ID CR2_HUMAN Reviewed; 1033 AA.
AC P20023; C9JHD2; Q13866; Q14212; Q53EL2; Q5BKT9; Q5SR46; Q5SR48;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 2.
DT 27-MAR-2024, entry version 226.
DE RecName: Full=Complement receptor type 2;
DE Short=Cr2;
DE AltName: Full=Complement C3d receptor;
DE AltName: Full=Epstein-Barr virus receptor;
DE Short=EBV receptor;
DE AltName: CD_antigen=CD21;
DE Flags: Precursor;
GN Name=CR2; Synonyms=C3DR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANT GLU-1003.
RX PubMed=2563370; DOI=10.1016/s0021-9258(18)94149-9;
RA Fujisaku A., Harley J.B., Frank M.B., Gruner B.A., Frazier B., Holers V.M.;
RT "Genomic organization and polymorphisms of the human C3d/Epstein-Barr virus
RT receptor.";
RL J. Biol. Chem. 264:2118-2125(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT VAL-993.
RC TISSUE=B-cell;
RX PubMed=2832506; DOI=10.1084/jem.167.3.1047;
RA Weis J.J., Toothaker L.E., Smith J.A., Weis J.H., Fearon D.T.;
RT "Structure of the human B lymphocyte receptor for C3d and the Epstein-Barr
RT virus and relatedness to other members of the family of C3/C4 binding
RT proteins.";
RL J. Exp. Med. 167:1047-1066(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C), AND VARIANT GLU-1003.
RX PubMed=2827171; DOI=10.1073/pnas.84.24.9194;
RA Moore M., Cooper N., Tack B., Nemerow G.;
RT "Molecular cloning of the cDNA encoding the Epstein-Barr virus.C3d receptor
RT (complement receptor type 2) of human b lymphocytes.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:9194-9198(1987).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; C AND D).
RX PubMed=10068037; DOI=10.1016/s0161-5890(98)00098-4;
RA Barel M., Balbo M., Frade R.;
RT "Evidence for a new transcript of the Epstein-Barr virus/C3d receptor (CR2,
RT CD21) which is due to alternative exon usage.";
RL Mol. Immunol. 35:1025-1031(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C).
RC TISSUE=Synovium;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C).
RC TISSUE=Spleen;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B.,
RA Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O.,
RA Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I.,
RA Nickerson D.A.;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A AND C), AND VARIANT
RP ASN-639.
RC TISSUE=Lymph;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP PROTEIN SEQUENCE OF 226-233; 256-267; 332-341; 667-677 AND 898-908.
RX PubMed=3016712; DOI=10.1073/pnas.83.15.5639;
RA Weis J.J., Fearon D.T., Klickstein L.B., Wong W.W., Richards S.A.,
RA de Bruyn Kops A., Smith J.A., Weis J.H.;
RT "Identification of a partial cDNA clone for the C3d/Epstein-Barr virus
RT receptor of human B lymphocytes: homology with the receptor for fragments
RT C3b and C4b of the third and fourth components of complement.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:5639-5643(1986).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 492-556 (ISOFORM B).
RX PubMed=8390533;
RA Sinha S.K., Todd S.C., Hedrick J.A., Speiser C.L., Lambris J.D.,
RA Tsoukas C.D.;
RT "Characterization of the EBV/C3d receptor on the human Jurkat T cell line:
RT evidence for a novel transcript.";
RL J. Immunol. 150:5311-5320(1993).
RN [12]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH EPSTEIN-BARR VIRUS
RP GP350 PROTEIN.
RX PubMed=2460635; DOI=10.1128/jvi.62.12.4452-4464.1988;
RA Tanner J., Whang Y., Sample J., Sears A., Kieff E.;
RT "Soluble gp350/220 and deletion mutant glycoproteins block Epstein-Barr
RT virus adsorption to lymphocytes.";
RL J. Virol. 62:4452-4464(1988).
