Serum amyloid A

Human Serum amyloid A1
Identifiers
Symbol	SAA1
Entrez	6288
HUGO	10513
OMIM	104750
RefSeq	NM_199161
UniProt	P0DJI8
Other data
Locus	Chr. 11 p15.1

Human Serum amyloid A2
Identifiers
Symbol	SAA2
Entrez	6289
HUGO	10514
OMIM	104751
RefSeq	NM_030754
UniProt	P02735
Other data
Locus	Chr. 11 p15.1-p14

Human Serum amyloid A3, pseudogene
Identifiers
Symbol	SAA3P
Alt. symbols	SAA3
Entrez	6290
HUGO	10515
UniProt	P22614
Other data
Locus	Chr. 11 p15.1-p14

Human Serum amyloid A4
Identifiers
Symbol	SAA4
Alt. symbols	C-SAA
Entrez	6291
HUGO	10516
OMIM	104752
RefSeq	NM_006512
UniProt	P35542
Other data
Locus	Chr. 11 p15.1-p14

Serum amyloid A (SAA) proteins are a family of apolipoproteins associated with high-density lipoprotein (HDL) in plasma. Different isoforms of SAA are expressed constitutively (constitutive SAAs) at different levels or in response to inflammatory stimuli (acute phase SAAs). These proteins are produced predominantly by the liver. The conservation of these proteins throughout invertebrates and vertebrates suggests that SAAs play a highly essential role in all animals.

Acute-phase serum amyloid A proteins

Acute-phase serum amyloid A proteins (A-SAAs) are secreted during the acute phase of inflammation. These proteins have several roles, including the transport of cholesterol to the liver for secretion into the bile, the recruitment of immune cells to inflammatory sites, and the induction of enzymes that degrade extracellular matrix. A-SAAs are implicated in several chronic inflammatory diseases, such as amyloidosis, atherosclerosis, and rheumatoid arthritis. Three acute-phase SAA isoforms have been reported in mice, called SAA1, SAA2, and SAA3. During inflammation, SAA1 and SAA2 are expressed and induced principally in the liver, whereas SAA3 is induced in many distinct tissues. SAA1 and SAA2 genes are regulated in liver cells by the proinflammatory cytokines IL-1, IL-6, and TNF-α. Both SAA1 and SAA2 are induced up to a 1000-fold in mice under acute inflammatory conditions following exposure to bacterial lipopolysaccharide (LPS). Three A-SAA genes have also been identified in humans, although the third gene, SAA3, is believed to represent a pseudogene that does not generate messenger RNA or protein. Molecular weights of the human proteins are estimated at 11.7 kDa for SAA1 and 12.8 kDa for SAA4.

Serum amyloid A (SAA) is also an acute phase marker that responds rapidly. Similar to CRP, levels of acute-phase SAA increase within hours after inflammatory stimulus, and the magnitude of increase may be greater than that of CRP. Relatively trivial inflammatory stimuli can lead to SAA responses. It has been suggested that SAA levels correlate better with disease activity in early inflammatory joint disease than do ESR and CRP. Although largely produced by hepatocytes, more recent studies show that SAA is produced by adipocytes as well, and its serum concentration is associated with body mass index.

Constitutive serum amyloid A proteins

A fourth SAA (SAA4) was identified in humans and is expressed constitutively in the liver and, thus, is defined as a constitutive SAA (C-SAA). A similar protein that is now also called SAA4 has since been identified in the mouse; it had originally been designated SAA5.