Full text data of APCS
APCS
(PTX2)
[Confidence: low (only semi-automatic identification from reviews)]
Serum amyloid P-component; SAP (9.5S alpha-1-glycoprotein; Serum amyloid P-component(1-203); Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Serum amyloid P-component; SAP (9.5S alpha-1-glycoprotein; Serum amyloid P-component(1-203); Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P02743
ID SAMP_HUMAN Reviewed; 223 AA.
AC P02743;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1995, sequence version 2.
DT 22-JAN-2014, entry version 163.
DE RecName: Full=Serum amyloid P-component;
DE Short=SAP;
DE AltName: Full=9.5S alpha-1-glycoprotein;
DE Contains:
DE RecName: Full=Serum amyloid P-component(1-203);
DE Flags: Precursor;
GN Name=APCS; Synonyms=PTX2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2987268;
RA Mantzouranis E.C., Dowton S.B., Whitehead A.S., Edge M.D.,
RA Bruns G.A.P., Colten H.R.;
RT "Human serum amyloid P component. cDNA isolation, complete sequence of
RT pre-serum amyloid P component, and localization of the gene to
RT chromosome 1.";
RL J. Biol. Chem. 260:7752-7756(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3029048;
RA Ohnishi S., Maeda S., Shimada K., Arao T.;
RT "Isolation and characterization of the complete complementary and
RT genomic DNA sequences of human serum amyloid P component.";
RL J. Biochem. 100:849-858(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skeletal muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 20-223.
RX PubMed=4055725;
RA Prelli F., Pras M., Frangione B.;
RT "The primary structure of human tissue amyloid P component from a
RT patient with primary idiopathic amyloidosis.";
RL J. Biol. Chem. 260:12895-12898(1985).
RN [8]
RP PROTEIN SEQUENCE OF 20-49.
RX PubMed=81686; DOI=10.1021/bi00613a030;
RA Thompson A.R., Enfield D.L.;
RT "Human plasma P component: isolation and characterization.";
RL Biochemistry 17:4304-4311(1978).
RN [9]
RP STRUCTURE OF CARBOHYDRATE, AND MASS SPECTROMETRY.
RX PubMed=8202534; DOI=10.1073/pnas.91.12.5602;
RA Pepys M.B., Rademacher T.W., Amatayakul-Chantler S., Williams P.,
RA Noble G.E., Hutchinson W.L., Hawkins P.N., Nelson S.R.,
RA Gallimore J.R., Herbert J., Hutton T., Dwek R.A.;
RT "Human serum amyloid P component is an invariant constituent of
RT amyloid deposits and has a uniquely homogeneous glycostructure.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:5602-5606(1994).
RN [10]
RP TISSUE SPECIFICITY, AND MASS SPECTROMETRY.
RX PubMed=15174148; DOI=10.1002/pmic.200300690;
RA Kiernan U.A., Nedelkov D., Tubbs K.A., Niederkofler E.E., Nelson R.W.;
RT "Proteomic characterization of novel serum amyloid P component
RT variants from human plasma and urine.";
RL Proteomics 4:1825-1829(2004).
RN [11]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-51, AND MASS SPECTROMETRY.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,
RA Moore R.J., Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [12]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-51, AND MASS SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=8114934; DOI=10.1038/367338a0;
RA Emsley J., White H.E., O'Hara B., Oliva G., Srinivasan N.,
RA Tickle I.J., Blundell T.L., Pepys M.B., Wood S.P.;
RT "Structure of pentameric human serum amyloid P component.";
RL Nature 367:338-345(1994).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX PubMed=9217261; DOI=10.1006/jmbi.1997.1075;
RA Hohenester E., Hutchinson W.L., Pepys M.B., Wood S.P.;
RT "Crystal structure of a decameric complex of human serum amyloid P
RT component with bound dAMP.";
RL J. Mol. Biol. 269:570-578(1997).
RN [16]
RP VARIANT [LARGE SCALE ANALYSIS] SER-141.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Can interact with DNA and histones and may scavenge
CC nuclear material released from damaged circulating cells. May also
CC function as a calcium-dependent lectin.
CC -!- COFACTOR: Binds 2 calcium ions per subunit.
CC -!- SUBUNIT: Homopentamer. Pentaxin (or pentraxin) have a discoid
CC arrangement of 5 non-covalently bound subunits.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Found in serum and urine.
CC -!- PTM: N-glycosylated with a complex biantennary oligosaccharide
CC chain with a sialic acid at the end (disialo-SAP). Monosialo-SAP
CC as well as asioalo-SAP are also detected (PubMed:15174148).
CC -!- MASS SPECTROMETRY: Mass=25462.5; Mass_error=1.1;
CC Method=Electrospray; Range=20-223; Source=PubMed:8202534;
CC -!- MASS SPECTROMETRY: Mass=25463; Mass_error=3; Method=MALDI;
CC Range=20-223; Source=PubMed:15174148;
CC -!- MASS SPECTROMETRY: Mass=1285.78; Method=MALDI; Range=213-223;
CC Source=PubMed:15174148;
CC -!- MASS SPECTROMETRY: Mass=1186.71; Method=MALDI; Range=213-222;
CC Source=PubMed:15174148;
CC -!- DISEASE: Note=SAP is a precursor of amyloid component P which is
CC found in basement membrane and associated with amyloid deposits.
CC -!- SIMILARITY: Belongs to the pentaxin family.
