Serum amyloid P component

SAP makes up 14% of the dry mass of amyloid deposits{{cite book |author1=Skinner M |author2=Pepys MB |author3=Cohen AS |author4=Heller LM |author5=Lian JB |editor1=Freitas, Antonio Falcão de |editor2=Glenner, George G. |editor3=Costa, Pedro Pinho e. | title = Amyloid and amyloidosis: proceedings of the Third International Symposium on Amyloidosis, Póvoa de Varzim, Portugal, 23–28 September 1979 | publisher = Excerpta Medica | location = Amsterdam | year = 1980| pages = 384–391| isbn = 0-444-90124-8 }} and is thought to be an important contributor to the pathogenesis of a related group of diseases called the Amyloidoses.{{cite journal | vauthors = Botto M, Hawkins PN, Bickerstaff MC, Herbert J, Bygrave AE, McBride A, Hutchinson WL, Tennent GA, Walport MJ, Pepys MB | title = Amyloid deposition is delayed in mice with targeted deletion of the serum amyloid P component gene | journal = Nature Medicine | volume = 3 | issue = 8 | pages = 855–9 | date = August 1997 | pmid = 9256275 | doi = 10.1038/9544 | s2cid = 19553541 }} These conditions are characterised by the ordered aggregation of normal globular proteins and peptides into insoluble fibres, which disrupt tissue architecture and are associated with cell death. SAP is thought to decorate and stabilise aggregates by preventing proteolytic cleavage and hence inhibiting fibril removal via the normal protein scavenging mechanisms.{{cite journal | vauthors = Tennent GA, Lovat LB, Pepys MB | title = Serum amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer disease and systemic amyloidosis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 92 | issue = 10 | pages = 4299–303 | date = May 1995 | pmid = 7753801 | pmc = 41931 | doi = 10.1073/pnas.92.10.4299 | url = http://www.pnas.org/cgi/reprint/92/10/4299.pdf | doi-access = free }} This association is utilised in the routine clinical diagnostic technique of SAP scintigraphy whereby radio-labelled protein is injected into patients to locate areas of amyloid deposition.{{cite journal | vauthors = Hawkins PN, Pepys MB | title = Imaging amyloidosis with radiolabelled SAP | journal = European Journal of Nuclear Medicine | volume = 22 | issue = 7 | pages = 595–9 | date = July 1995 | pmid = 7498219 | doi = 10.1007/BF01254559 | s2cid = 8549928 }} The SAP-amyloid association has also been identified as a possible drug target for anti-amyloid therapy, with the recent development and first stage clinical trials of a compound called CPHPC (R-1-[6-[R-2-carboxy-pyrrolidin-1-yl]-6-oxohexanoyl] pyrrolidine-2-carboxylic acid), a small molecule able to strip AP from deposits by reducing levels of circulating SAP.{{cite journal | vauthors = Pepys MB, Herbert J, Hutchinson WL, Tennent GA, Lachmann HJ, Gallimore JR, Lovat LB, Bartfai T, Alanine A, Hertel C, Hoffmann T, Jakob-Roetne R, Norcross RD, Kemp JA, Yamamura K, Suzuki M, Taylor GW, Murray S, Thompson D, Purvis A, Kolstoe S, Wood SP, Hawkins PN | title = Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis | journal = Nature | volume = 417 | issue = 6886 | pages = 254–9 | date = May 2002 | pmid = 12015594 | doi = 10.1038/417254a | s2cid = 733818 }}

SAP is a member of the pentraxins family, characterised by calcium-dependent ligand binding and a distinctive flattened β-jellyroll structure similar to that of the legume lectins.{{cite journal | vauthors = Emsley J, White HE, O'Hara BP, Oliva G, Srinivasan N, Tickle IJ, Blundell TL, Pepys MB, Wood SP | title = Structure of pentameric human serum amyloid P component | journal = Nature | volume = 367 | issue = 6461 | pages = 338–45 | date = January 1994 | pmid = 8114934 | doi = 10.1038/367338a0 | s2cid = 4284282 }} The name "pentraxin" is derived from the Greek words for five (penta) and berries (ragos), relating to the radial symmetry of five monomers forming a ring approximately 95 across and 35 deep. Human SAP has 51% sequence homology with C-reactive protein (CRP), a classical acute phase response plasma protein, and is a more distant relative to the "long" pentraxins such as PTX3 (a cytokine-modulated molecule) and several neuronal pentraxins. Both SAP and CRP are evolutionary conserved in all vertebrates and are also found in distant invertebrates such as the horseshoe crab (Limulus polyphemus).{{cite journal | vauthors = Pepys MB, Booth DR, Hutchinson WL, Gallimore JR, Collins PM, Hohenester E | title = Amyloid P component. A critical review | journal = Amyloid | volume = 4 | issue = 4| pages = 274–295 | year = 1997 | doi = 10.3109/13506129709003838 }}

{{Reflist}}

{{PDB_Gallery|geneid=325}}

{{Glycoproteins}}

{{Acute phase proteins}}

{{Amyloidosis}}

Category:Blood proteins

Category:Acute-phase proteins