P0DJI8 (SAA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serum amyloid A-1 protein
Short name=SAA

Cleaved into the following 6 chains:

1. Amyloid protein A
   Alternative name(s):
   Amyloid fibril protein AA
2. Serum amyloid protein A(2-104)
3. Serum amyloid protein A(3-104)
4. Serum amyloid protein A(2-103)
5. Serum amyloid protein A(2-102)
6. Serum amyloid protein A(4-101)

Gene names

Name:

SAA1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	122 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Major acute phase reactant. Apolipoprotein of the HDL complex.
Subcellular location	Secreted.
Tissue specificity	Expressed by the liver; secreted in plasma. Ref.18
Induction	Upon cytokine stimulation.
Post-translational modification	This protein is the precursor of amyloid protein A, which is formed by the removal of approximately 24 residues from the C-terminal end.
Polymorphism	At least 5 different SAA1 alleles have been described: SAA1.1 (SAA1alpha), SAA1.2 (SAA1beta), SAA1.3 (SAA1gamma), SAA1.4 (SAA1delta), SAA1.5 (also named SAA1beta but which differs from SAA1.2). We use here the revised nomenclature described in Ref.21. The sequence shown is that of SAA1.1.
Involvement in disease	Reactive, secondary amyloidosis is characterized by the extracellular accumulation in various tissues of the SAA1 protein. These deposits are highly insoluble and resistant to proteolysis; they disrupt tissue structure and compromise function. Ref.14 Elevated serum SAA1 protein levels may be associated with lung cancer. Ref.14
Sequence similarities	Belongs to the SAA family.
Mass spectrometry	Molecular mass is 11702±14 Da from positions 19 - 122. Determined by MALDI. Ref.18 Molecular mass is 11682.7 Da from positions 19 - 122. Determined by MALDI. Ref.22 Molecular mass is 11526.5 Da from positions 20 - 122. Determined by MALDI. Ref.22 Molecular mass is 11439.6 Da from positions 21 - 122. Determined by MALDI. Ref.22 Molecular mass is 11363.6 Da from positions 20 - 121. Determined by MALDI. Ref.22 Molecular mass is 11235.6 Da from positions 20 - 120. Determined by MALDI. Ref.22 Molecular mass is 10872.6 Da from positions 22 - 119. Determined by MALDI. Ref.22 Molecular mass is 8337.5±0.8 Da from positions 19 - 94. Determined by ESI. With variants Ala-70, Val-75, Asn-78 and 86-Leu-Thr-87. Ref.14 Molecular mass is 8390.9±0.2 Da from positions 19 - 94. Determined by ESI. With variant Ala-70. Ref.14