RN [13]
RP INTERACTION WITH CD19, AND SUBCELLULAR LOCATION.
RX PubMed=1702139; DOI=10.1084/jem.173.1.55;
RA Matsumoto A.K., Kopicky-Burd J., Carter R.H., Tuveson D.A., Tedder T.F.,
RA Fearon D.T.;
RT "Intersection of the complement and immune systems: a signal transduction
RT complex of the B lymphocyte-containing complement receptor type 2 and
RT CD19.";
RL J. Exp. Med. 173:55-64(1991).
RN [14]
RP IDENTIFICATION IN A COMPLEX WITH CD19; CD81 AND IFITM1, AND SUBCELLULAR
RP LOCATION.
RX PubMed=1383329;
RA Bradbury L.E., Kansas G.S., Levy S., Evans R.L., Tedder T.F.;
RT "The CD19/CD21 signal transducing complex of human B lymphocytes includes
RT the target of antiproliferative antibody-1 and Leu-13 molecules.";
RL J. Immunol. 149:2841-2850(1992).
RN [15]
RP FUNCTION AS A RECEPTOR FOR HNRNPU.
RX PubMed=7753047; DOI=10.1016/0161-5890(95)00005-y;
RA Barel M., Balbo M., Gauffre A., Frade R.;
RT "Binding sites of the Epstein-Barr virus and C3d receptor (CR2, CD21) for
RT its three intracellular ligands, the p53 anti-oncoprotein, the p68 calcium
RT binding protein and the nuclear p120 ribonucleoprotein.";
RL Mol. Immunol. 32:389-397(1995).
RN [16]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-623.
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-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [17]
RP INTERACTION WITH FCER2.
RX PubMed=16172256; DOI=10.1084/jem.20050811;
RA Hibbert R.G., Teriete P., Grundy G.J., Beavil R.L., Reljic R., Holers V.M.,
RA Hannan J.P., Sutton B.J., Gould H.J., McDonnell J.M.;
RT "The structure of human CD23 and its interactions with IgE and CD21.";
RL J. Exp. Med. 202:751-760(2005).
RN [18]
RP INVOLVEMENT IN CVID7.
RX PubMed=22035880; DOI=10.1016/j.jaci.2011.09.027;
RA Thiel J., Kimmig L., Salzer U., Grudzien M., Lebrecht D., Hagena T.,
RA Draeger R., Volxen N., Bergbreiter A., Jennings S., Gutenberger S.,
RA Aichem A., Illges H., Hannan J.P., Kienzler A.K., Rizzi M., Eibel H.,
RA Peter H.H., Warnatz K., Grimbacher B., Rump J.A., Schlesier M.;
RT "Genetic CD21 deficiency is associated with hypogammaglobulinemia.";
RL J. Allergy Clin. Immunol. 129:801-810(2012).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.04 ANGSTROMS) OF 21-153 IN COMPLEX WITH C3, AND
RP DISULFIDE BONDS.
RX PubMed=11387479; DOI=10.1126/science.1059118;
RA Szakonyi G., Guthridge J.M., Li D., Young K., Holers V.M., Chen X.S.;
RT "Structure of complement receptor 2 in complex with its C3d ligand.";
RL Science 292:1725-1728(2001).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 22-148, DISULFIDE BONDS, AND
RP GLYCOSYLATION AT ASN-121 AND ASN-127.
RX PubMed=12122212; DOI=10.1073/pnas.162360499;
RA Prota A.E., Sage D.R., Stehle T., Fingeroth J.D.;
RT "The crystal structure of human CD21: Implications for Epstein-Barr virus
RT and C3d binding.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:10641-10646(2002).
RN [21]
RP X-RAY SCATTERING SOLUTION STRUCTURE OF 21-971.
RX PubMed=16950392; DOI=10.1016/j.jmb.2006.08.012;
RA Gilbert H.E., Asokan R., Holers V.M., Perkins S.J.;
RT "The 15 SCR flexible extracellular domains of human complement receptor
RT type 2 can mediate multiple ligand and antigen interactions.";
RL J. Mol. Biol. 362:1132-1147(2006).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (3.16 ANGSTROMS) OF 996-1303 IN COMPLEX WITH C3,
RP INTERACTION WITH C3, DISULFIDE BONDS, AND MUTAGENESIS OF ARG-103; ASP-112
RP AND LYS-128.
RX PubMed=21527715; DOI=10.1126/science.1201954;
RA van den Elsen J.M., Isenman D.E.;
RT "A crystal structure of the complex between human complement receptor 2 and
RT its ligand C3d.";
RL Science 332:608-611(2011).
RN [23]
RP VARIANT ASN-639, AND INVOLVEMENT IN SLEB9.
RX PubMed=17360460; DOI=10.1073/pnas.0609101104;
RA Wu H., Boackle S.A., Hanvivadhanakul P., Ulgiati D., Grossman J.M., Lee Y.,
RA Shen N., Abraham L.J., Mercer T.R., Park E., Hebert L.A., Rovin B.H.,
RA Birmingham D.J., Chang D.-M., Chen C.J., McCurdy D., Badsha H.M.,
RA Thong B.Y.H., Chng H.H., Arnett F.C., Wallace D.J., Yu C.Y., Hahn B.H.,
RA Cantor R.M., Tsao B.P.;
RT "Association of a common complement receptor 2 haplotype with increased
RT risk of systemic lupus erythematosus.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:3961-3966(2007).
CC -!- FUNCTION: Receptor for complement C3, for the Epstein-Barr virus on
CC human B-cells and T-cells and for HNRNPU (PubMed:7753047). Participates
CC in B lymphocytes activation (PubMed:7753047).
CC {ECO:0000269|PubMed:7753047}.
CC -!- FUNCTION: (Microbial infection) Acts as a receptor for Epstein-Barr
CC virus. {ECO:0000269|PubMed:2460635}.
CC -!- SUBUNIT: Interacts (via Sushi domain 1 and 2) with C3 (PubMed:11387479,
CC PubMed:21527715). Interacts with CD19 (PubMed:1702139). Part of a
CC complex composed of CD19, CR2/CD21, CD81 and IFITM1/CD225 in the
CC membrane of mature B-cells (PubMed:1383329). Interacts (via Sushi
CC domain 1 and 2) with FCER2 (via the C-terminus).
CC {ECO:0000269|PubMed:11387479, ECO:0000269|PubMed:1383329,
CC ECO:0000269|PubMed:16172256, ECO:0000269|PubMed:1702139,
CC ECO:0000269|PubMed:21527715}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Epstein-Barr virus gp350
CC protein. {ECO:0000269|PubMed:2460635}.
CC -!- INTERACTION:
CC P20023; P01024: C3; NbExp=4; IntAct=EBI-2872467, EBI-905851;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1383329,
CC ECO:0000269|PubMed:1702139}; Single-pass type I membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=A;
CC IsoId=P20023-1; Sequence=Displayed;
CC Name=B;
CC IsoId=P20023-2; Sequence=VSP_001208, VSP_001209;
CC Name=C;
CC IsoId=P20023-3; Sequence=VSP_001210;
CC Name=D;
CC IsoId=P20023-4; Sequence=VSP_001210, VSP_001211;
CC -!- TISSUE SPECIFICITY: Mature B-lymphocytes, T-lymphocytes, pharyngeal
CC epithelial cells, astrocytes and follicular dendritic cells of the
CC spleen.
CC -!- DISEASE: Systemic lupus erythematosus 9 (SLEB9) [MIM:610927]: A
CC chronic, relapsing, inflammatory, and often febrile multisystemic
CC disorder of connective tissue, characterized principally by involvement
CC of the skin, joints, kidneys and serosal membranes. It is of unknown
CC etiology, but is thought to represent a failure of the regulatory
CC mechanisms of the autoimmune system. The disease is marked by a wide
CC range of system dysfunctions, an elevated erythrocyte sedimentation
CC rate, and the formation of LE cells in the blood or bone marrow.
