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Gene Review

SAA1  -  serum amyloid A1

Homo sapiens

Synonyms: PIG4, SAA, SAA2, Serum amyloid A-1 protein, TP53I4
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Disease relevance of SAA1


Psychiatry related information on SAA1


High impact information on SAA1


Chemical compound and disease context of SAA1


Biological context of SAA1


Anatomical context of SAA1


Associations of SAA1 with chemical compounds

  • The application of the synthetic glucocorticoid dexamethasone in the context of cytokine stimulation enhanced the transcriptional activity of the SAA1, but not the SAA2, promoter such that readout from the former became equivalent to that from the latter [27].
  • Mink SAA1 has alanine in position 10, isoleucine in positions 24, 67, and 71, lysine in position 27, and proline in position 105 [28].
  • To study the cis- and trans-activating promoter element involved in the SAA1 gene expression by HASMCs and HepG2 cells, we constructed plasmid vectors for luciferase reporter gene assay with varying lengths of SAA1 upstream regulatory region (up to 1431 bp), and examined their response to proinflammatory cytokines and/or steroid hormones [29].
  • Two of these, SAA1 and SAA4, have the same 20 NH2-terminal residues despite striking differences in electrophoretic mobility and solution properties [30].
  • In addition, SAA protects RA FLS against the apoptotic death induced by serum starvation, anti-Fas IgM, and sodium nitroprusside [31].

Physical interactions of SAA1


Regulatory relationships of SAA1


Other interactions of SAA1

  • Disease severity was mainly influenced by MEFV mutations and was not associated with genotypes at the SAA1 locus [39].
  • CONCLUSION: The up-regulation of the A-SAA and FPRL1 genes in inflamed synovial tissue suggests an important role in the pathophysiology of inflammatory arthritis [35].
  • OBJECTIVE: To evaluate the regulation of acute-phase serum amyloid A (A-SAA) production in inflamed synovial tissue, and to elucidate a possible pathophysiologic role in the induction of matrix metalloproteinase (MMP) release by fibroblast-like synoviocytes (FLS) [35].
  • Immunohistochemical analysis demonstrated the expression of A-SAA protein production by several synovial cell populations, and immunofluorescence analysis confirmed A-SAA colocalization with the macrophage marker CD68 [35].
  • The frequencies of the gamma/gamma genotype and gamma alleles at the SAA1 locus were significantly higher in the amyloidosis population than in the early RA population (34.9% versus 7.8%, and 58.1% versus 33.8%, chi2 test P=0.0001) [40].