CC -!- SIMILARITY: Contains 1 pentaxin domain.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Serum amyloid P component
CC entry;
CC URL="http://en.wikipedia.org/wiki/Serum_Amyloid_P_Component";
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DR EMBL; D00097; BAA00060.1; -; Genomic_DNA.
DR EMBL; M10944; AAA60302.1; -; mRNA.
DR EMBL; X04608; CAA28275.1; -; mRNA.
DR EMBL; CR450313; CAG29309.1; -; mRNA.
DR EMBL; AL445528; CAH73651.1; -; Genomic_DNA.
DR EMBL; BT006750; AAP35396.1; -; mRNA.
DR EMBL; BC007039; AAH07039.1; -; mRNA.
DR EMBL; BC007058; AAH07058.1; -; mRNA.
DR PIR; A25503; YLHUP.
DR RefSeq; NP_001630.1; NM_001639.3.
DR UniGene; Hs.507080; -.
DR PDB; 1GYK; X-ray; 2.20 A; A/B/C/D/E=20-223.
DR PDB; 1LGN; X-ray; 2.80 A; A/B/C/D/E=20-223.
DR PDB; 1SAC; X-ray; 2.00 A; A/B/C/D/E=20-223.
DR PDB; 2A3W; X-ray; 2.20 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T=20-223.
DR PDB; 2A3X; X-ray; 3.00 A; A/B/C/D/E/F/G/H/I/J=20-223.
DR PDB; 2A3Y; X-ray; 2.00 A; A/B/C/D/E=20-223.
DR PDB; 2W08; X-ray; 1.70 A; A/B/C/D/E=20-223.
DR PDB; 3D5O; X-ray; 2.80 A; A/B/C/D/E=20-223.
DR PDB; 3KQR; X-ray; 1.50 A; A/B/C/D/E=20-223.
DR PDB; 4AVS; X-ray; 1.40 A; A/B/C/D/E=20-223.
DR PDB; 4AVT; X-ray; 3.20 A; A/B/C/D/E/F/G/H/I/J=20-223.
DR PDB; 4AVV; X-ray; 1.60 A; A/B/C/D/E=20-223.
DR PDB; 4AYU; X-ray; 1.50 A; A/B/C/D/E=20-223.
DR PDBsum; 1GYK; -.
DR PDBsum; 1LGN; -.
DR PDBsum; 1SAC; -.
DR PDBsum; 2A3W; -.
DR PDBsum; 2A3X; -.
DR PDBsum; 2A3Y; -.
DR PDBsum; 2W08; -.
DR PDBsum; 3D5O; -.
DR PDBsum; 3KQR; -.
DR PDBsum; 4AVS; -.
DR PDBsum; 4AVT; -.
DR PDBsum; 4AVV; -.
DR PDBsum; 4AYU; -.
DR ProteinModelPortal; P02743; -.
DR SMR; P02743; 20-223.
DR DIP; DIP-46911N; -.
DR IntAct; P02743; 5.
DR MINT; MINT-4723480; -.
DR STRING; 9606.ENSP00000255040; -.
DR ChEMBL; CHEMBL4929; -.
DR TCDB; 1.C.92.1.2; the pentraxin (pentraxin) family.
DR PhosphoSite; P02743; -.
DR UniCarbKB; P02743; -.
DR DMDM; 730704; -.
DR DOSAC-COBS-2DPAGE; P02743; -.
DR OGP; P02743; -.
DR REPRODUCTION-2DPAGE; IPI00022391; -.
DR REPRODUCTION-2DPAGE; P02743; -.
DR SWISS-2DPAGE; P02743; -.
DR PaxDb; P02743; -.
DR PeptideAtlas; P02743; -.
DR PRIDE; P02743; -.
DR DNASU; 325; -.
DR Ensembl; ENST00000255040; ENSP00000255040; ENSG00000132703.
DR GeneID; 325; -.
DR KEGG; hsa:325; -.
DR UCSC; uc001ftv.3; human.
DR CTD; 325; -.
DR GeneCards; GC01P159557; -.
DR HGNC; HGNC:584; APCS.
DR HPA; CAB007817; -.
DR MIM; 104770; gene.
DR neXtProt; NX_P02743; -.
DR PharmGKB; PA24877; -.
DR eggNOG; NOG44770; -.
DR HOGENOM; HOG000247043; -.
DR HOVERGEN; HBG005405; -.
DR InParanoid; P02743; -.
DR OMA; AEFWING; -.
DR OrthoDB; EOG71RXMB; -.
DR PhylomeDB; P02743; -.
DR Reactome; REACT_116125; Disease.
DR EvolutionaryTrace; P02743; -.
DR GeneWiki; Serum_amyloid_P_component; -.
DR GenomeRNAi; 325; -.
DR NextBio; 1333; -.
DR PRO; PR:P02743; -.
DR Bgee; P02743; -.
DR CleanEx; HS_APCS; -.
DR Genevestigator; P02743; -.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0043234; C:protein complex; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0051082; F:unfolded protein binding; TAS:ProtInc.
DR GO; GO:0006953; P:acute-phase response; TAS:ProtInc.
DR GO; GO:0051131; P:chaperone-mediated protein complex assembly; TAS:ProtInc.
DR GO; GO:0006457; P:protein folding; TAS:ProtInc.
DR Gene3D; 2.60.120.200; -; 1.
DR InterPro; IPR008985; ConA-like_lec_gl_sf.
DR InterPro; IPR013320; ConA-like_subgrp.
DR InterPro; IPR001759; Pentaxin.
DR Pfam; PF00354; Pentaxin; 1.
DR PRINTS; PR00895; PENTAXIN.
DR SMART; SM00159; PTX; 1.
