Full text data of CD47
CD47
(MER6)
[Confidence: high (present in two of the MS resources)]
Leukocyte surface antigen CD47 (Antigenic surface determinant protein OA3; Integrin-associated protein; IAP; Protein MER6; CD47; Flags: Precursor)
Leukocyte surface antigen CD47 (Antigenic surface determinant protein OA3; Integrin-associated protein; IAP; Protein MER6; CD47; Flags: Precursor)
hRBCD
IPI00216514
IPI00216514 Splice isoform OA3-293 of Q08722 Leukocyte surface antigen CD47 precursor Splice isoform OA3-293 of Q08722 Leukocyte surface antigen CD47 precursor membrane n/a 2 3 4 4 1 5 4 9 3 4 1 n/a 2 2 1 3 4 3 3 integral membrane protein different splice isoforms expected molecular weight found in band ~ 43 kDa
IPI00216514 Splice isoform OA3-293 of Q08722 Leukocyte surface antigen CD47 precursor Splice isoform OA3-293 of Q08722 Leukocyte surface antigen CD47 precursor membrane n/a 2 3 4 4 1 5 4 9 3 4 1 n/a 2 2 1 3 4 3 3 integral membrane protein different splice isoforms expected molecular weight found in band ~ 43 kDa
Comments
Isoform Q08722-3 was detected.
Isoform Q08722-3 was detected.
UniProt
Q08722
ID CD47_HUMAN Reviewed; 323 AA.
AC Q08722; A8K198; D3DN59; Q53Y71; Q96A60;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1995, sequence version 1.
DT 22-JAN-2014, entry version 131.
DE RecName: Full=Leukocyte surface antigen CD47;
DE AltName: Full=Antigenic surface determinant protein OA3;
DE AltName: Full=Integrin-associated protein;
DE Short=IAP;
DE AltName: Full=Protein MER6;
DE AltName: CD_antigen=CD47;
DE Flags: Precursor;
GN Name=CD47; Synonyms=MER6;
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] (ISOFORM OA3-323).
RC TISSUE=Ovary;
RX PubMed=1394148;
RA Campbell I.G., Freemont P.S., Foulkes W., Trowsdale J.;
RT "An ovarian tumor marker with homology to vaccinia virus contains an
RT IgV-like region and multiple transmembrane domains.";
RL Cancer Res. 52:5416-5420(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM OA3-305), FUNCTION, SUBCELLULAR
RP LOCATION, AND TOPOLOGY.
RC TISSUE=Myelomonocyte;
RX PubMed=7691831; DOI=10.1083/jcb.123.2.485;
RA Lindberg F.P., Gresham H.D., Schwarz E., Brown E.J.;
RT "Molecular cloning of integrin-associated protein: an immunoglobulin
RT family member with multiple membrane spanning domains implicated in
RT alpha-v beta-3-dependent ligand binding.";
RL J. Cell Biol. 123:485-496(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM OA3-305).
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] (ISOFORM OA3-323).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM OA3-305).
RC TISSUE=Hippocampus, Leiomyosarcoma, and Ovarian adenocarcinoma;
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 PARTIAL PROTEIN SEQUENCE, AND IDENTIFICATION AS CD47.
RC TISSUE=Erythrocyte;
RX PubMed=7998989;
RA Mawby W.J., Holmes C.H., Anstee D.J., Spring F.A., Tanner M.J.A.;
RT "Isolation and characterization of CD47 glycoprotein: a multispanning
RT membrane protein which is the same as integrin-associated protein
RT (IAP) and the ovarian tumour marker OA3.";
RL Biochem. J. 304:525-530(1994).
RN [8]
RP INTERACTION WITH UBQLN1 AND UBQLN2.
RX PubMed=10549293; DOI=10.1016/S1097-2765(00)80212-9;
RA Wu A.-L., Wang J., Zheleznyak A., Brown E.J.;
RT "Ubiquitin-related proteins regulate interaction of vimentin
RT intermediate filaments with the plasma membrane.";
RL Mol. Cell 4:619-625(1999).
RN [9]
RP DISULFIDE BOND.
RX PubMed=11454874; DOI=10.1074/jbc.M106107200;
RA Rebres R.A., Vaz L.E., Green J.M., Brown E.J.;
RT "Normal ligand binding and signaling by CD47 (integrin-associated
RT protein) requires a long range disulfide bond between the
RT extracellular and membrane-spanning domains.";
RL J. Biol. Chem. 276:34607-34616(2001).
RN [10]
RP FUNCTION, AND INTERACTION WITH SIRPA.
RX PubMed=11509594;
RA Latour S., Tanaka H., Demeure C., Mateo V., Rubio M., Brown E.J.,
RA Maliszewski C., Lindberg F.P., Oldenborg A., Ullrich A.,
RA Delespesse G., Sarfati M.;
RT "Bidirectional negative regulation of human T and dendritic cells by
RT CD47 and its cognate receptor signal-regulator protein-alpha: down-
RT regulation of IL-12 responsiveness and inhibition of dendritic cell
RT activation.";
RL J. Immunol. 167:2547-2554(2001).
RN [11]
RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA Hillman R.T., Green R.E., Brenner S.E.;
RT "An unappreciated role for RNA surveillance.";
RL Genome Biol. 5:R8.1-R8.16(2004).
RN [12]
RP FUNCTION, AND INTERACTION WITH SIRPG.
RC TISSUE=T-cell;
RX PubMed=15383453; DOI=10.1182/blood-2004-07-2823;
RA Piccio L., Vermi W., Boles K.S., Fuchs A., Strader C.A., Facchetti F.,
RA Cella M., Colonna M.;
RT "Adhesion of human T cells to antigen-presenting cells through
RT SIRPbeta2-CD47 interaction costimulates T-cell proliferation.";
RL Blood 105:2421-2427(2005).
RN [13]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-73 AND ASN-111, AND MASS
RP 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 [14]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-50 AND ASN-73, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-
RT linked cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 19-136 IN COMPLEX WITH
RP SIRPA, DISULFIDE BOND, GLYCOSYLATION AT ASN-23; ASN-50; ASN-73 AND
RP ASN-111, AND PYROGLUTAMATE FORMATION AT GLN-19.
