P20023 (CR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Complement receptor type 2
Short name=Cr2

Alternative name(s):
Complement C3d receptor
Epstein-Barr virus receptor
Short name=EBV receptor
CD_antigen=CD21

Gene names

Name:	CR2
Synonyms:	C3DR

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	1033 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	Receptor for complement C3Dd, for the Epstein-Barr virus on human B-cells and T-cells and for HNRPU. Participates in B lymphocytes activation. Ref.12
Subunit structure	Interacts (via Sushi domain 1 and 2) with C3dg. Ref.18
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Mature B-lymphocytes, T-lymphocytes, pharyngeal epithelial cells, astrocytes and follicular dendritic cells of the spleen.
Involvement in disease	Genetic variations in CR2 are associated with susceptibility to systemic lupus erythematosus type 9 (SLEB9) [MIM:610927]. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a complex genetic basis. SLE is an inflammatory, and often febrile multisystemic disorder of connective tissue characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is thought to represent a failure of the regulatory mechanisms of the autoimmune system. Ref.19
Sequence similarities	Belongs to the receptors of complement activation (RCA) family. Contains 15 Sushi (CCP/SCR) domains.
Sequence caution	The sequence AAA35784.1 differs from that shown. Reason: Frameshift at positions 758, 769 and 776.

Ontologies

Keywords
Biological process	Complement pathway Immunity Innate immunity
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Systemic lupus erythematosus
Domain	Repeat Signal Sushi Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	complement activation, classical pathway Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to membrane Non-traceable author statement Ref.3. Source: UniProtKB plasma membrane Non-traceable author statement. Source: ProtInc
Molecular function	complement receptor activity Non-traceable author statement Ref.3. Source: UniProtKB protein homodimerization activity Inferred from direct assay. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform A (identifier: P20023-1) 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 B (identifier: P20023-2) The sequence of this isoform differs from the canonical sequence as follows:      499-524: Missing.      525-556: ITCPPPPVIYNGAHTGSSLEDFPYGTTVTYTC → NHLPTTPCYLQWGTHREFLRRFSIWNHGHLHM
Isoform C (identifier: P20023-3) The sequence of this isoform differs from the canonical sequence as follows:      659-659: K → KGCQSPPGLHHGRHTGGNTVFFVSGMTVDYTCDPGYLLVGNKSIHCMPSGNWSPSAPRCE
Sequence annotation (Features)
	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
	Sequence conflict	663	1	S → P in AAA35784. Ref.3
Isoform D (identifier: P20023-4) The sequence of this isoform differs from the canonical sequence as follows:      659-659: K → KGCQSPPGLHHGRHTGGNTVFFVSGMTVDYTCDPGYLLVGNKSIHCMPSGNWSPSAPRCE      716-723: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

