CD19

Protein identityUniProt · HPA

UniProt accession

P15391

Gene

CD19

Ensembl

ENSG00000177455

Chromosome

16

Canonical length

556 aa

Protein class

CD markers, Disease related genes, FDA approved drug targets, Human disease related genes, Predicted membrane proteins

OverviewNCBI Gene

This gene encodes a member of the immunoglobulin gene superfamily. Expression of this cell surface protein is restricted to B cell lymphocytes. This protein is a reliable marker for pre-B cells but its expression diminishes during terminal B cell differentiation in antibody secreting plasma cells. The protein has two N-terminal extracellular Ig-like domains separated by a non-Ig-like domain, a hydrophobic transmembrane domain, and a large C-terminal cytoplasmic domain. This protein forms a complex with several membrane proteins including complement receptor type 2 (CD21) and tetraspanin (CD81) and this complex reduces the threshold for antigen-initiated B cell activation. Activation of this B-cell antigen receptor complex activates the phosphatidylinositol 3-kinase signalling pathway and the subsequent release of intracellular stores of calcium ions. This protein is a target of chimeric antigen receptor (CAR) T-cells used in the treatment of lymphoblastic leukemia. Mutations in this gene are associated with the disease common variable immunodeficiency 3 (CVID3) which results in a failure of B-cell differentiation and impaired secretion of immunoglobulins. CVID3 is characterized by hypogammaglobulinemia, an inability to mount an antibody response to antigen, and recurrent bacterial infections. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2020]

Canonical amino-acid sequenceUniProt

556 residues, UniProt reviewed canonical sequence.

>P15391|CD19
     1  MPPPRLLFFL LFLTPMEVRP EEPLVVKVEE GDNAVLQCLK GTSDGPTQQL TWSRESPLKP
    61  FLKLSLGLPG LGIHMRPLAI WLFIFNVSQQ MGGFYLCQPG PPSEKAWQPG WTVNVEGSGE
   121  LFRWNVSDLG GLGCGLKNRS SEGPSSPSGK LMSPKLYVWA KDRPEIWEGE PPCLPPRDSL
   181  NQSLSQDLTM APGSTLWLSC GVPPDSVSRG PLSWTHVHPK GPKSLLSLEL KDDRPARDMW
   241  VMETGLLLPR ATAQDAGKYY CHRGNLTMSF HLEITARPVL WHWLLRTGGW KVSAVTLAYL
   301  IFCLCSLVGI LHLQRALVLR RKRKRMTDPT RRFFKVTPPP GSGPQNQYGN VLSLPTPTSG
   361  LGRAQRWAAG LGGTAPSYGN PSSDVQADGA LGSRSPPGVG PEEEEGEGYE EPDSEEDSEF
   421  YENDSNLGQD QLSQDGSGYE NPEDEPLGPE DEDSFSNAES YENEDEELTQ PVARTMDFLS
   481  PHGSAWDPSR EATSLGSQSY EDMRGILYAA PQLRSIRGQP GPNHEEDADS YENMDNPDGP
   541  DPAWGGGGRM GTWSTR

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CD19 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.52

Highest tissue expression

71 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CD19.

Disease | AllUniProt

Conditions CD19 is implicated in, by any mechanism.

• Immunodeficiency, common variable, 3 (CVID3) MIM:613493

Disease | GeneticClinVar

16 pathogenic / likely-pathogenic of 419 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Immunodeficiency, common variable, 3
• Inherited Immunodeficiency Diseases

Disease | ImmuneIEDB

Conditions an epitope on CD19 was assayed in.

• chronic lymphocytic leukemia T cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against CD19 are reported. Each links to that disease's full target list.

• Neuromyelitis Optica 5

ReferencesPubMed · IEDB

Publications for CD19 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.36

gnomAD pLI

0.9

gnomAD missense Z

1.03

DepMap mean gene effect

-0.11

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• antigen receptor-mediated signaling pathway
• B cell proliferation
• B cell proliferation involved in immune response
• B cell receptor signaling pathway
• B-1 B cell differentiation
• immunoglobulin mediated immune response
• positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• positive regulation of release of sequestered calcium ion into cytosol
• regulation of B cell activation
• regulation of B cell receptor signaling pathway

Cellular components

• external side of plasma membrane
• extracellular exosome
• membrane raft
• plasma membrane
• protein-containing complex

Protein domainsUniProt · Pfam · InterPro

• Immunoglobulin domain subtype
• Immunoglobulin-like domain
• Immunoglobulin-like fold
• Immunoglobulin-like domain superfamily
• B-lymphocyte antigen CD19

KeywordsUniProt

• Adaptive immunity
• Cell membrane
• Disulfide bond
• Glycoprotein
• Immunity
• Immunoglobulin domain
• Membrane
• Phosphoprotein
• Repeat
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of CD19 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CD81
• GRB2
• LYN
• VAV
• FCRL5
• CR2