Reviewed, UniProtKB/Swiss-Prot Q08722 (CD47_HUMAN)

Names and origin

Protein names

Recommended name:
    Leukocyte surface antigen CD47
Alternative name(s):
    Integrin-associated protein
      Short name=IAP
    Antigenic surface determinant protein OA3
    Protein MER6
    CD_antigen=CD47

Gene names

Name:	CD47
Synonyms:	MER6

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	323 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Has a role in both cell adhesion by acting as an adhesion receptor for THBS1 on platelets, and in the modulation of integrins. Plays an important role in memory formation and synaptic plasticity in the hippocampus By similarity. Receptor for SIRPA, binding to which prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells. Interaction with SIRPG mediates cell-cell adhesion, enhances superantigen-dependent T-cell-mediated proliferation and costimulates T-cell activation. May play a role in membrane transport and/or integrin dependent signal transduction. May prevent premature elimination of red blood cells. May be involved in membrane permeability changes induced following virus infection.
Subunit structure	Interacts with THBS1 and fibrinogen By similarity. Monomer. Interacts with SIRPA, SIRPG, UBQLN1 and UBQLN2.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Very broadly distributed on normal adult tissues, as well as ovarian tumors, being especially abundant in some epithelia and the brain.
Sequence similarities	Contains 1 Ig-like V-type (immunoglobulin-like) domain.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Immunoglobulin domain Signal Transmembrane
PTM	Glycoprotein Pyrrolidone carboxylic acid
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	integrin-mediated signaling pathway Traceable author statement. Source: ProtInc positive regulation of T cell activation Ref.10 Inferred from direct assay. Source: UniProtKB positive regulation of cell proliferation Ref.10 Inferred from direct assay. Source: UniProtKB positive regulation of cell-cell adhesion Ref.10 Inferred from direct assay. Source: UniProtKB
Cellular component	integral to plasma membrane Ref.5 Traceable author statement. Source: ProtInc
Molecular function	protein binding Ref.10 Inferred from physical interaction. Source: UniProtKB thrombospondin receptor activity Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform OA3-323 (identifier: Q08722-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform OA3-293 (identifier: Q08722-2)

The sequence of this isoform differs from the canonical sequence as follows:
     293-323: Missing.

Isoform OA3-305 (identifier: Q08722-3)

The sequence of this isoform differs from the canonical sequence as follows:
     304-305: KA → NN
     306-323: Missing.

Notes: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoform OA3-312 (identifier: Q08722-4)

The sequence of this isoform differs from the canonical sequence as follows:
     312-323: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Potential
	Chain	19 – 323	305	Leukocyte surface antigen CD47		PRO_0000014880
Regions
	Topological domain	19 – 141	123	Extracellular Potential
	Transmembrane	142 – 162	21	Potential
	Topological domain	163 – 176	14	Cytoplasmic Potential
	Transmembrane	177 – 197	21	Potential
	Topological domain	198 – 207	10	Extracellular Potential
	Transmembrane	208 – 228	21	Potential
	Topological domain	229 – 235	7	Cytoplasmic Potential
	Transmembrane	236 – 256	21	Potential
	Topological domain	257 – 268	12	Extracellular Potential
	Transmembrane	269 – 289	21	Potential
	Topological domain	290 – 323	34	Cytoplasmic Potential
	Domain	19 – 127	109	Ig-like V-type
Amino acid modifications
	Modified residue	19	1	Pyrrolidone carboxylic acid Probable
	Glycosylation	23	1	N-linked (GlcNAc...) Potential
	Glycosylation	34	1	N-linked (GlcNAc...)
	Glycosylation	50	1	N-linked (GlcNAc...) Potential
	Glycosylation	73	1	N-linked (GlcNAc...)
	Glycosylation	111	1	N-linked (GlcNAc...)
	Glycosylation	206	1	N-linked (GlcNAc...) Potential
	Disulfide bond	33 ↔ 263
	Disulfide bond	41 ↔ 114		By similarity
Natural variations
	Alternative sequence	293 – 323	31	Missing in isoform OA3-293.		VSP_002535
	Alternative sequence	304 – 305	2	KA → NN in isoform OA3-305.		VSP_002536
	Alternative sequence	306 – 323	18	Missing in isoform OA3-305.		VSP_002537
	Alternative sequence	312 – 323	12	Missing in isoform OA3-312.		VSP_002538

