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P0DJI8 (SAA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 22. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serum amyloid A-1 protein

Short name=SAA
Gene names
Name:SAA1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length122 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Major acute phase protein.

Subunit structure

Homohexamer; dimer of trimers. Can form amyloid fibrils after partial proteolysis; the native, undenatured protein does not form amyloid fibrils (in vitro). Apolipoprotein of the HDL complex. Binds to heparin. Ref.8 Ref.24

Subcellular location

Secreted Ref.8.

Tissue specificity

Expressed by the liver; secreted in plasma (at protein level). Ref.8 Ref.13 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 processAcute phase
   Cellular componentAmyloid
HDL
Secreted
   Coding sequence diversityPolymorphism
   DiseaseAmyloidosis
   DomainSignal
   LigandHeparin-binding
   PTMMethylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processacute-phase response

Non-traceable author statement PubMed 9815279. Source: UniProtKB

innate immune response

Traceable author statement. Source: Reactome

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 cytokine secretion

Inferred from direct assay PubMed 12857601. Source: UniProtKB

positive regulation of cytosolic calcium ion concentration

Inferred from direct assay PubMed 9892621. Source: UniProtKB

positive regulation of interleukin-1 secretion

Non-traceable author statement PubMed 12857601. Source: UniProtKB

regulation of protein secretion

Non-traceable author statement PubMed 9605178. Source: UniProtKB

   Cellular_componentendocytic vesicle lumen

Traceable author statement. Source: Reactome

extracellular region

Non-traceable author statement PubMed 14718574PubMed 7516407. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 19199708. Source: UniProt

high-density lipoprotein particle

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionG-protein coupled receptor binding

Inferred from direct assay PubMed 9892621. Source: UniProtKB

heparin binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16
Chain19 – 122104Serum amyloid A-1 protein
PRO_0000031575
Chain19 – 9476Amyloid protein A
PRO_0000031576
Chain20 – 122103Serum amyloid protein A(2-104)
PRO_0000031577
Chain20 – 121102Serum amyloid protein A(2-103)
PRO_0000031578
Chain20 – 120101Serum amyloid protein A(2-102)
PRO_0000031579
Chain21 – 122102Serum amyloid protein A(3-104)
PRO_0000031580
Chain22 – 11998Serum amyloid protein A(4-101)
PRO_0000031581
Propeptide95 – 12228Often cleaved during amyloidogenesis
PRO_0000031582

Regions

Region19 – 4527Important for amyloid formation; forms amyloid fibrils in vitro

Amino acid modifications

Modified residue1011N4,N4-dimethylasparagine Probable

Natural variations

Natural variant151G → S.
Corresponds to variant rs712021 [ dbSNP | Ensembl ].
VAR_006925
Natural variant701V → A in allele SAA1.2, SAA1.3, SAA1.4 and SAA1.5. Ref.14
VAR_006926
Natural variant751A → V in allele SAA1.2, SAA1.4 and SAA1.5. Ref.7 Ref.14
VAR_006927
Natural variant781D → N in allele SAA1.4. Ref.7 Ref.14
VAR_006928
Natural variant861F → L.
Corresponds to variant rs1059559 [ dbSNP | Ensembl ].
VAR_057167
Natural variant901G → D in allele SAA1.2.
VAR_006931

Experimental info

Mutagenesis191R → A: Reduces affinity for heparin and nearly abolishes association with HDL; when associated with A-80 and A-89. Ref.24
Mutagenesis331R → A: Reduces affinity for heparin; when associated with A-37 and A-65. Ref.24
Mutagenesis371R → A: Reduces affinity for heparin; when associated with A-33 and A-65. Ref.24
Mutagenesis651R → A: Reduces affinity for heparin; when associated with A-33 and A-37. Ref.24
Mutagenesis801R → A: Reduces affinity for heparin and nearly abolishes association with HDL; when associated with A-18 and A-89. Ref.24
Mutagenesis891H → A: Reduces affinity for heparin and nearly abolishes association with HDL; when associated with A-18 and A-80. Ref.24
Sequence conflict711W → R AA sequence Ref.10
Sequence conflict711W → R AA sequence Ref.11
Sequence conflict771S → T in AC107948. Ref.5
Sequence conflict96 – 1016ADQAAN → SEATVK AA sequence Ref.9
Sequence conflict1011N → D in AAH07022. Ref.6
Sequence conflict1191P → S in AAA60297. Ref.1

Secondary structure

........... 122
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P0DJI8 [UniParc].

Last modified July 11, 2012. Version 1.
Checksum: 43A57D56B37CB173

FASTA12213,532
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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, SUBCELLULAR LOCATION, SUBUNIT, TISSUE SPECIFICITY.
[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, TISSUE SPECIFICITY.
[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.
[24]"Structural mechanism of serum amyloid A-mediated inflammatory amyloidosis."
Lu J., Yu Y., Zhu I., Cheng Y., Sun P.D.
Proc. Natl. Acad. Sci. U.S.A. 111:5189-5194(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.19 ANGSTROMS) OF 19-122, SUBUNIT, MUTAGENESIS OF ARG-19; ARG-33; ARG-37; ARG-65; ARG-80 AND HIS-89.
+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.
CCDSCCDS7835.1.
PIRYLHUS. A22342.
I39456.
RefSeqNP_000322.2. NM_000331.4.
NP_001171477.1. NM_001178006.1.
NP_954630.1. NM_199161.3.
UniGeneHs.632144.
Hs.731376.
Hs.734161.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4IP8X-ray2.19A/B/C/D19-122[»]
4IP9X-ray2.50A/B19-122[»]
ProteinModelPortalP0DJI8.
SMRP0DJI8. Positions 19-122.
ModBaseSearch...
MobiDBSearch...

Chemistry

DrugBankDB00062. Human Serum Albumin.
DB00064. Serum albumin iodonated.

Polymorphism databases

DMDM395406826.

2D gel databases

UCD-2DPAGEP02735.

Proteomic databases

PeptideAtlasP02735.
PRIDEP0DJI8.

Protocols and materials databases

DNASU6288.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000356524; ENSP00000348918; ENSG00000173432.
ENST00000405158; ENSP00000384906; ENSG00000173432.
GeneID6288.
KEGGhsa:6288.

Organism-specific databases

CTD6288.
GeneCardsGC11P018287.
H-InvDBHIX0009484.
HGNCHGNC:10513. SAA1.
MIM104750. gene.
neXtProtNX_P0DJI8.
Orphanet85445. Secondary amyloidosis.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG26520.
HOVERGENHBG016327.
InParanoidP02735.
KOK17310.
OrthoDBEOG7QVM4V.
PhylomeDBP0DJI8.
TreeFamTF332544.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_160300. Binding and Uptake of Ligands by Scavenger Receptors.
REACT_6900. Immune System.

Gene expression databases

BgeeP0DJI8.
CleanExHS_SAA1.
GenevestigatorP02735.

Family and domain databases

InterProIPR000096. Serum_amyloid_A.
[Graphical view]
PfamPF00277. SAA. 1 hit.
[Graphical view]
PIRSFPIRSF002472. Serum_amyloid_A. 1 hit.
PRINTSPR00306. SERUMAMYLOID.
SMARTSM00197. SAA. 1 hit.
[Graphical view]
PROSITEPS00992. SAA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSAA1. human.
GeneWikiSerum_amyloid_A1.
GenomeRNAi6288.
NextBio24415.
PMAP-CutDBQ6FG67.
PROP0DJI8.
SOURCESearch...

Entry information

Entry nameSAA1_HUMAN
AccessionPrimary (citable) accession number: P0DJI8
Secondary accession number(s): P02735 expand/collapse secondary AC list , 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: July 9, 2014
This is version 22 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM