P15391 (CD19_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
B-lymphocyte antigen CD19

Alternative name(s):
B-lymphocyte surface antigen B4
Differentiation antigen CD19
T-cell surface antigen Leu-12
CD_antigen=CD19

Gene names

Name:

CD19

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	556 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Assembles with the antigen receptor of B-lymphocytes in order to decrease the threshold for antigen receptor-dependent stimulation.
Subunit structure	Forms a complex with CD21, CD81 and CD225 in the membrane of mature B-cells. Interacts with VAV. Interacts with GRB2 and SOS when phosphorylated on Tyr-348 and/or Tyr-378. Interacts with PLCG2 when phosphorylated on Tyr-409. Interacts with LYN. Ref.10 Ref.12
Subcellular location	Membrane; Single-pass type I membrane protein.
Post-translational modification	Phosphorylated on serine and threonine upon DNA damage, probably by ATM or ATR. Phosphorylated on tyrosine following B-cell activation. Phosphorylated on tyrosine residues by LYN. Ref.10 Ref.11 Ref.12
Involvement in disease	Immunodeficiency, common variable, 3 (CVID3) [MIM:613493]: A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B cells is usually in the normal range, but can be low. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13
Sequence similarities	Contains 2 Ig-like C2-type (immunoglobulin-like) domains.
Sequence caution	The sequence AAA35533.1 differs from that shown. Reason: Frameshift at position 396.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular defense response Traceable author statement PubMed 1373518. Source: ProtInc epidermal growth factor receptor signaling pathway Traceable author statement. Source: Reactome fibroblast growth factor receptor signaling pathway Traceable author statement. Source: Reactome innate immune response Traceable author statement. Source: Reactome neurotrophin TRK receptor signaling pathway Traceable author statement. Source: Reactome phosphatidylinositol-mediated signaling Traceable author statement. Source: Reactome regulation of immune response Traceable author statement. Source: Reactome
Cellular_component	external side of plasma membrane Inferred from direct assay PubMed 17213291PubMed 20660734. Source: MGI integral to plasma membrane Traceable author statement Ref.2. Source: ProtInc
Molecular_function	receptor signaling protein activity Traceable author statement PubMed 1373518. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19	Potential
	Chain	20 – 556	537	B-lymphocyte antigen CD19		PRO_0000014648
Regions
	Topological domain	20 – 291	272	Extracellular Potential
	Transmembrane	292 – 313	22	Helical; Potential
	Topological domain	314 – 556	243	Cytoplasmic Potential
	Domain	20 – 113	94	Ig-like C2-type 1
	Domain	176 – 277	102	Ig-like C2-type 2
Amino acid modifications
	Modified residue	227	1	Phosphoserine By similarity
	Modified residue	348	1	Phosphotyrosine Ref.12
	Modified residue	378	1	Phosphotyrosine Ref.12
	Modified residue	409	1	Phosphotyrosine Ref.12
	Modified residue	439	1	Phosphotyrosine Ref.12
	Modified residue	497	1	Phosphoserine
	Glycosylation	86	1	N-linked (GlcNAc...) Potential
	Glycosylation	125	1	N-linked (GlcNAc...) Potential
	Glycosylation	138	1	N-linked (GlcNAc...) Potential
	Glycosylation	181	1	N-linked (GlcNAc...) Potential
	Glycosylation	265	1	N-linked (GlcNAc...) Potential
	Disulfide bond	38 ↔ 97		Potential
	Disulfide bond	200 ↔ 261		Potential
Natural variations
	Natural variant	174	1	L → V. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.6 Ref.8 Corresponds to variant rs2904880 [ dbSNP | Ensembl ].		VAR_026963
	Natural variant	514	1	R → H. Ref.1 Ref.2 Corresponds to variant rs34763945 [ dbSNP | Ensembl ].		VAR_036987
Experimental info
	Sequence conflict	29	1	E → EG in AAB60697. Ref.4
	Sequence conflict	80	1	I → S in AAA68490. Ref.2
	Sequence conflict	80	1	I → S in AAA69966. Ref.3
	Sequence conflict	80	1	I → S in AAB60697. Ref.4
	Sequence conflict	80	1	I → S in BAB60954. Ref.5
	Sequence conflict	186	1	Q → QAFLVLSLPVP in AAA69966. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P15391 [UniParc]. Last modified November 13, 2007. Version 6. Checksum: A0E08DD628B69E51	FASTA	556	61,128
