B-cell antigen receptor complex-associated protein alpha chain precursor

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P11911 (CD79A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 133. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
B-cell antigen receptor complex-associated protein alpha chain

Alternative name(s):
Ig-alpha
MB-1 membrane glycoprotein
Membrane-bound immunoglobulin-associated protein
Surface IgM-associated protein
CD_antigen=CD79a

Gene names

Name:	Cd79a
Synonyms:	Iga, Mb-1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	220 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	Required in cooperation with CD79B for initiation of the signal transduction cascade activated by binding of antigen to the B-cell antigen receptor complex (BCR) which leads to internalization of the complex, trafficking to late endosomes and antigen presentation. Also required for BCR surface expression and for efficient differentiation of pro- and pre-B-cells. Stimulates SYK autophosphorylation and activation. Binds to BLNK, bringing BLNK into proximity with SYK and allowing SYK to phosphorylate BLNK. Also interacts with and increases activity of some Src-family tyrosine kinases. Represses BCR signaling during development of immature B-cells. Ref.12 Ref.15 Ref.16 Ref.18 Ref.20 Ref.22 Ref.23 Ref.24 Ref.26 Ref.27 Ref.28
Subunit structure	Heterodimer of alpha and beta chains; disulfide-linked. Part of the B-cell antigen receptor complex where the alpha/beta chain heterodimer is non-covalently associated with an antigen-specific membrane-bound surface immunoglobulin of two heavy chains and two light chains. Interacts through its phosphorylated ITAM domain with the SH2 domains of SYK which stimulates SYK autophosphorylation and activation. Also interacts, when phosphorylated on Tyr-204, with the SH2 domain of BLNK/SLP65, bringing BLNK into proximity with SYK and allowing SYK to phosphorylate BLNK which is necessary for trafficking of the BCR to late endosomes. Interacts with Src-family tyrosine kinases including FYN and LYN, increasing their activity. Ref.8 Ref.9 Ref.11 Ref.13 Ref.14 Ref.19 Ref.23 Ref.25
Subcellular location	Cell membrane; Single-pass type I membrane protein. Note: Following antigen binding, the BCR has been shown to translocate from detergent-soluble regions of the cell membrane to lipid rafts although signal transduction through the complex can also occur outside lipid rafts. Ref.17 Ref.21 Ref.26
Tissue specificity	B-cells.
Post-translational modification	Phosphorylated on tyrosine, serine and threonine residues upon B-cell activation. Phosphorylation of tyrosine residues by Src-family kinases, including LYN, is an early and essential feature of the BCR signaling cascade. The phosphorylated tyrosines serve as docking sites for SH2-domain containing kinases, leading to their activation which in turn leads to phosphorylation of downstream targets. Phosphorylation of serine and threonine residues may prevent subsequent tyrosine phosphorylation. Ref.9 Ref.10 Ref.14 Ref.19 Arginine methylation in the ITAM domain may interfere with the binding of SYK. It promotes signals leading to B cell differentiation.
Disruption phenotype	Mice display impaired B-cell development which does not progress pass the progenitor stage. Ref.24
Sequence similarities	Contains 1 Ig-like C2-type (immunoglobulin-like) domain. Contains 1 ITAM domain.

Ontologies

Keywords
Biological process	Adaptive immunity Immunity
Cellular component	Cell membrane Membrane
Domain	Immunoglobulin domain Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein Methylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	B cell differentiation Inferred from mutant phenotype Ref.20 Ref.24. Source: UniProtKB B cell proliferation Inferred from mutant phenotype Ref.27. Source: UniProtKB B cell receptor signaling pathway Inferred from direct assay PubMed 1373499 PubMed 8626447. Source: MGI
Cellular_component	B cell receptor complex Inferred from direct assay PubMed 1373499 PubMed 8626447. Source: MGI external side of plasma membrane Inferred from direct assay PubMed 1373499. Source: MGI integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW membrane raft Inferred from direct assay Ref.17 Ref.21. Source: UniProtKB multivesicular body Inferred from direct assay PubMed 11854359. Source: MGI
Molecular_function	transmembrane signaling receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 28

Ref.6 Ref.7

Chain

29 – 220

192

B-cell antigen receptor complex-associated protein alpha chain

PRO_0000014559

Regions

Topological domain

29 – 137

109

Extracellular Potential

Transmembrane

138 – 159

Helical; Potential

Topological domain

160 – 220

Cytoplasmic Potential

Domain

29 – 117

Ig-like C2-type

Domain

171 – 199

ITAM

Sites

Site

204

Required for binding to BLNK

Amino acid modifications

Modified residue

182

Phosphotyrosine; by SRC-type Tyr-kinases Ref.10 Ref.14

Modified residue

193

Phosphotyrosine; by SRC-type Tyr-kinases Ref.14

Modified residue

198

Asymmetric dimethylarginine; by PRMT1 Ref.29

Modified residue

204

Phosphotyrosine; by Tyr-kinases Ref.19

Glycosylation

N-linked (GlcNAc...) Potential

Glycosylation

N-linked (GlcNAc...) Potential

Disulfide bond

50 ↔ 101

Potential

Disulfide bond

113

Interchain (with C-135 in beta chain) Potential

Experimental info

Mutagenesis

176

Y → F: Increases tyrosine phosphorylation. Inhibits phosphorylation of BLNK. Impaired antigen presentation; when associated with F-204. Ref.10 Ref.23 Ref.25 Ref.27 Ref.28

Mutagenesis

182

Y → F: Strongly reduces tyrosine phosphorylation and pre-B-cell differentiation; when associated with F-193. Abolishes constitutive internalization of BCR. Ref.10 Ref.15 Ref.20 Ref.28

Mutagenesis

193

Y → F: Strongly reduces tyrosine phosphorylation and pre-B-cell differentiation; when associated with F-182. No effect on constitutive internalization of BCR. Ref.10 Ref.15 Ref.20 Ref.28

Mutagenesis

198

R → K: Associates more strongly with SYK. Increases calcium response upon BCR ligation. Ref.29

Mutagenesis

204

Y → F: Has little effect on tyrosine phosphorylation. Reduces pre-B-cell differentiation. Abolishes binding to BLNK. Inhibits phosphorylation of BLNK. No effect on cap formation or BCR internalization. Impaired antigen presentation; when associated with F-176. Ref.19 Ref.23 Ref.25 Ref.27 Ref.28

Sequence conflict

95 – 100

HRGLYW → TGACTG in CAA31801. Ref.1

Sequence conflict

95 – 100

HRGLYW → TGACTG in AAA39494. Ref.2

Sequences

Sequence

Length

Mass (Da)

Tools

P11911 [UniParc].

Last modified July 24, 2007. Version 2.
Checksum: A4C648C2BE6D3E38
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FASTA

220

24,583

        10         20         30         40         50         60 
MPGGLEALRA LPLLLFLSYA CLGPGCQALR VEGGPPSLTV NLGEEARLTC ENNGRNPNIT 

        70         80         90        100        110        120 
WWFSLQSNIT WPPVPLGPGQ GTTGQLFFPE VNKNHRGLYW CQVIENNILK RSCGTYLRVR 

       130        140        150        160        170        180 
NPVPRPFLDM GEGTKNRIIT AEGIILLFCA VVPGTLLLFR KRWQNEKFGV DMPDDYEDEN 