RX PubMed=18657508; DOI=10.1016/j.molcel.2008.05.026;
RA Hatherley D., Graham S.C., Turner J., Harlos K., Stuart D.I.,
RA Barclay A.N.;
RT "Paired receptor specificity explained by structures of signal
RT regulatory proteins alone and complexed with CD47.";
RL Mol. Cell 31:266-277(2008).
CC -!- FUNCTION: Has a role in both cell adhesion by acting as an
CC adhesion receptor for THBS1 on platelets, and in the modulation of
CC integrins. Plays an important role in memory formation and
CC synaptic plasticity in the hippocampus (By similarity). Receptor
CC for SIRPA, binding to which prevents maturation of immature
CC dendritic cells and inhibits cytokine production by mature
CC dendritic cells. Interaction with SIRPG mediates cell-cell
CC adhesion, enhances superantigen-dependent T-cell-mediated
CC proliferation and costimulates T-cell activation. May play a role
CC in membrane transport and/or integrin dependent signal
CC transduction. May prevent premature elimination of red blood
CC cells. May be involved in membrane permeability changes induced
CC following virus infection.
CC -!- SUBUNIT: Interacts with THBS1 and fibrinogen (By similarity).
CC Monomer. Interacts with SIRPA, SIRPG, UBQLN1 and UBQLN2.
CC -!- INTERACTION:
CC Q9P1W8:SIRPG; NbExp=2; IntAct=EBI-1268321, EBI-1268284;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=OA3-323;
CC IsoId=Q08722-1; Sequence=Displayed;
CC Name=OA3-293;
CC IsoId=Q08722-2; Sequence=VSP_002535;
CC Name=OA3-305;
CC IsoId=Q08722-3; Sequence=VSP_002536, VSP_002537;
CC Note=May be produced at very low levels due to a premature stop
CC codon in the mRNA, leading to nonsense-mediated mRNA decay;
CC Name=OA3-312;
CC IsoId=Q08722-4; Sequence=VSP_002538;
CC -!- TISSUE SPECIFICITY: Very broadly distributed on normal adult
CC tissues, as well as ovarian tumors, being especially abundant in
CC some epithelia and the brain.
CC -!- SIMILARITY: Contains 1 Ig-like V-type (immunoglobulin-like)
CC domain.
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DR EMBL; X69398; CAA49196.1; -; mRNA.
DR EMBL; Z25521; CAA80977.1; -; mRNA.
DR EMBL; BT006907; AAP35553.1; -; mRNA.
DR EMBL; AK289813; BAF82502.1; -; mRNA.
DR EMBL; CH471052; EAW79733.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79734.1; -; Genomic_DNA.
DR EMBL; BC010016; AAH10016.1; -; mRNA.
DR EMBL; BC012884; AAH12884.1; -; mRNA.
DR EMBL; BC037306; AAH37306.1; -; mRNA.
DR PIR; A48997; A48997.
DR RefSeq; NP_001768.1; NM_001777.3.
DR RefSeq; NP_942088.1; NM_198793.2.
DR UniGene; Hs.446414; -.
DR PDB; 2JJS; X-ray; 1.85 A; C/D=20-136.
DR PDB; 2JJT; X-ray; 2.30 A; C/D=20-136.
DR PDB; 2VSC; X-ray; 1.90 A; A/B/C/D=20-136.
DR PDB; 4KJY; X-ray; 1.93 A; A/C=20-135.
DR PDBsum; 2JJS; -.
DR PDBsum; 2JJT; -.
DR PDBsum; 2VSC; -.
DR PDBsum; 4KJY; -.
DR ProteinModelPortal; Q08722; -.
DR SMR; Q08722; 19-134.
DR IntAct; Q08722; 2.
DR STRING; 9606.ENSP00000355361; -.
DR PhosphoSite; Q08722; -.
DR DMDM; 1171879; -.
DR PaxDb; Q08722; -.
DR PRIDE; Q08722; -.
DR DNASU; 961; -.
DR Ensembl; ENST00000355354; ENSP00000347512; ENSG00000196776.
DR Ensembl; ENST00000361309; ENSP00000355361; ENSG00000196776.
DR GeneID; 961; -.
DR KEGG; hsa:961; -.
DR UCSC; uc003dwt.1; human.
DR CTD; 961; -.
DR GeneCards; GC03M107761; -.
DR HGNC; HGNC:1682; CD47.
DR HPA; CAB016055; -.
DR MIM; 601028; gene.
DR neXtProt; NX_Q08722; -.
DR PharmGKB; PA26222; -.
DR eggNOG; NOG42016; -.
DR HOGENOM; HOG000013020; -.
DR HOVERGEN; HBG003808; -.
DR KO; K06266; -.
DR OMA; VYMKFVA; -.
DR OrthoDB; EOG79GT78; -.
DR PhylomeDB; Q08722; -.
DR Reactome; REACT_111155; Cell-Cell communication.
DR Reactome; REACT_118779; Extracellular matrix organization.
DR Reactome; REACT_604; Hemostasis.
DR ChiTaRS; CD47; human.
DR EvolutionaryTrace; Q08722; -.
DR GeneWiki; CD47; -.
DR GenomeRNAi; 961; -.
DR NextBio; 4012; -.
DR PRO; PR:Q08722; -.
DR Bgee; Q08722; -.
DR CleanEx; HS_CD47; -.
DR Genevestigator; Q08722; -.
DR GO; GO:0070062; C:extracellular vesicular exosome; IEA:Ensembl.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0070053; F:thrombospondin receptor activity; IPI:BHF-UCL.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; TAS:ProtInc.
DR GO; GO:0050900; P:leukocyte migration; TAS:Reactome.
DR GO; GO:0008228; P:opsonization; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell proliferation; IDA:UniProtKB.
DR GO; GO:0022409; P:positive regulation of cell-cell adhesion; IDA:UniProtKB.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:0050766; P:positive regulation of phagocytosis; IEA:Ensembl.
DR GO; GO:0050870; P:positive regulation of T cell activation; IDA:UniProtKB.
DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR006704; CD47.
DR InterPro; IPR013147; CD47_TM.
DR InterPro; IPR013270; CD47_Vset.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR013783; Ig-like_fold.
DR PANTHER; PTHR10613; PTHR10613; 1.
DR Pfam; PF04549; CD47; 1.