CC {ECO:0000269|PubMed:17360460}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC -!- DISEASE: Immunodeficiency, common variable, 7 (CVID7) [MIM:614699]: A
CC primary immunodeficiency characterized by antibody deficiency,
CC hypogammaglobulinemia, recurrent bacterial infections and an inability
CC to mount an antibody response to antigen. The defect results from a
CC failure of B-cell differentiation and impaired secretion of
CC immunoglobulins; the numbers of circulating B-cells is usually in the
CC normal range, but can be low. {ECO:0000269|PubMed:22035880}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the receptors of complement activation (RCA)
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA35784.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; M26004; AAA35786.1; -; mRNA.
DR EMBL; M26016; AAB04638.1; -; Genomic_DNA.
DR EMBL; M24007; AAB04638.1; JOINED; Genomic_DNA.
DR EMBL; M24008; AAB04638.1; JOINED; Genomic_DNA.
DR EMBL; M24009; AAB04638.1; JOINED; Genomic_DNA.
DR EMBL; M24010; AAB04638.1; JOINED; Genomic_DNA.
DR EMBL; M24011; AAB04638.1; JOINED; Genomic_DNA.
DR EMBL; M26009; AAB04638.1; JOINED; Genomic_DNA.
DR EMBL; M26010; AAB04638.1; JOINED; Genomic_DNA.
DR EMBL; M26011; AAB04638.1; JOINED; Genomic_DNA.
DR EMBL; M26012; AAB04638.1; JOINED; Genomic_DNA.
DR EMBL; M26013; AAB04638.1; JOINED; Genomic_DNA.
DR EMBL; M26014; AAB04638.1; JOINED; Genomic_DNA.
DR EMBL; M26015; AAB04638.1; JOINED; Genomic_DNA.
DR EMBL; Y00649; CAA68674.1; -; mRNA.
DR EMBL; J03565; AAA35784.1; ALT_FRAME; mRNA.
DR EMBL; AK223627; BAD97347.1; -; mRNA.
DR EMBL; AK301496; BAG63007.1; -; mRNA.
DR EMBL; EF064746; ABK41929.1; -; Genomic_DNA.
DR EMBL; AL391597; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL691452; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC090937; AAH90937.1; -; mRNA.
DR EMBL; BC136394; AAI36395.1; -; mRNA.
DR EMBL; S62696; AAB27186.1; -; mRNA.
DR CCDS; CCDS1478.1; -. [P20023-1]
DR CCDS; CCDS31007.1; -. [P20023-3]
DR PIR; JL0028; PL0009.
DR RefSeq; NP_001006659.1; NM_001006658.2. [P20023-3]
DR RefSeq; NP_001868.2; NM_001877.4. [P20023-1]
DR PDB; 1GHQ; X-ray; 2.04 A; B/C=21-153.
DR PDB; 1LY2; X-ray; 1.80 A; A=22-148.
DR PDB; 1W2R; X-ray; -; A=21-153.
DR PDB; 1W2S; X-ray; -; B=21-153.
DR PDB; 2ATY; X-ray; -; A/B=21-153.
DR PDB; 2GSX; X-ray; -; A=21-971.
DR PDB; 3OED; X-ray; 3.16 A; C/D=20-153.
DR PDBsum; 1GHQ; -.
DR PDBsum; 1LY2; -.
DR PDBsum; 1W2R; -.
DR PDBsum; 1W2S; -.
DR PDBsum; 2ATY; -.
DR PDBsum; 2GSX; -.
DR PDBsum; 3OED; -.
DR AlphaFoldDB; P20023; -.
DR SMR; P20023; -.
DR BioGRID; 107771; 13.