20

Chain

21 – 1033

1013

Complement receptor type 2

PRO_0000006010

Regions

Topological domain

21 – 971

951

Extracellular Potential

Transmembrane

972 – 999

28

Helical; Potential

Topological domain

1000 – 1033

34

Cytoplasmic Potential

Domain

21 – 84

64

Sushi 1

Domain

89 – 148

60

Sushi 2

Domain

152 – 212

61

Sushi 3

Domain

213 – 273

61

Sushi 4

Domain

274 – 344

71

Sushi 5

Domain

349 – 408

60

Sushi 6

Domain

409 – 468

60

Sushi 7

Domain

469 – 524

56

Sushi 8

Domain

525 – 595

71

Sushi 9

Domain

600 – 659

60

Sushi 10

Domain

660 – 716

57

Sushi 11

Domain

717 – 781

65

Sushi 12

Domain

786 – 845

60

Sushi 13

Domain

849 – 909

61

Sushi 14

Domain

910 – 970

61

Sushi 15

Amino acid modifications

Modified residue

1029

1

Phosphotyrosine Ref.13

Glycosylation

121

1

N-linked (GlcNAc...) Ref.16

Glycosylation

127

1

N-linked (GlcNAc...) Ref.16

Glycosylation

294

1

N-linked (GlcNAc...) Potential

Glycosylation

372

1

N-linked (GlcNAc...) Potential

Glycosylation

492

1

N-linked (GlcNAc...) Potential

Glycosylation

623

1

N-linked (GlcNAc...) Ref.14

Glycosylation

682

1

N-linked (GlcNAc...) Potential

Glycosylation

800

1

N-linked (GlcNAc...) Potential

Glycosylation

823

1

N-linked (GlcNAc...) Potential

Glycosylation

861

1

N-linked (GlcNAc...) Potential

Glycosylation

911

1

N-linked (GlcNAc...) Potential

Disulfide bond

23 ↔ 65

Ref.15 Ref.16 Ref.18

Disulfide bond

51 ↔ 82

Ref.15 Ref.16 Ref.18

Disulfide bond

91 ↔ 132

Ref.15 Ref.16 Ref.18

Disulfide bond

118 ↔ 146

Ref.15 Ref.16 Ref.18

Disulfide bond

154 ↔ 197

By similarity

Disulfide bond

183 ↔ 210

By similarity

Disulfide bond

215 ↔ 256

By similarity

Disulfide bond

242 ↔ 271

By similarity

Disulfide bond

276 ↔ 325

By similarity

Disulfide bond

305 ↔ 342

By similarity

Disulfide bond

351 ↔ 393

By similarity

Disulfide bond

379 ↔ 406

By similarity

Disulfide bond

410 ↔ 453

By similarity

Disulfide bond

439 ↔ 466

By similarity

Disulfide bond

471 ↔ 509

By similarity

Disulfide bond

495 ↔ 522

By similarity

Disulfide bond

527 ↔ 576

By similarity

Disulfide bond

556 ↔ 593

By similarity

Disulfide bond

602 ↔ 644

By similarity

Disulfide bond

630 ↔ 657

By similarity

Disulfide bond

662 ↔ 699

By similarity

Disulfide bond

685 ↔ 714

By similarity

Disulfide bond

719 ↔ 762

By similarity

Disulfide bond

748 ↔ 779

By similarity

Disulfide bond

788 ↔ 830

By similarity

Disulfide bond

816 ↔ 843

By similarity

Disulfide bond

851 ↔ 894

By similarity

Disulfide bond

880 ↔ 907

By similarity

Disulfide bond

912 ↔ 955

By similarity

Disulfide bond

941 ↔ 968

By similarity

Natural variations

Alternative sequence

499 – 524

26

Missing in isoform B.

VSP_001208

Alternative sequence

525 – 556

32

ITCPP…VTYTC → NHLPTTPCYLQWGTHREFLR RFSIWNHGHLHM in isoform B.

VSP_001209

Alternative sequence

659

1

K → KGCQSPPGLHHGRHTGGNTV FFVSGMTVDYTCDPGYLLVG NKSIHCMPSGNWSPSAPRCE in isoform C and isoform D.

VSP_001210

Alternative sequence

716 – 723

8

Missing in isoform D.

VSP_001211

Natural variant

639

1

S → N. Ref.9 Ref.19
Corresponds to variant rs17615 [ dbSNP | Ensembl ].

VAR_016164

Natural variant

993

1

I → V. Ref.2
Corresponds to variant rs17258982 [ dbSNP | Ensembl ].

VAR_016165

Natural variant

1003

1

A → E. Ref.1 Ref.3
Corresponds to variant rs6540433 [ dbSNP | Ensembl ].

VAR_016166

Experimental info

Mutagenesis

103

1

R → A: No effect on affinity for C3. Ref.18

Mutagenesis

112

1

D → A: Reduced affinity for C3. Ref.18

Mutagenesis

128

1

K → A: Strongly reduced affinity for C3. Ref.18

Sequence conflict

457

1

Missing in CAA68674. Ref.2

Sequence conflict

646

1

A → R in AAA35784. Ref.3

Sequence conflict

667

1

Q → D AA sequence Ref.10

Sequence conflict

774

1

G → E in AAA35784. Ref.3

Sequence conflict

783 – 787

5

PPVTR → L in AAA35784. Ref.3

Sequence conflict

844

1

I → M in AAA35786. Ref.1

Sequence conflict

844

1

I → M in AAB04638. Ref.1

Sequence conflict

886

1

L → V in AAA35784. Ref.3

Sequence conflict

890

1

A → P in AAA35784. Ref.3

Sequence conflict

902

1

Q → G AA sequence Ref.10

Sequence conflict

906

1

H → L AA sequence Ref.10

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

1033

Helix Strand Turn

Details...

Beta strand

32 – 34

3

Beta strand

39 – 42

4

Beta strand

46 – 51

6

Beta strand

55 – 59

5

Beta strand

61 – 66

6

Beta strand

68 – 72

5

Beta strand

74 – 77

4

Beta strand

81 – 84

4

Beta strand

99 – 103

5

Beta strand

113 – 118

6

Beta strand

123 – 126

4

Beta strand

128 – 132

5

Beta strand

145 – 147

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform A [UniParc]. Last modified November 25, 2008. Version 2. Checksum: 7D89DB4A07847E9A	FASTA	1,033	112,916
	10 20 30 40 50 60 MGAAGLLGVF LALVAPGVLG ISCGSPPPIL NGRISYYSTP IAVGTVIRYS CSGTFRLIGE 70 80 90 100 110 120 KSLLCITKDK VDGTWDKPAP KCEYFNKYSS CPEPIVPGGY KIRGSTPYRH GDSVTFACKT 130 140 150 160 170 180 NFSMNGNKSV WCQANNMWGP TRLPTCVSVF PLECPALPMI HNGHHTSENV GSIAPGLSVT 190 200 210 220 230 240 YSCESGYLLV GEKIINCLSS GKWSAVPPTC EEARCKSLGR FPNGKVKEPP ILRVGVTANF 250 260 270 280 290 300 FCDEGYRLQG PPSSRCVIAG QGVAWTKMPV CEEIFCPSPP PILNGRHIGN SLANVSYGSI 310 320 330 340 350 360 VTYTCDPDPE EGVNFILIGE STLRCTVDSQ KTGTWSGPAP RCELSTSAVQ CPHPQILRGR 370 380 390 400 410 420 MVSGQKDRYT YNDTVIFACM FGFTLKGSKQ IRCNAQGTWE PSAPVCEKEC QAPPNILNGQ 430 440 450 460 470 480 KEDRHMVRFD PGTSIKYSCN PGYVLVGEES IQCTSEGVWT PPVPQCKVAA CEATGRQLLT 490 500 510 520 530 540 KPQHQFVRPD VNSSCGEGYK LSGSVYQECQ GTIPWFMEIR LCKEITCPPP PVIYNGAHTG 550 560 570 580 590 600 SSLEDFPYGT TVTYTCNPGP ERGVEFSLIG ESTIRCTSND QERGTWSGPA PLCKLSLLAV 610 620 630 640 650 660 QCSHVHIANG YKISGKEAPY FYNDTVTFKC YSGFTLKGSS QIRCKADNTW DPEIPVCEKE 670 680 690 700 710 720 TCQHVRQSLQ ELPAGSRVEL VNTSCQDGYQ LTGHAYQMCQ DAENGIWFKK IPLCKVIHCH 730 740 750 760 770 780 PPPVIVNGKH TGMMAENFLY GNEVSYECDQ GFYLLGEKKL QCRSDSKGHG SWSGPSPQCL 790 800 810 820 830 840 RSPPVTRCPN PEVKHGYKLN KTHSAYSHND IVYVDCNPGF IMNGSRVIRC HTDNTWVPGV 850 860 870 880 890 900 PTCIKKAFIG CPPPPKTPNG NHTGGNIARF SPGMSILYSC DQGYLLVGEA LLLCTHEGTW 910 920 930 940 950 960 SQPAPHCKEV NCSSPADMDG IQKGLEPRKM YQYGAVVTLE CEDGYMLEGS PQSQCQSDHQ 970 980 990 1000 1010 1020 WNPPLAVCRS RSLAPVLCGI AAGLILLTFL IVITLYVISK HRARNYYTDT SQKEAFHLEA 1030 REVYSVDPYN PAS