DR SUPFAM; SSF49899; SSF49899; 1.
DR PROSITE; PS00289; PENTAXIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amyloid; Calcium; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Lectin;
KW Metal-binding; Polymorphism; Reference proteome; Secreted; Signal.
FT SIGNAL 1 19
FT CHAIN 20 223 Serum amyloid P-component.
FT /FTId=PRO_0000023540.
FT CHAIN 20 222 Serum amyloid P-component(1-203).
FT /FTId=PRO_0000023541.
FT DOMAIN 20 223 Pentaxin.
FT METAL 77 77 Calcium 1.
FT METAL 78 78 Calcium 1.
FT METAL 155 155 Calcium 1.
FT METAL 155 155 Calcium 2.
FT METAL 156 156 Calcium 1; via carbonyl oxygen.
FT METAL 157 157 Calcium 1.
FT METAL 157 157 Calcium 2.
FT METAL 167 167 Calcium 2.
FT CARBOHYD 51 51 N-linked (GlcNAc...).
FT /FTId=CAR_000169.
FT DISULFID 55 114
FT VARIANT 141 141 G -> S (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_035814.
FT VARIANT 155 155 E -> G.
FT /FTId=VAR_006054.
FT VARIANT 158 158 S -> G.
FT /FTId=VAR_006055.
FT CONFLICT 101 101 S -> P (in Ref. 1; AAA60302).
FT STRAND 26 30
FT STRAND 38 41
FT STRAND 49 59
FT STRAND 66 73
FT STRAND 76 86
FT STRAND 89 94
FT STRAND 97 102
FT STRAND 111 118
FT TURN 119 121
FT STRAND 123 128
FT STRAND 149 154
FT STRAND 157 160
FT HELIX 165 167
FT STRAND 171 181
FT HELIX 185 193
FT STRAND 200 203
FT HELIX 204 206
FT STRAND 209 214
FT STRAND 216 219
SQ SEQUENCE 223 AA; 25387 MW; 6C88A515FE88B393 CRC64;
MNKPLLWISV LTSLLEAFAH TDLSGKVFVF PRESVTDHVN LITPLEKPLQ NFTLCFRAYS
DLSRAYSLFS YNTQGRDNEL LVYKERVGEY SLYIGRHKVT SKVIEKFPAP VHICVSWESS
SGIAEFWING TPLVKKGLRQ GYFVEAQPKI VLGQEQDSYG GKFDRSQSFV GEIGDLYMWD
SVLPPENILS AYQGTPLPAN ILDWQALNYE IRGYVIIKPL VWV
//
ID SAMP_HUMAN Reviewed; 223 AA.
AC P02743;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1995, sequence version 2.
DT 22-JAN-2014, entry version 163.
DE RecName: Full=Serum amyloid P-component;
DE Short=SAP;
DE AltName: Full=9.5S alpha-1-glycoprotein;
DE Contains:
DE RecName: Full=Serum amyloid P-component(1-203);
DE Flags: Precursor;
GN Name=APCS; Synonyms=PTX2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2987268;
RA Mantzouranis E.C., Dowton S.B., Whitehead A.S., Edge M.D.,
RA Bruns G.A.P., Colten H.R.;
RT "Human serum amyloid P component. cDNA isolation, complete sequence of
RT pre-serum amyloid P component, and localization of the gene to
RT chromosome 1.";
RL J. Biol. Chem. 260:7752-7756(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3029048;
RA Ohnishi S., Maeda S., Shimada K., Arao T.;
RT "Isolation and characterization of the complete complementary and
RT genomic DNA sequences of human serum amyloid P component.";
RL J. Biochem. 100:849-858(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skeletal muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 20-223.
RX PubMed=4055725;
RA Prelli F., Pras M., Frangione B.;
RT "The primary structure of human tissue amyloid P component from a
RT patient with primary idiopathic amyloidosis.";
RL J. Biol. Chem. 260:12895-12898(1985).
RN [8]
RP PROTEIN SEQUENCE OF 20-49.
RX PubMed=81686; DOI=10.1021/bi00613a030;
RA Thompson A.R., Enfield D.L.;
RT "Human plasma P component: isolation and characterization.";
RL Biochemistry 17:4304-4311(1978).
RN [9]
RP STRUCTURE OF CARBOHYDRATE, AND MASS SPECTROMETRY.
RX PubMed=8202534; DOI=10.1073/pnas.91.12.5602;
RA Pepys M.B., Rademacher T.W., Amatayakul-Chantler S., Williams P.,
RA Noble G.E., Hutchinson W.L., Hawkins P.N., Nelson S.R.,
RA Gallimore J.R., Herbert J., Hutton T., Dwek R.A.;
RT "Human serum amyloid P component is an invariant constituent of
RT amyloid deposits and has a uniquely homogeneous glycostructure.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:5602-5606(1994).
RN [10]
RP TISSUE SPECIFICITY, AND MASS SPECTROMETRY.
RX PubMed=15174148; DOI=10.1002/pmic.200300690;
RA Kiernan U.A., Nedelkov D., Tubbs K.A., Niederkofler E.E., Nelson R.W.;
RT "Proteomic characterization of novel serum amyloid P component
RT variants from human plasma and urine.";
RL Proteomics 4:1825-1829(2004).