Ontologies

Keywords
Biological process	Acute phase
Cellular component	Amyloid HDL Secreted
Coding sequence diversity	Polymorphism
Disease	Amyloidosis
Domain	Signal
PTM	Methylation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	acute-phase response Non-traceable author statement PubMed 9815279. Source: UniProtKB elevation of cytosolic calcium ion concentration Inferred from direct assay PubMed 9892621. Source: UniProtKB lymphocyte chemotaxis Inferred from direct assay PubMed 7636186. Source: UniProtKB macrophage chemotaxis Inferred from direct assay PubMed 7561109. Source: UniProtKB negative regulation of inflammatory response Non-traceable author statement PubMed 9823935. Source: UniProtKB neutrophil chemotaxis Non-traceable author statement PubMed 12557751. Source: UniProtKB platelet activation Non-traceable author statement PubMed 1697614. Source: UniProtKB positive regulation of cell adhesion Inferred from direct assay PubMed 11830469PubMed 9252455. Source: UniProtKB positive regulation of interleukin-1 secretion Non-traceable author statement PubMed 12857601. Source: UniProtKB
Cellular_component	extracellular region Non-traceable author statement PubMed 14718574PubMed 7516407. Source: UniProtKB high-density lipoprotein particle Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	G-protein coupled receptor binding Inferred from direct assay PubMed 9892621. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16
	Chain	19 – 122	104	Serum amyloid A-1 protein		PRO_0000031575
	Chain	19 – 94	76	Amyloid protein A		PRO_0000031576
	Chain	20 – 122	103	Serum amyloid protein A(2-104)		PRO_0000031577
	Chain	20 – 121	102	Serum amyloid protein A(2-103)		PRO_0000031578
	Chain	20 – 120	101	Serum amyloid protein A(2-102)		PRO_0000031579
	Chain	21 – 122	102	Serum amyloid protein A(3-104)		PRO_0000031580
	Chain	22 – 119	98	Serum amyloid protein A(4-101)		PRO_0000031581
	Propeptide	95 – 122	28	Often cleaved during amyloidogenesis		PRO_0000031582
Amino acid modifications
	Modified residue	101	1	N4,N4-dimethylasparagine Probable
Natural variations
	Natural variant	15	1	G → S. Corresponds to variant rs712021 [ dbSNP | Ensembl ].		VAR_006925
	Natural variant	70	1	V → A in allele SAA1.2, SAA1.3, SAA1.4 and SAA1.5. Ref.14		VAR_006926
	Natural variant	75	1	A → V in allele SAA1.2, SAA1.4 and SAA1.5. Ref.7 Ref.14		VAR_006927
	Natural variant	78	1	D → N in allele SAA1.4. Ref.7 Ref.14		VAR_006928
	Natural variant	86	1	F → L. Corresponds to variant rs1059559 [ dbSNP | Ensembl ].		VAR_057167
	Natural variant	90	1	G → D in allele SAA1.2.		VAR_006931
Experimental info
	Sequence conflict	71	1	W → R AA sequence Ref.10
	Sequence conflict	71	1	W → R AA sequence Ref.11
	Sequence conflict	77	1	S → T in AC107948. Ref.5
	Sequence conflict	96 – 101	6	ADQAAN → SEATVK AA sequence Ref.9
	Sequence conflict	101	1	N → D in AAH07022. Ref.6
	Sequence conflict	119	1	P → S in AAA60297. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P0DJI8 [UniParc]. Last modified July 11, 2012. Version 1. Checksum: 43A57D56B37CB173	FASTA	122	13,532
	10 20 30 40 50 60 MKLLTGLVFC SLVLGVSSRS FFSFLGEAFD GARDMWRAYS DMREANYIGS DKYFHARGNY 70 80 90 100 110 120 DAAKRGPGGV WAAEAISDAR ENIQRFFGHG AEDSLADQAA NEWGRSGKDP NHFRPAGLPE KY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human serum amyloid A (SAA): biosynthesis and postsynthetic processing of preSAA and structural variants defined by complementary DNA." Sipe J.D., Colten H.R., Goldberger G., Edge M.D., Tack B.F., Cohen A.S., Whitehead A.S. Biochemistry 24:2931-2936(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE SAA1.1).
[2]	"Human serum amyloid A. Three hepatic mRNAs and the corresponding proteins in one person." Kluve-Beckerman B., Dwulet F.E., Benson M.D. J. Clin. Invest. 82:1670-1675(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE SAA1.1). Tissue: Liver.