Sequences

	Sequence		Length	Mass (Da)
	Isoform OA3-323 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 5D20730A2632D550	FASTA	323	35,214
	10 20 30 40 50 60 MWPLVAALLL GSACCGSAQL LFNKTKSVEF TFCNDTVVIP CFVTNMEAQN TTEVYVKWKF 70 80 90 100 110 120 KGRDIYTFDG ALNKSTVPTD FSSAKIEVSQ LLKGDASLKM DKSDAVSHTG NYTCEVTELT 130 140 150 160 170 180 REGETIIELK YRVVSWFSPN ENILIVIFPI FAILLFWGQF GIKTLKYRSG GMDEKTIALL 190 200 210 220 230 240 VAGLVITVIV IVGAILFVPG EYSLKNATGL GLIVTSTGIL ILLHYYVFST AIGLTSFVIA 250 260 270 280 290 300 ILVIQVIAYI LAVVGLSLCI AACIPMHGPL LISGLSILAL AQLLGLVYMK FVASNQKTIQ 310 320 PPRKAVEEPL NAFKESKGMM NDE
	Isoform OA3-293 [UniParc]. Checksum: 81A2F6696D11F4E1		292	31,743
	10 20 30 40 50 60 MWPLVAALLL GSACCGSAQL LFNKTKSVEF TFCNDTVVIP CFVTNMEAQN TTEVYVKWKF 70 80 90 100 110 120 KGRDIYTFDG ALNKSTVPTD FSSAKIEVSQ LLKGDASLKM DKSDAVSHTG NYTCEVTELT 130 140 150 160 170 180 REGETIIELK YRVVSWFSPN ENILIVIFPI FAILLFWGQF GIKTLKYRSG GMDEKTIALL 190 200 210 220 230 240 VAGLVITVIV IVGAILFVPG EYSLKNATGL GLIVTSTGIL ILLHYYVFST AIGLTSFVIA 250 260 270 280 290 ILVIQVIAYI LAVVGLSLCI AACIPMHGPL LISGLSILAL AQLLGLVYMK FV
	Isoform OA3-305 [UniParc]. Checksum: 145DD178068F8DBD		305	33,192
	10 20 30 40 50 60 MWPLVAALLL GSACCGSAQL LFNKTKSVEF TFCNDTVVIP CFVTNMEAQN TTEVYVKWKF 70 80 90 100 110 120 KGRDIYTFDG ALNKSTVPTD FSSAKIEVSQ LLKGDASLKM DKSDAVSHTG NYTCEVTELT 130 140 150 160 170 180 REGETIIELK YRVVSWFSPN ENILIVIFPI FAILLFWGQF GIKTLKYRSG GMDEKTIALL 190 200 210 220 230 240 VAGLVITVIV IVGAILFVPG EYSLKNATGL GLIVTSTGIL ILLHYYVFST AIGLTSFVIA 250 260 270 280 290 300 ILVIQVIAYI LAVVGLSLCI AACIPMHGPL LISGLSILAL AQLLGLVYMK FVASNQKTIQ PPRNN
	Isoform OA3-312 [UniParc]. Checksum: 8BBBB21A590D4DCA		311	33,845
	10 20 30 40 50 60 MWPLVAALLL GSACCGSAQL LFNKTKSVEF TFCNDTVVIP CFVTNMEAQN TTEVYVKWKF 70 80 90 100 110 120 KGRDIYTFDG ALNKSTVPTD FSSAKIEVSQ LLKGDASLKM DKSDAVSHTG NYTCEVTELT 130 140 150 160 170 180 REGETIIELK YRVVSWFSPN ENILIVIFPI FAILLFWGQF GIKTLKYRSG GMDEKTIALL 190 200 210 220 230 240 VAGLVITVIV IVGAILFVPG EYSLKNATGL GLIVTSTGIL ILLHYYVFST AIGLTSFVIA 250 260 270 280 290 300 ILVIQVIAYI LAVVGLSLCI AACIPMHGPL LISGLSILAL AQLLGLVYMK FVASNQKTIQ 310 PPRKAVEEPL N