DR Pfam; PF08204; V-set_CD47; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell adhesion; Cell membrane;
KW Complete proteome; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Immunoglobulin domain; Membrane;
KW Pyrrolidone carboxylic acid; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1 18 Potential.
FT CHAIN 19 323 Leukocyte surface antigen CD47.
FT /FTId=PRO_0000014880.
FT TOPO_DOM 19 141 Extracellular (Potential).
FT TRANSMEM 142 162 Helical; (Potential).
FT TOPO_DOM 163 176 Cytoplasmic (Potential).
FT TRANSMEM 177 197 Helical; (Potential).
FT TOPO_DOM 198 207 Extracellular (Potential).
FT TRANSMEM 208 228 Helical; (Potential).
FT TOPO_DOM 229 235 Cytoplasmic (Potential).
FT TRANSMEM 236 256 Helical; (Potential).
FT TOPO_DOM 257 268 Extracellular (Potential).
FT TRANSMEM 269 289 Helical; (Potential).
FT TOPO_DOM 290 323 Cytoplasmic (Potential).
FT DOMAIN 19 127 Ig-like V-type.
FT MOD_RES 19 19 Pyrrolidone carboxylic acid.
FT CARBOHYD 23 23 N-linked (GlcNAc...).
FT CARBOHYD 34 34 N-linked (GlcNAc...).
FT CARBOHYD 50 50 N-linked (GlcNAc...).
FT CARBOHYD 73 73 N-linked (GlcNAc...).
FT CARBOHYD 111 111 N-linked (GlcNAc...).
FT CARBOHYD 206 206 N-linked (GlcNAc...) (Potential).
FT DISULFID 33 263
FT DISULFID 41 114
FT VAR_SEQ 293 323 Missing (in isoform OA3-293).
FT /FTId=VSP_002535.
FT VAR_SEQ 304 305 KA -> NN (in isoform OA3-305).
FT /FTId=VSP_002536.
FT VAR_SEQ 306 323 Missing (in isoform OA3-305).
FT /FTId=VSP_002537.
FT VAR_SEQ 312 323 Missing (in isoform OA3-312).
FT /FTId=VSP_002538.
FT STRAND 26 30
FT STRAND 35 39
FT STRAND 42 45
FT HELIX 51 53
FT STRAND 54 60
FT STRAND 63 69
FT HELIX 70 72
FT STRAND 74 76
FT HELIX 79 81
FT HELIX 88 93
FT STRAND 98 101
FT HELIX 102 106
FT STRAND 110 118
FT STRAND 121 131
SQ SEQUENCE 323 AA; 35214 MW; 5D20730A2632D550 CRC64;
MWPLVAALLL GSACCGSAQL LFNKTKSVEF TFCNDTVVIP CFVTNMEAQN TTEVYVKWKF
KGRDIYTFDG ALNKSTVPTD FSSAKIEVSQ LLKGDASLKM DKSDAVSHTG NYTCEVTELT
REGETIIELK YRVVSWFSPN ENILIVIFPI FAILLFWGQF GIKTLKYRSG GMDEKTIALL
VAGLVITVIV IVGAILFVPG EYSLKNATGL GLIVTSTGIL ILLHYYVFST AIGLTSFVIA
ILVIQVIAYI LAVVGLSLCI AACIPMHGPL LISGLSILAL AQLLGLVYMK FVASNQKTIQ
PPRKAVEEPL NAFKESKGMM NDE
//
ID CD47_HUMAN Reviewed; 323 AA.
AC Q08722; A8K198; D3DN59; Q53Y71; Q96A60;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1995, sequence version 1.
DT 22-JAN-2014, entry version 131.
DE RecName: Full=Leukocyte surface antigen CD47;
DE AltName: Full=Antigenic surface determinant protein OA3;
DE AltName: Full=Integrin-associated protein;
DE Short=IAP;
DE AltName: Full=Protein MER6;
DE AltName: CD_antigen=CD47;
DE Flags: Precursor;
GN Name=CD47; Synonyms=MER6;
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] (ISOFORM OA3-323).
RC TISSUE=Ovary;
RX PubMed=1394148;
RA Campbell I.G., Freemont P.S., Foulkes W., Trowsdale J.;
RT "An ovarian tumor marker with homology to vaccinia virus contains an
RT IgV-like region and multiple transmembrane domains.";
RL Cancer Res. 52:5416-5420(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM OA3-305), FUNCTION, SUBCELLULAR
RP LOCATION, AND TOPOLOGY.
RC TISSUE=Myelomonocyte;
RX PubMed=7691831; DOI=10.1083/jcb.123.2.485;
RA Lindberg F.P., Gresham H.D., Schwarz E., Brown E.J.;
RT "Molecular cloning of integrin-associated protein: an immunoglobulin
RT family member with multiple membrane spanning domains implicated in
RT alpha-v beta-3-dependent ligand binding.";
RL J. Cell Biol. 123:485-496(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM OA3-305).
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] (ISOFORM OA3-323).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM OA3-305).
RC TISSUE=Hippocampus, Leiomyosarcoma, and Ovarian adenocarcinoma;
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 PARTIAL PROTEIN SEQUENCE, AND IDENTIFICATION AS CD47.
RC TISSUE=Erythrocyte;
RX PubMed=7998989;
RA Mawby W.J., Holmes C.H., Anstee D.J., Spring F.A., Tanner M.J.A.;
RT "Isolation and characterization of CD47 glycoprotein: a multispanning
RT membrane protein which is the same as integrin-associated protein
RT (IAP) and the ovarian tumour marker OA3.";
RL Biochem. J. 304:525-530(1994).
RN [8]
RP INTERACTION WITH UBQLN1 AND UBQLN2.
RX PubMed=10549293; DOI=10.1016/S1097-2765(00)80212-9;
RA Wu A.-L., Wang J., Zheleznyak A., Brown E.J.;
RT "Ubiquitin-related proteins regulate interaction of vimentin
RT intermediate filaments with the plasma membrane.";
RL Mol. Cell 4:619-625(1999).
RN [9]
RP DISULFIDE BOND.
RX PubMed=11454874; DOI=10.1074/jbc.M106107200;
RA Rebres R.A., Vaz L.E., Green J.M., Brown E.J.;
RT "Normal ligand binding and signaling by CD47 (integrin-associated
RT protein) requires a long range disulfide bond between the
RT extracellular and membrane-spanning domains.";
RL J. Biol. Chem. 276:34607-34616(2001).