RN [11]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-51, AND MASS SPECTROMETRY.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,
RA Moore R.J., Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [12]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-51, AND MASS SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=8114934; DOI=10.1038/367338a0;
RA Emsley J., White H.E., O'Hara B., Oliva G., Srinivasan N.,
RA Tickle I.J., Blundell T.L., Pepys M.B., Wood S.P.;
RT "Structure of pentameric human serum amyloid P component.";
RL Nature 367:338-345(1994).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX PubMed=9217261; DOI=10.1006/jmbi.1997.1075;
RA Hohenester E., Hutchinson W.L., Pepys M.B., Wood S.P.;
RT "Crystal structure of a decameric complex of human serum amyloid P
RT component with bound dAMP.";
RL J. Mol. Biol. 269:570-578(1997).
RN [16]
RP VARIANT [LARGE SCALE ANALYSIS] SER-141.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Can interact with DNA and histones and may scavenge
CC nuclear material released from damaged circulating cells. May also
CC function as a calcium-dependent lectin.
CC -!- COFACTOR: Binds 2 calcium ions per subunit.
CC -!- SUBUNIT: Homopentamer. Pentaxin (or pentraxin) have a discoid
CC arrangement of 5 non-covalently bound subunits.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Found in serum and urine.
CC -!- PTM: N-glycosylated with a complex biantennary oligosaccharide
CC chain with a sialic acid at the end (disialo-SAP). Monosialo-SAP
CC as well as asioalo-SAP are also detected (PubMed:15174148).
CC -!- MASS SPECTROMETRY: Mass=25462.5; Mass_error=1.1;
CC Method=Electrospray; Range=20-223; Source=PubMed:8202534;
CC -!- MASS SPECTROMETRY: Mass=25463; Mass_error=3; Method=MALDI;
CC Range=20-223; Source=PubMed:15174148;
CC -!- MASS SPECTROMETRY: Mass=1285.78; Method=MALDI; Range=213-223;
CC Source=PubMed:15174148;
CC -!- MASS SPECTROMETRY: Mass=1186.71; Method=MALDI; Range=213-222;
CC Source=PubMed:15174148;
CC -!- DISEASE: Note=SAP is a precursor of amyloid component P which is
CC found in basement membrane and associated with amyloid deposits.
CC -!- SIMILARITY: Belongs to the pentaxin family.
CC -!- SIMILARITY: Contains 1 pentaxin domain.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Serum amyloid P component
CC entry;
CC URL="http://en.wikipedia.org/wiki/Serum_Amyloid_P_Component";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; D00097; BAA00060.1; -; Genomic_DNA.
DR EMBL; M10944; AAA60302.1; -; mRNA.
DR EMBL; X04608; CAA28275.1; -; mRNA.
DR EMBL; CR450313; CAG29309.1; -; mRNA.
DR EMBL; AL445528; CAH73651.1; -; Genomic_DNA.
DR EMBL; BT006750; AAP35396.1; -; mRNA.
DR EMBL; BC007039; AAH07039.1; -; mRNA.
DR EMBL; BC007058; AAH07058.1; -; mRNA.
DR PIR; A25503; YLHUP.
DR RefSeq; NP_001630.1; NM_001639.3.
DR UniGene; Hs.507080; -.
DR PDB; 1GYK; X-ray; 2.20 A; A/B/C/D/E=20-223.
DR PDB; 1LGN; X-ray; 2.80 A; A/B/C/D/E=20-223.
DR PDB; 1SAC; X-ray; 2.00 A; A/B/C/D/E=20-223.
DR PDB; 2A3W; X-ray; 2.20 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T=20-223.
DR PDB; 2A3X; X-ray; 3.00 A; A/B/C/D/E/F/G/H/I/J=20-223.
DR PDB; 2A3Y; X-ray; 2.00 A; A/B/C/D/E=20-223.
DR PDB; 2W08; X-ray; 1.70 A; A/B/C/D/E=20-223.
DR PDB; 3D5O; X-ray; 2.80 A; A/B/C/D/E=20-223.
DR PDB; 3KQR; X-ray; 1.50 A; A/B/C/D/E=20-223.
DR PDB; 4AVS; X-ray; 1.40 A; A/B/C/D/E=20-223.
DR PDB; 4AVT; X-ray; 3.20 A; A/B/C/D/E/F/G/H/I/J=20-223.
DR PDB; 4AVV; X-ray; 1.60 A; A/B/C/D/E=20-223.
DR PDB; 4AYU; X-ray; 1.50 A; A/B/C/D/E=20-223.
DR PDBsum; 1GYK; -.
DR PDBsum; 1LGN; -.
DR PDBsum; 1SAC; -.
DR PDBsum; 2A3W; -.
DR PDBsum; 2A3X; -.
DR PDBsum; 2A3Y; -.
DR PDBsum; 2W08; -.
DR PDBsum; 3D5O; -.
DR PDBsum; 3KQR; -.
DR PDBsum; 4AVS; -.
DR PDBsum; 4AVT; -.
DR PDBsum; 4AVV; -.
DR PDBsum; 4AYU; -.
DR ProteinModelPortal; P02743; -.
DR SMR; P02743; 20-223.
DR DIP; DIP-46911N; -.
DR IntAct; P02743; 5.
DR MINT; MINT-4723480; -.
DR STRING; 9606.ENSP00000255040; -.
DR ChEMBL; CHEMBL4929; -.
DR TCDB; 1.C.92.1.2; the pentraxin (pentraxin) family.
DR PhosphoSite; P02743; -.
DR UniCarbKB; P02743; -.
DR DMDM; 730704; -.
DR DOSAC-COBS-2DPAGE; P02743; -.
DR OGP; P02743; -.
DR REPRODUCTION-2DPAGE; IPI00022391; -.