	Isoform B [UniParc]. Checksum: BA75D3B0A8EB5511	FASTA	1,007	110,408
	10 20 30 40 50 60 MGAAGLLGVF LALVAPGVLG ISCGSPPPIL NGRISYYSTP IAVGTVIRYS CSGTFRLIGE 70 80 90 100 110 120 KSLLCITKDK VDGTWDKPAP KCEYFNKYSS CPEPIVPGGY KIRGSTPYRH GDSVTFACKT 130 140 150 160 170 180 NFSMNGNKSV WCQANNMWGP TRLPTCVSVF PLECPALPMI HNGHHTSENV GSIAPGLSVT 190 200 210 220 230 240 YSCESGYLLV GEKIINCLSS GKWSAVPPTC EEARCKSLGR FPNGKVKEPP ILRVGVTANF 250 260 270 280 290 300 FCDEGYRLQG PPSSRCVIAG QGVAWTKMPV CEEIFCPSPP PILNGRHIGN SLANVSYGSI 310 320 330 340 350 360 VTYTCDPDPE EGVNFILIGE STLRCTVDSQ KTGTWSGPAP RCELSTSAVQ CPHPQILRGR 370 380 390 400 410 420 MVSGQKDRYT YNDTVIFACM FGFTLKGSKQ IRCNAQGTWE PSAPVCEKEC QAPPNILNGQ 430 440 450 460 470 480 KEDRHMVRFD PGTSIKYSCN PGYVLVGEES IQCTSEGVWT PPVPQCKVAA CEATGRQLLT 490 500 510 520 530 540 KPQHQFVRPD VNSSCGEGNH LPTTPCYLQW GTHREFLRRF SIWNHGHLHM NPGPERGVEF 550 560 570 580 590 600 SLIGESTIRC TSNDQERGTW SGPAPLCKLS LLAVQCSHVH IANGYKISGK EAPYFYNDTV 610 620 630 640 650 660 TFKCYSGFTL KGSSQIRCKA DNTWDPEIPV CEKETCQHVR QSLQELPAGS RVELVNTSCQ 670 680 690 700 710 720 DGYQLTGHAY QMCQDAENGI WFKKIPLCKV IHCHPPPVIV NGKHTGMMAE NFLYGNEVSY 730 740 750 760 770 780 ECDQGFYLLG EKKLQCRSDS KGHGSWSGPS PQCLRSPPVT RCPNPEVKHG YKLNKTHSAY 790 800 810 820 830 840 SHNDIVYVDC NPGFIMNGSR VIRCHTDNTW VPGVPTCIKK AFIGCPPPPK TPNGNHTGGN 850 860 870 880 890 900 IARFSPGMSI LYSCDQGYLL VGEALLLCTH EGTWSQPAPH CKEVNCSSPA DMDGIQKGLE 910 920 930 940 950 960 PRKMYQYGAV VTLECEDGYM LEGSPQSQCQ SDHQWNPPLA VCRSRSLAPV LCGIAAGLIL 970 980 990 1000 LTFLIVITLY VISKHRARNY YTDTSQKEAF HLEAREVYSV DPYNPAS
	Isoform C [UniParc]. Checksum: A52592EB53DE7374	FASTA	1,092	119,160
	10 20 30 40 50 60 MGAAGLLGVF LALVAPGVLG ISCGSPPPIL NGRISYYSTP IAVGTVIRYS CSGTFRLIGE 70 80 90 100 110 120 KSLLCITKDK VDGTWDKPAP KCEYFNKYSS CPEPIVPGGY KIRGSTPYRH GDSVTFACKT 130 140 150 160 170 180 NFSMNGNKSV WCQANNMWGP TRLPTCVSVF PLECPALPMI HNGHHTSENV GSIAPGLSVT 190 200 210 220 230 240 YSCESGYLLV GEKIINCLSS GKWSAVPPTC EEARCKSLGR FPNGKVKEPP ILRVGVTANF 250 260 270 280 290 300 FCDEGYRLQG PPSSRCVIAG QGVAWTKMPV CEEIFCPSPP PILNGRHIGN SLANVSYGSI 310 320 330 340 350 360 VTYTCDPDPE EGVNFILIGE STLRCTVDSQ KTGTWSGPAP RCELSTSAVQ CPHPQILRGR 370 380 390 400 410 420 MVSGQKDRYT YNDTVIFACM FGFTLKGSKQ IRCNAQGTWE PSAPVCEKEC QAPPNILNGQ 430 440 450 460 470 480 KEDRHMVRFD PGTSIKYSCN PGYVLVGEES IQCTSEGVWT PPVPQCKVAA CEATGRQLLT 490 500 510 520 530 540 KPQHQFVRPD VNSSCGEGYK LSGSVYQECQ GTIPWFMEIR LCKEITCPPP PVIYNGAHTG 550 560 570 580 590 600 SSLEDFPYGT TVTYTCNPGP ERGVEFSLIG ESTIRCTSND QERGTWSGPA PLCKLSLLAV 610 620 630 640 650 660 QCSHVHIANG YKISGKEAPY FYNDTVTFKC YSGFTLKGSS QIRCKADNTW DPEIPVCEKG 670 680 