Serum amyloid P component

APCS
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4AYU, 1GYK, 1LGN, 1SAC, 2A3W, 2A3X, 2A3Y, 2W08, 3D5O, 3KQR, 4AVS, 4AVT, 4AVV
Identifiers
Aliases	APCS, HEL-S-92n, PTX2, SAP, amyloid P component, serum
External IDs	OMIM: 104770 MGI: 98229 HomoloGene: 123932 GeneCards: APCS
Targeted by Drug
miridesap[1]
Gene ontology Molecular function • calcium ion binding • unfolded protein binding • metal ion binding • virion binding • complement component C1q binding • carbohydrate binding Cellular component • blood microparticle • extracellular matrix • extracellular fluid • extracellular region • extracellular exosome • nucleus Biological process • cellular protein metabolic process • negative regulation of monocyte differentiation • negative regulation of acute inflammatory response • negative regulation of viral entry into host cell • chaperone-mediated protein complex assembly • negative regulation of viral process • negative regulation of glycoprotein metabolic process • negative regulation by host of viral glycoprotein metabolic process • protein folding • acute-phase response • negative regulation of exo-alpha-sialidase activity • negative regulation of wound healing • negative regulation by host of viral exo-alpha-sialidase activity • innate immune response Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	325	20219
Ensembl	ENSG00000132703	ENSMUSG00000026542
UniProt	P02743	P12246
RefSeq (mRNA)	NM_001639	NM_011318
RefSeq (protein)	NP_001630.1	NP_035448.2
Location (UCSC)	Chr 1: 159.59 – 159.59 Mb	Chr 1: 172.89 – 172.9 Mb
PubMed search	[2]	[3]
Wikidata

View/Edit Human

View/Edit Mouse

The serum amyloid P component (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".^[4] APCS is its human gene.^[5]

In amyloidosis

AP makes up 14% of the dry mass of amyloid deposits^[6] and is thought to be an important contributor to the pathogenesis of a related group of diseases called the Amyloidoses.^[7] 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.^[8] 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.^[9] 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.^[10]

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.^[11] 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).^[12]

References

1. "Drugs that physically interact with Serum amyloid P-component view/edit references on wikidata".
2. "Human PubMed Reference:".
3. "Mouse PubMed Reference:".
4. Cathcart ES; Shirahama T; Cohen AS (1967). "Isolation and identification of a plasma component of amyloid". Biochim. Biophys. Acta. 147: 392–393. doi:10.1016/0005-2795(67)90420-5.
5. "Entrez Gene: APCS amyloid P component, serum".
6. Skinner M; Pepys MB; Cohen AS; Heller LM; Lian JB (1980). Freitas, Antonio Falcão de; Glenner, George G.; Costa, Pedro Pinho e., eds. Amyloid and amyloidosis: proceedings of the Third International Symposium on Amyloidosis, Póvoa de Varzim, Portugal, 23–28 September 1979. Amsterdam: Excerpta Medica. pp. 384–391. ISBN 0-444-90124-8.
7. 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.
8. Tennent GA; Lovat LB; Pepys MB (1995). "Serum amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer disease and systemic amyloidosis" (PDF). Proc. Natl. Acad. Sci. U.S.A. 92 (10): 4299–303. doi:10.1073/pnas.92.10.4299. PMC 41931. PMID 7753801.
9. Hawkins PN; Pepys MB (1995). "Imaging amyloidosis with radiolabelled SAP". Eur J Nucl Med. 22 (7): 595–9. doi:10.1007/BF01254559. PMID 7498219.
10. 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.
11. 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.
12. Pepys MB; Booth DR; Hutchinson WL; Gallimore JR; Collins PM; Hohenester E (1997). "Amyloid P component. A critical review". Amyloid. 4: 274–295. doi:10.3109/13506129709003838.