RN [10]
RP FUNCTION, AND INTERACTION WITH SIRPA.
RX PubMed=11509594;
RA Latour S., Tanaka H., Demeure C., Mateo V., Rubio M., Brown E.J.,
RA Maliszewski C., Lindberg F.P., Oldenborg A., Ullrich A.,
RA Delespesse G., Sarfati M.;
RT "Bidirectional negative regulation of human T and dendritic cells by
RT CD47 and its cognate receptor signal-regulator protein-alpha: down-
RT regulation of IL-12 responsiveness and inhibition of dendritic cell
RT activation.";
RL J. Immunol. 167:2547-2554(2001).
RN [11]
RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA Hillman R.T., Green R.E., Brenner S.E.;
RT "An unappreciated role for RNA surveillance.";
RL Genome Biol. 5:R8.1-R8.16(2004).
RN [12]
RP FUNCTION, AND INTERACTION WITH SIRPG.
RC TISSUE=T-cell;
RX PubMed=15383453; DOI=10.1182/blood-2004-07-2823;
RA Piccio L., Vermi W., Boles K.S., Fuchs A., Strader C.A., Facchetti F.,
RA Cella M., Colonna M.;
RT "Adhesion of human T cells to antigen-presenting cells through
RT SIRPbeta2-CD47 interaction costimulates T-cell proliferation.";
RL Blood 105:2421-2427(2005).
RN [13]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-73 AND ASN-111, AND MASS
RP 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 [14]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-50 AND ASN-73, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-
RT linked cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 19-136 IN COMPLEX WITH
RP SIRPA, DISULFIDE BOND, GLYCOSYLATION AT ASN-23; ASN-50; ASN-73 AND
RP ASN-111, AND PYROGLUTAMATE FORMATION AT GLN-19.
RX PubMed=18657508; DOI=10.1016/j.molcel.2008.05.026;
RA Hatherley D., Graham S.C., Turner J., Harlos K., Stuart D.I.,
RA Barclay A.N.;
RT "Paired receptor specificity explained by structures of signal
RT regulatory proteins alone and complexed with CD47.";
RL Mol. Cell 31:266-277(2008).
CC -!- FUNCTION: Has a role in both cell adhesion by acting as an
CC adhesion receptor for THBS1 on platelets, and in the modulation of
CC integrins. Plays an important role in memory formation and
CC synaptic plasticity in the hippocampus (By similarity). Receptor
CC for SIRPA, binding to which prevents maturation of immature
CC dendritic cells and inhibits cytokine production by mature
CC dendritic cells. Interaction with SIRPG mediates cell-cell
CC adhesion, enhances superantigen-dependent T-cell-mediated
CC proliferation and costimulates T-cell activation. May play a role
CC in membrane transport and/or integrin dependent signal
CC transduction. May prevent premature elimination of red blood
CC cells. May be involved in membrane permeability changes induced
CC following virus infection.
CC -!- SUBUNIT: Interacts with THBS1 and fibrinogen (By similarity).
CC Monomer. Interacts with SIRPA, SIRPG, UBQLN1 and UBQLN2.
CC -!- INTERACTION:
CC Q9P1W8:SIRPG; NbExp=2; IntAct=EBI-1268321, EBI-1268284;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=OA3-323;
CC IsoId=Q08722-1; Sequence=Displayed;
CC Name=OA3-293;
CC IsoId=Q08722-2; Sequence=VSP_002535;
CC Name=OA3-305;
CC IsoId=Q08722-3; Sequence=VSP_002536, VSP_002537;
CC Note=May be produced at very low levels due to a premature stop
CC codon in the mRNA, leading to nonsense-mediated mRNA decay;
CC Name=OA3-312;
CC IsoId=Q08722-4; Sequence=VSP_002538;
CC -!- TISSUE SPECIFICITY: Very broadly distributed on normal adult
CC tissues, as well as ovarian tumors, being especially abundant in
CC some epithelia and the brain.
CC -!- SIMILARITY: Contains 1 Ig-like V-type (immunoglobulin-like)
CC domain.
CC -----------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; X69398; CAA49196.1; -; mRNA.
DR EMBL; Z25521; CAA80977.1; -; mRNA.
DR EMBL; BT006907; AAP35553.1; -; mRNA.
DR EMBL; AK289813; BAF82502.1; -; mRNA.
DR EMBL; CH471052; EAW79733.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79734.1; -; Genomic_DNA.
DR EMBL; BC010016; AAH10016.1; -; mRNA.
DR EMBL; BC012884; AAH12884.1; -; mRNA.
DR EMBL; BC037306; AAH37306.1; -; mRNA.
DR PIR; A48997; A48997.
DR RefSeq; NP_001768.1; NM_001777.3.
DR RefSeq; NP_942088.1; NM_198793.2.
DR UniGene; Hs.446414; -.
DR PDB; 2JJS; X-ray; 1.85 A; C/D=20-136.
DR PDB; 2JJT; X-ray; 2.30 A; C/D=20-136.
DR PDB; 2VSC; X-ray; 1.90 A; A/B/C/D=20-136.
DR PDB; 4KJY; X-ray; 1.93 A; A/C=20-135.
DR PDBsum; 2JJS; -.
DR PDBsum; 2JJT; -.
DR PDBsum; 2VSC; -.
DR PDBsum; 4KJY; -.
DR ProteinModelPortal; Q08722; -.
DR SMR; Q08722; 19-134.
DR IntAct; Q08722; 2.
DR STRING; 9606.ENSP00000355361; -.
DR PhosphoSite; Q08722; -.
DR DMDM; 1171879; -.
DR PaxDb; Q08722; -.
DR PRIDE; Q08722; -.
DR DNASU; 961; -.
DR Ensembl; ENST00000355354; ENSP00000347512; ENSG00000196776.
DR Ensembl; ENST00000361309; ENSP00000355361; ENSG00000196776.
DR GeneID; 961; -.
DR KEGG; hsa:961; -.
DR UCSC; uc003dwt.1; human.
DR CTD; 961; -.
DR GeneCards; GC03M107761; -.
DR HGNC; HGNC:1682; CD47.
DR HPA; CAB016055; -.
DR MIM; 601028; gene.
DR neXtProt; NX_Q08722; -.
DR PharmGKB; PA26222; -.
DR eggNOG; NOG42016; -.
DR HOGENOM; HOG000013020; -.
DR HOVERGEN; HBG003808; -.
DR KO; K06266; -.
DR OMA; VYMKFVA; -.
DR OrthoDB; EOG79GT78; -.
DR PhylomeDB; Q08722; -.
DR Reactome; REACT_111155; Cell-Cell communication.
DR Reactome; REACT_118779; Extracellular matrix organization.
DR Reactome; REACT_604; Hemostasis.
DR ChiTaRS; CD47; human.
DR EvolutionaryTrace; Q08722; -.
DR GeneWiki; CD47; -.
DR GenomeRNAi; 961; -.
DR NextBio; 4012; -.
DR PRO; PR:Q08722; -.
DR Bgee; Q08722; -.
DR CleanEx; HS_CD47; -.
DR Genevestigator; Q08722; -.
DR GO; GO:0070062; C:extracellular vesicular exosome; IEA:Ensembl.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0070053; F:thrombospondin receptor activity; IPI:BHF-UCL.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; TAS:ProtInc.
DR GO; GO:0050900; P:leukocyte migration; TAS:Reactome.
DR GO; GO:0008228; P:opsonization; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell proliferation; IDA:UniProtKB.
DR GO; GO:0022409; P:positive regulation of cell-cell adhesion; IDA:UniProtKB.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:0050766; P:positive regulation of phagocytosis; IEA:Ensembl.
DR GO; GO:0050870; P:positive regulation of T cell activation; IDA:UniProtKB.
DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR006704; CD47.
DR InterPro; IPR013147; CD47_TM.
DR InterPro; IPR013270; CD47_Vset.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR013783; Ig-like_fold.
DR PANTHER; PTHR10613; PTHR10613; 1.
DR Pfam; PF04549; CD47; 1.
DR Pfam; PF08204; V-set_CD47; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell adhesion; Cell membrane;
KW Complete proteome; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Immunoglobulin domain; Membrane;
KW Pyrrolidone carboxylic acid; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1 18 Potential.
FT CHAIN 19 323 Leukocyte surface antigen CD47.
FT /FTId=PRO_0000014880.
FT TOPO_DOM 19 141 Extracellular (Potential).
FT TRANSMEM 142 162 Helical; (Potential).
FT TOPO_DOM 163 176 Cytoplasmic (Potential).
FT TRANSMEM 177 197 Helical; (Potential).
FT TOPO_DOM 198 207 Extracellular (Potential).
FT TRANSMEM 208 228 Helical; (Potential).
FT TOPO_DOM 229 235 Cytoplasmic (Potential).
FT TRANSMEM 236 256 Helical; (Potential).
FT TOPO_DOM 257 268 Extracellular (Potential).
FT TRANSMEM 269 289 Helical; (Potential).
FT TOPO_DOM 290 323 Cytoplasmic (Potential).
FT DOMAIN 19 127 Ig-like V-type.
FT MOD_RES 19 19 Pyrrolidone carboxylic acid.
FT CARBOHYD 23 23 N-linked (GlcNAc...).
FT CARBOHYD 34 34 N-linked (GlcNAc...).
FT CARBOHYD 50 50 N-linked (GlcNAc...).
FT CARBOHYD 73 73 N-linked (GlcNAc...).
FT CARBOHYD 111 111 N-linked (GlcNAc...).
FT CARBOHYD 206 206 N-linked (GlcNAc...) (Potential).
FT DISULFID 33 263
FT DISULFID 41 114
FT VAR_SEQ 293 323 Missing (in isoform OA3-293).
FT /FTId=VSP_002535.
FT VAR_SEQ 304 305 KA -> NN (in isoform OA3-305).
FT /FTId=VSP_002536.
FT VAR_SEQ 306 323 Missing (in isoform OA3-305).
FT /FTId=VSP_002537.
FT VAR_SEQ 312 323 Missing (in isoform OA3-312).
FT /FTId=VSP_002538.
FT STRAND 26 30
FT STRAND 35 39
FT STRAND 42 45
FT HELIX 51 53
FT STRAND 54 60
FT STRAND 63 69
FT HELIX 70 72
FT STRAND 74 76
FT HELIX 79 81
FT HELIX 88 93
FT STRAND 98 101
FT HELIX 102 106
FT STRAND 110 118
FT STRAND 121 131
SQ SEQUENCE 323 AA; 35214 MW; 5D20730A2632D550 CRC64;
MWPLVAALLL GSACCGSAQL LFNKTKSVEF TFCNDTVVIP CFVTNMEAQN TTEVYVKWKF
KGRDIYTFDG ALNKSTVPTD FSSAKIEVSQ LLKGDASLKM DKSDAVSHTG NYTCEVTELT
REGETIIELK YRVVSWFSPN ENILIVIFPI FAILLFWGQF GIKTLKYRSG GMDEKTIALL
VAGLVITVIV IVGAILFVPG EYSLKNATGL GLIVTSTGIL ILLHYYVFST AIGLTSFVIA
ILVIQVIAYI LAVVGLSLCI AACIPMHGPL LISGLSILAL AQLLGLVYMK FVASNQKTIQ
PPRKAVEEPL NAFKESKGMM NDE
//
MIM
601028
*RECORD*
*FIELD* NO
601028
*FIELD* TI
*601028 CD47 ANTIGEN; CD47
;;SURFACE ANTIGEN IDENTIFIED BY MONOCLONAL ANTIBODY 1D8; MER6;;
read moreINTEGRIN-ASSOCIATED PROTEIN; IAP;;
CD47 GLYCOPROTEIN
*FIELD* TX
CLONING
By testing hybrids containing various deletions of chromosome 3, Miller
et al. (1987) described an IgM monoclonal antibody, 1D8, that recognized
an antigen coded by a gene located in the region 3cen-q22. The
monoclonal antibody was designated MER6. The antigen was absent in the
Rh deficiency syndrome, Rh-null hemolytic anemia (268150). However, this
antigen probably had no pathogenetic role in the Rh deficiency, which
was shown by Cherif-Zahar et al. (1996) to be due to mutation in the
Rh50 gene (180297) on chromosome 6. Cherif-Zahar et al. (1996) noted
that many cell membrane components are missing from the multisubunit Rh
complex when the RH50A gene is mutant.
Lindberg et al. (1994) stated that IAP is a 50-kD membrane protein with
an N-terminal immunoglobulin domain and a C-terminal multiple
membrane-spanning region. IAP is identical to the ovarian tumor marker
OA3 (Mawby et al., 1994). It is involved in the increase in
intracellular calcium concentration that occurs upon cell adhesion to
extracellular matrix. IAP is also expressed on erythrocytes, which have
no known integrins. Lindberg et al. (1994) found that IAP expression was
reduced on Rh(null) erythrocytes. Using FISH, Lindberg et al. (1994)
mapped IAP within a region of chromosome 3 known to contain the gene
encoding the Rh-associated 1D8 antigen. By expression studies on human
erythrocytes and IAP transfectants, IAP was found to be identical to the
1D8 antigen and to CD47, a cell surface protein with broad tissue
distribution and reduced expression on Rh(null) erythrocytes. Lindberg
et al. (1994) stated that these studies demonstrated an unexpected link
between integrin signal transduction and erythrocyte membrane structure.
GENE FUNCTION
The immune system recognizes invaders as foreign because they express
determinants that are absent on host cells or because they lack 'markers
of self' that are normally present. Oldenborg et al. (2000) found that
Cd47 functioned as a marker of self on murine red blood cells. Red blood
cells lacking Cd47 were rapidly cleared from the bloodstream by splenic
red pulp macrophages. Cd47 on normal red blood cells prevented this
elimination by binding to the inhibitory receptor signal regulatory
protein (SIRP)-alpha (PTPNS1; 602461). Oldenborg et al. (2000) concluded
that macrophages may use a number of nonspecific activating receptors
and rely on the presence or absence of CD47 to distinguish self from
foreign. They suggested that CD47-SIRP-alpha may represent a potential
pathway for the control of hemolytic anemia.
Osteoclasts and giant cells are multinucleated and resorb the substrate
onto which they adhere. They are thought to originate from the fusion of
mononuclear phagocytes. Han et al. (2000) used immunofluorescence
microscopy to show that at the onset of fusion macrophages express not
only the macrophage fusion receptor (MFR, or SIRP-alpha) but also, at a
lower level than MFR, the hemopoietic form of CD47. Immunoprecipitation
and immunoblot experiments confirmed the association of the CD47
variable domain and the MFR immunoglobulin V1 domain. Macrophage fusion
could be blocked by either anti-CD47 monoclonal antibodies or a CD47
fusion protein.
Type III, or necrosis-like, programmed cell death (PCD) is defined
exclusively by cytoplasmic features and seems to operate in a
caspase-independent manner. Bras et al. (2007) showed that ligation of
CD47 triggered type III PCD in B cells from healthy volunteers and
patients with chronic lymphocytic leukemia (CLL; 151400), and they
identified DRP1 (DNM1L; 603850) as a key mediator of this PCD. CD47
ligation induced DRP1 translocation from the cytosol to mitochondria. In
mitochondria, DRP1 provoked impairment of the mitochondrial electron
transport chain, resulting in dissipation of mitochondrial transmembrane
potential, generation of reactive oxygen species, and a drop in ATP
levels. Responsiveness of cells to CD47 ligation increased following
DRP1 overexpression, while resistance to CD47-mediated death was
observed following DRP1 downregulation. In CLL B cells, DRP1 mRNA levels
strongly correlated with death sensitivity.
CD47 is an antiphagocytic signal that cancer cells employ to inhibit
macrophage-mediated destruction. Weiskopf et al. (2013) modified the
binding domain of human SIRP-alpha, the receptor for CD47, for use as a
CD47 antagonist. Weiskopf et al. (2013) engineered high-affinity
SIRP-alpha variants with about a 50,000-fold increased affinity for
human CD47 relative to wildtype SIRP-alpha As high-affinity SIRP-alpha
monomers, they potently antagonized CD47 on cancer cells but did not
induce macrophage phagocytosis on their own. Instead, they exhibited
remarkable synergy with all tumor-specific monoclonal antibodies tested
by increasing phagocytosis in vitro and enhancing antitumor responses in
vivo. This 'one-two punch' directs immune responses against tumor cells
while lowering the threshold for macrophage activation, thereby
providing a universal method for augmenting the efficacy of therapeutic
anticancer antibodies.
MAPPING
By testing hybrids containing various deletions of chromosome 3, Miller
et al. (1987) described an IgM monoclonal antibody, 1D8, that recognized
an antigen coded by a gene, CD47, on chromosome 3cen-q22.
By FISH, Lindberg et al. (1994) mapped the CD47 gene to chromosome
3q13.1-q13.2.
ANIMAL MODEL
Lindberg et al. (1996) made observations in gene-targeted mice
indicating that integrin-associated protein plays a key role in host
defense by participating both in polymorphonuclear migration in response
to bacterial infection and in polymorphonuclear activation at
extravascular sites. Mice homozygous for knockout of the Iap gene
succumbed to Escherichia coli peritonitis at inoccula survived by
heterozygous littermates. In vivo, they had an early defect in PMN
accumulation at the site of infection. In vivo, they showed deficiency
of several manifestations of PMN activation.
*FIELD* RF
1. Bras, M.; Yuste, V. J.; Roue, G.; Barbier, S.; Sancho, P.; Virely,
C.; Rubio, M.; Baudet, S.; Esquerda, J. E.; Merle-Beral, H.; Sarfati,
M.; Susin, S. A.: Drp1 mediates caspase-independent type III cell
death in normal and leukemic cells. Molec. Cell. Biol. 27: 7073-7088,
2007.
2. Cherif-Zahar, B.; Raynal, V.; Gane, P.; Mattei, M.-G.; Bailly,
P.; Gibbs, B.; Colin, Y.; Cartron, J.-P.: Candidate gene acting as
a suppressor of the RH locus in most cases of Rh-deficiency. Nature
Genet. 12: 168-173, 1996.
3. Han, X.; Sterling, H.; Chen, Y.; Saginario, C.; Brown, E. J.; Frazier,
W. A.; Lindberg, F. P.; Vignery, A.: CD47, a ligand for the macrophage
fusion receptor, participates in macrophage multinucleation. J. Biol.