[3]	"The human acute-phase serum amyloid A gene family: structure, evolution and expression in hepatoma cells." Betts J., Edbrooke M., Thakker R., Woo P. Scand. J. Immunol. 34:471-482(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE SAA1.5). Tissue: Liver.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELE SAA1.5).
[5]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ALLELE SAA1.5).
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELE SAA1.1). Tissue: Liver.
[7]	"Heterogeneity of human serum amyloid A protein. Five different variants from one individual demonstrated by cDNA sequence analysis." Steinkasserer A., Weiss E.H., Schwaeble W., Linke R.P. Biochem. J. 268:187-193(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 73-122, VARIANTS VAL-75 AND ASN-78. Tissue: Liver.
[8]	"Amino acid sequence of amyloid-related apoprotein (apoSAA1) from human high-density lipoprotein." Parmelee D.C., Titani K., Ericsson L.H., Eriksen N., Benditt E.P., Walsh K.A. Biochemistry 21:3298-3303(1982) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-122.
[9]	"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. 282:615-620(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-122 (ALLELE SAA1.2).
[10]	"An unusually large (83 amino acid residues) amyloid fibril protein AA from a patient with Waldenstrom's macroglobulinaemia and amyloidosis." Moyner K., Sletten K., Husby G., Natvig J.B. Scand. J. Immunol. 11:549-554(1980) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-101.
[11]	"Amino acid sequence of an amyloid fibril protein of unknown origin." Ein D., Kimura S., Terry W.D., Magnotta J., Glenner G.G. J. Biol. Chem. 247:5653-5655(1972) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-94.
[12]	"The amino acid sequence of a major nonimmunoglobulin component of some amyloid fibrils." Levin M., Franklin E.C., Frangione B., Pras M. J. Clin. Invest. 51:2773-2776(1972) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-94 (FAMILIAL MEDITERRANEAN FEVER PATIENT).
[13]	"The complete amino-acid sequence of non-immunoglobulin amyloid fibril protein AS in rheumatoid arthritis." Sletten K., Husby G. Eur. J. Biochem. 41:117-125(1974) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-94.
[14]	"Identification of two novel amyloid A protein subsets coexisting in an individual patient of AA-amyloidosis." Baba S., Takahashi T., Kasama T., Shirasawa H. Biochim. Biophys. Acta 1180:195-200(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-94, MASS SPECTROMETRY, DISEASE, VARIANTS ALA-70; VAL-75 AND ASN-78, ALLELE SAA1.3. Tissue: Thyroid.
[15]	"The complete amino acid sequence of an amyloid fibril protein AA1 of unusual size (64 residues)." Sletten K., Husby G., Natvig J.B. Biochem. Biophys. Res. Commun. 69:19-25(1976) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-82.
[16]	"The major proteins of human and monkey amyloid substance: common properties including unusual N-terminal amino acid sequences." Benditt E.P., Eriksen N., Hermodson M.A., Ericsson L.H. FEBS Lett. 19:169-173(1971) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-42.
[17]	"Degradation and deposition of amyloid AA fibrils are tissue specific." Prelli F., Pras M., Frangione B. Biochemistry 26:8251-8256(1987) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-100.
[18]	"Identification and validation of a potential lung cancer serum biomarker detected by matrix-assisted laser desorption/ionization-time of flight spectra analysis." Howard B.A., Wang M.Z., Campa M.J., Corro C., Fitzgerald M.C., Patz E.F. Jr. Proteomics 3:1720-1724(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-33; 44-57; 64-80 AND 86-122, TISSUE SPECIFICITY, MASS SPECTROMETRY.