690 700 710 720 CQSPPGLHHG RHTGGNTVFF VSGMTVDYTC DPGYLLVGNK SIHCMPSGNW SPSAPRCEET 730 740 750 760 770 780 CQHVRQSLQE LPAGSRVELV NTSCQDGYQL TGHAYQMCQD AENGIWFKKI PLCKVIHCHP 790 800 810 820 830 840 PPVIVNGKHT GMMAENFLYG NEVSYECDQG FYLLGEKKLQ CRSDSKGHGS WSGPSPQCLR 850 860 870 880 890 900 SPPVTRCPNP EVKHGYKLNK THSAYSHNDI VYVDCNPGFI MNGSRVIRCH TDNTWVPGVP 910 920 930 940 950 960 TCIKKAFIGC PPPPKTPNGN HTGGNIARFS PGMSILYSCD QGYLLVGEAL LLCTHEGTWS 970 980 990 1000 1010 1020 QPAPHCKEVN CSSPADMDGI QKGLEPRKMY QYGAVVTLEC EDGYMLEGSP QSQCQSDHQW 1030 1040 1050 1060 1070 1080 NPPLAVCRSR SLAPVLCGIA AGLILLTFLI VITLYVISKH RARNYYTDTS QKEAFHLEAR 1090 EVYSVDPYNP AS
	Isoform D [UniParc]. Checksum: 9C232F47D384E59B	FASTA	1,084	118,279
	10 20 30 40 50 60 MGAAGLLGVF LALVAPGVLG ISCGSPPPIL NGRISYYSTP IAVGTVIRYS CSGTFRLIGE 70 80 90 100 110 120 KSLLCITKDK VDGTWDKPAP KCEYFNKYSS CPEPIVPGGY KIRGSTPYRH GDSVTFACKT 130 140 150 160 170 180 NFSMNGNKSV WCQANNMWGP TRLPTCVSVF PLECPALPMI HNGHHTSENV GSIAPGLSVT 190 200 210 220 230 240 YSCESGYLLV GEKIINCLSS GKWSAVPPTC EEARCKSLGR FPNGKVKEPP ILRVGVTANF 250 260 270 280 290 300 FCDEGYRLQG PPSSRCVIAG QGVAWTKMPV CEEIFCPSPP PILNGRHIGN SLANVSYGSI 310 320 330 340 350 360 VTYTCDPDPE EGVNFILIGE STLRCTVDSQ KTGTWSGPAP RCELSTSAVQ CPHPQILRGR 370 380 390 400 410 420 MVSGQKDRYT YNDTVIFACM FGFTLKGSKQ IRCNAQGTWE PSAPVCEKEC QAPPNILNGQ 430 440 450 460 470 480 KEDRHMVRFD PGTSIKYSCN PGYVLVGEES IQCTSEGVWT PPVPQCKVAA CEATGRQLLT 490 500 510 520 530 540 KPQHQFVRPD VNSSCGEGYK LSGSVYQECQ GTIPWFMEIR LCKEITCPPP PVIYNGAHTG 550 560 570 580 590 600 SSLEDFPYGT TVTYTCNPGP ERGVEFSLIG ESTIRCTSND QERGTWSGPA PLCKLSLLAV 610 620 630 640 650 660 QCSHVHIANG YKISGKEAPY FYNDTVTFKC YSGFTLKGSS QIRCKADNTW DPEIPVCEKG 670 680 690 700 710 720 CQSPPGLHHG RHTGGNTVFF VSGMTVDYTC DPGYLLVGNK SIHCMPSGNW SPSAPRCEET 730 740 750 760 770 780 CQHVRQSLQE LPAGSRVELV NTSCQDGYQL TGHAYQMCQD AENGIWFKKI PLCKVIVNGK 790 800 810 820 830 840 HTGMMAENFL YGNEVSYECD QGFYLLGEKK LQCRSDSKGH GSWSGPSPQC LRSPPVTRCP 850 860 870 880 890 900 NPEVKHGYKL NKTHSAYSHN DIVYVDCNPG FIMNGSRVIR CHTDNTWVPG VPTCIKKAFI 910 920 930 940 950 960 GCPPPPKTPN GNHTGGNIAR FSPGMSILYS CDQGYLLVGE ALLLCTHEGT WSQPAPHCKE 970 980 990 1000 1010 1020 VNCSSPADMD GIQKGLEPRK MYQYGAVVTL ECEDGYMLEG SPQSQCQSDH QWNPPLAVCR 1030 1040 1050 1060 1070 1080 SRSLAPVLCG IAAGLILLTF LIVITLYVIS KHRARNYYTD TSQKEAFHLE AREVYSVDPY NPAS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Genomic organization and polymorphisms of the human C3d/Epstein-Barr virus receptor." Fujisaku A., Harley J.B., Frank M.B., Gruner B.A., Frazier B., Holers V.M. J. Biol. Chem. 264:2118-2125(1989) [PubMed: 2563370] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT GLU-1003.
