Amyloid fiber formation (Homo sapiens)

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3825372642629, 398, 11, 12, 33141-3, 5-7, 9...15, 3425161637Golgi lumenendoplasmic reticulum lumenendosome lumencytosolAPCS(20-223) GGA2 HIST1H2AC HIST1H2BJ HIST2H2AA3 APP(672-713),APP(672-711)Systemic amyloid fibril monomers HIST1H2BL H2AFB1 Serum amyloid PdecamerAPCS(20-223)CH3COO-Localized amyloid fibril main peptide chains APP(712-770)H2BFS BACE1HIST1H2BA HIST1H2BC BACE1(46-501) H2BFS HIST1H3A APP(714-770)GGA1 HIST1H2BC HIST3H2BB APP(672-711)Double-stranded DNAand chromatinLocalized amyloid fibril monomers Double-stranded DNA BACE1:GGA1,2,3APCS(20-223) APP(672-711) NAT8 HSPG2(22-4391) HIST2H2AC HIST1H4A Amyloid fibril mainpeptide chainsBACE1HIST1H2BB APP(672-713) HIST1H2BL Localized amyloid fibril main peptide chains HIST1H2BM GGA1,2,3HIST2H2BE HIST1H2BA Ca2+ BACE1(46-501)HIST1H2BD HIST1H2BB HIST1H2BH HIST2H3A H2OAPP(672-713),APP(672-711)APCS(20-223) HIST1H2AJ Ac-CoASerum amyloidP-componenthomopentamerNAT8B Amyloid fibrilmonomersGAG APP(672-711) HIST1H2BK APP(672-713)GAGHIST2H2AC HIST2H2BE GGA2 SerumamyloidP-componentpentamer:Double-stranded DNAHIST1H2BN HIST1H2BH GGA1 HIST1H2BM APP(18-770)HIST1H2AJ HIST1H2BO HIST1H2BN BACE1(22-45)Systemic amyloid fibril main peptide chains HIST1H2AB H2AFZ GGA3 NAT8, 8BHIST2H2AA3 H3F3A HSPG2(22-4391)H3F3A HIST1H2AD Ca2+ H2AFZ HIST1H2AD HIST1H4A FURIN7K-BACE1(46-501)H2AFX Ca2+ Double-stranded DNA 7K-BACE1HIST1H2BK GGA3 Ca2+HIST1H2AC BACE1(46-501)HIST1H3A HIST1H2BJ CoA-SHHIST3H2BB H2AFB1 HIST1H2AB BACE1 deacetylaseSystemic amyloid fibril main peptide chains Amyloid fibrilsAPP(18-671)HIST1H2BO APCS(20-223) H2AFX HIST1H2BD APP(672-713) Ca2+ HIST2H3A 7K-BACE13838423838


Description

Amyloid is a term used to describe typically extracellular deposits of aggregated proteins, sometimes known as plaques. Abnormal accumulation of amyloid is amyloidosis, a term associated with diseased organs and tissues, particularly neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntingdon's. Amyloid deposits consist predominantly of amyloid fibrils, rigid, non-branching structures that form ordered assemblies, characteristically with a cross beta-sheet structure where the sheets run parallel to the direction of the fibril (Sawaya et al. 2007). Often the fibril has a left-handed twist (Nelson & Eisenberg 2006). At least 27 human proteins form amyloid fibrils (Sipe et al. 2010). Many of these proteins have non-pathological functions; the trigger that leads to abnormal aggregations differs between proteins and is not well understood but in many cases the peptides are abnormal fragments or mutant forms arising from polymorphisms, suggesting that the initial event may be aggregation of misfolded or unfolded peptides. Early studies of Amyloid-Beta assembly led to a widely accepted model that assembly was a nucleation-dependent polymerization reaction (Teplow 1998) but it is now understood to be more complex, with multiple 'off-pathway' events leading to a variety of oligomeric structures in addition to fibrils (Roychaudhuri et al. 2008). An increasing body of evidence suggests that these oligomeric forms are primarily responsible for the neurotoxic effects of Amyloid-beta (Roychaudhuri et al. 2008), alpha-synuclein (Winner et al. 2011) and tau (Dance & Strobel 2009, Meraz-Rios et al. 2010). Amyloid oligomers are believed to have a common structural motif that is independent of the protein involved and not present in fibrils (Kayed et al. 2003). Conformation dependent, aggregation specific antibodies suggest that there are 3 general classes of amyloid oligomer structures (Glabe 2009) including annular structures which may be responsible for the widely reported membrane permeabilization effect of amyloid oligomers. Toxicity of amyloid oligomers preceeds the appearance of plaques in mouse models (Ferretti et al. 2011).

