ID CD19_HUMAN Reviewed; 556 AA. AC P15391; A0N0P9; F5H635; Q96S68; Q9BRD6; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 13-NOV-2007, sequence version 6. DT 27-MAR-2024, entry version 231. DE RecName: Full=B-lymphocyte antigen CD19; DE AltName: Full=B-lymphocyte surface antigen B4; DE AltName: Full=Differentiation antigen CD19; DE AltName: Full=T-cell surface antigen Leu-12; DE AltName: CD_antigen=CD19; DE Flags: Precursor; GN Name=CD19; 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 [MRNA] (ISOFORM 1), AND VARIANTS VAL-174 AND HIS-514. RX PubMed=2459292; DOI=10.1084/jem.168.3.1205; RA Stamenkovic I., Seed B.; RT "CD19, the earliest differentiation antigen of the B cell lineage, bears RT three extracellular immunoglobulin-like domains and an Epstein-Barr virus- RT related cytoplasmic tail."; RL J. Exp. Med. 168:1205-1210(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS VAL-174 AND HIS-514. RC TISSUE=Tonsil; RX PubMed=2472450; RA Tedder T.F., Isaacs C.M.; RT "Isolation of cDNAs encoding the CD19 antigen of human and mouse B RT lymphocytes. A new member of the immunoglobulin superfamily."; RL J. Immunol. 143:712-717(1989). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-174. RX PubMed=1375324; DOI=10.1128/mcb.12.6.2662-2672.1992; RA Kozmik Z., Wang S., Doerfler P., Adams B., Busslinger M.; RT "The promoter of the CD19 gene is a target for the B-cell-specific RT transcription factor BSAP."; RL Mol. Cell. Biol. 12:2662-2672(1992). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-174. RC TISSUE=Blood; RX PubMed=1370948; DOI=10.1007/bf00189519; RA Zhou L.J., Ord D.C., Omori S.A., Tedder T.F.; RT "Structure of the genes encoding the CD19 antigen of human and mouse B RT lymphocytes."; RL Immunogenetics 35:102-111(1992). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-174. RX PubMed=12215898; DOI=10.1038/sj.gene.6363906; RA Kuroki K., Tsuchiya N., Tsao B.P., Grossman J.M., Fukazawa T., Hagiwara K., RA Kano H., Takazoe M., Iwata T., Hashimoto H., Tokunaga K.; RT "Polymorphisms of human CD19 gene: possible association with susceptibility RT to systemic lupus erythematosus in Japanese."; RL Genes Immun. 3:S21-S30(2002). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT VAL-174. RC TISSUE=Spleen; 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 [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-174. 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=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT VAL-174. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=B-cell; 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 [11] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=2463100; DOI=10.1016/0008-8749(89)90385-7; RA de Rie M.A., Schumacher T.N., van Schijndel G.M., van Lier R.A., RA Miedema F.; RT "Regulatory role of CD19 molecules in B-cell activation and RT differentiation."; RL Cell. Immunol. 118:368-381(1989). RN [12] RP INTERACTION WITH CR2, 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 [13] RP IDENTIFICATION IN A COMPLEX WITH CR2; 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 [14] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=1373518; DOI=10.1126/science.1373518; RA Carter R.H., Fearon D.T.; RT "CD19: lowering the threshold for antigen receptor stimulation of B RT lymphocytes."; RL Science 256:105-107(1992). RN [15] RP PHOSPHORYLATION, AND INTERACTION WITH LYN. RX PubMed=7687428; DOI=10.1006/bbrc.1993.1807; RA Roifman C.M., Ke S.; RT "CD19 is a substrate of the antigen receptor-associated protein tyrosine RT kinase in human B cells."; RL Biochem. Biophys. Res. Commun. 194:222-225(1993). RN [16] RP PHOSPHORYLATION. RX PubMed=7687539; DOI=10.1002/j.1460-2075.1993.tb05930.x; RA Chalupny N.J., Kanner S.B., Schieven G.L., Wee S., Gilliland L.K., RA Aruffo A., Ledbetter J.A.; RT "Tyrosine phosphorylation of CD19 in pre-B and mature B cells."; RL EMBO J. 12:2691-2696(1993). RN [17] RP INTERACTION WITH PHOSPHATIDYLINOSITOL 3-KINASE 85 KDA REGULATORY SUBUNIT RP PIK3R, PHOSPHORYLATION AT TYR-500 AND TYR-531, AND MUTAGENESIS OF TYR-500 RP AND TYR-531. RX PubMed=7684160; DOI=10.1126/science.7684160; RA Tuveson D.A., Carter R.H., Soltoff S.P., Fearon D.T.; RT "CD19 of B cells as a surrogate kinase insert region to bind RT phosphatidylinositol 3-kinase."; RL Science 260:986-989(1993). RN [18] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF TYR-500 AND TYR-531. RX PubMed=9382888; DOI=10.1084/jem.186.11.1897; RA Buhl A.M., Pleiman C.M., Rickert R.C., Cambier J.C.; RT "Qualitative regulation of B cell antigen receptor signaling by CD19: RT selective requirement for PI3-kinase activation, inositol-1,4,5- RT trisphosphate production and Ca2+ mobilization."; RL J. Exp. Med. 186:1897-1910(1997). RN [19] RP FUNCTION, MUTAGENESIS OF 339-GLY--ARG-556, AND SUBCELLULAR LOCATION. RX PubMed=9317126; RA Sato S., Miller A.S., Howard M.C., Tedder T.F.; RT "Regulation of B lymphocyte development and activation by the RT CD19/CD21/CD81/Leu 13 complex requires the cytoplasmic domain of CD19."; RL J. Immunol. 159:3278-3287(1997). RN [20] RP INTERACTION WITH GRB2; SOS; VAV AND PLCG2, AND PHOSPHORYLATION AT TYR-348; RP TYR-378; TYR-409 AND TYR-439. RX PubMed=10706702; DOI=10.4049/jimmunol.164.6.3123; RA Brooks S.R., Li X., Volanakis E.J., Carter R.H.; RT "Systematic analysis of the role of CD19 cytoplasmic tyrosines in RT enhancement of activation in Daudi human B cells: clustering of RT phospholipase C and Vav and of Grb2 and Sos with different CD19 RT tyrosines."; RL J. Immunol. 164:3123-3131(2000). RN [21] RP FUNCTION, MUTAGENESIS OF TYR-348; TYR-378; TYR-409; TYR-421; TYR-439; RP TYR-461; TYR-500 AND TYR-531, AND PHOSPHORYLATION. RX PubMed=12387743; DOI=10.1016/s1074-7613(02)00426-0; RA Wang Y., Brooks S.R., Li X., Anzelon A.N., Rickert R.C., Carter R.H.; RT "The physiologic role of CD19 cytoplasmic tyrosines."; RL Immunity 17:501-514(2002). RN [22] RP INTERACTION WITH CD81. RX PubMed=16449649; DOI=10.1128/mcb.26.4.1373-1385.2006; RA Shoham T., Rajapaksa R., Kuo C.C., Haimovich J., Levy S.; RT "Building of the tetraspanin web: distinct structural domains of CD81 RT function in different cellular compartments."; RL Mol. Cell. Biol. 26:1373-1385(2006). RN [23] RP INVOLVEMENT IN CVID3, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX PubMed=16672701; DOI=10.1056/nejmoa051568; RA van Zelm M.C., Reisli I., van der Burg M., Castano D., van Noesel C.J.M., RA van Tol M.J.D., Woellner C., Grimbacher B., Patino P.J., van Dongen J.J.M., RA Franco J.L.; RT "An antibody-deficiency syndrome due to mutations in the CD19 gene."; RL N. Engl. J. Med. 354:1901-1912(2006). RN [24] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [25] {ECO:0007744|PDB:6AL5} RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 21-277, GLYCOSYLATION AT ASN-86 RP AND ASN-125, AND DISULFIDE BONDS. RX PubMed=29490423; DOI=10.1002/prot.25485; RA Teplyakov A., Obmolova G., Luo J., Gilliland G.L.; RT "Crystal structure of B-cell co-receptor CD19 in complex with antibody B43 RT reveals an unexpected fold."; RL Proteins 86:495-500(2018). CC -!- FUNCTION: Functions as a coreceptor for the B-cell antigen receptor CC complex (BCR) on B-lymphocytes. Decreases the threshold for activation CC of downstream signaling pathways and for triggering B-cell responses to CC antigens (PubMed:2463100, PubMed:1373518, PubMed:16672701). Activates CC signaling pathways that lead to the activation of phosphatidylinositol CC 3-kinase and the mobilization of intracellular Ca(2+) stores CC (PubMed:9382888, PubMed:9317126, PubMed:12387743, PubMed:16672701). Is CC not required for early steps during B cell differentiation in the blood CC marrow (PubMed:9317126). Required for normal differentiation of B-1 CC cells (By similarity). Required for normal B cell differentiation and CC proliferation in response to antigen challenges (PubMed:2463100, CC PubMed:1373518). Required for normal levels of serum immunoglobulins, CC and for production of high-affinity antibodies in response to antigen CC challenge (PubMed:9317126, PubMed:12387743, PubMed:16672701). CC {ECO:0000250|UniProtKB:P25918, ECO:0000269|PubMed:12387743, CC ECO:0000269|PubMed:1373518, ECO:0000269|PubMed:16672701, CC ECO:0000269|PubMed:2463100, ECO:0000269|PubMed:9317126, CC ECO:0000269|PubMed:9382888}. CC -!- SUBUNIT: Interacts with CR2/CD21 (PubMed:1702139). Part of a complex CC composed of CD19, CR2/CD21, CD81 and IFITM1/CD225 in the membrane of CC mature B-cells (PubMed:1383329). Interacts directly with CD81 (via the CC second extracellular domain); this interaction is initiated early CC during biosynthesis in the ER/pre-Golgi compartments and is essential CC for trafficking and compartmentalization of CD19 receptor on the cell CC surface of activated B cells (PubMed:16449649). Interacts with VAV CC (PubMed:10706702). Interacts with GRB2 and SOS when phosphorylated on CC Tyr-348 and/or Tyr-378. Interacts with PLCG2 when phosphorylated on CC Tyr-409 (PubMed:10706702). Interacts with LYN (PubMed:7687428). CC Interacts (when tyrosine phosphorylated) with the regulatory p85 CC subunit of phosphatidylinositol 3-kinase (PIK3R1 or PIK3R2) CC (PubMed:7684160). {ECO:0000269|PubMed:10706702, CC ECO:0000269|PubMed:1383329, ECO:0000269|PubMed:16449649, CC ECO:0000269|PubMed:1702139, ECO:0000269|PubMed:7684160, CC ECO:0000269|PubMed:7687428}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1373518, CC ECO:0000269|PubMed:1383329, ECO:0000269|PubMed:16672701, CC ECO:0000269|PubMed:1702139, ECO:0000269|PubMed:2463100, CC ECO:0000269|PubMed:9317126, ECO:0000269|PubMed:9382888}; Single-pass CC type I membrane protein {ECO:0000305}. Membrane raft CC {ECO:0000250|UniProtKB:P25918}; Single-pass type I membrane protein CC {ECO:0000250|UniProtKB:P25918}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P15391-1; Sequence=Displayed; CC Name=2; CC IsoId=P15391-2; Sequence=VSP_047194; CC -!- TISSUE SPECIFICITY: Detected on marginal zone and germinal center B CC cells in lymph nodes (PubMed:2463100). Detected on blood B cells (at CC protein level) (PubMed:2463100, PubMed:16672701). CC {ECO:0000269|PubMed:16672701, ECO:0000269|PubMed:2463100}. CC -!