DR REPRODUCTION-2DPAGE; P02743; -.
DR SWISS-2DPAGE; P02743; -.
DR PaxDb; P02743; -.
DR PeptideAtlas; P02743; -.
DR PRIDE; P02743; -.
DR DNASU; 325; -.
DR Ensembl; ENST00000255040; ENSP00000255040; ENSG00000132703.
DR GeneID; 325; -.
DR KEGG; hsa:325; -.
DR UCSC; uc001ftv.3; human.
DR CTD; 325; -.
DR GeneCards; GC01P159557; -.
DR HGNC; HGNC:584; APCS.
DR HPA; CAB007817; -.
DR MIM; 104770; gene.
DR neXtProt; NX_P02743; -.
DR PharmGKB; PA24877; -.
DR eggNOG; NOG44770; -.
DR HOGENOM; HOG000247043; -.
DR HOVERGEN; HBG005405; -.
DR InParanoid; P02743; -.
DR OMA; AEFWING; -.
DR OrthoDB; EOG71RXMB; -.
DR PhylomeDB; P02743; -.
DR Reactome; REACT_116125; Disease.
DR EvolutionaryTrace; P02743; -.
DR GeneWiki; Serum_amyloid_P_component; -.
DR GenomeRNAi; 325; -.
DR NextBio; 1333; -.
DR PRO; PR:P02743; -.
DR Bgee; P02743; -.
DR CleanEx; HS_APCS; -.
DR Genevestigator; P02743; -.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0043234; C:protein complex; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0051082; F:unfolded protein binding; TAS:ProtInc.
DR GO; GO:0006953; P:acute-phase response; TAS:ProtInc.
DR GO; GO:0051131; P:chaperone-mediated protein complex assembly; TAS:ProtInc.
DR GO; GO:0006457; P:protein folding; TAS:ProtInc.
DR Gene3D; 2.60.120.200; -; 1.
DR InterPro; IPR008985; ConA-like_lec_gl_sf.
DR InterPro; IPR013320; ConA-like_subgrp.
DR InterPro; IPR001759; Pentaxin.
DR Pfam; PF00354; Pentaxin; 1.
DR PRINTS; PR00895; PENTAXIN.
DR SMART; SM00159; PTX; 1.
DR SUPFAM; SSF49899; SSF49899; 1.
DR PROSITE; PS00289; PENTAXIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amyloid; Calcium; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Lectin;
KW Metal-binding; Polymorphism; Reference proteome; Secreted; Signal.
FT SIGNAL 1 19
FT CHAIN 20 223 Serum amyloid P-component.
FT /FTId=PRO_0000023540.
FT CHAIN 20 222 Serum amyloid P-component(1-203).
FT /FTId=PRO_0000023541.
FT DOMAIN 20 223 Pentaxin.
FT METAL 77 77 Calcium 1.
FT METAL 78 78 Calcium 1.
FT METAL 155 155 Calcium 1.
FT METAL 155 155 Calcium 2.
FT METAL 156 156 Calcium 1; via carbonyl oxygen.
FT METAL 157 157 Calcium 1.
FT METAL 157 157 Calcium 2.
FT METAL 167 167 Calcium 2.
FT CARBOHYD 51 51 N-linked (GlcNAc...).
FT /FTId=CAR_000169.
FT DISULFID 55 114
FT VARIANT 141 141 G -> S (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_035814.
FT VARIANT 155 155 E -> G.
FT /FTId=VAR_006054.
FT VARIANT 158 158 S -> G.
FT /FTId=VAR_006055.
FT CONFLICT 101 101 S -> P (in Ref. 1; AAA60302).
FT STRAND 26 30
FT STRAND 38 41
FT STRAND 49 59
FT STRAND 66 73
FT STRAND 76 86
FT STRAND 89 94
FT STRAND 97 102
FT STRAND 111 118
FT TURN 119 121
FT STRAND 123 128
FT STRAND 149 154
FT STRAND 157 160
FT HELIX 165 167
FT STRAND 171 181
FT HELIX 185 193
FT STRAND 200 203
FT HELIX 204 206
FT STRAND 209 214
FT STRAND 216 219
SQ SEQUENCE 223 AA; 25387 MW; 6C88A515FE88B393 CRC64;
MNKPLLWISV LTSLLEAFAH TDLSGKVFVF PRESVTDHVN LITPLEKPLQ NFTLCFRAYS
DLSRAYSLFS YNTQGRDNEL LVYKERVGEY SLYIGRHKVT SKVIEKFPAP VHICVSWESS
SGIAEFWING TPLVKKGLRQ GYFVEAQPKI VLGQEQDSYG GKFDRSQSFV GEIGDLYMWD
SVLPPENILS AYQGTPLPAN ILDWQALNYE IRGYVIIKPL VWV
//
MIM
104770
*RECORD*
*FIELD* NO
104770
*FIELD* TI
*104770 AMYLOID P COMPONENT, SERUM; APCS
;;SERUM AMYLOID P; SAP;;
PENTRAXIN 2, SHORT; PTX2
read more*FIELD* TX
CLONING
Mantzouranis et al. (1985) isolated cDNA for the P component of human
serum amyloid and determined the complete sequence of the precursor.
MAPPING
Mantzouranis et al. (1985) assigned the APCS gene to chromosome 1 by
studies of somatic cell hybrids. The gene is probably closely situated
to that for C-reactive protein (CRP; 123260) with which it shows
homology. By in situ hybridization, the assignment was made to segment
1q12-q23 (Floyd-Smith et al., 1985, 1986).