Fibrils are often associated with other molecules, notably heparan sulfate proteoglycans and Serum Amyloid P-component, which are universally associated and seem to stabilize fibrils, possibly by protecting them from degradation.

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Bibliography

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History

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CompareRevisionActionTimeUserComment
114869view16:37, 25 January 2021ReactomeTeamReactome version 75
113315view11:38, 2 November 2020ReactomeTeamReactome version 74
112526view15:48, 9 October 2020ReactomeTeamReactome version 73
101438view11:31, 1 November 2018ReactomeTeamreactome version 66
100977view21:09, 31 October 2018ReactomeTeamreactome version 65
100513view19:42, 31 October 2018ReactomeTeamreactome version 64
100059view16:26, 31 October 2018ReactomeTeamreactome version 63
99611view15:00, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99221view12:44, 31 October 2018ReactomeTeamreactome version 62
93929view13:45, 16 August 2017ReactomeTeamreactome version 61
93515view11:25, 9 August 2017ReactomeTeamreactome version 61
88058view13:48, 25 July 2016MkutmonOntology Term : 'peptide and protein metabolic process' added !
88054view13:47, 25 July 2016ReactomeTeamReactome version 56
83437view12:25, 18 November 2015ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
7K-BACE1(46-501)ProteinP56817 (Uniprot-TrEMBL)
7K-BACE1ProteinP56817 (Uniprot-TrEMBL)
APCS(20-223) ProteinP02743 (Uniprot-TrEMBL)
APCS(20-223)ProteinP02743 (Uniprot-TrEMBL)
APP(18-671)ProteinP05067 (Uniprot-TrEMBL)
APP(18-770)ProteinP05067 (Uniprot-TrEMBL)
APP(672-711) ProteinP05067 (Uniprot-TrEMBL)
APP(672-711)ProteinP05067 (Uniprot-TrEMBL)
APP(672-713) ProteinP05067 (Uniprot-TrEMBL)
APP(672-713), APP(672-711)ComplexR-HSA-6783330 (Reactome)
APP(672-713), APP(672-711)ComplexR-HSA-976800 (Reactome)
APP(672-713)ProteinP05067 (Uniprot-TrEMBL)
APP(712-770)ProteinP05067 (Uniprot-TrEMBL)
APP(714-770)ProteinP05067 (Uniprot-TrEMBL)
Ac-CoAMetaboliteCHEBI:15351 (ChEBI)
Amyloid fibril monomersComplexR-HSA-977175 (Reactome)
Amyloid fibril main peptide chainsComplexR-HSA-977144 (Reactome)
Amyloid fibrilsComplexR-HSA-977084 (Reactome)
BACE1 deacetylaseR-HSA-5693080 (Reactome)
BACE1(22-45)ProteinP56817 (Uniprot-TrEMBL)
BACE1(46-501) ProteinP56817 (Uniprot-TrEMBL)
BACE1(46-501)ProteinP56817 (Uniprot-TrEMBL)
BACE1:GGA1,2,3ComplexR-HSA-5692928 (Reactome)
BACE1ProteinP56817 (Uniprot-TrEMBL)
CH3COO-MetaboliteCHEBI:15366 (ChEBI)
Ca2+ MetaboliteCHEBI:29108 (ChEBI)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
CoA-SHMetaboliteCHEBI:15346 (ChEBI)
Double-stranded DNA and chromatinComplexR-HSA-977589 (Reactome)
Double-stranded DNA MetaboliteCHEBI:16991 (ChEBI)
FURINProteinP09958 (Uniprot-TrEMBL)
GAG MetaboliteCHEBI:18085 (ChEBI)
GAGMetaboliteCHEBI:18085 (ChEBI)
GGA1 ProteinQ9UJY5 (Uniprot-TrEMBL)
GGA1,2,3ComplexR-HSA-5692940 (Reactome)
GGA2 ProteinQ9UJY4 (Uniprot-TrEMBL)
GGA3 ProteinQ9NZ52 (Uniprot-TrEMBL)
H2AFB1 ProteinP0C5Y9 (Uniprot-TrEMBL)
H2AFX ProteinP16104 (Uniprot-TrEMBL)
H2AFZ ProteinP0C0S5 (Uniprot-TrEMBL)
H2BFS ProteinP57053 (Uniprot-TrEMBL)
H2OMetaboliteCHEBI:15377 (ChEBI)
H3F3A ProteinP84243 (Uniprot-TrEMBL)
HIST1H2AB ProteinP04908 (Uniprot-TrEMBL)
HIST1H2AC ProteinQ93077 (Uniprot-TrEMBL)
HIST1H2AD ProteinP20671 (Uniprot-TrEMBL)
HIST1H2AJ ProteinQ99878 (Uniprot-TrEMBL)
HIST1H2BA ProteinQ96A08 (Uniprot-TrEMBL)