Chem. 275: 37984-37992, 2000.
4. Lindberg, F. P.; Bullard, D. C.; Caver, T. E.; Gresham, H. D.;
Beaudet, A. L.; Brown, E. J.: Decreased resistance to bacterial infection
and granulocyte defects in IAP-deficient mice. Science 274: 795-798,
1996.
5. Lindberg, F. P.; Lublin, D. M.; Telen, M. J.; Veile, R. A.; Miller,
Y. E.; Donis-Keller, H.; Brown, E. J.: Rh-related antigen CD47 is
the signal-transducer integrin-associated protein. J. Biol. Chem. 269:
1567-1570, 1994.
6. Mawby, W. J.; Holmes, C. H.; Anstee, D. J.; Spring, F. A.; Tanner,
M. J. A.: Isolation and characterization of CD47 glycoprotein: a
multispanning membrane protein which is the same as integrin-associated
protein (IAP) and the ovarian tumour marker OA3. Biochem. J. 304:
525-530, 1994.
7. Miller, Y. E.; Daniels, G. L.; Jones, C.; Palmer, D. K.: Identification
of a cell-surface antigen produced by a gene on human chromosome 3
(cen-q22) and not expressed by Rh(null) cells. Am. J. Hum. Genet. 41:
1061-1070, 1987.
8. Oldenborg, P.-A.; Zheleznyak, A.; Fang, Y.-F.; Lagenaur, C. F.;
Gresham, H. D.; Lindberg, F. P.: Role of CD47 as a marker of self
on red blood cells. Science 288: 2051-2054, 2000.
9. Weiskopf, K.; Ring, A. M.; Ho, C. C. M.; Volkmer, J.-P.; Levin,
A. M.; Volkmer, A. K.; Ozkan, E.; Fernhoff, N. B.; van de Rijn, M.;
Weissman, I. L.; Garcia, K. C.: Engineered SIRP-alpha variants as
immunotherapeutic adjuvants to anticancer antibodies. Science 341:
88-91, 2013.
*FIELD* CN
Ada Hamosh - updated: 10/29/2013
Patricia A. Hartz - updated: 1/25/2010
Paul J. Converse - updated: 2/1/2001
Ada Hamosh - updated: 6/15/2000
*FIELD* CD
Victor A. McKusick: 2/1/1996
*FIELD* ED
alopez: 10/29/2013
mgross: 1/25/2010
carol: 7/21/2006
mcapotos: 2/7/2001
mcapotos: 2/1/2001
alopez: 6/15/2000
alopez: 1/14/2000
terry: 12/6/1996
terry: 5/14/1996
terry: 5/10/1996
mark: 2/1/1996
*RECORD*
*FIELD* NO
601028
*FIELD* TI
*601028 CD47 ANTIGEN; CD47
;;SURFACE ANTIGEN IDENTIFIED BY MONOCLONAL ANTIBODY 1D8; MER6;;
read moreINTEGRIN-ASSOCIATED PROTEIN; IAP;;
CD47 GLYCOPROTEIN
*FIELD* TX
CLONING
By testing hybrids containing various deletions of chromosome 3, Miller
et al. (1987) described an IgM monoclonal antibody, 1D8, that recognized
an antigen coded by a gene located in the region 3cen-q22. The
monoclonal antibody was designated MER6. The antigen was absent in the
Rh deficiency syndrome, Rh-null hemolytic anemia (268150). However, this
antigen probably had no pathogenetic role in the Rh deficiency, which
was shown by Cherif-Zahar et al. (1996) to be due to mutation in the
Rh50 gene (180297) on chromosome 6. Cherif-Zahar et al. (1996) noted
that many cell membrane components are missing from the multisubunit Rh
complex when the RH50A gene is mutant.
Lindberg et al. (1994) stated that IAP is a 50-kD membrane protein with
an N-terminal immunoglobulin domain and a C-terminal multiple
membrane-spanning region. IAP is identical to the ovarian tumor marker
OA3 (Mawby et al., 1994). It is involved in the increase in
intracellular calcium concentration that occurs upon cell adhesion to
extracellular matrix. IAP is also expressed on erythrocytes, which have
no known integrins. Lindberg et al. (1994) found that IAP expression was
reduced on Rh(null) erythrocytes. Using FISH, Lindberg et al. (1994)
mapped IAP within a region of chromosome 3 known to contain the gene
encoding the Rh-associated 1D8 antigen. By expression studies on human
erythrocytes and IAP transfectants, IAP was found to be identical to the
1D8 antigen and to CD47, a cell surface protein with broad tissue
distribution and reduced expression on Rh(null) erythrocytes. Lindberg
et al. (1994) stated that these studies demonstrated an unexpected link
between integrin signal transduction and erythrocyte membrane structure.
GENE FUNCTION
The immune system recognizes invaders as foreign because they express
determinants that are absent on host cells or because they lack 'markers
of self' that are normally present. Oldenborg et al. (2000) found that
Cd47 functioned as a marker of self on murine red blood cells. Red blood
cells lacking Cd47 were rapidly cleared from the bloodstream by splenic
red pulp macrophages. Cd47 on normal red blood cells prevented this
elimination by binding to the inhibitory receptor signal regulatory
protein (SIRP)-alpha (PTPNS1; 602461). Oldenborg et al. (2000) concluded
that macrophages may use a number of nonspecific activating receptors
and rely on the presence or absence of CD47 to distinguish self from
foreign. They suggested that CD47-SIRP-alpha may represent a potential
pathway for the control of hemolytic anemia.
Osteoclasts and giant cells are multinucleated and resorb the substrate
onto which they adhere. They are thought to originate from the fusion of
mononuclear phagocytes. Han et al. (2000) used immunofluorescence
microscopy to show that at the onset of fusion macrophages express not
only the macrophage fusion receptor (MFR, or SIRP-alpha) but also, at a
lower level than MFR, the hemopoietic form of CD47. Immunoprecipitation
and immunoblot experiments confirmed the association of the CD47
variable domain and the MFR immunoglobulin V1 domain. Macrophage fusion
could be blocked by either anti-CD47 monoclonal antibodies or a CD47
fusion protein.
