Serum amyloid P component

Amyloid P component, serum
250px Cartoon model of SAP showing helices in red, sheets in yellow and coils in green.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1GYK, 1LGN, 1SAC, 2A3W, 2A3X, 2A3Y, 2W08, 3D5O, 3KQR, 4AVS, 4AVT, 4AVV, 4AYU
Identifiers
Symbols	APCS ; HEL-S-92n; PTX2; SAP
External IDs	OMIM: 104770 MGI: 98229 HomoloGene: 123932 ChEMBL: 4929 GeneCards: APCS Gene
Gene ontology Molecular function • complement component C1q binding • calcium ion binding • carbohydrate binding • virion binding • unfolded protein binding Cellular component • extracellular region • extracellular space • nucleus • extracellular matrix • protein complex • extracellular exosome • blood microparticle Biological process • negative regulation of acute inflammatory response • protein folding • acute-phase response • negative regulation by host of viral exo-alpha-sialidase activity • negative regulation by host of viral glycoprotein metabolic process • innate immune response • negative regulation of monocyte differentiation • negative regulation of viral entry into host cell • negative regulation of viral process • chaperone-mediated protein complex assembly • negative regulation of wound healing • negative regulation of exo-alpha-sialidase activity • negative regulation of glycoprotein metabolic process Sources: Amigo / QuickGO
RNA expression pattern
File:PBB GE APCS 206350 at tn.png
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	NP_035448
Location (UCSC)	Chr 1: 159.59 – 159.59 Mb	Chr 1: 172.89 – 172.9 Mb
PubMed search	[1]	[2]

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". APCS is its human gene.

In amyloidosis

AP makes up 14% of the dry mass of amyloid deposits and is thought to be an important contributor to the pathogenesis of a related group of diseases called the Amyloidoses. 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. 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. 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.

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. 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).