DR CORUM; P20023; -.
DR IntAct; P20023; 2.
DR STRING; 9606.ENSP00000356024; -.
DR GlyCosmos; P20023; 11 sites, No reported glycans.
DR GlyGen; P20023; 13 sites.
DR iPTMnet; P20023; -.
DR PhosphoSitePlus; P20023; -.
DR BioMuta; CR2; -.
DR DMDM; 215273962; -.
DR EPD; P20023; -.
DR MassIVE; P20023; -.
DR PaxDb; 9606-ENSP00000356024; -.
DR PeptideAtlas; P20023; -.
DR ProteomicsDB; 53712; -. [P20023-1]
DR ProteomicsDB; 53713; -. [P20023-2]
DR ProteomicsDB; 53714; -. [P20023-3]
DR ProteomicsDB; 53715; -. [P20023-4]
DR ABCD; P20023; 1 sequenced antibody.
DR Antibodypedia; 3624; 1787 antibodies from 49 providers.
DR DNASU; 1380; -.
DR Ensembl; ENST00000367057.8; ENSP00000356024.3; ENSG00000117322.19. [P20023-3]
DR Ensembl; ENST00000367058.7; ENSP00000356025.3; ENSG00000117322.19. [P20023-1]
DR GeneID; 1380; -.
DR KEGG; hsa:1380; -.
DR MANE-Select; ENST00000367057.8; ENSP00000356024.3; NM_001006658.3; NP_001006659.1. [P20023-3]
DR UCSC; uc001hfv.4; human. [P20023-1]
DR AGR; HGNC:2336; -.
DR CTD; 1380; -.
DR DisGeNET; 1380; -.
DR GeneCards; CR2; -.
DR HGNC; HGNC:2336; CR2.
DR HPA; ENSG00000117322; Tissue enriched (lymphoid).
DR MalaCards; CR2; -.
DR MIM; 120650; gene.
DR MIM; 610927; phenotype.
DR MIM; 614699; phenotype.
DR neXtProt; NX_P20023; -.
DR OpenTargets; ENSG00000117322; -.
DR Orphanet; 1572; Common variable immunodeficiency.
DR Orphanet; 536; Systemic lupus erythematosus.
DR PharmGKB; PA26857; -.
DR VEuPathDB; HostDB:ENSG00000117322; -.
DR eggNOG; KOG4297; Eukaryota.
DR GeneTree; ENSGT00940000161110; -.
DR HOGENOM; CLU_005124_0_0_1; -.
DR InParanoid; P20023; -.
DR OMA; WTQAVPT; -.
DR OrthoDB; 5395408at2759; -.
DR PhylomeDB; P20023; -.
DR TreeFam; TF316872; -.
DR PathwayCommons; P20023; -.
DR Reactome; R-HSA-977606; Regulation of Complement cascade.
DR SignaLink; P20023; -.
DR SIGNOR; P20023; -.
DR BioGRID-ORCS; 1380; 11 hits in 1139 CRISPR screens.
DR ChiTaRS; CR2; human.
DR EvolutionaryTrace; P20023; -.
DR GeneWiki; Complement_receptor_2; -.
DR GenomeRNAi; 1380; -.
DR Pharos; P20023; Tbio.
DR PRO; PR:P20023; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P20023; Protein.
DR Bgee; ENSG00000117322; Expressed in secondary oocyte and 112 other cell types or tissues.
DR ExpressionAtlas; P20023; baseline and differential.
DR Genevisible; P20023; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; NAS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0043235; C:receptor complex; IDA:MGI.
DR GO; GO:0001848; F:complement binding; IDA:UniProtKB.
DR GO; GO:0004875; F:complement receptor activity; TAS:ProtInc.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0034987; F:immunoglobulin receptor binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:MGI.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; NAS:UniProtKB.
DR GO; GO:0001618; F:virus receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0030183; P:B cell differentiation; IDA:UniProtKB.
DR GO; GO:0042100; P:B cell proliferation; IDA:UniProtKB.
DR GO; GO:0006957; P:complement activation, alternative pathway; IMP:ARUK-UCL.
DR GO; GO:0006958; P:complement activation, classical pathway; IEA:UniProtKB-KW.
DR GO; GO:0006955; P:immune response; NAS:UniProtKB.
DR GO; GO:0045959; P:negative regulation of complement activation, classical pathway; IBA:GO_Central.
DR GO; GO:0002456; P:T cell mediated immunity; IBA:GO_Central.
DR CDD; cd00033; CCP; 13.
DR Gene3D; 2.10.70.10; Complement Module, domain 1; 14.
DR InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR InterPro; IPR000436; Sushi_SCR_CCP_dom.
DR PANTHER; PTHR19325; COMPLEMENT COMPONENT-RELATED SUSHI DOMAIN-CONTAINING; 1.
DR PANTHER; PTHR19325:SF573; SUSHI DOMAIN-CONTAINING PROTEIN; 1.
DR Pfam; PF00084; Sushi; 13.
DR SMART; SM00032; CCP; 14.
DR SUPFAM; SSF57535; Complement control module/SCR domain; 15.
DR PROSITE; PS50923; SUSHI; 15.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Complement pathway;
KW Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Host cell receptor for virus entry; Host-virus interaction; Immunity;
KW Innate immunity; Membrane; Receptor; Reference proteome; Repeat; Signal;
KW Sushi; Systemic lupus erythematosus; Transmembrane; Transmembrane helix.
FT SIGNAL 1..20
FT CHAIN 21..1033
FT /note="Complement receptor type 2"
FT /id="PRO_0000006010"
FT TOPO_DOM 21..971
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 972..999
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1000..1033
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 21..84
FT /note="Sushi 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 89..148
FT /note="Sushi 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 152..212
FT /note="Sushi 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 213..273
FT /note="Sushi 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 274..344
FT /note="Sushi 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 349..408
FT /note="Sushi 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 409..468
FT /note="Sushi 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 469..524
FT /note="Sushi 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 525..595
FT /note="Sushi 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 600..659
FT /note="Sushi 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 660..716
FT /note="Sushi 11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 717..781
FT /note="Sushi 12"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 786..845
FT /note="Sushi 13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 849..909
FT /note="Sushi 14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 910..970
FT /note="Sushi 15"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT CARBOHYD 121
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12122212,
FT ECO:0007744|PDB:1LY2"
FT CARBOHYD 127
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12122212,
FT ECO:0007744|PDB:1LY2"
FT CARBOHYD 294
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 372
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 492
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 623
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 682
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 800
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 823
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 861
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 911
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 23..65
FT /evidence="ECO:0000269|PubMed:11387479,
FT ECO:0000269|PubMed:12122212, ECO:0000269|PubMed:21527715,
FT ECO:0007744|PDB:1GHQ, ECO:0007744|PDB:1LY2,
FT ECO:0007744|PDB:3OED"
FT DISULFID 51..82
FT /evidence="ECO:0000269|PubMed:11387479,
FT ECO:0000269|PubMed:12122212, ECO:0000269|PubMed:21527715,
FT ECO:0007744|PDB:1GHQ, ECO:0007744|PDB:1LY2,
FT ECO:0007744|PDB:3OED"
FT DISULFID 91..132
FT /evidence="ECO:0000269|PubMed:11387479,
FT ECO:0000269|PubMed:12122212, ECO:0000269|PubMed:21527715,
FT ECO:0007744|PDB:1GHQ, ECO:0007744|PDB:1LY2,
FT ECO:0007744|PDB:3OED"
FT DISULFID 118..146
FT /evidence="ECO:0000269|PubMed:11387479,
FT ECO:0000269|PubMed:12122212, ECO:0000269|PubMed:21527715,
FT ECO:0007744|PDB:1GHQ, ECO:0007744|PDB:1LY2,
FT ECO:0007744|PDB:3OED"
FT DISULFID 154..197
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 183..210
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 215..256
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 242..271
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 276..325
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 305..342
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 351..393
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 379..406
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 410..453
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 439..466
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 471..509
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 495..522
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 527..576
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 556..593
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 602..644
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 630..657
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 662..699
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 685..714
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 719..762
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 748..779
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 788..830
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 816..843
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 851..894
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 880..907
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 912..955
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 941..968
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT VAR_SEQ 499..524
FT /note="Missing (in isoform B)"
FT /evidence="ECO:0000303|PubMed:8390533"
FT /id="VSP_001208"
FT VAR_SEQ 525..556
FT /note="ITCPPPPVIYNGAHTGSSLEDFPYGTTVTYTC -> NHLPTTPCYLQWGTHR
FT EFLRRFSIWNHGHLHM (in isoform B)"
FT /evidence="ECO:0000303|PubMed:8390533"
FT /id="VSP_001209"
FT VAR_SEQ 659
FT /note="K -> KGCQSPPGLHHGRHTGGNTVFFVSGMTVDYTCDPGYLLVGNKSIHCM
FT PSGNWSPSAPRCE (in isoform C and isoform D)"
FT /evidence="ECO:0000303|PubMed:10068037,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:2827171, ECO:0000303|Ref.6"
FT /id="VSP_001210"
FT VAR_SEQ 716..723
FT /note="Missing (in isoform D)"
FT /evidence="ECO:0000303|PubMed:10068037"
FT /id="VSP_001211"
FT VARIANT 639
FT /note="S -> N (in dbSNP:rs17615)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17360460"
FT /id="VAR_016164"
FT VARIANT 993
FT /note="I -> V (in dbSNP:rs17618)"
FT /evidence="ECO:0000269|PubMed:2832506"
FT /id="VAR_016165"
FT VARIANT 1003
FT /note="A -> E (in dbSNP:rs17617)"
FT /evidence="ECO:0000269|PubMed:2563370,
FT ECO:0000269|PubMed:2827171"
FT /id="VAR_016166"
FT MUTAGEN 103
FT /note="R->A: No effect on affinity for C3."
FT /evidence="ECO:0000269|PubMed:21527715"
FT MUTAGEN 112
FT /note="D->A: Reduced affinity for C3."
FT /evidence="ECO:0000269|PubMed:21527715"
FT MUTAGEN 128
FT /note="K->A: Strongly reduced affinity for C3."
FT /evidence="ECO:0000269|PubMed:21527715"
FT CONFLICT 457
FT /note="Missing (in Ref. 2; CAA68674)"
FT /evidence="ECO:0000305"
FT CONFLICT 646
FT /note="A -> R (in Ref. 3; AAA35784)"
FT /evidence="ECO:0000305"
FT CONFLICT 667
FT /note="Q -> D (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 774
FT /note="G -> E (in Ref. 3; AAA35784)"
FT /evidence="ECO:0000305"
FT CONFLICT 783..787
FT /note="PPVTR -> L (in Ref. 3; AAA35784)"
FT /evidence="ECO:0000305"
FT CONFLICT 844
FT /note="I -> M (in Ref. 1; AAA35786/AAB04638)"
FT /evidence="ECO:0000305"
FT CONFLICT 886
FT /note="L -> V (in Ref. 3; AAA35784)"
FT /evidence="ECO:0000305"
FT CONFLICT 890
FT /note="A -> P (in Ref. 3; AAA35784)"
FT /evidence="ECO:0000305"
FT CONFLICT 902
FT /note="Q -> G (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 906
FT /note="H -> L (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 32..34
FT /evidence="ECO:0007829|PDB:1LY2"
FT STRAND 39..42
FT /evidence="ECO:0007829|PDB:1LY2"
FT STRAND 46..51
FT /evidence="ECO:0007829|PDB:1LY2"
FT STRAND 55..59
FT /evidence="ECO:0007829|PDB:1LY2"
FT STRAND 61..66
FT /evidence="ECO:0007829|PDB:1LY2"
FT STRAND 68..72
FT /evidence="ECO:0007829|PDB:1LY2"
FT STRAND 74..77
FT /evidence="ECO:0007829|PDB:1LY2"
FT STRAND 81..84
FT /evidence="ECO:0007829|PDB:1LY2"
FT STRAND 99..103
FT /evidence="ECO:0007829|PDB:1LY2"
FT STRAND 106..109
FT /evidence="ECO:0007829|PDB:1LY2"
FT STRAND 113..118
FT /evidence="ECO:0007829|PDB:1LY2"
FT STRAND 122..126
FT /evidence="ECO:0007829|PDB:1LY2"
FT STRAND 128..132
FT /evidence="ECO:0007829|PDB:1LY2"
FT STRAND 136..141
FT /evidence="ECO:0007829|PDB:1LY2"
FT STRAND 145..148
FT /evidence="ECO:0007829|PDB:1LY2"
FT CONFLICT P20023-3:663
FT /note="S -> P (in Ref. 3; AAA35784)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1033 AA; 112916 MW; 7D89DB4A07847E9A CRC64;
MGAAGLLGVF LALVAPGVLG ISCGSPPPIL NGRISYYSTP IAVGTVIRYS CSGTFRLIGE
KSLLCITKDK VDGTWDKPAP KCEYFNKYSS CPEPIVPGGY KIRGSTPYRH GDSVTFACKT
NFSMNGNKSV WCQANNMWGP TRLPTCVSVF PLECPALPMI HNGHHTSENV GSIAPGLSVT
YSCESGYLLV GEKIINCLSS GKWSAVPPTC EEARCKSLGR FPNGKVKEPP ILRVGVTANF
FCDEGYRLQG PPSSRCVIAG QGVAWTKMPV CEEIFCPSPP PILNGRHIGN SLANVSYGSI
VTYTCDPDPE EGVNFILIGE STLRCTVDSQ KTGTWSGPAP RCELSTSAVQ CPHPQILRGR
MVSGQKDRYT YNDTVIFACM FGFTLKGSKQ IRCNAQGTWE PSAPVCEKEC QAPPNILNGQ
KEDRHMVRFD PGTSIKYSCN PGYVLVGEES IQCTSEGVWT PPVPQCKVAA CEATGRQLLT
KPQHQFVRPD VNSSCGEGYK LSGSVYQECQ GTIPWFMEIR LCKEITCPPP PVIYNGAHTG
SSLEDFPYGT TVTYTCNPGP ERGVEFSLIG ESTIRCTSND QERGTWSGPA PLCKLSLLAV
QCSHVHIANG YKISGKEAPY FYNDTVTFKC YSGFTLKGSS QIRCKADNTW DPEIPVCEKE
TCQHVRQSLQ ELPAGSRVEL VNTSCQDGYQ LTGHAYQMCQ DAENGIWFKK IPLCKVIHCH
PPPVIVNGKH TGMMAENFLY GNEVSYECDQ GFYLLGEKKL QCRSDSKGHG SWSGPSPQCL
RSPPVTRCPN PEVKHGYKLN KTHSAYSHND IVYVDCNPGF IMNGSRVIRC HTDNTWVPGV
PTCIKKAFIG CPPPPKTPNG NHTGGNIARF SPGMSILYSC DQGYLLVGEA LLLCTHEGTW
SQPAPHCKEV NCSSPADMDG IQKGLEPRKM YQYGAVVTLE CEDGYMLEGS PQSQCQSDHQ
WNPPLAVCRS RSLAPVLCGI AAGLILLTFL IVITLYVISK HRARNYYTDT SQKEAFHLEA
REVYSVDPYN PAS
//
