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Serum amyloid A1

Serum amyloid A1 (SAA1) is a protein that in humans is encoded by the SAA1 gene. SAA1 is a major acute-phase protein mainly produced by hepatocytes in response to infection, tissue injury and malignancy. When released into blood circulation, SAA1 is present as an apolipoprotein associated with high-density lipoprotein (HDL). SAA1 is a major precursor of amyloid A (AA), the deposit of which leads to inflammatory amyloidosis.

SAA1
Available structures
PDBOrtholog search:PDBe RCSB
List of PDB id codes

4IP8, 4IP9

Identifiers
AliasesSAA1, PIG4, SAA, SAA2, TP53I4, Serum amyloid A1
External IDsOMIM: 104750 MGI: 98222 HomoloGene: 128033 GeneCards: SAA1
Gene location (Human)
Chr.Chromosome 11 (human)
Band11p15.1Start18,266,260 bp
End18,269,977 bp
Gene location (Mouse)
Chr.Chromosome 7 (mouse)
Band7 B3|7 30.56 cMStart46,751,790 bp
End46,754,313 bp
RNA expression pattern
Bgee
Top expressed in
  • liver
  • Right lobe of liver
  • adipose tissue
  • minor salivary gland
  • fundus
  • urinary bladder
  • muscle tissue
More reference expression data
BioGPS
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)Chr 11: 18.27 – 18.27 MbChr 7: 46.75 – 46.75 Mb
PubMed search
Wikidata

Contents

The gene coding for human SAA1 is one of the 4 SAA genes mapped to a region in the short arm on Chromosome 15. Two of these genes, SAA1 and SAA2, are inducible during acute-phase response, whereas SAA3 is a pseudogene in humans and SAA4 is constitutively expressed in a variety of tissues and cells. Single nucleotide polymorphisms (SNPs) are found in SAA1 in both coding and non-coding sequences, with those located in the coding sequence defining 5 isoforms of SAA1 (SAA1.1 – 1.5). Genetic studies have shown association of some of these SNPs with the disposition to several human diseases including familiar Mediterranean fever, coronary artery diseases, cerebral infarction, and osteoporosis. Mice also have 4 Saa genes. A major difference between human and mouse SAA genes is the expression of the mouse Saa3 gene for a functional protein, generally considered an inducible SAA in inflammatory tissues.

The product of human SAA1 is a pre-protein of 122 amino acids, with a cleavable signal peptide of 18 amino acids. Mature SAA1 consists of 104 amino acids with an apparent molecular weight of 12,500. A crystal structure of SAA1.1 has been solved recently (Figure 1). Native SAA1 is a hexamer with each subunit assuming an antiparallel 4-helix bundle structure. The structure is cone-shaped with its apex forming a binding site for HDL and heparin. The N-terminal helices 1 and 3 have been identified as amyloidogenic peptides of SAA1.1, that are not presence on protein surface in native SAA1 protein. These findings provide the structural basis for the formation of amyloid A fibrils. The human SAA1.1 is comparable at the subunit level with the recently solved structure of mouse Saa3.

SAA1 and SAA2 are highly inducible and hence called acute-phase SAA. Inflammatory cytokines such as IL-1β, IL-6 and TNF-α are major stimulants for hepatocyte expression of the SAA1 gene. Inducible expression of the acute-phase SAA genes is mainly regulated at the transcription level and involves the transcription factors C/EBP, NF-κB, AP2, SAF, Sp1 and STAT3. Elevation of the transcript of SAA1 is often seen in cDNA arrays used for detection of proinflammatory cytokine expression. SAA1 protein level correlates with its transcript level, and has long been considered a clinical indicator for inflammatory conditions.

In addition to its association with HDL, SAA1 interacts with a number of mammalian proteins, mostly cell surface proteins such as receptors. SAA1 binding to the αvβ3 integrin produces an inhibitory effect on the growth of nasopharyngeal carcinoma. Several receptors for SAA1 have been identified using an SAA1 hybrid protein containing two amino acid substitutions from SAA2. These receptors include the G protein-coupled chemoattractant receptor FPR2 (formyl peptide receptor 2), believed to mediate the chemotactic activity of the recombinant SAA1; the murine scavenger receptor SR-BI and the human equivalent CLA-1., for a possible role in SAA1-dependent cholesterol metabolism. Moreover, the Toll-like receptors TLR2 and TLR4 mediate SAA1-induced cytokine gene expression. The P2X7 purinergic receptor is another receptor used by SAA1 for a number of cellular functions including the activation of NLRP3 inflammasomes.

SAA1 has been found to interact with outer membrane protein A (ompA) of several Gram-negative bacteria including E. coli, Salmonella typhimurium, Shigella flexneri, Vibrio cholerae and P. aeruginosa. Exposure of these Gram-negative bacteria to SAA1 promotes uptake of the bacteria by neutrophils, suggesting that SAA1 serves as an opsonin that enhances bacteria clearance. A more recent study identified SAA1 interaction with retinol, resulting in reduced bacterial burden. These findings suggest that SAA1 has a function in host defense against bacterial infection.

The biological function of SAA1 has not been fully understood despite intensive research in the last three decades. Research tools such as the SAA1 knockout mice and transgenic mice have become available only recently. It has been well established, however, that elevated plasma concentration of SAA1 is associated with a multitude of inflammatory conditions. As a result, SAA1 has been a clinical indicator and reliable biomarker for inflammatory diseases, chronic metabolic disorders and late-stage malignancy. Inflammatory amyloidosis results from chronic inflammation with increased production of SAA1, which is a major precursor of amyloid A fibril deposit in various tissues.

SAA1 has been extensively studied for its binding to HDL, with results suggesting a role in lipid metabolism. During the acute-phase response, elevated levels of SAA1 in the plasma displaces ApoA-I and becomes a major apolipoprotein of HDL. The exact biological consequence of HDL remodeling by SAA1 is still under investigation, using recently developed tools such as the Saa1 and Saa2 knockout mice. SAA1 is also believed to contribute to the development of atherosclerosis. However, in an ApoE-deficient mouse model, deletion of the Saa1/Saa2 genes does not appear to affect atherosclerotic lesions.

Ex vivo and in vitro studies have shown that the recombinant human SAA1 hybrid protein has strong chemotactic activity for neutrophils and macrophages. This effect is believed to be mediated through FPR2, a G protein-coupled chemoattractant receptor. The same receptor also mediates the cytokine-like activity of the recombinant SAA1, resulting in an elevated expression of IL-8 in neutrophils. The recombinant SAA1 has been reported to induce the expression of a variety of inflammatory cytokines including IL-1β, TNF-α, IL-6, IL-12p40, as well as immunoregulatory cytokines such as IL-23, IL-33 and growth-stimulatory cytokines such as G-CSF.

SAA1 may also be produced by macrophages and epithelial cells in various tissues. It has been shown to promote local Th17 response in the gut. This finding, which is based on both Saa1/Saa2 knockout mice and ex vivo studies of T cells, strongly suggest a local immunomodulatory function of SAA1 as opposed to its established role as an acute-phase protein produced in the liver and present in the plasma as an apolipoprotein of HDL. Transgenic expression of human SAA1.1 in mouse liver aggravates T cell-mediated hepatitis through elevated production of chemokines, which involves the SAA1 receptor TLR2. Secretion of SAA1 by melanoma cells may induce anti-inflammatory IL-10-secreting neutrophils that interact with invariant natural killer T cells (iNKT cells). In addition, SAA1 can skew macrophages to a M2 phenotype.

Published reports link SAA1 to a number of malignancies, but a causal relationship has not been established. SAA1 has been associated with tumor pathogenesis, and its gene polymorphism is a contributing factor to certain types of malignant tumors. SAA1 has also been shown to affect the tumor microenvironment and contribute to tumor cell metastasis.

Some of the results obtained with the recombinant human SAA1 hybrid remain controversial, as the protein does not have exactly the same sequence of human SAA1 and its properties may be different from the native SAA1. Other studies have shown that native human SAA1 retains some of the cytokine-like activities such as the G-CSF-induction capability

Recent studies using the Saa1/Saa2 knockout mice showed weakened Th17 response in gut epithelial cells, suggesting that SAA1 plays a role in vivo in the regulation of immunity.

The 2016 version of this article was updated by an external expert under a dual publication model. The corresponding academic peer reviewed article was published in Gene and can be cited as:
Lei Sun; Richard D Ye (2 March 2016). "Serum amyloid A1: Structure, function and gene polymorphism". Gene. Gene Wiki Review Series. 583 (1): 48–57. doi:10.1016/J.GENE.2016.02.044. ISSN 0378-1119. PMC5683722. PMID 26945629. Wikidata Q38761950.
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  • Overview of all the structural information available in the PDB for UniProt: P0DJI8 (Serum amyloid A-1 protein) at the PDBe-KB.