HIST1H2BB ProteinP33778 (Uniprot-TrEMBL)
HIST1H2BC ProteinP62807 (Uniprot-TrEMBL)
HIST1H2BD ProteinP58876 (Uniprot-TrEMBL)
HIST1H2BH ProteinQ93079 (Uniprot-TrEMBL)
HIST1H2BJ ProteinP06899 (Uniprot-TrEMBL)
HIST1H2BK ProteinO60814 (Uniprot-TrEMBL)
HIST1H2BL ProteinQ99880 (Uniprot-TrEMBL)
HIST1H2BM ProteinQ99879 (Uniprot-TrEMBL)
HIST1H2BN ProteinQ99877 (Uniprot-TrEMBL)
HIST1H2BO ProteinP23527 (Uniprot-TrEMBL)
HIST1H3A ProteinP68431 (Uniprot-TrEMBL)
HIST1H4A ProteinP62805 (Uniprot-TrEMBL)
HIST2H2AA3 ProteinQ6FI13 (Uniprot-TrEMBL)
HIST2H2AC ProteinQ16777 (Uniprot-TrEMBL)
HIST2H2BE ProteinQ16778 (Uniprot-TrEMBL)
HIST2H3A ProteinQ71DI3 (Uniprot-TrEMBL)
HIST3H2BB ProteinQ8N257 (Uniprot-TrEMBL)
HSPG2(22-4391) ProteinP98160 (Uniprot-TrEMBL)
HSPG2(22-4391)ProteinP98160 (Uniprot-TrEMBL)
Localized amyloid fibril main peptide chains R-HSA-976963 (Reactome) Amyloid is a term used to describe typically extracellular deposits of aggregated proteins, sometimes known as plaques. Abnormal accumulation of amyloid is amyloidosis, a term associated with diseased organs and tissues, particularly neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntingdon's. Amyloid deposits consist predominantly of amyloid fibrils, rigid, non-branching structures that form ordered assemblies, characteristically with a cross beta-sheet structure where the sheets run parallel to the direction of the fibril (Sawaya et al. 2007). Often the fibril has a left-handed twist (Nelson & Eisenberg 2006). At least 27 human proteins form amyloid fibrils (Sipe et al. 2010). Many of these proteins have non-pathological functions; the trigger that leads to abnormal aggregations differs between proteins and is not well understood but in many cases the peptides are abnormal fragments or mutant forms arising from polymorphisms, suggesting that the initial event may be aggregation of misfolded or unfolded peptides. Early studies of Amyloid-Beta assembly led to a widely accepted model that assembly was a nucleation-dependent polymerization reaction (Teplow 1998) but it is now understood to be more complex, with multiple 'off-pathway' events leading to a variety of oligomeric structures in addition to fibrils (Roychaudhuri et al. 2008). An increasing body of evidence suggests that these oligomeric forms are primarily responsible for the neurotoxic effects of Amyloid-beta (Roychaudhuri et al. 2008), alpha-synuclein (Winner et al. 2011) and tau (Dance & Strobel 2009, Meraz-Rios et al. 2010). Amyloid oligomers are believed to have a common structural motif that is independent of the protein involved and not present in fibrils (Kayed et al. 2003). Conformation dependent, aggregation specific antibodies suggest that there are 3 general classes of amyloid oligomer structures (Glabe 2009) including annular structures which may be responsible for the widely reported membrane permeabilization effect of amyloid oligomers. Toxicity of amyloid oligomers preceeds the appearance of plaques in mouse models (Ferretti et al. 2011). Fibrils are often associated with other molecules, notably heparan sulfate proteoglycans and Serum Amyloid P-component, which are universally associated and seem to stabilize fibrils, possibly by protecting them from degradation.
Localized amyloid fibril monomers R-HSA-977181 (Reactome)
NAT8 ProteinQ9UHE5 (Uniprot-TrEMBL)
NAT8, 8BComplexR-HSA-5692996 (Reactome)
NAT8B ProteinQ9UHF3 (Uniprot-TrEMBL)
Serum

