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07-SEPTEMBER-2008 03:17:44 - P component Amyloid P component, serum Cartoon model of SAP showing helices in red, sheets in yellow and coils in green. Available structures: 1gyk, 1lgn, 1sac, 2a3w, 2a3x, 2a3y Identifiers Symbols APCS; MGC88159; PTX2; SAP External IDs OMIM: 104770 MGI: 98229 HomoloGene: 1239 Gene ontology Molecular function: calcium ion binding sugar binding unfolded protein binding Cellular component: extracellular region extracellular space Biological process: protein folding acute-phase response chaperone-mediated protein complex assembly RNA expression pattern More reference expression data Orthologs Human Mouse Entrez 325 20219 Ensembl ENSG00000132703 ENSMUSG00000026542 Uniprot P02743 Q4JFI8 Refseq NM_001639 mRNA NP_001630 protein NM_011318 mRNA NP_035448 protein Location Chr 1: 157.82 - 157.83 Mb Chr 1: 174.73 - 174.73 Mb Pubmed search 1 2 Amyloid P component, serum SAP is the identical serum form of amyloid P component AP, a 25kDa pentameric protein first identified as the pentagonal constituent of in vivo pathological deposits called amyloid.1. APCS is its human gene.2 In amyloidosis AP makes up 14% of the dry mass of amyloid deposits3 and is thought to be an important contributor to the pathogenesis of a related group of diseases called the Amyloidoses.4 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. AP is thought to decorate and stabilise aggregates by preventing proteolytic cleavage and hence inhibiting fibril removal via the normal protein scavenging mechanisms.5 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.6 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.7 Structure SAP is a member of the pentraxins family, characterised by calcium dependent ligand binding and distinctive flattened β-jellyroll structure similar to that of the legume lectins.8 The name pentraxin is derived from the Greek word for five penta and berries ragos relating to the radial symmetry of five monomers forming a ring approximately 95 Å across and 35 Å 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 also found in distant invertebrates such as the horseshoe crab Limulus polyphemus.9 References ^ Cathcart ES, Shirahama T, Cohen AS 1967. Isolation and identification of a plasma component of amyloid. Biochim. Biophy. Acta. 147: 392-393. ^ Entrez Gene: APCS amyloid P component, serum. ^ Skinner M, Pepys MB, Cohen AS, Heller LM, Lian JB 1980. in Freitas, Antonio Falcão de; Glenner, George G.; Costa, Pedro Pinho e. ors: Amyloid and amyloidosis: proceedings of the Third International Symposium on Amyloidosis, Póvoa de Varzim, Portugal, 23-28 September 1979. Amsterdam: Excerpta Medica, pages 384-391. ISBN 0-444-90124-8. ^ Botto M, Hawkins PN, Bickerstaff MC, Herbert J, Bygrave AE, McBride A, Hutchinson WL, Tennent GA, Walport MJ, Pepys MB 1997. Amyloid deposition is delayed in mice with targeted deletion of the serum amyloid P component gene. Nat. Med. 3 8: 855-9. doi:10.1038/9544. PMID 9256275. ^ Tennent GA, Lovat LB, Pepys MB 1995. Serum amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer disease and systemic amyloidosis. Proc. Natl. Acad. Sci. U.S.A. 92 10: 4299-303. doi:10.1073/pnas.92.10.4299. PMID 7753801. ^ Hawkins PN, Pepys MB 1995. Imaging amyloidosis with radiolabelled SAP. Eur J Nucl Med 22 7: 595-9. PMID 7498219. ^ 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 2002. Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis. Nature 417 6886: 254-9. doi:10.1038/417254a. PMID 12015594. ^ Emsley J, White HE, O'Hara BP, Oliva G, Srinivasan N, Tickle IJ, Blundell TL, Pepys MB, Wood SP 1994. Structure of pentameric human serum amyloid P component. Nature 367 6461: 338-45. doi:10.1038/367338a0. PMID 8114934. ^ Pepys MB, Booth DR, Hutchinson WL, Gallimore JR, Collins PM, Hohenester E 1997. Amyloid P component. A critical review. Amyloid-International Journal of Experimental and Clinical Investigation 4: 274-295. v d e Protein: glycoproteins Activin - ADAM protein - Alpha 1-antichymotrypsin - Apolipoprotein H - CD70 - Asialoglycoprotein - Avidin - B-cell activating factor - 4-1BB ligand - Cholesterylester transfer protein - Clusterin - Colony-stimulating factor - Haemopexin - Inhibin - Lactoferrin - Membrane glycoproteins - Mucoprotein - Myelin protein zero - Osteonectin - Protein C - Protein S - Proteoglycan - Serum amyloid P component - Sialoglycoprotein CD43, Glycophorin, Glycophorin C - Thrombopoietin - Thyroglobulin - Thyroxine-binding proteins - Transcortin - Tumor necrosis factor-alpha - Uteroglobin - Vitronectin v d e Acute phase proteins Amyloid SAP - SAA Other positive Alpha 1-antichymotrypsin - Alpha 1-antitrypsin - Alpha 2-macroglobulin - C-reactive protein - Ceruloplasmin - C3 - Fibrin - Haptoglobin - Haemopexin - Orosomucoid - Transferrin Negative Serum albumin v d e Metabolic disease: amyloidosis E85, 277.3 Forms of amyloid Serum amyloid P component - Serum amyloid A - Transthyretin - Beta-2 microglobulin - Bence Jones protein/Multiple myeloma - Amyloid precursor protein/Beta amyloid - Amylin Systemic amyloidosis AL amyloidosis - AA amyloidosis - Haemodialysis-associated amyloidosis - Senile systemic amyloidosis - Finnish type amyloidosis - Familial Merranean fever Organ-limited amyloidosis heart: Cardiac amyloidosis brain: Familial amyloid neuropathy - Cerebral amyloid angiopathy - Alzheimer's disease kidney: Familial renal amyloidosis cutaneous: Primary cutaneous amyloidosis Retrieved from http://en..org/wiki/Serum_amyloid_P_component Categories: Genes on chromosome 1 | Human proteins | Metabolic disorders | Blood proteins | Acute phase proteins Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Svenska 中文 This page was last modified on 7 August 2008, at 10:49
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