Protein S

Protein S (alpha)
PDB rendering based on 1z6c.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1Z6C
Identifiers
Symbols	PROS1 ; PROS; PS21; PS22; PS23; PS24; PS25; PSA; THPH5; THPH6
External IDs	OMIM: 176880 MGI: 1095733 HomoloGene: 264 GeneCards: PROS1 Gene
Gene ontology Molecular function • endopeptidase inhibitor activity • calcium ion binding • protein complex binding Cellular component • Golgi membrane • extracellular region • extracellular space • endoplasmic reticulum membrane • Golgi lumen • plasma membrane • platelet alpha granule lumen • protein complex • extracellular exosome • blood microparticle Biological process • platelet degranulation • proteolysis • blood coagulation • negative regulation of endopeptidase activity • peptidyl-glutamic acid carboxylation • platelet activation • regulation of complement activation • response to lipopolysaccharide • fibrinolysis • post-translational protein modification • cellular protein metabolic process • innate immune response • positive regulation of phagocytosis • leukocyte migration Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5627	19128
Ensembl	ENSG00000184500	ENSMUSG00000022912
UniProt	P07225	Q08761
RefSeq (mRNA)	NM_000313	NM_011173
RefSeq (protein)	NP_000304	NP_035303
Location (UCSC)	Chr 3: 93.87 – 93.97 Mb	Chr 16: 62.85 – 62.93 Mb
PubMed search	[1]	[2]

Protein S (also known as S-Protein) is a vitamin K-dependent plasma glycoprotein synthesized in the endothelium. In the circulation, Protein S exists in two forms: a free form and a complex form bound to complement protein C4b-binding protein (C4BP). In humans, protein S is encoded by the PROS1 gene.

Function

The best characterized function of Protein S is its role in the anti coagulation pathway, where it functions as a cofactor to Protein C in the inactivation of Factors Va and VIIIa. Only the free form has cofactor activity.

Protein S can bind to negatively charged phospholipids via the carboxylated GLA domain. This property allows Protein S to function in the removal of cells which are undergoing apoptosis. Apoptosis is a form of cell death that is used by the body to remove unwanted or damaged cells from tissues. Cells, which are apoptotic (i.e. in the process of apoptosis), no longer actively manage the distribution of phospholipids in their outer membrane and hence begin to display negatively charged phospholipids, such as phosphatidyl serine, on the cell surface. In healthy cells, an ATP (Adenosine triphosphate)-dependent enzyme removes these from the outer leaflet of the cell membrane. These negatively charged phospholipids are recognized by phagocytes such as macrophages. Protein S can bind to the negatively charged phospholipids and function as a bridging molecule between the apoptotic cell and the phagocyte. The bridging property of Protein S enhances the phagocytosis of the apoptotic cell, allowing it to be removed 'cleanly' without any symptoms of tissue damage such as inflammation occurring.

Protein S also binds to the nascent complement complex C5,6,7 and prevents this complex from inserting into a membrane. This function prevents the inappropriate activation of the complement system, which would cause uncontrolled systemic inflammation. In fact, Protein S was first discovered in 1977 in this role and it is named after the membrane site that it occupies in the complex.

Pathology

Mutations in the PROS1 gene can lead to Protein S deficiency which is a rare blood disorder which can lead to an increased risk of thrombosis.

Interactions

Protein S has been shown to interact with Factor V.

See also

• hemostasis