amyloid P-component

pentamer:Double-stranded DNA		ComplexR-HSA-977223 (Reactome)
Serum amyloid

P-component

homopentamer		ComplexR-HSA-976776 (Reactome)
Serum amyloid P decamerComplexR-HSA-976787 (Reactome)
Systemic amyloid fibril main peptide chains R-HSA-976760 (Reactome) Amyloid is a term used to describe typically extracellular deposits of aggregated proteins, sometimes known as plaques. Abnormal accumulation of amyloid is amyloidosis, a term associated with diseased organs and tissues, particularly neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntingdon's. Amyloid deposits consist predominantly of amyloid fibrils, rigid, non-branching structures that form ordered assemblies, characteristically with a cross beta-sheet structure where the sheets run parallel to the direction of the fibril (Sawaya et al. 2007). Often the fibril has a left-handed twist (Nelson & Eisenberg 2006). At least 27 human proteins form amyloid fibrils (Sipe et al. 2010). Many of these proteins have non-pathological functions; the trigger that leads to abnormal aggregations differs between proteins and is not well understood but in many cases the peptides are abnormal fragments or mutant forms arising from polymorphisms, suggesting that the initial event may be aggregation of misfolded or unfolded peptides. Early studies of Amyloid-Beta assembly led to a widely accepted model that assembly was a nucleation-dependent polymerization reaction (Teplow 1998) but it is now understood to be more complex, with multiple 'off-pathway' events leading to a variety of oligomeric structures in addition to fibrils (Roychaudhuri et al. 2008). An increasing body of evidence suggests that these oligomeric forms are primarily responsible for the neurotoxic effects of Amyloid-beta (Roychaudhuri et al. 2008), alpha-synuclein (Winner et al. 2011) and tau (Dance & Strobel 2009, Meraz-Rios et al. 2010). Amyloid oligomers are believed to have a common structural motif that is independent of the protein involved and not present in fibrils (Kayed et al. 2003). Conformation dependent, aggregation specific antibodies suggest that there are 3 general classes of amyloid oligomer structures (Glabe 2009) including annular structures which may be responsible for the widely reported membrane permeabilization effect of amyloid oligomers. Toxicity of amyloid oligomers preceeds the appearance of plaques in mouse models (Ferretti et al. 2011). Fibrils are often associated with other molecules, notably heparan sulfate proteoglycans and Serum Amyloid P-component, which are universally associated and seem to stabilize fibrils, possibly by protecting them from degradation.
Systemic amyloid fibril monomers R-HSA-977105 (Reactome)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
7K-BACE1(46-501)ArrowR-HSA-5693081 (Reactome)
7K-BACE1(46-501)R-HSA-5693092 (Reactome)
7K-BACE1ArrowR-HSA-5693001 (Reactome)
7K-BACE1ArrowR-HSA-5693071 (Reactome)
7K-BACE1R-HSA-5693071 (Reactome)
7K-BACE1R-HSA-5693081 (Reactome)
APCS(20-223)R-HSA-976723 (Reactome)
APP(18-671)ArrowR-HSA-5692495 (Reactome)
APP(18-770)R-HSA-5692495 (Reactome)
APP(672-711)ArrowR-HSA-5692495 (Reactome)
APP(672-713), APP(672-711)ArrowR-HSA-6783332 (Reactome)
APP(672-713), APP(672-711)R-HSA-6783332 (Reactome)
APP(672-713)ArrowR-HSA-5692495 (Reactome)
APP(712-770)ArrowR-HSA-5692495 (Reactome)
APP(714-770)ArrowR-HSA-5692495 (Reactome)
Ac-CoAR-HSA-5693001 (Reactome)
Amyloid fibril monomersR-HSA-977136 (Reactome)
Amyloid fibril main peptide chainsArrowR-HSA-977136 (Reactome)
Amyloid fibril main peptide chainsR-HSA-976734 (Reactome)
Amyloid fibrilsArrowR-HSA-976734 (Reactome)
BACE1 deacetylasemim-catalysisR-HSA-5693092 (Reactome)
BACE1(22-45)ArrowR-HSA-5693081 (Reactome)
BACE1(46-501)ArrowR-HSA-5693086 (Reactome)
BACE1(46-501)ArrowR-HSA-5693092 (Reactome)
BACE1(46-501)R-HSA-5692934 (Reactome)
BACE1(46-501)R-HSA-5693086 (Reactome)
BACE1:GGA1,2,3ArrowR-HSA-5692934 (Reactome)
BACE1:GGA1,2,3R-HSA-5692941 (Reactome)
BACE1ArrowR-HSA-5692941 (Reactome)
BACE1R-HSA-5693001 (Reactome)
BACE1mim-catalysisR-HSA-5692495 (Reactome)
CH3COO-ArrowR-HSA-5693092 (Reactome)
Ca2+R-HSA-976723 (Reactome)
CoA-SHArrowR-HSA-5693001 (Reactome)
Double-stranded DNA and chromatinR-HSA-977224 (Reactome)
FURINmim-catalysisR-HSA-5693081 (Reactome)
GAGR-HSA-976734 (Reactome)