Serum amyloid A1
Serum amyloid A1 Language Watch Edit 160 160 Redirected from SAA1 Serum amyloid A1 SAA1 is a protein that in humans is encoded by the SAA1 gene 5 6 7 SAA1 is a major acute phase protein mainly produced by hepatocytes in response to infection tissue injury and malignancy 8 When released into blood circulation SAA1 is present as an apolipoprotein associated with high density lipoprotein HDL 9 SAA1 is a major precursor of amyloid A AA the deposit of which leads to inflammatory amyloidosis 10 11 SAA1Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes4IP8 4IP9IdentifiersAliasesSAA1 PIG4 SAA SAA2 TP53I4 Serum amyloid A1External IDsOMIM 104750 MGI 98222 HomoloGene 128033 GeneCards SAA1Gene location Human Chr Chromosome 11 human 1 Band11p15 1Start18 266 260 bp 1 End18 269 977 bp 1 Gene location Mouse Chr Chromosome 7 mouse 2 Band7 B3 7 30 56 cMStart46 751 790 bp 2 End46 754 313 bp 2 RNA expression patternBgeeTop expressed inliver Right lobe of liver adipose tissue minor salivary gland fundus urinary bladder muscle tissueMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionheparin binding chemoattractant activity G protein coupled receptor bindingCellular componentendocytic vesicle lumen extracellular region high density lipoprotein particle cytoplasmic microtubule extracellular exosome extracellular spaceBiological processcellular protein metabolic process positive regulation of cytosolic calcium ion concentration receptor mediated endocytosis neutrophil chemotaxis platelet activation macrophage chemotaxis acute phase response lymphocyte chemotaxis innate immune response negative regulation of inflammatory response positive regulation of cell adhesion regulation of protein secretion positive chemotaxis G protein coupled receptor signaling pathway cytokine mediated signaling pathway cell chemotaxisSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez628820209EnsemblENSG00000173432 ENSG00000288411ENSMUSG00000057465UniProtP0DJI8P05367RefSeq mRNA NM 199161 NM 000331 NM 001178006NM 011314 NM 001357491 NM 001379268 NM 001379269RefSeq protein NP 000322 NP 001171477 NP 954630NP 035444 NP 001344420 NP 001366197 NP 001366198Location UCSC Chr 11 18 27 18 27 MbChr 7 46 75 46 75 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Gene 2 Protein structure 3 Inducible expression 4 Interactions 5 Functions and clinical relevance 6 Notes 7 References 8 Further reading 9 External linksGene EditThe gene coding for human SAA1 is one of the 4 SAA genes mapped to a region in the short arm on Chromosome 15 12 Two of these genes SAA1 and SAA2 are inducible during acute phase response whereas SAA3 is a pseudogene in humans 13 and SAA4 is constitutively expressed in a variety of tissues and cells Single nucleotide polymorphisms SNPs are found in SAA1 in both coding and non coding sequences with those located in the coding sequence defining 5 isoforms of SAA1 SAA1 1 1 5 Genetic studies have shown association of some of these SNPs with the disposition to several human diseases including familiar Mediterranean fever coronary artery diseases cerebral infarction and osteoporosis Mice also have 4 Saa genes A major difference between human and mouse SAA genes is the expression of the mouse Saa3 gene for a functional protein generally considered an inducible SAA in inflammatory tissues Protein structure EditThe product of human SAA1 is a pre protein of 122 amino acids with a cleavable signal peptide of 18 amino acids Mature SAA1 consists of 104 amino acids with an apparent molecular weight of 12 500 A crystal structure of SAA1 1 has been solved recently Figure 1 Native SAA1 is a hexamer with each subunit assuming an antiparallel 4 helix bundle structure 14 The structure is cone shaped with its apex forming a binding site for HDL and heparin The N terminal helices 1 and 3 have been identified as amyloidogenic peptides of SAA1 1 that are not presence on protein surface in native SAA1 protein These findings provide the structural basis for the formation of amyloid A fibrils The human SAA1 1 is comparable at the subunit level with the recently solved structure of mouse Saa3 15 Inducible expression EditSAA1 and SAA2 are highly inducible and hence called acute phase SAA Inflammatory cytokines such as IL 1b IL 6 and TNF a are major stimulants for hepatocyte expression of the SAA1 gene 16 Inducible expression of the acute phase SAA genes is mainly regulated at the transcription level and involves the transcription factors C EBP NF kB AP2 SAF Sp1 and STAT3 Elevation of the transcript of SAA1 is often seen in cDNA arrays used for detection of proinflammatory cytokine expression SAA1 protein level correlates with its transcript level and has long been considered a clinical indicator for inflammatory conditions Interactions EditIn addition to its association with HDL SAA1 interacts with a number of mammalian proteins mostly cell surface proteins such as receptors SAA1 binding to the avb3 integrin produces an inhibitory effect on the growth of nasopharyngeal carcinoma 17 Several receptors for SAA1 have been identified using an SAA1 hybrid protein containing two amino acid substitutions from SAA2 18 These receptors include the G protein coupled chemoattractant receptor FPR2 formyl peptide receptor 2 19 believed to mediate the chemotactic activity of the recombinant SAA1 the murine scavenger receptor SR BI 20 and the human equivalent CLA 1 21 for a possible role in SAA1 dependent cholesterol metabolism Moreover the Toll like receptors TLR2 22 and TLR4 23 mediate SAA1 induced cytokine gene expression The P2X7 purinergic receptor is another receptor used by SAA1 for a number of cellular functions including the activation of NLRP3 inflammasomes 24 SAA1 has been found to interact with outer membrane protein A ompA of several Gram negative bacteria including E coli Salmonella typhimurium Shigella flexneri Vibrio cholerae and P aeruginosa 25 Exposure of these Gram negative bacteria to SAA1 promotes uptake of the bacteria by neutrophils suggesting that SAA1 serves as an opsonin that enhances bacteria clearance 26 A more recent study identified SAA1 interaction with retinol resulting in reduced bacterial burden 27 These findings suggest that SAA1 has a function in host defense against bacterial infection Functions and clinical relevance EditThe biological function of SAA1 has not been fully understood despite intensive research in the last three decades Research tools such as the SAA1 knockout mice and transgenic mice have become available only recently It has been well established however that elevated plasma concentration of SAA1 is associated with a multitude of inflammatory conditions As a result SAA1 has been a clinical indicator and reliable biomarker for inflammatory diseases chronic metabolic disorders and late stage malignancy 28 Inflammatory amyloidosis results from chronic inflammation with increased production of SAA1 which is a major precursor of amyloid A fibril deposit in various tissues 29 SAA1 has been extensively studied for its binding to HDL with results suggesting a role in lipid metabolism During the acute phase response elevated levels of SAA1 in the plasma displaces ApoA I and becomes a major apolipoprotein of HDL 30 The exact biological consequence of HDL remodeling by SAA1 is still under investigation using recently developed tools such as the Saa1 and Saa2 knockout mice SAA1 is also believed to contribute to the development of atherosclerosis 31 32 However in an ApoE deficient mouse model deletion of the Saa1 Saa2 genes does not appear to affect atherosclerotic lesions 33 Ex vivo and in vitro studies have shown that the recombinant human SAA1 hybrid protein has strong chemotactic activity for neutrophils and macrophages 34 This effect is believed to be mediated through FPR2 a G protein coupled chemoattractant receptor 35 The same receptor also mediates the cytokine like activity of the recombinant SAA1 resulting in an elevated expression of IL 8 in neutrophils 36 The recombinant SAA1 has been reported to induce the expression of a variety of inflammatory cytokines including IL 1b TNF a IL 6 IL 12p40 37 38 as well as immunoregulatory cytokines such as IL 23 39 IL 33 40 and growth stimulatory cytokines such as G CSF 41 SAA1 may also be produced by macrophages and epithelial cells in various tissues It has been shown to promote local Th17 response in the gut 42 This finding which is based on both Saa1 Saa2 knockout mice and ex vivo studies of T cells strongly suggest a local immunomodulatory function of SAA1 as opposed to its established role as an acute phase protein produced in the liver and present in the plasma as an apolipoprotein of HDL Transgenic expression of human SAA1 1 in mouse liver aggravates T cell mediated hepatitis through elevated production of chemokines 43 which involves the SAA1 receptor TLR2 Secretion of SAA1 by melanoma cells may induce anti inflammatory IL 10 secreting neutrophils that interact with invariant natural killer T cells iNKT cells 44 In addition SAA1 can skew macrophages to a M2 phenotype 45 Published reports link SAA1 to a number of malignancies but a causal relationship has not been established SAA1 has been associated with tumor pathogenesis 46 and its gene polymorphism is a contributing factor to certain types of malignant tumors 47 SAA1 has also been shown to affect the tumor microenvironment and contribute to tumor cell metastasis 48 Some of the results obtained with the recombinant human SAA1 hybrid remain controversial as the protein does not have exactly the same sequence of human SAA1 and its properties may be different from the native SAA1 49 Other studies have shown that native human SAA1 retains some of the cytokine like activities such as the G CSF induction capability 50 Recent studies using the Saa1 Saa2 knockout mice showed weakened Th17 response in gut epithelial cells 51 suggesting that SAA1 plays a role in vivo in the regulation of immunity Notes EditThe 2016 version of this article was updated by an external expert under a dual publication model The corresponding academic peer reviewed article was published in Gene and can be cited as Lei Sun Richard D Ye 2 March 2016 Serum amyloid A1 Structure function and gene polymorphism Gene Gene Wiki Review Series 583 1 48 57 doi 10 1016 J GENE 2016 02 044 ISSN 0378 1119 PMC 5683722 PMID 26945629 Wikidata Q38761950 References Edit a b c ENSG00000288411 GRCh38 Ensembl release 89 ENSG00000173432 ENSG00000288411 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000057465 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Glaser T Housman D Lewis WH Gerhard D Jones C Nov 1989 A fine structure deletion map of human 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tb01431 x PMID 3922050 S2CID 29482438 Tape C Tan R Nesheim M Kisilevsky R Sep 1988 Direct evidence for circulating apoSAA as the precursor of tissue AA amyloid deposits Scandinavian Journal of Immunology 28 3 317 24 doi 10 1111 j 1365 3083 1988 tb01455 x PMID 3194701 S2CID 35274998 Uhlar CM Burgess CJ Sharp PM Whitehead AS Jan 1994 Evolution of the serum amyloid A SAA protein superfamily Genomics 19 2 228 35 doi 10 1006 geno 1994 1052 PMID 8188253 Kluve Beckerman B Drumm ML Benson MD Nov 1991 Nonexpression of the human serum amyloid A three SAA3 gene DNA and Cell Biology 10 9 651 61 doi 10 1089 dna 1991 10 651 PMID 1755958 Lu J Yu Y Zhu I Cheng Y Sun PD Apr 2014 Structural mechanism of serum amyloid A mediated inflammatory amyloidosis Proceedings of the National Academy of Sciences of the United States of America 111 14 5189 94 doi 10 1073 pnas 1322357111 PMC 3986191 PMID 24706838 Derebe MG Zlatkov CM Gattu S Ruhn KA Vaishnava S Diehl GE MacMillan JB Williams NS Hooper LV Jul 2014 Serum amyloid A is a retinol binding protein that transports retinol during bacterial infection eLife 3 e03206 doi 10 7554 eLife 03206 PMC 4129439 PMID 25073702 Jensen LE Whitehead AS Sep 1998 Regulation of serum amyloid A protein expression during the acute phase response The Biochemical Journal 334 3 489 503 doi 10 1042 bj3340489 PMC 1219714 PMID 9729453 Lung HL Man OY Yeung MC Ko JM Cheung AK Law EW Yu Z Shuen WH Tung E Chan SH Bangarusamy DK Cheng Y Yang X Kan R Phoon Y Chan KC Chua D Kwong DL Lee AW Ji MF Lung ML Feb 2015 SAA1 polymorphisms are associated with variation in antiangiogenic and tumor suppressive activities in nasopharyngeal carcinoma Oncogene 34 7 878 89 doi 10 1038 onc 2014 12 PMID 24608426 S2CID 9519362 Recombinant human Apo SAA Su SB Gong W Gao JL Shen W Murphy PM Oppenheim JJ Wang JM Jan 1999 A seven transmembrane G protein coupled receptor FPRL1 mediates the chemotactic activity of serum amyloid A for human phagocytic cells The Journal of Experimental Medicine 189 2 395 402 doi 10 1084 jem 189 2 395 PMC 2192984 PMID 9892621 Cai L de Beer MC de Beer FC van der Westhuyzen DR Jan 2005 Serum amyloid A is a ligand for scavenger receptor class B type I and inhibits high density lipoprotein binding and selective lipid uptake The Journal of Biological Chemistry 280 4 2954 61 doi 10 1074 jbc M411555200 PMID 15561721 Baranova IN Vishnyakova TG Bocharov AV Kurlander R Chen Z Kimelman ML Remaley AT Csako G Thomas F Eggerman TL Patterson AP Mar 2005 Serum amyloid A binding to CLA 1 CD36 and LIMPII analogous 1 mediates serum amyloid A protein induced activation of ERK1 2 and p38 mitogen activated protein kinases The Journal of Biological Chemistry 280 9 8031 40 doi 10 1074 jbc M405009200 PMID 15576377 Cheng N He R Tian J Ye PP Ye RD Jul 2008 Cutting edge TLR2 is a functional receptor for acute phase serum amyloid A Journal of Immunology 181 1 22 6 doi 10 4049 jimmunol 181 1 22 PMC 2464454 PMID 18566366 Sandri S Rodriguez D Gomes E Monteiro HP Russo M Campa A May 2008 Is serum amyloid A an endogenous TLR4 agonist Journal of Leukocyte Biology 83 5 1174 80 doi 10 1189 jlb 0407203 PMID 18252871 S2CID 17352286 Niemi K Teirila L Lappalainen J Rajamaki K Baumann MH Oorni K Wolff H Kovanen PT Matikainen S Eklund KK Jun 2011 Serum amyloid A activates the NLRP3 inflammasome via P2X7 receptor and a cathepsin B sensitive pathway Journal of Immunology 186 11 6119 28 doi 10 4049 jimmunol 1002843 PMID 21508263 Hari Dass R Shah C Meyer DJ Raynes JG May 2005 Serum amyloid A protein binds to outer membrane protein A of gram negative bacteria The Journal of Biological Chemistry 280 19 18562 7 doi 10 1074 jbc M500490200 PMID 15705572 Shah C Hari Dass R Raynes JG Sep 2006 Serum amyloid A is an innate immune opsonin for Gram negative bacteria Blood 108 5 1751 7 doi 10 1182 blood 2005 11 011932 PMID 16735604 Derebe MG Zlatkov CM Gattu S Ruhn KA Vaishnava S Diehl GE MacMillan JB Williams NS Hooper LV 29 July 2014 Serum amyloid A is a retinol binding protein that transports retinol during bacterial infection eLife 3 e03206 doi 10 7554 eLife 03206 PMC 4129439 PMID 25073702 Malle E Sodin Semrl S Kovacevic A Jan 2009 Serum amyloid A an acute phase protein involved in tumour pathogenesis Cellular and Molecular Life Sciences 66 1 9 26 doi 10 1007 s00018 008 8321 x PMC 4864400 PMID 18726069 Tape C Tan R Nesheim M Kisilevsky R Sep 1988 Direct evidence for circulating apoSAA as the precursor of tissue AA amyloid deposits Scandinavian Journal of Immunology 28 3 317 24 doi 10 1111 j 1365 3083 1988 tb01455 x PMID 3194701 S2CID 35274998 Kisilevsky R Manley PN Mar 2012 Acute phase serum amyloid A perspectives on its physiological and pathological roles Amyloid 19 1 5 14 doi 10 3109 13506129 2011 654294 PMID 22320226 S2CID 43235598 King VL Thompson J Tannock LR Aug 2011 Serum amyloid A in atherosclerosis Current Opinion in Lipidology 22 4 302 7 doi 10 1097 MOL 0b013e3283488c39 PMID 21734573 S2CID 10073239 Thompson JC Jayne C Thompson J Wilson PG Yoder MH Webb N Tannock LR Feb 2015 A brief elevation of serum amyloid A is sufficient to increase atherosclerosis Journal of Lipid Research 56 2 286 93 doi 10 1194 jlr M054015 PMC 4306683 PMID 25429103 De Beer MC Wroblewski JM Noffsinger VP Rateri DL Howatt DA Balakrishnan A Ji A Shridas P Thompson JC van der Westhuyzen DR Tannock LR Daugherty A Webb NR De Beer FC Feb 2014 Deficiency of endogenous acute phase serum amyloid A does not affect atherosclerotic lesions in apolipoprotein E deficient mice Arteriosclerosis Thrombosis and Vascular Biology 34 2 255 61 doi 10 1161 ATVBAHA 113 302247 PMC 3951741 PMID 24265416 Badolato R Wang JM Murphy WJ Lloyd AR Michiel DF Bausserman LL Kelvin DJ Oppenheim JJ Jul 1994 Serum amyloid A is a chemoattractant induction of migration adhesion and tissue infiltration of monocytes and polymorphonuclear leukocytes The Journal of Experimental Medicine 180 1 203 9 doi 10 1084 jem 180 1 203 PMC 2191543 PMID 7516407 Su SB Gong W Gao JL Shen W Murphy PM Oppenheim JJ Wang JM Jan 1999 A seven transmembrane G protein coupled receptor FPRL1 mediates the chemotactic activity of serum amyloid A for human phagocytic cells The Journal of Experimental Medicine 189 2 395 402 doi 10 1084 jem 189 2 395 PMC 2192984 PMID 9892621 He R Sang H Ye RD Feb 2003 Serum amyloid A induces IL 8 secretion through a G protein coupled receptor FPRL1 LXA4R Blood 101 4 1572 81 doi 10 1182 blood 2002 05 1431 PMID 12393391 Patel H Fellowes R Coade S Woo P Oct 1998 Human serum amyloid A has cytokine like properties Scandinavian Journal of Immunology 48 4 410 8 doi 10 1046 j 1365 3083 1998 00394 x PMID 9790312 S2CID 44779960 Cheng N He R Tian J Ye PP Ye RD Jul 2008 Cutting edge TLR2 is a functional receptor for acute phase serum amyloid A Journal of Immunology 181 1 22 6 doi 10 4049 jimmunol 181 1 22 PMC 2464454 PMID 18566366 He R Shepard LW Chen J Pan ZK Ye RD Sep 2006 Serum amyloid A is an endogenous ligand that differentially induces IL 12 and IL 23 Journal of Immunology 177 6 4072 9 doi 10 4049 jimmunol 177 6 4072 PMID 16951371 Sun L Zhu Z Cheng N Yan Q Ye RD Jul 2014 Serum amyloid A induces interleukin 33 expression through an IRF7 dependent pathway European Journal of Immunology 44 7 2153 64 doi 10 1002 eji 201344310 PMC 4118754 PMID 24777946 He RL Zhou J Hanson CZ Chen J Cheng N Ye RD Jan 2009 Serum amyloid A induces G CSF expression and neutrophilia via Toll like receptor 2 Blood 113 2 429 37 doi 10 1182 blood 2008 03 139923 PMC 2615655 PMID 18952897 Sano T Huang W Hall JA Yang Y Chen A Gavzy SJ Lee JY Ziel JW Miraldi ER Domingos AI Bonneau R Littman DR Oct 2015 An IL 23R IL 22 Circuit Regulates Epithelial Serum Amyloid A to Promote Local Effector Th17 Responses Cell 163 2 381 93 doi 10 1016 j cell 2015 08 061 PMC 4621768 PMID 26411290 Ji YR Kim HJ Bae KB Lee S Kim MO Ryoo ZY May 2015 Hepatic serum amyloid A1 aggravates T cell mediated hepatitis by inducing chemokines via Toll like receptor 2 in mice The Journal of Biological Chemistry 290 20 12804 11 doi 10 1074 jbc M114 635763 PMC 4432296 PMID 25847238 De Santo C Arscott R Booth S Karydis I Jones M Asher R Salio M Middleton M Cerundolo V Nov 2010 Invariant NKT cells modulate the suppressive activity of IL 10 secreting neutrophils differentiated with serum amyloid A Nature Immunology 11 11 1039 46 doi 10 1038 ni 1942 PMC 3001335 PMID 20890286 Sun L Zhou H Zhu Z Yan Q Wang L Liang Q Ye RD May 2015 Ex vivo and in vitro effect of serum amyloid a in the induction of macrophage M2 markers and efferocytosis of apoptotic neutrophils Journal of Immunology 194 10 4891 900 doi 10 4049 jimmunol 1402164 PMC 4417396 PMID 25870242 Malle E Sodin Semrl S Kovacevic A Jan 2009 Serum amyloid A an acute phase protein involved in tumour pathogenesis Cellular and Molecular Life Sciences 66 1 9 26 doi 10 1007 s00018 008 8321 x PMC 4864400 PMID 18726069 Lung HL Man OY Yeung MC Ko JM Cheung AK Law EW Yu Z Shuen WH Tung E Chan SH Bangarusamy DK Cheng Y Yang X Kan R Phoon Y Chan KC Chua D Kwong DL Lee AW Ji MF Lung ML Feb 2015 SAA1 polymorphisms are associated with variation in antiangiogenic and tumor suppressive activities in nasopharyngeal carcinoma Oncogene 34 7 878 89 doi 10 1038 onc 2014 12 PMID 24608426 S2CID 9519362 Hansen MT Forst B Cremers N Quagliata L Ambartsumian N Grum Schwensen B Klingelhofer J Abdul Al A Herrmann P Osterland M Stein U Nielsen GH Scherer PE Lukanidin E Sleeman JP Grigorian M Jan 2015 A link between inflammation and metastasis serum amyloid A1 and A3 induce metastasis and are targets of metastasis inducing S100A4 Oncogene 34 4 424 35 doi 10 1038 onc 2013 568 PMID 24469032 S2CID 5774746 Christenson K Bjorkman L Ahlin S Olsson M Sjoholm K Karlsson A Bylund J 2013 Endogenous Acute Phase Serum Amyloid A Lacks Pro Inflammatory Activity Contrasting the Two Recombinant Variants That Activate Human Neutrophils through Different Receptors Frontiers in Immunology 4 92 doi 10 3389 fimmu 2013 00092 PMC 3631709 PMID 23626589 Kim MH de Beer MC Wroblewski JM Webb NR de Beer FC Feb 2013 SAA does not induce cytokine production in physiological conditions Cytokine 61 2 506 12 doi 10 1016 j cyto 2012 10 019 PMC 3616876 PMID 23165195 Sano T Huang W Hall JA Yang Y Chen A Gavzy SJ Lee JY Ziel JW Miraldi ER Domingos AI Bonneau R Littman DR Oct 2015 An IL 23R IL 22 Circuit Regulates Epithelial Serum Amyloid A to Promote Local Effector Th17 Responses Cell 163 2 381 93 doi 10 1016 j cell 2015 08 061 PMC 4621768 PMID 26411290 Further reading EditKisilevsky R Tam SP 2002 Acute phase serum amyloid A cholesterol metabolism and cardiovascular disease Pediatric Pathology amp Molecular Medicine 21 3 291 305 doi 10 1080 02770930290056523 PMID 12056504 Sletten K Husby G Natvig JB Mar 1976 The complete amino acid sequence of an amyloid fibril protein AA1 of unusual size 64 residues Biochemical and Biophysical Research Communications 69 1 19 25 doi 10 1016 S0006 291X 76 80266 5 PMID 1259755 Beach CM De Beer MC Sipe JD Loose LD De Beer FC Mar 1992 Human serum amyloid A protein Complete amino acid sequence of a new variant The Biochemical Journal 282 2 615 20 doi 10 1042 bj2820615 PMC 1130826 PMID 1546977 Betts JC Edbrooke MR Thakker RV Woo P Oct 1991 The human acute phase serum amyloid A gene family structure evolution and expression in hepatoma cells Scandinavian Journal of Immunology 34 4 471 82 doi 10 1111 j 1365 3083 1991 tb01570 x PMID 1656519 S2CID 26076389 Zimlichman S Danon A Nathan I Mozes G Shainkin Kestenbaum R Aug 1990 Serum amyloid A an acute phase protein inhibits platelet activation The Journal of Laboratory and Clinical Medicine 116 2 180 6 PMID 1697614 Steinkasserer A Weiss EH Schwaeble W Linke RP May 1990 Heterogeneity of human serum amyloid A protein Five different variants from one individual demonstrated by cDNA sequence analysis The Biochemical Journal 268 1 187 93 doi 10 1042 bj2680187 PMC 1131410 PMID 1971508 Sack GH Talbot CC Apr 1991 Highly polymorphic domains of the human serum amyloid A SAA gene GSAA1 Scandinavian Journal of Immunology 33 4 485 8 doi 10 1111 j 1365 3083 1991 tb01797 x PMID 2017667 S2CID 11491762 Woo P Sipe J Dinarello CA Colten HR Nov 1987 Structure of a human serum amyloid A gene and modulation of its expression in transfected L cells The Journal of Biological Chemistry 262 32 15790 5 doi 10 1016 S0021 9258 18 47798 8 PMID 2890635 Kluve Beckerman B Dwulet FE Benson MD Nov 1988 Human serum amyloid A Three hepatic mRNAs and the corresponding proteins in one person The Journal of Clinical Investigation 82 5 1670 5 doi 10 1172 JCI113779 PMC 442736 PMID 3183061 Prelli F Pras M Frangione B Dec 1987 Degradation and deposition of amyloid AA fibrils are tissue specific Biochemistry 26 25 8251 6 doi 10 1021 bi00399a035 PMID 3442653 Kluve Beckerman B Long GL Benson MD Dec 1986 DNA sequence evidence for polymorphic forms of human serum amyloid A SAA Biochemical Genetics 24 11 12 795 803 doi 10 1007 BF00554519 PMID 3800865 S2CID 8124689 Sipe JD Colten HR Goldberger G Edge MD Tack BF Cohen AS Whitehead AS Jun 1985 Human serum amyloid A SAA biosynthesis and postsynthetic processing of preSAA and structural variants defined by complementary DNA Biochemistry 24 12 2931 6 doi 10 1021 bi00333a018 PMID 3839415 Sletten K Husby G Jan 1974 The complete amino acid sequence of non immunoglobulin amyloid fibril protein AS in rheumatoid arthritis European Journal of Biochemistry 41 1 117 25 doi 10 1111 j 1432 1033 1974 tb03251 x PMID 4816450 Ein D Kimura S Terry WD Magnotta J Glenner GG Sep 1972 Amino acid sequence of an amyloid fibril protein of unknown origin The Journal of Biological Chemistry 247 17 5653 5 doi 10 1016 S0021 9258 20 81154 5 PMID 5055786 Levin M Franklin EC Frangione B Pras M Oct 1972 The amino acid sequence of a major nonimmunoglobulin component of some amyloid fibrils The Journal of Clinical Investigation 51 10 2773 6 doi 10 1172 JCI107098 PMC 332979 PMID 5056669 Moyner K Sletten K Husby G Natvig JB 1980 An unusually large 83 amino acid residues amyloid fibril protein AA from a patient with Waldenstrom s macroglobulinaemia and amyloidosis Scandinavian Journal of Immunology 11 5 549 54 doi 10 1111 j 1365 3083 1980 tb00023 x PMID 6155694 S2CID 35057732 Parmelee DC Titani K Ericsson LH Eriksen N Benditt EP Walsh KA Jul 1982 Amino acid sequence of amyloid related apoprotein apoSAA1 from human high density lipoprotein Biochemistry 21 14 3298 303 doi 10 1021 bi00257a008 PMID 7115671 Badolato R Wang JM Murphy WJ Lloyd AR Michiel DF Bausserman LL Kelvin DJ Oppenheim JJ Jul 1994 Serum amyloid A is a chemoattractant induction of migration adhesion and tissue infiltration of monocytes and polymorphonuclear leukocytes The Journal of Experimental Medicine 180 1 203 9 doi 10 1084 jem 180 1 203 PMC 2191543 PMID 7516407 Badolato R Johnston JA Wang JM McVicar D Xu LL Oppenheim JJ Kelvin DJ Oct 1995 Serum amyloid A induces calcium mobilization and chemotaxis of human monocytes by activating a pertussis toxin sensitive signaling pathway Journal of Immunology 155 8 4004 10 PMID 7561109 External links EditOverview of all the structural information available in the PDB for UniProt P0DJI8 Serum amyloid A 1 protein at the PDBe KB Retrieved from https en wikipedia org w index php title Serum amyloid A1 amp oldid 1053700748, wikipedia, wiki, book,

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