Ionasescu et al. (1987) found a maximum lod score of 3.26 at theta =
0.05 for linkage of APCS with the Duffy blood group locus (110700). A
RFLP marker of APCS was used. The linkage is consistent with the
physical assignment of the 2 loci.
GENETIC VARIABILITY
Woo et al. (1987) found a genetic marker for susceptibility to
amyloidosis in juvenile arthritis: an 8.8-kb RFLP band determined by a
polymorphic DNA site 5-prime to the SAP gene. Homozygosity for the
alternative 5.6-kb band was found in none of 28 amyloid patients. Among
19 juvenile arthritic patients without amyloidosis, the distribution of
the polymorphism was the same as that in the normal group. With a RFLP
of the cloned mouse Sap gene, Whitehead et al. (1988) demonstrated that
the gene maps to chromosome 1 in the same region specified by
quantitative variation in Sap levels. They thought it might be
significant that the same region includes CRP, SAP, and histone genes,
all of which have products that interact with DNA.
BIOCHEMICAL FEATURES
- Crystal Structure
Lu et al. (2008) described the structural mechanism for pentraxin's
binding to Fc-gamma-R and its functional activation of
Fc-gamma-R-mediated phagocytosis and cytokine secretion. The complex
structure between human SAP and Fc-gamma-RIIa (146790) showed a
diagonally bound receptor on each SAP pentamer with both D1 and D2
domains of the receptor contacting the ridge helices from 2 SAP
subunits. The 1:1 stoichiometry between SAP and Fc-gamma-RIIa implied
the requirement for multivalent pathogen binding for receptor
aggregation. Mutational and binding studies showed that pentraxins are
diverse in their binding specificity for Fc-gamma-R isoforms but
conserved in their recognition structure. The shared binding site for
SAP and IgG caused competition for Fc-gamma-R binding and the inhibition
of immune complex-mediated phagocytosis by soluble pentraxins. Lu et al.
(2008) concluded that their results established antibody-like functions
for pentraxins in the Fc-gamma-R pathway, suggested an evolutionary
overlap between the innate and adaptive immune systems, and had
therapeutic implications for autoimmune diseases.
ANIMAL MODEL
Botto et al. (1997) generated mice with a targeted deletion of the SAP
gene. Induction of reactive amyloidosis was retarded in these mice,
demonstrating the participation of SAP in pathogenesis of amyloidosis in
vivo and confirming that inhibition of SAP binding to amyloid fibrils is
an attractive therapeutic target. Pepys et al. (2002) developed a drug
that is a competitive inhibitor of SAP binding to amyloid fibrils. This
palindromic compound also crosslinks and dimerizes SAP molecules,
leading to their very rapid clearance by the liver and thus producing a
marked depletion of circulating human SAP. Pepys et al. (2002) suggested
that this mechanism of drug action potently removes SAP from human
amyloid deposits in tissues and may provide a new therapeutic approach
to both systemic amyloidosis and diseases associated with local amyloid,
including Alzheimer disease (104300) and type 2 diabetes (125853).
Bodin et al. (2010) demonstrated that administration of anti-human SAP
antibodies to mice with amyloid deposits containing human SAP triggers a
potent, complement-dependent, macrophage-derived giant cell reaction
that swiftly removes massive visceral amyloid deposits (see 105200)
without adverse effects. Anti-SAP antibody treatment is clinically
feasible because circulating human SAP can be depleted in patients by
the bis-D-proline compound CPHPC, thereby enabling injected anti-SAP
antibodies to reach residual SAP in the amyloid deposits.
*FIELD* SA
Mortensen et al. (1985); Prelli et al. (1985)
*FIELD* RF
1. Bodin, K.; Ellmerich, S.; Kahan, M. C.; Tennent, G. A.; Loesch,
A.; Gilbertson, J. A.; Hutchinson, W. L.; Mangione, P. P.; Gallimore,
J. R.; Millar, D. J.; Minogue, S.; Dhillon, A. P.; Taylor, G. W.;
Bradwell, A. R.; Petrie, A.; Gillmore, J. D.; Bellotti, V.; Botto,
M.; Hawkins, P. N.; Pepys, M. B.: Antibodies to human serum amyloid
P component eliminate visceral amyloid deposits. Nature 468: 93-97,
2010.
2. Botto, M.; Hawkins, P. N.; Bickerstaff, M. C.; Herbert, J.; Bygrave,
A. E.; McBride, A.; Hutchinson, W. L.; Tennent, G. A.; Walport, M.
J.; Pepys, M. B.: Amyloid deposition is delayed in mice with targeted
deletion of the serum amyloid P component gene. Nature Med. 3: 855-859,
1997.
3. Floyd-Smith, G. A.; Whitehead, A. S.; Colten, H. R.; Francke, U.
: The human C-reactive protein gene (CRP) and serum amyloid P component
gene (APCS) are located on the proximal long arm of chromosome 1. Immunogenetics 24:
171-176, 1986.
4. Floyd-Smith, G. A.; Whitehead, A. S.; Colten, H. R.; Francke, U.
: Human serum amyloid P component (SAP) is located on the proximal
long arm of chromosome 1. (Abstract) Cytogenet. Cell Genet. 40:
631 only, 1985.
5. Ionasescu, V.; Burns, T.; Searby, C.; Ionasescu, R.: Linkage between
the loci for Duffy (FY) and serum amyloid P component (APCS) on human
chromosome 1. Cytogenet. Cell Genet. 45: 240-241, 1987.
6. Lu, J.; Marnell, L. L.; Marjon, K. D.; Mold, C.; Du Clos, T. W.;
Sun, P. D.: Structural recognition and functional activation of Fc-gamma-R
by innate pentraxins. Nature 456: 989-992, 2008.
7. Mantzouranis, E. C.; Dowton, S. B.; Whitehead, A. S.; Edge, M.
D.; Bruns, G. A. P.; Colten, H. R.: Human serum amyloid P component:
cDNA isolation, complete sequence of pre-serum amyloid P component,
and localization of the gene to chromosome 1. J. Biol. Chem. 260:
7752-7756, 1985.
8. Mortensen, R. F.; Le, P. T.; Taylor, B. A.: Mouse serum amyloid
P-component (SAP) levels controlled by a locus on chromosome 1. Immunogenetics 22:
367-375, 1985.
9. Pepys, M. B.; Herbert, J.; Hutchinson, W. L.; Tennent, G. A.; Lachmann,
H. J.; Gallimore, J. R.; Lovat, L. B.; Bartfai, T.; Alanine, A.; Hertel,
C.; Hoffmann, T.; Jakob-Roetne, R.; and 11 others: Targeted pharmacological
depletion of serum amyloid P component for treatment of human amyloidosis. Nature 417:
254-259, 2002.
10. Prelli, F.; Pras, M.; Frangione, B.: The primary structure of
human tissue amyloid P component from a patient with primary idiopathic
amyloidosis. J. Biol. Chem. 260: 12895-12898, 1985.
11. Whitehead, A. S.; Rits, M.; Michaelson, J.: Molecular genetics
of mouse serum amyloid P component (SAP): cloning and gene mapping. Immunogenetics 28:
388-390, 1988.
12. Woo, P.; O'Brien, J.; Robson, M.; Ansell, B. M.: A genetic marker
for systemic amyloidosis in juvenile arthritis. Lancet 330: 767-769,
1987. Note: Originally Volume I.
*FIELD* CN
Ada Hamosh - updated: 1/4/2011
Ada Hamosh - updated: 2/18/2009
Ada Hamosh - updated: 5/29/2002
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
alopez: 01/04/2011
terry: 1/4/2011
mgross: 6/14/2010
alopez: 2/23/2009
terry: 2/18/2009
terry: 1/7/2009
alopez: 5/30/2002
terry: 5/29/2002
carol: 3/23/1992
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/26/1989
root: 11/15/1988
marie: 3/25/1988
*RECORD*
*FIELD* NO
104770
*FIELD* TI
*104770 AMYLOID P COMPONENT, SERUM; APCS
;;SERUM AMYLOID P; SAP;;
PENTRAXIN 2, SHORT; PTX2
read more*FIELD* TX
CLONING
Mantzouranis et al. (1985) isolated cDNA for the P component of human
serum amyloid and determined the complete sequence of the precursor.
MAPPING
Mantzouranis et al. (1985) assigned the APCS gene to chromosome 1 by
studies of somatic cell hybrids. The gene is probably closely situated
to that for C-reactive protein (CRP; 123260) with which it shows
homology. By in situ hybridization, the assignment was made to segment
1q12-q23 (Floyd-Smith et al., 1985, 1986).
Ionasescu et al. (1987) found a maximum lod score of 3.26 at theta =
0.05 for linkage of APCS with the Duffy blood group locus (110700). A
RFLP marker of APCS was used. The linkage is consistent with the
physical assignment of the 2 loci.
GENETIC VARIABILITY
Woo et al. (1987) found a genetic marker for susceptibility to
amyloidosis in juvenile arthritis: an 8.8-kb RFLP band determined by a
polymorphic DNA site 5-prime to the SAP gene. Homozygosity for the
alternative 5.6-kb band was found in none of 28 amyloid patients. Among
19 juvenile arthritic patients without amyloidosis, the distribution of
the polymorphism was the same as that in the normal group. With a RFLP
of the cloned mouse Sap gene, Whitehead et al. (1988) demonstrated that
the gene maps to chromosome 1 in the same region specified by
quantitative variation in Sap levels. They thought it might be
significant that the same region includes CRP, SAP, and histone genes,
all of which have products that interact with DNA.
BIOCHEMICAL FEATURES
- Crystal Structure
Lu et al. (2008) described the structural mechanism for pentraxin's
binding to Fc-gamma-R and its functional activation of
Fc-gamma-R-mediated phagocytosis and cytokine secretion. The complex
structure between human SAP and Fc-gamma-RIIa (146790) showed a
diagonally bound receptor on each SAP pentamer with both D1 and D2
domains of the receptor contacting the ridge helices from 2 SAP
subunits. The 1:1 stoichiometry between SAP and Fc-gamma-RIIa implied
the requirement for multivalent pathogen binding for receptor
aggregation. Mutational and binding studies showed that pentraxins are
diverse in their binding specificity for Fc-gamma-R isoforms but
conserved in their recognition structure. The shared binding site for
SAP and IgG caused competition for Fc-gamma-R binding and the inhibition
of immune complex-mediated phagocytosis by soluble pentraxins. Lu et al.
(2008) concluded that their results established antibody-like functions
for pentraxins in the Fc-gamma-R pathway, suggested an evolutionary
overlap between the innate and adaptive immune systems, and had
therapeutic implications for autoimmune diseases.