GGA1,2,3ArrowR-HSA-5692941 (Reactome)
GGA1,2,3R-HSA-5692934 (Reactome)
H2OR-HSA-5693092 (Reactome)
HSPG2(22-4391)R-HSA-976734 (Reactome)
NAT8, 8Bmim-catalysisR-HSA-5693001 (Reactome)
R-HSA-5692495 (Reactome) Beta-secretase 1 (BACE1) catalyses the rate-limiting step of the cleavage of amyloid precursor protein (APP(18-770)), resulting in the generation of the beta-amyloid proteins 42 and 40 (APP(672-713) and APP(673-711) respectively). These peptides are thought to be the main fibril-forming peptides (Qui et al. 2015).
R-HSA-5692934 (Reactome) Beta-secretase 1 (BACE1, memapsin-2) mediates the proteolytic processing of amyloid precursor protein (APP). BACE1 is transported from the plasma membrane to endosomes where APP hydrolysis takes place. The acid-cluster-dileucine (ACDL) motif in the cytosolic domain of BACE1 is able to bind to the VHS domain of ADP-ribosylation factor-binding proteins 1, 2 and 3 (GGA1,2,3) which play a role in protein sorting and trafficking between the trans-Golgi network (TGN) and endosomes. This is the presumed recognition step for BACE1 transport to endosomes (He et al. 2003).
R-HSA-5692941 (Reactome) Beta-secretase 1 (BACE1, memapsin-2) mediates the proteolytic processing of amyloid precursor protein (APP). BACE1 is transported from the cell surface to endosomes where APP hydrolysis takes place. The acid-cluster-dileucine (ACDL) motif in the cytosolic domain of BACE1 is able to bind to the VHS domain of ADP-ribosylation factor-binding proteins 1, 2 and 3 (GGA1,2,3) which play a role in protein sorting and trafficking between the trans-Golgi network (TGN) and endosomes. This is the presumed recognition step for BACE1 transport to endosomes (He et al. 2003).
R-HSA-5693001 (Reactome) N-acetyltransferase 8 and 8B (NAT8, 8B) can mediate the molecular stabilisation of BACE1, the membrane protein that acts as the rate-limiting enzyme in the generation of the Alzheimer disease amyloid beta-peptide. Specifically, nascent BACE1 is transiently acetylated on seven lysine residues in the ER lumen which protects the nascent protein from degradation in the ER Golgi intermediate compartment (ERGIC) and allows it to reach the Golgi apparatus (Ko & Puglielli 2009, Costantini et al. 2007). Lysine-acetylated BACE1 (7K-BACE1) is deacetylated in the Golgi apparatus.
R-HSA-5693071 (Reactome) Beta secretase 1 (BACE1) is acetylated on 7 lysine residues inthe ER lumen (7K-BACE1). This protects the nascent protein from degradation in the ER Golgi intermediate compartment (ERGIC) and allows it to reach the Golgi apparatus (Kandalepas & Vassar 2014). The mechanism of this translocation is unknown.
R-HSA-5693081 (Reactome) FURIN is the most likely endopeptidase that cleaves the BACE propeptide domain (BACE1(22-45)) to form the mature enzyme (7K-BACE1(46-501). Although the pro-enzyme possesses proteolytic activity, this activity is approximately doubled following removal of the prodomain (Bennett et al. 2000).
R-HSA-5693086 (Reactome) BACE1(46-501) translocates from the Golgi lumen to the plasma membrane (Walter et al. 2001).
R-HSA-5693092 (Reactome) Mature beta secretase 1, acetylated on 7 lysine residues (7K-BACE1(46-501), is deacetylated by an unknown deacetylase in the Golgi apparatus (Kandalepas & Vassar 2014).
R-HSA-6783332 (Reactome) The beta-amyloid proteins 42 and 40 (APP(672-713) and APP(673-711) respectively) are thought to be the main fibril-forming peptides implicated in neurodegenerative disorders. They translocate from the endosomal lumen to the extracellular region by an unknown mechanism (Qui et al. 2015).
R-HSA-976723 (Reactome) Serum amyloid P component (SAP) is a member of the pentraxin family, characterized by the formation of pentameric ring structures. Each member of the ring has two associated calcium ions. SAP is an acute phase reactant, highly induced by IL-6. It has 50% homology with the related C-reactive peptide.
R-HSA-976734 (Reactome) In addition to the main fibril peptide, mature amyloid fibrils have additional components. Serum amyloid P component (SAP) binds to all types of amyloid fibrils and is a universal constituent of amyloid deposits. SAP binding protects amyloid fibrils from proteolytic degradation (Tennent et al. 1995, Westermark 2005). SAP may function as a chaperone for amyloid formation (Coker et al. 2000).