Type III, or necrosis-like, programmed cell death (PCD) is defined
exclusively by cytoplasmic features and seems to operate in a
caspase-independent manner. Bras et al. (2007) showed that ligation of
CD47 triggered type III PCD in B cells from healthy volunteers and
patients with chronic lymphocytic leukemia (CLL; 151400), and they
identified DRP1 (DNM1L; 603850) as a key mediator of this PCD. CD47
ligation induced DRP1 translocation from the cytosol to mitochondria. In
mitochondria, DRP1 provoked impairment of the mitochondrial electron
transport chain, resulting in dissipation of mitochondrial transmembrane
potential, generation of reactive oxygen species, and a drop in ATP
levels. Responsiveness of cells to CD47 ligation increased following
DRP1 overexpression, while resistance to CD47-mediated death was
observed following DRP1 downregulation. In CLL B cells, DRP1 mRNA levels
strongly correlated with death sensitivity.
CD47 is an antiphagocytic signal that cancer cells employ to inhibit
macrophage-mediated destruction. Weiskopf et al. (2013) modified the
binding domain of human SIRP-alpha, the receptor for CD47, for use as a
CD47 antagonist. Weiskopf et al. (2013) engineered high-affinity
SIRP-alpha variants with about a 50,000-fold increased affinity for
human CD47 relative to wildtype SIRP-alpha As high-affinity SIRP-alpha
monomers, they potently antagonized CD47 on cancer cells but did not
induce macrophage phagocytosis on their own. Instead, they exhibited
remarkable synergy with all tumor-specific monoclonal antibodies tested
by increasing phagocytosis in vitro and enhancing antitumor responses in
vivo. This 'one-two punch' directs immune responses against tumor cells
while lowering the threshold for macrophage activation, thereby
providing a universal method for augmenting the efficacy of therapeutic
anticancer antibodies.
MAPPING
By testing hybrids containing various deletions of chromosome 3, Miller
et al. (1987) described an IgM monoclonal antibody, 1D8, that recognized
an antigen coded by a gene, CD47, on chromosome 3cen-q22.
By FISH, Lindberg et al. (1994) mapped the CD47 gene to chromosome
3q13.1-q13.2.
ANIMAL MODEL
Lindberg et al. (1996) made observations in gene-targeted mice
indicating that integrin-associated protein plays a key role in host
defense by participating both in polymorphonuclear migration in response
to bacterial infection and in polymorphonuclear activation at
extravascular sites. Mice homozygous for knockout of the Iap gene
succumbed to Escherichia coli peritonitis at inoccula survived by
heterozygous littermates. In vivo, they had an early defect in PMN
accumulation at the site of infection. In vivo, they showed deficiency
of several manifestations of PMN activation.
*FIELD* RF
1. Bras, M.; Yuste, V. J.; Roue, G.; Barbier, S.; Sancho, P.; Virely,
C.; Rubio, M.; Baudet, S.; Esquerda, J. E.; Merle-Beral, H.; Sarfati,
M.; Susin, S. A.: Drp1 mediates caspase-independent type III cell
death in normal and leukemic cells. Molec. Cell. Biol. 27: 7073-7088,
2007.
2. Cherif-Zahar, B.; Raynal, V.; Gane, P.; Mattei, M.-G.; Bailly,
P.; Gibbs, B.; Colin, Y.; Cartron, J.-P.: Candidate gene acting as
a suppressor of the RH locus in most cases of Rh-deficiency. Nature
Genet. 12: 168-173, 1996.
3. Han, X.; Sterling, H.; Chen, Y.; Saginario, C.; Brown, E. J.; Frazier,
W. A.; Lindberg, F. P.; Vignery, A.: CD47, a ligand for the macrophage
fusion receptor, participates in macrophage multinucleation. J. Biol.
Chem. 275: 37984-37992, 2000.
4. Lindberg, F. P.; Bullard, D. C.; Caver, T. E.; Gresham, H. D.;
Beaudet, A. L.; Brown, E. J.: Decreased resistance to bacterial infection
and granulocyte defects in IAP-deficient mice. Science 274: 795-798,
1996.
5. Lindberg, F. P.; Lublin, D. M.; Telen, M. J.; Veile, R. A.; Miller,
Y. E.; Donis-Keller, H.; Brown, E. J.: Rh-related antigen CD47 is
the signal-transducer integrin-associated protein. J. Biol. Chem. 269:
1567-1570, 1994.
6. Mawby, W. J.; Holmes, C. H.; Anstee, D. J.; Spring, F. A.; Tanner,
M. J. A.: Isolation and characterization of CD47 glycoprotein: a
multispanning membrane protein which is the same as integrin-associated
protein (IAP) and the ovarian tumour marker OA3. Biochem. J. 304:
525-530, 1994.
7. Miller, Y. E.; Daniels, G. L.; Jones, C.; Palmer, D. K.: Identification
of a cell-surface antigen produced by a gene on human chromosome 3
(cen-q22) and not expressed by Rh(null) cells. Am. J. Hum. Genet. 41:
1061-1070, 1987.
8. Oldenborg, P.-A.; Zheleznyak, A.; Fang, Y.-F.; Lagenaur, C. F.;
Gresham, H. D.; Lindberg, F. P.: Role of CD47 as a marker of self
on red blood cells. Science 288: 2051-2054, 2000.
9. Weiskopf, K.; Ring, A. M.; Ho, C. C. M.; Volkmer, J.-P.; Levin,
A. M.; Volkmer, A. K.; Ozkan, E.; Fernhoff, N. B.; van de Rijn, M.;
Weissman, I. L.; Garcia, K. C.: Engineered SIRP-alpha variants as
immunotherapeutic adjuvants to anticancer antibodies. Science 341:
88-91, 2013.
*FIELD* CN
Ada Hamosh - updated: 10/29/2013
Patricia A. Hartz - updated: 1/25/2010
Paul J. Converse - updated: 2/1/2001
Ada Hamosh - updated: 6/15/2000
*FIELD* CD
Victor A. McKusick: 2/1/1996
*FIELD* ED
alopez: 10/29/2013
mgross: 1/25/2010
carol: 7/21/2006
mcapotos: 2/7/2001
mcapotos: 2/1/2001
alopez: 6/15/2000
alopez: 1/14/2000
terry: 12/6/1996
terry: 5/14/1996
terry: 5/10/1996
mark: 2/1/1996