       190        200        210        220 
LYEGLNLDDC SMYEDISRGL QGTYQDVGNL HIGDAQLEKP

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"B lymphocyte lineage-restricted expression of mb-1, a gene with CD3-like structural properties." Sakaguchi N., Kashiwamura S., Kimoto M., Thalmann P., Melchers F. EMBO J. 7:3457-3464(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: C57BL/6 X DBA/2J.
[2]	"Structure of the murine mb-1 gene encoding a putative sIgM-associated molecule." Kashiwamura S., Koyama T., Matsuo T., Steinmetz M., Kimoto M., Sakaguchi N. J. Immunol. 145:337-343(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: BALB/c. Tissue: Liver.
[3]	"Molecular cloning of the Ig-alpha subunit of the human B-cell antigen receptor complex." Flaswinkel H., Reth M. Immunogenetics 36:266-269(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE.
[4]	"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 [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Mammary gland.
[5]	"Heterogeneously initiated transcription from the pre-B- and B-cell-specific mb-1 promoter: analysis of the requirement for upstream factor-binding sites and initiation site sequences." Travis A., Hagman J., Grosschedl R. Mol. Cell. Biol. 11:5756-5766(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-15.
[6]	"Identification of the genes encoding the IgM-alpha and Ig-beta components of the IgM antigen receptor complex by amino-terminal sequencing." Hombach J., Lottspeich F., Reth M. Eur. J. Immunol. 20:2795-2799(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 29-38.
[7]	"IgM antigen receptor complex contains phosphoprotein products of B29 and mb-1 genes." Campbell K.S., Hager E.J., Friedrich R.J., Cambier J.C. Proc. Natl. Acad. Sci. U.S.A. 88:3982-3986(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 29-38.
[8]	"The MB-1/B29 heterodimer couples the B cell antigen receptor to multiple src family protein tyrosine kinases." Lin J., Justement L.B. J. Immunol. 149:1548-1555(1992) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BLK.
[9]	"B-cell antigen receptor motifs have redundant signalling capabilities and bind the tyrosine kinases PTK72, Lyn and Fyn." Law D.A., Chan V.W., Datta S.K., DeFranco A.L. Curr. Biol. 3:645-657(1993) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LYN, PHOSPHORYLATION.
[10]	"Dual role of the tyrosine activation motif of the Ig-alpha protein during signal transduction via the B cell antigen receptor." Flaswinkel H., Reth M. EMBO J. 13:83-89(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-182, MUTAGENESIS OF TYR-176; TYR-182 AND TYR-193.
[11]	"Analysis of Ig-alpha-tyrosine kinase interaction reveals two levels of binding specificity and tyrosine phosphorylated Ig-alpha stimulation of Fyn activity." Clark M.R., Johnson S.A., Cambier J.C. EMBO J. 13:1911-1919(1994) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FYN AND LYN.
[12]	"Activation of B- and T-cells by the cytoplasmic domains of the B-cell antigen receptor proteins Ig-alpha and Ig-beta." Taddie J.A., Hurley T.R., Hardwick B.S., Sefton B.M. J. Biol. Chem. 269:13529-13535(1994) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[13]	"Syk protein-tyrosine kinase is regulated by tyrosine-phosphorylated Ig alpha/Ig beta immunoreceptor tyrosine activation motif binding and autophosphorylation." Rowley R.B., Burkhardt A.L., Chao H.-G., Matsueda G.R., Bolen J.B. J. Biol. Chem. 270:11590-11594(1995) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SYK.
[14]	"Reconstitution of the B cell antigen receptor signaling components in COS cells." Saouaf S.J., Kut S.A., Fargnoli J., Rowley R.B., Bolen J.B., Mahajan S. J. Biol. Chem. 270:27072-27078(1995) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BLK, PHOSPHORYLATION AT TYR-182 AND TYR-193.
[15]	"A tyrosine-based signal present in Ig alpha mediates B cell receptor constitutive internalization." Cassard S., Salamero J., Hanau D., Spehner D., Davoust J., Fridman W.H., Bonnerot C. J. Immunol. 160:1767-1773(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF TYR-182 AND TYR-193.
[16]	"A negative regulatory role for Ig-alpha during B cell development." Torres R.M., Hafen K. Immunity 11:527-536(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[17]	"A role for lipid rafts in B cell antigen receptor signaling and antigen targeting." Cheng P.C., Dykstra M.L., Mitchell R.N., Pierce S.K. J. Exp. Med. 190:1549-1560(1999) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[18]	"Ig alpha and Ig beta are required for efficient trafficking to late endosomes and to enhance antigen presentation." Siemasko K., Eisfelder B.J., Stebbins C., Kabak S., Sant A.J., Song W., Clark M.R. J. Immunol. 162:6518-6525(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[19]	"Association of SLP-65/BLNK with the B cell antigen receptor through a non-ITAM tyrosine of Ig-alpha." Engels N., Wollscheid B., Wienands J. Eur. J. Immunol. 31:2126-2134(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BLNK, PHOSPHORYLATION AT TYR-204, MUTAGENESIS OF TYR-204.