ANIMAL MODEL
Botto et al. (1997) generated mice with a targeted deletion of the SAP
gene. Induction of reactive amyloidosis was retarded in these mice,
demonstrating the participation of SAP in pathogenesis of amyloidosis in
vivo and confirming that inhibition of SAP binding to amyloid fibrils is
an attractive therapeutic target. Pepys et al. (2002) developed a drug
that is a competitive inhibitor of SAP binding to amyloid fibrils. This
palindromic compound also crosslinks and dimerizes SAP molecules,
leading to their very rapid clearance by the liver and thus producing a
marked depletion of circulating human SAP. Pepys et al. (2002) suggested
that this mechanism of drug action potently removes SAP from human
amyloid deposits in tissues and may provide a new therapeutic approach
to both systemic amyloidosis and diseases associated with local amyloid,
including Alzheimer disease (104300) and type 2 diabetes (125853).
Bodin et al. (2010) demonstrated that administration of anti-human SAP
antibodies to mice with amyloid deposits containing human SAP triggers a
potent, complement-dependent, macrophage-derived giant cell reaction
that swiftly removes massive visceral amyloid deposits (see 105200)
without adverse effects. Anti-SAP antibody treatment is clinically
feasible because circulating human SAP can be depleted in patients by
the bis-D-proline compound CPHPC, thereby enabling injected anti-SAP
antibodies to reach residual SAP in the amyloid deposits.
*FIELD* SA
Mortensen et al. (1985); Prelli et al. (1985)
*FIELD* RF
1. Bodin, K.; Ellmerich, S.; Kahan, M. C.; Tennent, G. A.; Loesch,
A.; Gilbertson, J. A.; Hutchinson, W. L.; Mangione, P. P.; Gallimore,
J. R.; Millar, D. J.; Minogue, S.; Dhillon, A. P.; Taylor, G. W.;
Bradwell, A. R.; Petrie, A.; Gillmore, J. D.; Bellotti, V.; Botto,
M.; Hawkins, P. N.; Pepys, M. B.: Antibodies to human serum amyloid
P component eliminate visceral amyloid deposits. Nature 468: 93-97,
2010.
2. Botto, M.; Hawkins, P. N.; Bickerstaff, M. C.; Herbert, J.; Bygrave,
A. E.; McBride, A.; Hutchinson, W. L.; Tennent, G. A.; Walport, M.
J.; Pepys, M. B.: Amyloid deposition is delayed in mice with targeted
deletion of the serum amyloid P component gene. Nature Med. 3: 855-859,
1997.
3. Floyd-Smith, G. A.; Whitehead, A. S.; Colten, H. R.; Francke, U.
: The human C-reactive protein gene (CRP) and serum amyloid P component
gene (APCS) are located on the proximal long arm of chromosome 1. Immunogenetics 24:
171-176, 1986.
4. Floyd-Smith, G. A.; Whitehead, A. S.; Colten, H. R.; Francke, U.
: Human serum amyloid P component (SAP) is located on the proximal
long arm of chromosome 1. (Abstract) Cytogenet. Cell Genet. 40:
631 only, 1985.
5. Ionasescu, V.; Burns, T.; Searby, C.; Ionasescu, R.: Linkage between
the loci for Duffy (FY) and serum amyloid P component (APCS) on human
chromosome 1. Cytogenet. Cell Genet. 45: 240-241, 1987.
6. Lu, J.; Marnell, L. L.; Marjon, K. D.; Mold, C.; Du Clos, T. W.;
Sun, P. D.: Structural recognition and functional activation of Fc-gamma-R
by innate pentraxins. Nature 456: 989-992, 2008.
7. Mantzouranis, E. C.; Dowton, S. B.; Whitehead, A. S.; Edge, M.
D.; Bruns, G. A. P.; Colten, H. R.: Human serum amyloid P component:
cDNA isolation, complete sequence of pre-serum amyloid P component,
and localization of the gene to chromosome 1. J. Biol. Chem. 260:
7752-7756, 1985.
8. Mortensen, R. F.; Le, P. T.; Taylor, B. A.: Mouse serum amyloid
P-component (SAP) levels controlled by a locus on chromosome 1. Immunogenetics 22:
367-375, 1985.
9. Pepys, M. B.; Herbert, J.; Hutchinson, W. L.; Tennent, G. A.; Lachmann,
H. J.; Gallimore, J. R.; Lovat, L. B.; Bartfai, T.; Alanine, A.; Hertel,
C.; Hoffmann, T.; Jakob-Roetne, R.; and 11 others: Targeted pharmacological
depletion of serum amyloid P component for treatment of human amyloidosis. Nature 417:
254-259, 2002.
10. Prelli, F.; Pras, M.; Frangione, B.: The primary structure of
human tissue amyloid P component from a patient with primary idiopathic
amyloidosis. J. Biol. Chem. 260: 12895-12898, 1985.
11. Whitehead, A. S.; Rits, M.; Michaelson, J.: Molecular genetics
of mouse serum amyloid P component (SAP): cloning and gene mapping. Immunogenetics 28:
388-390, 1988.
12. Woo, P.; O'Brien, J.; Robson, M.; Ansell, B. M.: A genetic marker
for systemic amyloidosis in juvenile arthritis. Lancet 330: 767-769,
1987. Note: Originally Volume I.
*FIELD* CN
Ada Hamosh - updated: 1/4/2011
Ada Hamosh - updated: 2/18/2009
Ada Hamosh - updated: 5/29/2002
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
alopez: 01/04/2011
terry: 1/4/2011
mgross: 6/14/2010
alopez: 2/23/2009
terry: 2/18/2009
terry: 1/7/2009
alopez: 5/30/2002
terry: 5/29/2002
carol: 3/23/1992
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/26/1989
root: 11/15/1988
marie: 3/25/1988