A high confidence, manually validated human blood plasma protein reference set

Schenk, Susann; Schoenhals, Gary J.; Souza, Gustavo; Mann, Matthias

doi:10.1186/1755-8794-1-41

Cited by 157 publications

(174 citation statements)

References 25 publications

Supporting

Mentioning

157

Contrasting

Order By: Relevance

“…Proteomic analyses of plasma identified 603 noncytosolic proteins bearing lectin ligands consisting of Gal linkages, which constituted 99% of the protein mass isolated (Table S1). This diversity further represents the majority of the plasma proteome identified (10,11). At steady state in healthy WT mice, the fraction of secreted proteins in plasma bearing Gal ligands averaged 2%.…”

mentioning

confidence: 87%

An intrinsic mechanism of secreted protein aging and turnover

Yang

Aziz

Heithoff

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The composition and functions of the secreted proteome are controlled by the life spans of different proteins. However, unlike intracellular protein fate, intrinsic factors determining secreted protein aging and turnover have not been identified and characterized. Almost all secreted proteins are posttranslationally modified with the covalent attachment of N-glycans. We have discovered an intrinsic mechanism of secreted protein aging and turnover linked to the stepwise elimination of saccharides attached to the termini of N-glycans. Endogenous glycosidases, including neuraminidase 1 (Neu1), neuraminidase 3 (Neu3), beta-galactosidase 1 (Glb1), and hexosaminidase B (HexB), possess hydrolytic activities that temporally remodel N-glycan structures, progressively exposing different saccharides with increased protein age. Subsequently, endocytic lectins with distinct binding specificities, including the Ashwell-Morell receptor, integrin αM, and macrophage mannose receptor, are engaged in N-glycan ligand recognition and the turnover of secreted proteins. Glycosidase inhibition and lectin deficiencies increased protein life spans and abundance, and the basal rate of N-glycan remodeling varied among distinct proteins, accounting for differences in their life spans. This intrinsic multifactorial mechanism of secreted protein aging and turnover contributes to health and the outcomes of disease.glycosylation | protein | homeostasis | glycosidase | lectin

show abstract

mentioning

confidence: 87%

An intrinsic mechanism of secreted protein aging and turnover

Yang

Aziz

Heithoff

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…More recently, Mann and co-workers reported an ultra-highconfidence list of 697 plasma proteins with a false discovery rate of 0.29% and a confidence of at least 99%. An average of 14 peptides per protein was reported, with a median of 6 peptides per protein (Schenk et al, 2008). Proteins reported by the HUPO PPP, David Clemmer's group at Indiana University, PeptideAtlas (Deutsch et al, 2005), and Leigh Anderson's group have been compiled into a list of 12,787 proteins from 86,831 peptides (Saha et al, 2008).…”

Section: Capillary Isoelectric Focusing (Cief)-ms/ms Was Applied Bymentioning

confidence: 99%

Comparative Human Salivary and Plasma Proteomes

et al. 2010

View full text Add to dashboard Cite

The protein compositions, or the proteomes, found in human salivary and plasma fluids are compared. From recent experimental work by many laboratories, a catalogue of 2290 proteins found in whole saliva has been compiled. This list of salivary proteins is compared with the 2698 proteins found in plasma. Approximately 27% of the whole-saliva proteins are found in plasma. However, despite this apparent low degree of overlap, the distribution found across Gene Ontological categories, such as molecular function, biological processes, and cellular components, shows significant similarities. Moreover, nearly 40% of the proteins that have been suggested to be candidate markers for diseases such as cancer, cardiovascular disease, and stroke can be found in whole saliva. These comparisons and correlations should encourage researchers to consider the use of saliva to discover new protein markers of disease and as a diagnostic non-proximal fluid to detect early signs of disease throughout the body.

show abstract

“…The function of GNMT in extra hepatic tissues is less clear. GNMT also is present in pancreas, prostate, intestinal mucosa, plasma and semen (12)(13)(14)(15)(16)(17). The localization of GNMT in the exocrine cells in the above tissues suggests a potential role in secretion (12).…”

Section: Gnmt Expression Increases Hepatic Folate Contents and Folatementioning

confidence: 99%

GNMT Expression Increases Hepatic Folate Contents and Folate-Dependent Methionine Synthase-Mediated Homocysteine Remethylation

Wang

Lin

Liu³

et al. 2011

Mol Med

View full text Add to dashboard Cite

Glycine N-methyltransferase (GNMT) is a major hepatic enzyme that converts S-adenosylmethionine to S-adenosylhomocysteine while generating sarcosine from glycine, hence it can regulate mediating methyl group availability in mammalian cells. GNMT is also a major hepatic folate binding protein that binds to, and, subsequently, may be inhibited by 5-methyltetrafolate. GNMT is commonly diminished in human hepatoma; yet its role in cellular folate metabolism, in tumorigenesis and antifolate therapies, is not understood completely. In the present study, we investigated the impacts of GNMT expression on cell growth, folate status, methylfolate-dependent reactions and antifolate cytotoxicity. GNMT-diminished hepatoma cell lines transfected with GNMT were cultured under folate abundance or restriction. Folate-dependent homocysteine remethylation fluxes were investigated using stable isotopic tracers and gas chromatography/mass spectrometry. Folate status was compared between wild-type (WT), GNMT transgenic (GNMT tg ) and GNMT knockout (GNMT ko ) mice. In the cell model, GNMT expression increased folate concentration, induced folate-dependent homocysteine remethylation, and reduced antifolate methotrexate cytotoxicity. In the mouse models, GNMT tg had increased hepatic folate significantly, whereas GNMT ko had reduced folate. Liver folate levels correlated well with GNMT expressions (r = 0.53, P = 0.002); and methionine synthase expression was reduced significantly in GNMT ko , demonstrating impaired methylfolate-dependent metabolism by GNMT deletion. In conclusion, we demonstrated novel findings that restoring GNMT assists methylfolate-dependent reactions and ameliorates the consequences of folate depletion. GNMT expression in vivo improves folate retention and bioavailability in the liver. Studies on how GNMT expression impacts the distribution of different folate cofactors and the regulation of specific folate dependent reactions are underway.

show abstract

A high confidence, manually validated human blood plasma protein reference set

Cited by 157 publications

References 25 publications

An intrinsic mechanism of secreted protein aging and turnover

An intrinsic mechanism of secreted protein aging and turnover

Comparative Human Salivary and Plasma Proteomes

GNMT Expression Increases Hepatic Folate Contents and Folate-Dependent Methionine Synthase-Mediated Homocysteine Remethylation

Contact Info

Product

Resources

About