	10 20 30 40 50 60 MPPPRLLFFL LFLTPMEVRP EEPLVVKVEE GDNAVLQCLK GTSDGPTQQL TWSRESPLKP 70 80 90 100 110 120 FLKLSLGLPG LGIHMRPLAI WLFIFNVSQQ MGGFYLCQPG PPSEKAWQPG WTVNVEGSGE 130 140 150 160 170 180 LFRWNVSDLG GLGCGLKNRS SEGPSSPSGK LMSPKLYVWA KDRPEIWEGE PPCLPPRDSL 190 200 210 220 230 240 NQSLSQDLTM APGSTLWLSC GVPPDSVSRG PLSWTHVHPK GPKSLLSLEL KDDRPARDMW 250 260 270 280 290 300 VMETGLLLPR ATAQDAGKYY CHRGNLTMSF HLEITARPVL WHWLLRTGGW KVSAVTLAYL 310 320 330 340 350 360 IFCLCSLVGI LHLQRALVLR RKRKRMTDPT RRFFKVTPPP GSGPQNQYGN VLSLPTPTSG 370 380 390 400 410 420 LGRAQRWAAG LGGTAPSYGN PSSDVQADGA LGSRSPPGVG PEEEEGEGYE EPDSEEDSEF 430 440 450 460 470 480 YENDSNLGQD QLSQDGSGYE NPEDEPLGPE DEDSFSNAES YENEDEELTQ PVARTMDFLS 490 500 510 520 530 540 PHGSAWDPSR EATSLGSQSY EDMRGILYAA PQLRSIRGQP GPNHEEDADS YENMDNPDGP 550 DPAWGGGGRM GTWSTR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"CD19, the earliest differentiation antigen of the B cell lineage, bears three extracellular immunoglobulin-like domains and an Epstein-Barr virus-related cytoplasmic tail." Stamenkovic I., Seed B. J. Exp. Med. 168:1205-1210(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS VAL-174 AND HIS-514.
[2]	"Isolation of cDNAs encoding the CD19 antigen of human and mouse B lymphocytes. A new member of the immunoglobulin superfamily." Tedder T.F., Isaacs C.M. J. Immunol. 143:712-717(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS VAL-174 AND HIS-514. Tissue: Tonsil.
[3]	"The promoter of the CD19 gene is a target for the B-cell-specific transcription factor BSAP." Kozmik Z., Wang S., Doerfler P., Adams B., Busslinger M. Mol. Cell. Biol. 12:2662-2672(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-174.
[4]	"Structure of the genes encoding the CD19 antigen of human and mouse B lymphocytes." Zhou L.J., Ord D.C., Omori S.A., Tedder T.F. Immunogenetics 35:102-111(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-174. Tissue: Blood.
[5]	"Polymorphisms of human CD19 gene: possible association with susceptibility to systemic lupus erythematosus in Japanese." Kuroki K., Tsuchiya N., Tsao B.P., Grossman J.M., Fukazawa T., Hagiwara K., Kano H., Takazoe M., Iwata T., Hashimoto H., Tokunaga K. Genes Immun. 3:S21-S30(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-174.
[6]	Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B., Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O., Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I., Nickerson D.A. Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-174.
[7]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT VAL-174.
[9]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: B-cell.
[10]	"CD19 is a substrate of the antigen receptor-associated protein tyrosine kinase in human B cells." Roifman C.M., Ke S. Biochem. Biophys. Res. Commun. 194:222-225(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION, INTERACTION WITH LYN.
[11]	"Tyrosine phosphorylation of CD19 in pre-B and mature B cells." Chalupny N.J., Kanner S.B., Schieven G.L., Wee S., Gilliland L.K., Aruffo A., Ledbetter J.A. EMBO J. 12:2691-2696(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION.
[12]	"Systematic analysis of the role of CD19 cytoplasmic tyrosines in enhancement of activation in Daudi human B cells: clustering of phospholipase C and Vav and of Grb2 and Sos with different CD19 tyrosines." Brooks S.R., Li X., Volanakis E.J., Carter R.H. J. Immunol. 164:3123-3131(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GRB2; SOS; VAV AND PLCG2, PHOSPHORYLATION AT TYR-348; TYR-378; TYR-409 AND TYR-439.
[13]	"An antibody-deficiency syndrome due to mutations in the CD19 gene." van Zelm M.C., Reisli I., van der Burg M., Castano D., van Noesel C.J.M., van Tol M.J.D., Woellner C., Grimbacher B., Patino P.J., van Dongen J.J.M., Franco J.L. N. Engl. J. Med. 354:1901-1912(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN CVID3.
[14]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Embryonic kidney.
+	Additional computationally mapped references.

Web resources

CD19base

CD19 mutation db

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	M21097 mRNA. Translation: AAA35533.1. Frameshift. M28170 mRNA. Translation: AAA68490.1. M84371 Genomic DNA. Translation: AAA69966.1. M62550 , M62544, M62545, M62546, M62547, M62548, M62549 Genomic DNA. Translation: AAB60697.1. AB052799 Genomic DNA. Translation: BAB60954.1. EF064757 Genomic DNA. Translation: ABK41940.1. AC109460 Genomic DNA. No translation available. CH471267 Genomic DNA. Translation: EAW52012.1. BC006338 mRNA. Translation: AAH06338.1.
IPI	IPI00305031.
PIR	A44441.
RefSeq	NP_001171569.1. NM_001178098.1. NP_001761.3. NM_001770.5.
UniGene	Hs.652262.
3D structure databases
ProteinModelPortal	P15391.
ModBase	Search...
Protein-protein interaction databases
IntAct	P15391. 1 interaction.
MINT	MINT-1508267.
STRING	9606.ENSP00000313419.
PTM databases
PhosphoSite	P15391.
Polymorphism databases
DMDM	160332376.
Proteomic databases
PaxDb	P15391.
PRIDE	P15391.
Protocols and materials databases
DNASU	930.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000324662; ENSP00000313419; ENSG00000177455.
GeneID	930.
KEGG	hsa:930.
UCSC	uc002drs.3. human.
Organism-specific databases
CTD	930.
GeneCards	GC16P028943.
HGNC	HGNC:1633. CD19.
HPA	CAB016110.
MIM	107265. gene. 613493. phenotype.
neXtProt	NX_P15391.
Orphanet	77303. Common variable immunodeficiency due to an intrinsic B cell defect.
PharmGKB	PA26192.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG46561.
HOGENOM	HOG000111478.
HOVERGEN	HBG003388.
InParanoid	P15391.
KO	K06465.
OrthoDB	EOG4TMR2B.
PhylomeDB	P15391.
Enzyme and pathway databases
Pathway_Interaction_DB	bcr_5pathway. BCR signaling pathway.
Reactome	REACT_111102. Signal Transduction. REACT_116125. Disease. REACT_6900. Immune System.
SignaLink	P15391.
Gene expression databases
ArrayExpress	P15391.
Bgee	P15391.
CleanEx	HS_CD19.
Genevestigator	P15391.
GermOnline	ENSG00000177455. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.10. 1 hit.
InterPro	IPR007110. Ig-like_dom. IPR013783. Ig-like_fold. IPR003599. Ig_sub. [Graphical view]
SMART	SM00409. IG. 2 hits. [Graphical view]
PROSITE	PS50835. IG_LIKE. 2 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	930.
NextBio	3856.
SOURCE	Search...

Entry information

Entry name

CD19_HUMAN

Accession

Primary (citable) accession number: P15391
Secondary accession number(s): A0N0P9, Q96S68, Q9BRD6

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	November 13, 2007
Last modified:	May 29, 2013
This is version 144 of the entry and version 6 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.