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"An ovarian tumor marker with homology to vaccinia virus contains an IgV-like region and multiple transmembrane domains." Campbell I.G., Freemont P.S., Foulkes W., Trowsdale J. Cancer Res. 52:5416-5420(1992) [PubMed: 1394148] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM OA3-323). Tissue: Ovary.
[2]	"Molecular cloning of integrin-associated protein: an immunoglobulin family member with multiple membrane spanning domains implicated in alpha-v beta-3-dependent ligand binding." Lindberg F.P., Gresham H.D., Schwarz E., Brown E.J. J. Cell Biol. 123:485-496(1993) [PubMed: 7691831] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM OA3-305), FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY. Tissue: Myelomonocyte.
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM OA3-305).
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM OA3-305). Tissue: Hippocampus, Leiomyosarcoma and Ovarian adenocarcinoma.
[5]	"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." Mawby W.J., Holmes C.H., Anstee D.J., Spring F.A., Tanner M.J.A. Biochem. J. 304:525-530(1994) [PubMed: 7998989] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, IDENTIFICATION AS CD47. Tissue: Erythrocyte.
[6]	"Ubiquitin-related proteins regulate interaction of vimentin intermediate filaments with the plasma membrane." Wu A.-L., Wang J., Zheleznyak A., Brown E.J. Mol. Cell 4:619-625(1999) [PubMed: 10549293] [Abstract] Cited for: INTERACTION WITH UBQLN1 AND UBQLN2.
[7]	"Normal ligand binding and signaling by CD47 (integrin-associated protein) requires a long range disulfide bond between the extracellular and membrane-spanning domains." Rebres R.A., Vaz L.E., Green J.M., Brown E.J. J. Biol. Chem. 276:34607-34616(2001) [PubMed: 11454874] [Abstract] Cited for: DISULFIDE BOND.
[8]	"Bidirectional negative regulation of human T and dendritic cells by CD47 and its cognate receptor signal-regulator protein-alpha: down-regulation of IL-12 responsiveness and inhibition of dendritic cell activation." Latour S., Tanaka H., Demeure C., Mateo V., Rubio M., Brown E.J., Maliszewski C., Lindberg F.P., Oldenborg A., Ullrich A., Delespesse G., Sarfati M. J. Immunol. 167:2547-2554(2001) [PubMed: 11509594] [Abstract] Cited for: FUNCTION, INTERACTION WITH SIRPA.
[9]	"An unappreciated role for RNA surveillance." Hillman R.T., Green R.E., Brenner S.E. Genome Biol. 5:RESEARCH008.1-RESEARCH008.16(2004) [PubMed: 14759258] [Abstract] Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[10]	"Adhesion of human T cells to antigen-presenting cells through SIRPbeta2-CD47 interaction costimulates T-cell proliferation." Piccio L., Vermi W., Boles K.S., Fuchs A., Strader C.A., Facchetti F., Cella M., Colonna M. Blood 105:2421-2427(2005) [PubMed: 15383453] [Abstract] Cited for: FUNCTION, INTERACTION WITH SIRPG. Tissue: T-cell.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

X69398 mRNA. Translation: CAA49196.1.
Z25521 mRNA. Translation: CAA80977.1.
BT006907 mRNA. Translation: AAP35553.1.
BC010016 mRNA. Translation: AAH10016.1.
BC012884 mRNA. Translation: AAH12884.1.
BC037306 mRNA. Translation: AAH37306.1.

PIR

A48997.

RefSeq

NP_001020250.1.
NP_001768.1.
NP_942088.1.

UniGene

Hs.446414

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2JJS	X-ray	1.85	C/D	19-136	[»]
2JJT	X-ray	2.30	C/D	19-136	[»]
2VSC	X-ray	1.90	A/B/C/D	19-136	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q08722.

Genome annotation databases

Ensembl

ENSG00000196776. Homo sapiens. [Contig view]

GeneID

961.

KEGG

hsa:961.

Organism-specific databases

H-InvDB

HIX0003524.

HGNC

HGNC:1682. CD47.

HPA

CAB016055.

MIM

601028. gene.

PharmGKB

PA26222.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

Q08722.

HOVERGEN

Q08722.

Gene expression databases

ArrayExpress

Q08722.

CleanEx

HS_CD47.

GermOnline

ENSG00000196776. Homo sapiens.

Family and domain databases

InterPro

IPR006704. CD47.
IPR013147. CD47_TM.
IPR013270. CD47_Vset.
IPR007110. Ig-like.
[Graphical view]

PANTHER

PTHR10613. CD47. 1 hit.

Pfam

PF04549. CD47. 1 hit.
PF08204. V-set_CD47. 1 hit.
[Graphical view]

PROSITE

PS50835. IG_LIKE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

LinkHub

Q08722.

NextBio

4012.

SOURCE

Search...

Entry information

Entry name

CD47_HUMAN

Accession

Primary (citable) accession number: Q08722
Secondary accession number(s): Q53Y71, Q96A60

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	November 25, 2008
This is version 86 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)