[20]	"Interference with immunoglobulin (Ig)alpha immunoreceptor tyrosine-based activation motif (ITAM) phosphorylation modulates or blocks B cell development, depending on the availability of an Igbeta cytoplasmic tail." Kraus M., Pao L.I., Reichlin A., Hu Y., Canono B., Cambier J.C., Nussenzweig M.C., Rajewsky K. J. Exp. Med. 194:455-469(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF TYR-182 AND TYR-193.
[21]	"Translocation of the B cell antigen receptor into lipid rafts reveals a novel step in signaling." Cheng P.C., Brown B.K., Song W., Pierce S.K. J. Immunol. 166:3693-3701(2001) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[22]	"Cooperative interaction of Ig(alpha) and Ig(beta) of the BCR regulates the kinetics and specificity of antigen targeting." Li C., Siemasko K., Clark M.R., Song W. Int. Immunol. 14:1179-1191(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[23]	"Receptor-facilitated antigen presentation requires the recruitment of B cell linker protein to Igalpha." Siemasko K., Skaggs B.J., Kabak S., Williamson E., Brown B.K., Song W., Clark M.R. J. Immunol. 168:2127-2138(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH BLNK, MUTAGENESIS OF TYR-176 AND TYR-204.
[24]	"B cell progenitors are arrested in maturation but have intact VDJ recombination in the absence of Ig-alpha and Ig-beta." Pelanda R., Braun U., Hobeika E., Nussenzweig M.C., Reth M. J. Immunol. 169:865-872(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[25]	"The direct recruitment of BLNK to immunoglobulin alpha couples the B-cell antigen receptor to distal signaling pathways." Kabak S., Skaggs B.J., Gold M.R., Affolter M., West K.L., Foster M.S., Siemasko K., Chan A.C., Aebersold R., Clark M.R. Mol. Cell. Biol. 22:2524-2535(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BLNK, MUTAGENESIS OF TYR-176 AND TYR-204.
[26]	"Ig alpha/Ig beta complexes generate signals for B cell development independent of selective plasma membrane compartmentalization." Fuentes-Panana E.M., Bannish G., van der Voort D., King L.B., Monroe J.G. J. Immunol. 174:1245-1252(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[27]	"The B cell receptor promotes B cell activation and proliferation through a non-ITAM tyrosine in the Igalpha cytoplasmic domain." Patterson H.C.K., Kraus M., Kim Y.-M., Ploegh H., Rajewsky K. Immunity 25:55-65(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF TYR-176 AND TYR-204.
[28]	"The Ig-alpha ITAM is required for efficient differentiation but not proliferation of pre-B cells." Storch B., Meixlsperger S., Jumaa H. Eur. J. Immunol. 37:252-260(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF TYR-176; TYR-182; TYR-193 AND TYR-204.
[29]	"Arginine methylation of the B cell antigen receptor promotes differentiation." Infantino S., Benz B., Waldmann T., Jung M., Schneider R., Reth M. J. Exp. Med. 207:711-719(2010) [PubMed] [Europe PMC] [Abstract] Cited for: METHYLATION AT ARG-198 BY PRMT1, MUTAGENESIS OF ARG-198.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X13450 mRNA. Translation: CAA31801.1. M31773 Genomic DNA. Translation: AAA39494.1. BC027633 mRNA. Translation: AAH27633.1. S59359 Genomic DNA. No translation available.
IPI	IPI00118409.
PIR	A43540.
RefSeq	NP_031681.2. NM_007655.3.
UniGene	Mm.1355.
3D structure databases
ProteinModelPortal	P11911.
SMR	P11911. Positions 28-161.
ModBase	Search...
Protein-protein interaction databases
STRING	10090.ENSMUSP00000003469.
PTM databases
PhosphoSite	P11911.
Proteomic databases
PaxDb	P11911.
PRIDE	P11911.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000003469; ENSMUSP00000003469; ENSMUSG00000003379.
GeneID	12518.
KEGG	mmu:12518.
UCSC	uc009fqt.1. mouse.
Organism-specific databases
CTD	973.
MGI	MGI:101774. Cd79a.
Phylogenomic databases
eggNOG	NOG41728.
GeneTree	ENSGT00510000049127.
HOGENOM	HOG000074307.
HOVERGEN	HBG050854.
InParanoid	P11911.
KO	K06506.
OMA	PFLDMGE.
OrthoDB	EOG4H464J.
Enzyme and pathway databases
Reactome	REACT_107772. Immune System.
Gene expression databases
Bgee	P11911.
CleanEx	MM_CD79A.
Genevestigator	P11911.
GermOnline	ENSMUSG00000003379. Mus musculus.
Family and domain databases
Gene3D	2.60.40.10. 1 hit.
InterPro	IPR007110. Ig-like_dom. IPR013783. Ig-like_fold. IPR003599. Ig_sub. IPR003110. Phos_immunorcpt_sig_ITAM. [Graphical view]
Pfam	PF02189. ITAM. 1 hit. [Graphical view]
SMART	SM00409. IG. 1 hit. SM00077. ITAM. 1 hit. [Graphical view]
PROSITE	PS50835. IG_LIKE. 1 hit. PS51055. ITAM_1. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	281518.
SOURCE	Search...

Entry information

Entry name

CD79A_MOUSE

Accession

Primary (citable) accession number: P11911
Secondary accession number(s): Q6GTY0

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	July 24, 2007
Last modified:	May 1, 2013
This is version 133 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

Recent format changes

Overview of recent format changes

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents