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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 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. DR Genevisible; P20023; HS. 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 //