Analytical, diagnostic and therapeutic context of SAA1


  1. Identification of MEFV-independent modifying genetic factors for familial Mediterranean fever. Cazeneuve, C., Ajrapetyan, H., Papin, S., Roudot-Thoraval, F., Geneviève, D., Mndjoyan, E., Papazian, M., Sarkisian, A., Babloyan, A., Boissier, B., Duquesnoy, P., Kouyoumdjian, J.C., Girodon-Boulandet, E., Grateau, G., Sarkisian, T., Amselem, S. Am. J. Hum. Genet. (2000) [Pubmed]
  2. Structure of a human serum amyloid A gene and modulation of its expression in transfected L cells. Woo, P., Sipe, J., Dinarello, C.A., Colten, H.R. J. Biol. Chem. (1987) [Pubmed]
  3. Tissue-specific regulation of the human acute-phase serum amyloid A genes, SAA1 and SAA2, by glucocorticoids in hepatic and epithelial cells. Thorn, C.F., Lu, Z.Y., Whitehead, A.S. Eur. J. Immunol. (2003) [Pubmed]
  4. Expression of serum amyloid A, in normal, dysplastic, and neoplastic human colonic mucosa: implication for a role in colonic tumorigenesis. Gutfeld, O., Prus, D., Ackerman, Z., Dishon, S., Linke, R.P., Levin, M., Urieli-Shoval, S. J. Histochem. Cytochem. (2006) [Pubmed]
  5. Isolation and sequence analysis of amyloid protein AA from a patient with cystic fibrosis. Skinner, M., Pinnette, A., Travis, W.D., Shwachman, H., Cohen, A.S. J. Lab. Clin. Med. (1988) [Pubmed]
  6. Fish consumption among healthy adults is associated with decreased levels of inflammatory markers related to cardiovascular disease: the ATTICA study. Zampelas, A., Panagiotakos, D.B., Pitsavos, C., Das, U.N., Chrysohoou, C., Skoumas, Y., Stefanadis, C. J. Am. Coll. Cardiol. (2005) [Pubmed]
  7. The inflammatory markers C-reactive protein and serum amyloid A in refugees with and without posttraumatic stress disorder. Söndergaard, H.P., Hansson, L.O., Theorell, T. Clin. Chim. Acta (2004) [Pubmed]
  8. The associations between physical activity, inflammation, and coagulation markers, in people with metabolic syndrome: the ATTICA study. Pitsavos, C., Panagiotakos, D.B., Chrysohoou, C., Kavouras, S., Stefanadis, C. European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology. (2005) [Pubmed]
  9. Serum amyloid A protein, albumin and prealbumin in Alzheimer's disease and in demented patients with Down's syndrome. Elovaara, I., Maury, C.P., Palo, J. Acta neurologica Scandinavica. (1986) [Pubmed]
  10. C-reactive protein and serum amyloid A protein in unstable angina. Oltrona, L., Merlini, P.A., Pezzano, A. N. Engl. J. Med. (1995) [Pubmed]
  11. The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. Liuzzo, G., Biasucci, L.M., Gallimore, J.R., Grillo, R.L., Rebuzzi, A.G., Pepys, M.B., Maseri, A. N. Engl. J. Med. (1994) [Pubmed]
  12. Autocrine induction of collagenase by serum amyloid A-like and beta 2-microglobulin-like proteins. Brinckerhoff, C.E., Mitchell, T.I., Karmilowicz, M.J., Kluve-Beckerman, B., Benson, M.D. Science (1989) [Pubmed]
  13. Serum amyloid A is a chemoattractant: induction of migration, adhesion, and tissue infiltration of monocytes and polymorphonuclear leukocytes. Badolato, R., Wang, J.M., Murphy, W.J., Lloyd, A.R., Michiel, D.F., Bausserman, L.L., Kelvin, D.J., Oppenheim, J.J. J. Exp. Med. (1994) [Pubmed]
  14. Heterogeneity of human serum amyloid A proteins. Bausserman, L.L., Herbert, P.N., McAdam, K.P. J. Exp. Med. (1980) [Pubmed]
  15. Serum amyloid A predicts early mortality in acute coronary syndromes: A TIMI 11A substudy. Morrow, D.A., Rifai, N., Antman, E.M., Weiner, D.L., McCabe, C.H., Cannon, C.P., Braunwald, E. J. Am. Coll. Cardiol. (2000) [Pubmed]
