The Human Plasma Proteome

Abstract

We have merged four different views of the human plasma proteome, based on different methodologies, into a single nonredundant list of 1175 distinct gene products. The methodologies used were 1) literature search for proteins reported to occur in plasma or serum; 2) multidimensional chromatography of proteins followed by two-dimensional electrophoresis and mass spectroscopy (MS) identification of resolved proteins; 3) tryptic digestion and multidimensional chromatography of peptides followed by MS identification; and 4) tryptic digestion and multidimensional chromatography of peptides from low-molecularmass plasma components followed by MS identification. Of 1,175 nonredundant gene products, 195 were included in more than one of the four input datasets. Only 46 appeared in all four. Predictions of signal sequence and transmembrane domain occurrence, as well as Genome Ontology annotation assignments, allowed characterization of the nonredundant list and comparison of the data sources. The "nonproteomic" literature (468 input proteins) is strongly biased toward signal sequence-containing extracellular proteins, while the three proteomics methods showed a much higher representation of cellular proteins, including nuclear, cytoplasmic, and kinesin complex proteins. Cytokines and protein hormones were almost completely absent from the proteomics data (presumably due to low abundance), while categories like DNA-binding proteins were almost entirely absent from the literature data (perhaps unexpected and therefore not sought). Most major categories of proteins in the human proteome are represented in plasma, with the distribution at successively deeper layers shifting from mostly extracellular to a distribution more like the whole (primarily cellular) proteome. The resulting nonredundant list confirms the presence of a number of interesting candidate marker proteins in plasma and serum.

Human body fluid proteome analysis

“…A re-evaluation of three published plasma proteomic studies also indicated that there was minimum overlapping of proteins identified from different proteomics platforms. The proteins found through the literature search are strongly biased toward signal sequence-containing extracellular proteins, while the three proteomics methods showed a much higher representation of cellular proteins, including nuclear, cytoplasmic, and kinesin complex proteins [55].…”

Recent advances in blood‐related proteomics

“…Most of the relevant information is available in three leading articles published in 2004 [25][26][27]. Combination of several approaches, including a literature survey, permitted Anderson et al [25] to build one of the most precise available lists of human plasma proteins. Chan et al [26] analyzed the serum proteome by combining multidimensional peptide separation strategies and MS/MS [26].…”

Expression of the Calcium-binding Protein S100A4 Is Markedly Up-regulated by Osmotic Stress and Is Involved in the Renal Osmoadaptive Response

“…In this work we have applied the DIGE approach to study the changes in the cellular proteome in response to chronic adaptation to hypertonic stress in IMCD3 cells. As with any current proteomic technique, DIGE allows for the study of changes to only a fractional subset of the proteome (32,33). In our studies, the small, calcium-binding protein S100A4 was determined to be highly up-regulated by DIGE analysis, Western blot, gene chip analysis, and quantitative PCR.…”