[19]	"Characterization of human serum amyloid A protein isoforms separated by two-dimensional electrophoresis by liquid chromatography/electrospray ionization tandem mass spectrometry." Ducret A., Bruun C.F., Bures E.J., Marhaug G., Husby G., Aebersold R. Electrophoresis 17:866-876(1996) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE (VARIOUS FORMS), METHYLATION AT ASN-101.
[20]	"A protein AA-variant derived from a novel serum AA protein, SAA1 delta, in an individual from Papua New Guinea." Westermark P., Sletten K., Westermark G.T., Raynes J., McAdam K.P. Biochem. Biophys. Res. Commun. 223:320-323(1996) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION OF ALLELE SAA1.4.
[21]	"Revised nomenclature for serum amyloid A (SAA). Nomenclature Committee of the International Society of Amyloidosis. Part 2." Sipe J. Amyloid 6:67-70(1999) [PubMed] [Europe PMC] [Abstract] Cited for: POLYMORPHISM, NOMENCLATURE OF ALLELES.
[22]	"Detection of novel truncated forms of human serum amyloid A protein in human plasma." Kiernan U.A., Tubbs K.A., Nedelkov D., Niederkofler E.E., Nelson R.W. FEBS Lett. 537:166-170(2003) [PubMed] [Europe PMC] [Abstract] Cited for: MASS SPECTROMETRY.
[23]	"A novel polymorphism of human serum amyloid A protein, SAA1 gamma, is characterized by alanines at both residues 52 and 57." Baba S., Takahashi T., Kasama T., Fujie M., Shirasawa H. Arch. Biochem. Biophys. 303:361-366(1993) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION OF ALLELE SAA1.3.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M10906 mRNA. Translation: AAA60297.1. M23698 mRNA. Translation: AAA64799.1. X56652 Genomic DNA. Translation: CAA39974.1. CR542241 mRNA. Translation: CAG47037.1. AC107948 Genomic DNA. No translation available. BC007022 mRNA. Translation: AAH07022.1. BC105796 mRNA. Translation: AAI05797.1. X51439 mRNA. Translation: CAA35804.1. X51441 mRNA. Translation: CAA35806.1. X51442 mRNA. Translation: CAA35807.1.
IPI	IPI00552578.
PIR	YLHUS. A22342. I39456.
RefSeq	NP_000322.2. NM_000331.4. NP_001171477.1. NM_001178006.1. NP_954630.1. NM_199161.3.
UniGene	Hs.632144. Hs.731376. Hs.734161.
3D structure databases
ProteinModelPortal	P0DJI8.
ModBase	Search...
Polymorphism databases
DMDM	134167.
2D gel databases
UCD-2DPAGE	P02735.
Proteomic databases
PeptideAtlas	P02735.
PRIDE	P0DJI8.
Protocols and materials databases
DNASU	6288.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000356524; ENSP00000348918; ENSG00000173432. ENST00000405158; ENSP00000384906; ENSG00000173432.
GeneID	6288.
KEGG	hsa:6288.
Organism-specific databases
CTD	6288.
GeneCards	GC11P018287.
H-InvDB	HIX0009484.
HGNC	HGNC:10513. SAA1.
MIM	104750. gene.
neXtProt	NX_P0DJI8.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG26520.
HOVERGEN	HBG016327.
InParanoid	P02735.
OrthoDB	EOG4BP1D6.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction. REACT_116125. Disease. REACT_6900. Immune System.
Gene expression databases
ArrayExpress	P0DJI8.
Bgee	P0DJI8.
CleanEx	HS_SAA1.
Genevestigator	P02735.
GermOnline	ENSG00000173432. Homo sapiens.
Family and domain databases
InterPro	IPR000096. Serum_amyloid_A. [Graphical view]
PANTHER	PTHR23424. PTHR23424. 1 hit.
Pfam	PF00277. SAA. 1 hit. [Graphical view]
PIRSF	PIRSF002472. Serum_amyloid_A. 1 hit.
PRINTS	PR00306. SERUMAMYLOID.
SMART	SM00197. SAA. 1 hit. [Graphical view]
PROSITE	PS00992. SAA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	SAA1. human.
DrugBank	DB00062. Human Serum Albumin. DB00064. Serum albumin iodonated.
GenomeRNAi	6288.
NextBio	24415.
PMAP-CutDB	Q6FG67.
SOURCE	Search...

Entry information

Entry name

SAA1_HUMAN

Accession

Primary (citable) accession number: P0DJI8
Secondary accession number(s): P02735 , P02736, P02737, Q16730, Q16834, Q16835, Q16879, Q3KRB3, Q6FG67, Q96QN0, Q9UCK9, Q9UCL0

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 11, 2012
Last sequence update:	July 11, 2012
Last modified:	April 3, 2013
This is version 9 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.