  16. Elevated levels of C-reactive protein at discharge in patients with unstable angina predict recurrent instability. Biasucci, L.M., Liuzzo, G., Grillo, R.L., Caligiuri, G., Rebuzzi, A.G., Buffon, A., Summaria, F., Ginnetti, F., Fadda, G., Maseri, A. Circulation (1999) [Pubmed]
  17. Suppression of bone resorption by madindoline A, a novel nonpeptide antagonist to gp130. Hayashi, M., Rho, M.C., Enomoto, A., Fukami, A., Kim, Y.P., Kikuchi, Y., Sunazuka, T., Hirose, T., Komiyama, K., Omura, S. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  18. Amyloidosis and the serum amyloid A protein response to muramyl dipeptide analogs and different mycobacterial species. McAdam, K.P., Foss, N.T., Garcia, C., DeLellis, R., Chedid, L., Rees, R.J., Wolff, S.M. Infect. Immun. (1983) [Pubmed]
  19. Serum amyloid A and high density lipoproteins during the acute phase response. Bausserman, L.L., Bernier, D.N., McAdam, K.P., Herbert, P.N. Eur. J. Clin. Invest. (1988) [Pubmed]
  20. Complete primary structures of two major murine serum amyloid A proteins deduced from cDNA sequences. Yamamoto, K., Migita, S. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  21. A novel allelic variant of serum amyloid A, SAA1 gamma: genomic evidence, evolution, frequency, and implication as a risk factor for reactive systemic AA-amyloidosis. Baba, S., Masago, S.A., Takahashi, T., Kasama, T., Sugimura, H., Tsugane, S., Tsutsui, Y., Shirasawa, H. Hum. Mol. Genet. (1995) [Pubmed]
  22. Expression of rat serum amyloid A1 gene involves both C/EBP-like and NF kappa B-like transcription factors. Li, X.X., Liao, W.S. J. Biol. Chem. (1991) [Pubmed]
  23. A novel single-nucleotide polymorphism at the 5'-flanking region of SAA1 associated with risk of type AA amyloidosis secondary to rheumatoid arthritis. Moriguchi, M., Terai, C., Kaneko, H., Koseki, Y., Kajiyama, H., Uesato, M., Inada, S., Kamatani, N. Arthritis Rheum. (2001) [Pubmed]
  24. Cooperative effects of C/EBP-like and NF kappa B-like binding sites on rat serum amyloid A1 gene expression in liver cells. Li, X., Liao, W.S. Nucleic Acids Res. (1992) [Pubmed]
  25. An upstream repressor element that contributes to hepatocyte-specific expression of the rat serum amyloid A1 gene. Li, L., Liao, W.S. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  26. Induction of serum amyloid A inflammatory response genes in irradiated bone marrow cells. Goltry, K.L., Epperly, M.W., Greenberger, J.S. Radiat. Res. (1998) [Pubmed]
  27. Differential glucocorticoid enhancement of the cytokine-driven transcriptional activation of the human acute phase serum amyloid A genes, SAA1 and SAA2. Thorn, C.F., Whitehead, A.S. J. Immunol. (2002) [Pubmed]
  28. Mink serum amyloid A protein. Expression and primary structure based on cDNA sequences. Marhaug, G., Husby, G., Dowton, S.B. J. Biol. Chem. (1990) [Pubmed]
  29. Transcriptional regulation of serum amyloid A1 gene expression in human aortic smooth muscle cells involves CCAAT/enhancer binding proteins (C/EBP) and is distinct from HepG2 cells. Kumon, Y., Suehiro, T., Faulkes, D.J., Hosakawa, T., Ikeda, Y., Woo, P., Sipe, J.D., Hashimoto, K. Scand. J. Immunol. (2002) [Pubmed]
  30. NH2-terminal analysis of four of the polymorphic forms of human serum amyloid A proteins. Bausserman, L.L., Saritelli, A.L., Herbert, P.N., McAdam, K.P., Shulman, R.S. Biochim. Biophys. Acta (1982) [Pubmed]
  31. Serum amyloid a binding to formyl Peptide receptor-like 1 induces synovial hyperplasia and angiogenesis. Lee, M.S., Yoo, S.A., Cho, C.S., Suh, P.G., Kim, W.U., Ryu, S.H. J. Immunol. (2006) [Pubmed]
  32. Serum amyloid A binds specific extracellular matrix glycoproteins and induces the adhesion of resting CD4+ T cells. Preciado-Patt, L., Hershkoviz, R., Fridkin, M., Lider, O. J. Immunol. (1996) [Pubmed]
  33. Expression of recombinant human serum amyloid A in mammalian cells and demonstration of the region necessary for high-density lipoprotein binding and amyloid fibril formation by site-directed mutagenesis. Patel, H., Bramall, J., Waters, H., De Beer, M.C., Woo, P. Biochem. J. (1996) [Pubmed]
  34. Serum amyloid A (apoSAA) expression is up-regulated in rheumatoid arthritis and induces transcription of matrix metalloproteinases. Vallon, R., Freuler, F., Desta-Tsedu, N., Robeva, A., Dawson, J., Wenner, P., Engelhardt, P., Boes, L., Schnyder, J., Tschopp, C., Urfer, R., Baumann, G. J. Immunol. (2001) [Pubmed]
  35. Local expression of the serum amyloid A and formyl peptide receptor-like 1 genes in synovial tissue is associated with matrix metalloproteinase production in patients with inflammatory arthritis. O'Hara, R., Murphy, E.P., Whitehead, A.S., FitzGerald, O., Bresnihan, B. Arthritis Rheum. (2004) [Pubmed]
  36. Regulation of the human acute phase serum amyloid A genes by tumour necrosis factor-alpha, interleukin-6 and glucocorticoids in hepatic and epithelial cell lines. Thorn, C.F., Lu, Z.Y., Whitehead, A.S. Scand. J. Immunol. (2004) [Pubmed]
  37. mRNA expression and release of interleukin-8 induced by serum amyloid A in neutrophils and monocytes. Ribeiro, F.P., Furlaneto, C.J., Hatanaka, E., Ribeiro, W.B., Souza, G.M., Cassatella, M.A., Campa, A. Mediators of inflammation. (2003) [Pubmed]
  38. Cutting edge: TLR2 is a functional receptor for acute-phase serum amyloid A. Cheng, N., He, R., Tian, J., Ye, P.P., Ye, R.D. J. Immunol. (2008) [Pubmed]
  39. The contribution of genotypes at the MEFV and SAA1 loci to amyloidosis and disease severity in patients with familial Mediterranean fever. Gershoni-Baruch, R., Brik, R., Zacks, N., Shinawi, M., Lidar, M., Livneh, A. Arthritis Rheum. (2003) [Pubmed]
  40. Influence of genotypes at SAA1 and SAA2 loci on the development and the length of latent period of secondary AA-amyloidosis in patients with rheumatoid arthritis. Moriguchi, M., Terai, C., Koseki, Y., Uesato, M., Nakajima, A., Inada, S., Nishinarita, M., Uchida, S., Nakajima, A., Kim, S.Y., Chen, C.L., Kamatani, N. Hum. Genet. (1999) [Pubmed]
  41. Human serum amyloid A protein. Complete amino acid sequence of a new variant. Beach, C.M., De Beer, M.C., Sipe, J.D., Loose, L.D., De Beer, F.C. Biochem. J. (1992) [Pubmed]
  42. The human serum amyloid A protein (SAA) superfamily gene cluster: mapping to chromosome 11p15.1 by physical and genetic linkage analysis. Sellar, G.C., Jordan, S.A., Bickmore, W.A., Fantes, J.A., van Heyningen, V., Whitehead, A.S. Genomics (1994) [Pubmed]
  43. Acute-phase protein synthesis in human hepatoma cells: differential regulation of serum amyloid A (SAA) and haptoglobin by interleukin-1 and interleukin-6. Raynes, J.G., Eagling, S., McAdam, K.P. Clin. Exp. Immunol. (1991) [Pubmed]
  44. Influence of Serum Amyloid A (SAA1) and SAA2 gene polymorphisms on renal amyloidosis, and on SAA/C-reactive protein values in patients with familial mediterranean fever in the Turkish population. Bakkaloglu, A., Duzova, A., Ozen, S., Balci, B., Besbas, N., Topaloglu, R., Ozaltin, F., Yilmaz, E. J. Rheumatol. (2004) [Pubmed]
  45. Measurement of serum amyloid A1 (SAA1), a major isotype of acute phase SAA. Xu, Y., Yamada, T., Satoh, T., Okuda, Y. Clin. Chem. Lab. Med. (2006) [Pubmed]
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