Glycosaminoglycans (GAGs) and proteoglycans are found associated with all types of amyloid deposits (Alexandrescu 2005). Of the different types of GAG heparan sulfate and dermatan sulfate are the most prominent in amyloid deposits (Hirschfield & Hawkins, 2003). GAGs have been implicated in the nucleation of fibrils, they can also stabilize mature fibrils against dissociation (Yamaguchi et al. 2003) and proteolytic degradation (Gupta-Bansal et al. 1995).

Perlecan coimmunolocalizes with all types of amyloids (Snow & Wright 1989), accelerating fibril formation (Castillo et al. 1998), stabilizing them once formed (Castillo et al. 1997), and protecting them from proteolytic degradation (Gupta-Bansal et al. 1995).

ApoE tightly binds to soluble ABeta peptide forming complexes that resist dissociation; it also binds to ABeta in its fibril form (Bales et al. 2002).
R-HSA-976817 (Reactome) At physiological pH serum amyloid P component is a decamer of two pentameric rings lying face to face. This non-covalent interaction is readily dissociated by reducing the pH.
R-HSA-977136 (Reactome) Amyloid fibril formation is associated with a wide range of diseases (Chiti & Dobson 2006), though the accumulation and deposition of fibrillar material does not correlate well with disease pathogenesis and it is now widely believed that oligomeric amyloid forms are largely responsible for the cytotoxic effects of amyloid (Glabe 2009). Fibrils have been described as more like crystalline polymer structures than the protein monomers they are derived from (Wetzel et al. 2007). Fibril formation is usually preceded by the association of monomers into oligomeric structures (Kodali & Wetzel 2007). For Beta-amyloid, these are spherical structures with around 12 units (Bernstein et al. 2005). Larger structures called protofibrils are also observed, non-spherical filamentous structures lacking a periodic substructure (Goldsbury 2005).
R-HSA-977224 (Reactome) Serum amyloid P component (SAP) binds DNA and chromatin in a calcium dependent manner in physiological conditions (Pepys et al. 1987). This binding displaces H1-type histones (Butler et al. 1990), solubilizing chromatin which is otherwise insoluble in extracellular fluids. SAP may therefore participate in the in vivo handling of chromatin exposed by cell death. SAP knockout mice spontaneously develop antinuclear autoimmunity and severe glomerulonephritis, a phenotype resembling human systemic lupus erythematosus, a serious autoimmune disease, suggesting that SAP binding may play a role in reducing the immunogenicity of chromatin and preventing autoimmunity (Bickerstaff et al. 1999).
Serum

amyloid P-component

pentamer:Double-stranded DNA		ArrowR-HSA-977224 (Reactome)
Serum amyloid

P-component

homopentamer		ArrowR-HSA-976723 (Reactome)
Serum amyloid

P-component

homopentamer		R-HSA-976734 (Reactome)
Serum amyloid

P-component

homopentamer		R-HSA-976817 (Reactome)
Serum amyloid

P-component

homopentamer		R-HSA-977224 (Reactome)
Serum amyloid P decamerArrowR-HSA-976817 (Reactome)
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