission_2020-07-14_05:50:59.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alessandra Altomare
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-14 02:46:46	ID requested
⏵ 1	2020-07-14 05:51:00	announced

Dataset with its publication pending

submitter keyword: Receptor for advanced glycation end product (RAGE)

pattern recognition receptor (PRR)

scavenger receptor

prothrombin

coagulation factor

mass spectrometry (MS)

plasma

protein -carboxylation

lung injury

protein-protein interaction.

Alessandra Altomare
contact affiliation	University of Milan, DISFARM
contact email	alessandra.altomare@unimi.it
lab head
Alessandra Altomare
contact affiliation	University of Milan (DISFARM)
contact email	alessandra.altomare@unimi.it
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD020355
     1. Label: PRIDE project
     2. Name: Prothrombin is a binding partner of the human Receptor of Advanced Glycation End products