- PTM: Phosphorylated on tyrosine following B-cell activation CC (PubMed:7684160, PubMed:7687539, PubMed:10706702, PubMed:12387743). CC Phosphorylated on tyrosine residues by LYN (PubMed:7687428). Tyrosine CC residues are phosphorylated sequentially after activation of the B cell CC receptor. Phosphorylation of Tyr-531 is extremely rapid, followed by CC phosphorylation at Tyr-409. In contrast, phosphorylation of Tyr-500 CC appears more slowly and is more transient, returning rapidly to basal CC levels (By similarity). {ECO:0000250|UniProtKB:P25918, CC ECO:0000269|PubMed:10706702, ECO:0000269|PubMed:12387743, CC ECO:0000269|PubMed:7684160, ECO:0000269|PubMed:7687428, CC ECO:0000269|PubMed:7687539}. CC -!- DISEASE: Immunodeficiency, common variable, 3 (CVID3) [MIM:613493]: 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:16672701}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SEQUENCE CAUTION: CC Sequence=AAA35533.1; Type=Frameshift; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=CD19base; Note=CD19 mutation db; CC URL="http://structure.bmc.lu.se/idbase/CD19base/"; 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; M21097; AAA35533.1; ALT_FRAME; mRNA. DR EMBL; M28170; AAA68490.1; -; mRNA. DR EMBL; M84371; AAA69966.1; -; Genomic_DNA. DR EMBL; M62550; AAB60697.1; -; Genomic_DNA. DR EMBL; M62544; AAB60697.1; JOINED; Genomic_DNA. DR EMBL; M62545; AAB60697.1; JOINED; Genomic_DNA. DR EMBL; M62546; AAB60697.1; JOINED; Genomic_DNA. DR EMBL; M62547; AAB60697.1; JOINED; Genomic_DNA. DR EMBL; M62548; AAB60697.1; JOINED; Genomic_DNA. DR EMBL; M62549; AAB60697.1; JOINED; Genomic_DNA. DR EMBL; AB052799; BAB60954.1; -; Genomic_DNA. DR EMBL; AK313577; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; EF064757; ABK41940.1; -; Genomic_DNA. DR EMBL; AC109460; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471267; EAW52012.1; -; Genomic_DNA. DR EMBL; BC006338; AAH06338.1; -; mRNA. DR CCDS; CCDS10644.1; -. [P15391-1] DR CCDS; CCDS53998.1; -. [P15391-2] DR PIR; A44441; A44441. DR RefSeq; NP_001171569.1; NM_001178098.1. [P15391-2] DR RefSeq; NP_001761.3; NM_001770.5. [P15391-1] DR PDB; 6AL5; X-ray; 3.00 A; A=21-277. DR PDB; 7JIC; EM; 3.80 A; A=20-327. DR PDB; 7URV; EM; 3.05 A; C=21-277. DR PDB; 7URX; EM; 3.40 A; C=1-278. DR PDBsum; 6AL5; -. DR PDBsum; 7JIC; -. DR PDBsum; 7URV; -. DR PDBsum; 7URX; -. DR AlphaFoldDB; P15391; -. DR EMDB; EMD-22344; -. DR EMDB; EMD-26719; -. DR EMDB; EMD-26720; -. DR SMR; P15391; -. DR BioGRID; 107368; 21. DR CORUM; P15391; -. DR ELM; P15391; -. DR IntAct; P15391; 12. DR MINT; P15391; -. DR STRING; 9606.ENSP00000313419; -. DR ChEMBL; CHEMBL3390821; -. DR DrugBank; DB13915; Axicabtagene ciloleucel. DR DrugBank; DB09052; Blinatumomab. DR DrugBank; DB15699; Brexucabtagene autoleucel. DR DrugBank; DB06342; Coltuximab ravtansine. DR DrugBank; DB11731; Depatuxizumab mafodotin. DR DrugBank; DB12530; Inebilizumab. DR DrugBank; DB16582; Lisocabtagene maraleucel. DR DrugBank; DB16222; Loncastuximab tesirine. DR DrugBank; DB15044; Tafasitamab. DR DrugBank; DB13881; Tisagenlecleucel. DR DrugCentral; P15391; -. DR GuidetoPHARMACOLOGY; 2764; -. DR GlyCosmos; P15391; 5 sites, No reported glycans. DR GlyGen; P15391; 5 sites. DR iPTMnet; P15391; -. DR PhosphoSitePlus; P15391; -. DR BioMuta; CD19; -. DR DMDM; 160332376; -. DR MassIVE; P15391; -. DR PaxDb; 9606-ENSP00000437940; -. DR PeptideAtlas; P15391; -. DR ProteomicsDB; 27066; -. DR ProteomicsDB; 53135; -. [P15391-1] DR ABCD; P15391; 71 sequenced antibodies. DR Antibodypedia; 4237; 5787 antibodies from 56 providers. DR DNASU; 930; -. DR Ensembl; ENST00000324662.8; ENSP00000313419.4; ENSG00000177455.15. [P15391-2] DR Ensembl; ENST00000538922.8; ENSP00000437940.2; ENSG00000177455.15. [P15391-1] DR GeneID; 930; -. DR KEGG; hsa:930; -. DR MANE-Select; ENST00000538922.8; ENSP00000437940.2; NM_001770.6; NP_001761.3. DR UCSC; uc002drs.4; human. [P15391-1] DR AGR; HGNC:1633; -. DR CTD; 930; -. DR DisGeNET; 930; -. DR GeneCards; CD19; -. DR HGNC; HGNC:1633; CD19. DR HPA; ENSG00000177455; Group enriched (intestine, lymphoid tissue). DR MalaCards; CD19; -. DR MIM; 107265; gene. DR MIM; 613493; phenotype. DR neXtProt; NX_P15391; -. DR OpenTargets; ENSG00000177455; -. DR Orphanet; 1572; Common variable immunodeficiency. DR PharmGKB; PA26192; -. DR VEuPathDB; HostDB:ENSG00000177455; -. DR eggNOG; ENOG502STG8; Eukaryota. DR GeneTree; ENSGT00390000014991; -. DR HOGENOM; CLU_038774_0_0_1; -. DR InParanoid; P15391; -. DR OMA; ENMENPE; -. DR OrthoDB; 5319613at2759; -. DR PhylomeDB; P15391; -. DR TreeFam; TF338293; -. DR PathwayCommons; P15391; -. DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell. DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer. DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. DR Reactome; R-HSA-977606; Regulation of Complement cascade. DR Reactome; R-HSA-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers. DR SignaLink; P15391; -. DR SIGNOR; P15391; -. DR BioGRID-ORCS; 930; 20 hits in 1153 CRISPR screens. DR ChiTaRS; CD19; human. DR GeneWiki; CD19; -. DR GenomeRNAi; 930; -. DR Pharos; P15391; Tclin. DR PRO; PR:P15391; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; P15391; Protein. DR Bgee; ENSG00000177455; Expressed in spleen and 124 other cell types or tissues. DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:MGI. DR GO; GO:0050851; P:antigen receptor-mediated signaling pathway; IDA:UniProtKB. DR GO; GO:0002322; P:B cell proliferation involved in immune response; IDA:UniProtKB. DR GO; GO:0050853; P:B cell receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0001923; P:B-1 B cell differentiation; IEA:Ensembl. DR GO; GO:0016064; P:immunoglobulin mediated immune response; IMP:UniProtKB. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:UniProtKB. DR GO; GO:0051281; P:positive regulation of release of sequestered calcium ion into cytosol; IDA:UniProtKB. DR GO; GO:0050864; P:regulation of B cell activation; IDA:UniProtKB. DR GO; GO:0050855; P:regulation of B cell receptor signaling pathway; IMP:UniProtKB. DR CDD; cd04979; Ig_Semaphorin_C; 1. DR DisProt; DP02431; -. DR Gene3D; 2.60.40.10; Immunoglobulins; 1. DR InterPro; IPR042341; CD19. DR InterPro; IPR007110; Ig-like_dom. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR003599; Ig_sub. DR PANTHER; PTHR16674; B-LYMPHOCYTE ANTIGEN CD19; 1. DR PANTHER; PTHR16674:SF2; B-LYMPHOCYTE ANTIGEN CD19; 1. DR SMART; SM00409; IG; 2. DR SUPFAM; SSF48726; Immunoglobulin; 2. DR PROSITE; PS50835; IG_LIKE; 2. DR Genevisible; P15391; HS. PE 1: Evidence at protein level; KW 3D-structure; Adaptive immunity; Alternative splicing; Cell membrane; KW Disulfide bond; Glycoprotein; Immunity; Immunoglobulin domain; Membrane; KW Phosphoprotein; Reference proteome; Repeat; Signal; Transmembrane; KW Transmembrane helix. FT SIGNAL 1..19 FT /evidence="ECO:0000255" FT CHAIN 20..556 FT /note="B-lymphocyte antigen CD19" FT /id="PRO_0000014648" FT TOPO_DOM 20..291 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 