[2]	"Structure of the human B lymphocyte receptor for C3d and the Epstein-Barr virus and relatedness to other members of the family of C3/C4 binding proteins." Weis J.J., Toothaker L.E., Smith J.A., Weis J.H., Fearon D.T. J. Exp. Med. 167:1047-1066(1988) [PubMed: 2832506] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-993. Tissue: B-cell.
[3]	"Molecular cloning of the cDNA encoding the Epstein-Barr virus.C3d receptor (complement receptor type 2) of human b lymphocytes." Moore M., Cooper N., Tack B., Nemerow G. Proc. Natl. Acad. Sci. U.S.A. 84:9194-9198(1987) [PubMed: 2827171] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C), VARIANT GLU-1003.
[4]	"Evidence for a new transcript of the Epstein-Barr virus/C3d receptor (CR2, CD21) which is due to alternative exon usage." Barel M., Balbo M., Frade R. Mol. Immunol. 35:1025-1031(1998) [PubMed: 10068037] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; C AND D).
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C). Tissue: Synovium.
[6]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C). Tissue: Spleen.
[7]	Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B., Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O., Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I., Nickerson D.A. Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[8]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"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] (ISOFORMS A AND C), VARIANT ASN-639. Tissue: Lymph.
[10]	"Identification of a partial cDNA clone for the C3d/Epstein-Barr virus receptor of human B lymphocytes: homology with the receptor for fragments C3b and C4b of the third and fourth components of complement." Weis J.J., Fearon D.T., Klickstein L.B., Wong W.W., Richards S.A., de Bruyn Kops A., Smith J.A., Weis J.H. Proc. Natl. Acad. Sci. U.S.A. 83:5639-5643(1986) [PubMed: 3016712] [Abstract] Cited for: PROTEIN SEQUENCE OF 226-233; 256-267; 332-341; 667-677 AND 898-908.
[11]	"Characterization of the EBV/C3d receptor on the human Jurkat T cell line: evidence for a novel transcript." Sinha S.K., Todd S.C., Hedrick J.A., Speiser C.L., Lambris J.D., Tsoukas C.D. J. Immunol. 150:5311-5320(1993) [PubMed: 8390533] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 492-556 (ISOFORM B).
[12]	"Binding sites of the Epstein-Barr virus and C3d receptor (CR2, CD21) for its three intracellular ligands, the p53 anti-oncoprotein, the p68 calcium binding protein and the nuclear p120 ribonucleoprotein." Barel M., Balbo M., Gauffre A., Frade R. Mol. Immunol. 32:389-397(1995) [PubMed: 7753047] [Abstract] Cited for: FUNCTION AS A RECEPTOR FOR HNRPU.
[13]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1029, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[14]	"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins." Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D. Nat. Biotechnol. 27:378-386(2009) [PubMed: 19349973] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-623, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[15]	"Structure of complement receptor 2 in complex with its C3d ligand." Szakonyi G., Guthridge J.M., Li D., Young K., Holers V.M., Chen X.S. Science 292:1725-1728(2001) [PubMed: 11387479] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.04 ANGSTROMS) OF 21-153 IN COMPLEX WITH C3D, DISULFIDE BONDS.
[16]	"The crystal structure of human CD21: Implications for Epstein-Barr virus and C3d binding." Prota A.E., Sage D.R., Stehle T., Fingeroth J.D. Proc. Natl. Acad. Sci. U.S.A. 99:10641-10646(2002) [PubMed: 12122212] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 22-148, DISULFIDE BONDS, GLYCOSYLATION AT ASN-121 AND ASN-127.
[17]	"The 15 SCR flexible extracellular domains of human complement receptor type 2 can mediate multiple ligand and antigen interactions." Gilbert H.E., Asokan R., Holers V.M., Perkins S.J. J. Mol. Biol. 362:1132-1147(2006) [PubMed: 16950392] [Abstract] Cited for: X-RAY SCATTERING SOLUTION STRUCTURE OF 21-971.
[18]	"A crystal structure of the complex between human complement receptor 2 and its ligand C3d." van den Elsen J.M., Isenman D.E. Science 332:608-611(2011) [PubMed: 21527715] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.16 ANGSTROMS) OF 996-1303 IN COMPLEX WITH C3, INTERACTION WITH CR2, DISULFIDE BONDS, MUTAGENESIS OF ARG-103; ASP-112 AND LYS-128.
[19]	"Association of a common complement receptor 2 haplotype with increased risk of systemic lupus erythematosus." Wu H., Boackle S.A., Hanvivadhanakul P., Ulgiati D., Grossman J.M., Lee Y., Shen N., Abraham L.J., Mercer T.R., Park E., Hebert L.A., Rovin B.H., Birmingham D.J., Chang D.-M., Chen C.J., McCurdy D., Badsha H.M., Thong B.Y.H. , Chng H.H., Arnett F.C., Wallace D.J., Yu C.Y., Hahn B.H., Cantor R.M., Tsao B.P. Proc. Natl. Acad. Sci. U.S.A. 104:3961-3966(2007) [PubMed: 17360460] [Abstract] Cited for: VARIANT ASN-639, INVOLVEMENT IN SLEB9.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M26004 mRNA. Translation: AAA35786.1.
M26016 , M24007, M24008, M24009, M24010, M24011, M26009, M26010, M26011, M26012, M26013, M26014, M26015 Genomic DNA. Translation: AAB04638.1.
Y00649 mRNA. Translation: CAA68674.1.
J03565 mRNA. Translation: AAA35784.1. Frameshift.
AK223627 mRNA. Translation: BAD97347.1.
AK301496 mRNA. Translation: BAG63007.1.
EF064746 Genomic DNA. Translation: ABK41929.1.
AL391597, AL691452 Genomic DNA. Translation: CAH72949.1.
AL391597, AL691452 Genomic DNA. Translation: CAH72950.1.
AL691452, AL391597 Genomic DNA. Translation: CAI16729.1.
AL691452, AL391597 Genomic DNA. Translation: CAI16730.1.
BC090937 mRNA. Translation: AAH90937.1.
BC136394 mRNA. Translation: AAI36395.1.
S62696 mRNA. Translation: AAB27186.1.

IPI

IPI00216985.
IPI00216986.
IPI00216987.
IPI00292859.

PIR

PL0009. JL0028.

RefSeq

NP_001006659.1. NM_001006658.2.
NP_001868.2. NM_001877.4.

UniGene

Hs.445757.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1GHQ	X-ray	2.04	B/C	21-153	[»]
1LY2	X-ray	1.80	A	22-148	[»]
1W2R	X-ray	-	A	21-153	[»]
1W2S	X-ray	-	B	21-153	[»]
2GSX	X-ray	-	A	21-971	[»]
3OED	X-ray	3.16	C/D	20-153	[»]

ProteinModelPortal

P20023.

SMR

P20023. Positions 16-971.

ModBase

Search...

Protein-protein interaction databases

IntAct

P20023. 1 interaction.

STRING

P20023.

PTM databases

PhosphoSite

P20023.

Polymorphism databases

DMDM

215273962.

Proteomic databases

PRIDE

P20023.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000367058; ENSP00000356025; ENSG00000117322.

GeneID

1380.

KEGG

hsa:1380.

Organism-specific databases

CTD

1380.

GeneCards

GC01P207627.

HGNC

HGNC:2336. CR2.

HPA

CAB002659.

MIM

120650. gene.
610927. phenotype.

neXtProt

NX_P20023.

Orphanet

101994. Complement regulatory proteins anomaly.

PharmGKB

PA26857.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG08926.

GeneTree

ENSGT00600000084351.

HOVERGEN

HBG005399.

OrthoDB

EOG4DFPMK.

Gene expression databases

ArrayExpress

P20023.

Bgee

P20023.

CleanEx

HS_CR2.

Genevestigator

P20023.

GermOnline

ENSG00000117322. Homo sapiens.

Family and domain databases

InterPro

IPR016060. Complement_control_module.
IPR000436. Sushi_SCR_CCP.
[Graphical view]

Gene3D

G3DSA:2.10.70.10. Complement_control_module. 14 hits.

KO

K04012.

Pfam

PF00084. Sushi. 14 hits.
[Graphical view]

SMART

SM00032. CCP. 14 hits.
[Graphical view]

SUPFAM

SSF57535. Complement_control_module. 14 hits.

PROSITE

PS50923. SUSHI. 15 hits.
[Graphical view]

ProtoNet

Search...

Other

NextBio

5605.

SOURCE

Search...

Entry information

Entry name

CR2_HUMAN

Accession

Primary (citable) accession number: P20023
Secondary accession number(s): Q13866 , Q14212, Q53EL2, Q5BKT9, Q5SR46, Q5SR48

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	November 25, 2008
Last modified:	January 25, 2012
This is version 129 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

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