CD19_HUMAN
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 03-AUG-2022, entry version 222.
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 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/";
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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 PDBsum; 6AL5; -.
DR PDBsum; 7JIC; -.
DR AlphaFoldDB; P15391; -.
DR SMR; P15391; -.
DR BioGRID; 107368; 21.
DR CORUM; P15391; -.
DR ELM; P15391; -.
DR IntAct; P15391; 12.
DR MINT; P15391; -.
DR STRING; 9606.ENSP00000437940; -.
DR ChEMBL; CHEMBL3390821; -.
DR DrugBank; DB13915; Axicabtagene ciloleucel.
DR DrugBank; DB09052; Blinatumomab.
DR DrugBank; DB15699; Brexucabtagene autoleucel.
DR DrugBank; DB06342; Coltuximab ravtansine.
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 GlyGen; P15391; 5 sites.
DR iPTMnet; P15391; -.
DR PhosphoSitePlus; P15391; -.
DR BioMuta; CD19; -.
DR DMDM; 160332376; -.
DR MassIVE; P15391; -.
DR PaxDb; P15391; -.
DR PeptideAtlas; P15391; -.
DR PRIDE; P15391; -.
DR ProteomicsDB; 27066; -.
DR ProteomicsDB; 53135; -. [P15391-1]
DR ABCD; P15391; 71 sequenced antibodies.
DR Antibodypedia; 4237; 4853 antibodies from 55 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 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; LWLPCGV; -.
DR OrthoDB; 521520at2759; -.
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; 18 hits in 1067 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 122 other tissues.
DR Genevisible; P15391; HS.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
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:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; 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 DisProt; DP02431; -.
DR Gene3D; 2.60.40.10; -; 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; PTHR16674; 1.
DR SMART; SM00409; IG; 2.
DR SUPFAM; SSF48726; SSF48726; 2.
DR PROSITE; PS50835; IG_LIKE; 2.
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 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