292..313 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 314..556 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 20..113 FT /note="Ig-like C2-type 1" FT DOMAIN 176..277 FT /note="Ig-like C2-type 2" FT REGION 329..355 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 372..497 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 513..556 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 340..355 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 403..423 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 424..438 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 444..466 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 227 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P25918" FT MOD_RES 348 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:10706702" FT MOD_RES 378 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:10706702" FT MOD_RES 409 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:10706702" FT MOD_RES 439 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:10706702" FT MOD_RES 500 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:7684160" FT MOD_RES 531 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:7684160" FT CARBOHYD 86 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:29490423, FT ECO:0007744|PDB:6AL5" FT CARBOHYD 125 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:29490423, FT ECO:0007744|PDB:6AL5" FT CARBOHYD 138 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 181 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 265 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 38..261 FT /evidence="ECO:0000269|PubMed:29490423, FT ECO:0007744|PDB:6AL5" FT DISULFID 97..200 FT /evidence="ECO:0000269|PubMed:29490423, FT ECO:0007744|PDB:6AL5" FT DISULFID 134..173 FT /evidence="ECO:0000269|PubMed:29490423, FT ECO:0007744|PDB:6AL5" FT VAR_SEQ 495 FT /note="L -> LA (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_047194" FT VARIANT 174 FT /note="L -> V (in dbSNP:rs2904880)" FT /evidence="ECO:0000269|PubMed:12215898, FT ECO:0000269|PubMed:1370948, ECO:0000269|PubMed:1375324, FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:2459292, FT ECO:0000269|PubMed:2472450, ECO:0000269|Ref.7, FT ECO:0000269|Ref.9" FT /id="VAR_026963" FT VARIANT 514 FT /note="R -> H (in dbSNP:rs34763945)" FT /evidence="ECO:0000269|PubMed:2459292, FT ECO:0000269|PubMed:2472450" FT /id="VAR_036987" FT MUTAGEN 309..556 FT /note="Missing: Abolishes the ability to activate signaling FT pathways that mediate mobilization of cytoplasmic Ca(2+). FT Abolishes the ability to restore normal B cell functions FT and responses to antigenic stimuli." FT /evidence="ECO:0000269|PubMed:9317126" FT MUTAGEN 348 FT /note="Y->F: No effect on the ability to complement FT impaired B cell development and functions; when associated FT with F-378." FT /evidence="ECO:0000269|PubMed:12387743" FT MUTAGEN 378 FT /note="Y->F: No effect on the ability to complement FT impaired B cell development and functions; when associated FT with F-348." FT /evidence="ECO:0000269|PubMed:12387743" FT MUTAGEN 409 FT /note="Y->F: No effect on the ability to complement FT impaired B cell development and functions; when associated FT with F-439." FT /evidence="ECO:0000269|PubMed:12387743" FT MUTAGEN 421 FT /note="Y->F: No effect on the ability to complement FT impaired B cell development and functions; when associated FT with F-461." FT /evidence="ECO:0000269|PubMed:12387743" FT MUTAGEN 439 FT /note="Y->F: No effect on the ability to complement FT impaired B cell development and functions; when associated FT with F-409." FT /evidence="ECO:0000269|PubMed:12387743" FT MUTAGEN 461 FT /note="Y->F: No effect on the ability to complement FT impaired B cell development and functions; when associated FT with F-421." FT /evidence="ECO:0000269|PubMed:12387743" FT MUTAGEN 500 FT /note="Y->F: Strongly reduced tyrosine phosphorylation; FT when associated with F-531. Abolishes activation of FT signaling pathways that mediate mobilization of cytoplasmic FT Ca(2+); when associated with F-531. Abolishes the ability FT to complement impaired B cell development and functions; FT when associated with F-531." FT /evidence="ECO:0000269|PubMed:12387743, FT ECO:0000269|PubMed:7684160, ECO:0000269|PubMed:9382888" FT MUTAGEN 531 FT /note="Y->F: Strongly reduced tyrosine phosphorylation; FT when associated with F-500. Abolishes activation of FT signaling pathways that mediate mobilization of cytoplasmic FT Ca(2+); when associated with F-500. Abolishes the ability FT to complement impaired B cell development and functions; FT when associated with F-500." FT /evidence="ECO:0000269|PubMed:12387743, FT ECO:0000269|PubMed:7684160, ECO:0000269|PubMed:9382888" FT CONFLICT 29 FT /note="E -> EG (in Ref. 4; AAB60697)" FT /evidence="ECO:0000305" FT CONFLICT 80 FT /note="I -> S (in Ref. 2; AAA68490, 3; AAA69966, 4; FT AAB60697 and 5; BAB60954)" FT /evidence="ECO:0000305" FT CONFLICT 186 FT /note="Q -> QAFLVLSLPVP (in Ref. 3; AAA69966)" FT /evidence="ECO:0000305" FT STRAND 24..29 FT /evidence="ECO:0007829|PDB:6AL5" FT STRAND 34..36 FT /evidence="ECO:0007829|PDB:6AL5" FT STRAND 50..55 FT /evidence="ECO:0007829|PDB:6AL5" FT STRAND 61..75 FT /evidence="ECO:0007829|PDB:6AL5" FT STRAND 80..84 FT /evidence="ECO:0007829|PDB:6AL5" FT HELIX 89..91 FT /evidence="ECO:0007829|PDB:7URV" FT STRAND 93..100 FT /evidence="ECO:0007829|PDB:6AL5" FT STRAND 108..115 FT /evidence="ECO:0007829|PDB:6AL5" FT STRAND 119..125 FT /evidence="ECO:0007829|PDB:6AL5" FT STRAND 155..160 FT /evidence="ECO:0007829|PDB:6AL5" FT STRAND 163..166 FT /evidence="ECO:0007829|PDB:6AL5" FT STRAND 187..190 FT /evidence="ECO:0007829|PDB:6AL5" FT STRAND 196..198 FT /evidence="ECO:0007829|PDB:6AL5" FT HELIX 203..205 FT /evidence="ECO:0007829|PDB:6AL5" FT STRAND 208..218 FT /evidence="ECO:0007829|PDB:6AL5" FT STRAND 221..230 FT /evidence="ECO:0007829|PDB:6AL5" FT STRAND 239..242 FT /evidence="ECO:0007829|PDB:6AL5" FT STRAND 245..250 FT /evidence="ECO:0007829|PDB:6AL5" FT HELIX 253..255 FT /evidence="ECO:0007829|PDB:6AL5" FT STRAND 257..262 FT /evidence="ECO:0007829|PDB:6AL5" FT STRAND 267..275 FT /evidence="ECO:0007829|PDB:6AL5" SQ SEQUENCE 556 AA; 61128 MW; A0E08DD628B69E51 CRC64; MPPPRLLFFL LFLTPMEVRP EEPLVVKVEE GDNAVLQCLK GTSDGPTQQL TWSRESPLKP FLKLSLGLPG LGIHMRPLAI WLFIFNVSQQ MGGFYLCQPG PPSEKAWQPG WTVNVEGSGE LFRWNVSDLG GLGCGLKNRS SEGPSSPSGK LMSPKLYVWA KDRPEIWEGE PPCLPPRDSL NQSLSQDLTM APGSTLWLSC GVPPDSVSRG PLSWTHVHPK GPKSLLSLEL KDDRPARDMW VMETGLLLPR ATAQDAGKYY CHRGNLTMSF HLEITARPVL WHWLLRTGGW KVSAVTLAYL IFCLCSLVGI LHLQRALVLR RKRKRMTDPT RRFFKVTPPP GSGPQNQYGN VLSLPTPTSG LGRAQRWAAG LGGTAPSYGN PSSDVQADGA LGSRSPPGVG PEEEEGEGYE EPDSEEDSEF YENDSNLGQD QLSQDGSGYE NPEDEPLGPE DEDSFSNAES YENEDEELTQ PVARTMDFLS PHGSAWDPSR EATSLGSQSY EDMRGILYAA PQLRSIRGQP GPNHEEDADS YENMDNPDGP DPAWGGGGRM GTWSTR //