Vitamin K-dependent protein S (PROS1)
The protein contains 676 amino acids for an estimated molecular weight of 75123 Da.
Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
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Biological Process
Blood coagulation
Cellular protein metabolic process
Endoplasmic reticulum to Golgi vesicle-mediated transport
Fibrinolysis
Innate immune response
Leukocyte migration
Negative regulation of endopeptidase activity
Peptidyl-glutamic acid carboxylation
Platelet activation
Platelet degranulation
Post-translational protein modification
Proteolysis
Regulation of complement activation
Signal peptide processing
The reference OMIM entry for this protein is 176880
Protein s; pros1
Protein s, alpha; psa protein s pseudogene, included; prosp, included
Protein s, beta, included; psb, included
Pros2, included
DESCRIPTION
Protein S is a vitamin K-dependent plasma protein that inhibits blood clotting by serving as a nonenzymatic cofactor for activated protein C (PROC; 612283) in the inactivation of procoagulant factors V (F5; 612309) and VIII (F8; 300841). Protein S exists in 2 forms in plasma: the free, functionally active form, and the inactive form complexed with C4b-binding protein (C4BPA; 120830) (Dahlback and Stenflo, 1981).CLONING
Lundwall et al. (1986) isolated and sequenced cDNA clones for protein S. Human protein S is a single-chain protein of 635 amino acids with 82% homology to bovine protein S. Hoskins et al. (1987) isolated cDNA for a protein S precursor. Edenbrandt et al. (1990) isolated clones corresponding to the 3-prime part of the PROS1 gene, including the thrombin (F2; 176930)-sensitive region, 4 domains that are homologous to the epidermal growth factor (EGF; 131530) precursor, the COOH-terminal part of protein S that is homologous to a plasma sex hormone binding globulin (SHBG; 182205), and the 3-prime untranslated region.GENE FUNCTION
In human plasma, around 40% of protein S circulates as a free protein, while the remaining 60% forms a noncovalent 1:1 stoichiometric complex with the beta-chain of the complement C4b-binding protein (C4BPB; 120831) (Dahlback, 1991). This interaction is of high affinity and abolishes the anticoagulant properties of protein S. Therefore, in plasma, only the molar excess of protein S over C4BPB circulates in a free form and is active as a cofactor of activated protein C (APC) in the inactivation of the procoagulant factors Va and VIIIa (Griffin et al., 1992). Maillard et al. (1992) studied protein S synthesis and secretion by human osteosarcoma cell lines and by normal adult human osteoblast-like cells. They showed that protein S is synthesized by osteoblasts in an active form and incorporated in the mineralized matrix of bone. Previously, protein S was known to be synthesized mostly by hepatocytes. Heeb et al. (1994) presented data that demonstrated mechanisms of anticoagulant action for protein S that are independent of activated protein C and that involve direct binding to factors Xa and Va and direct inhibition of factor Xa. Anderson et al. (2003) identified protein S as the factor in serum that mediates serum-stimulated macrophage phagocytosis of apoptotic cells, a process thought to limit the development of inflammation and autoimmune disease. Flow cytometric and competitive inhibition analyses demonstrated that protein S binds exclusively to phosphatidylserine-positive apoptotic cells in a calcium-dependent manner. Anderson et al. (2003) concluded that protein S is a multifunctional protein that facilitates the clearance of early apoptotic cells in addition to regulating blood coagulation.GENE STRUCTURE
Schmidel et al. (1990) determined that the PROS1 gene contains 15 exons and spans more than 80 kb.MAPPING
By Southern blot analysis of DNA from somatic cell hybrids, Naylor et al. (1987) and Long et al. (1988) assigned the protein S gene to chromosome 3p21-q21. By study of somatic cell hybrids with cDNA probes, including hybrids with rearranged chromosomes, Watkins et al. (1987, 1988) assigned the protein S gene to 3p21-q21; see Stanislovitis et al. (1987). By in situ hybridization, Watkins et al. (1988) assigned the PROS gene to chromosome 3p11.1-q11.2, the region immediately surrounding the centromere. Hartz (2008) mapped the ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 176880 was added.
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed