[1]	NUCLEOTIDE SEQUENCE [MRNA]. STRAIN=C57BL/6 X DBA/2J; PubMed=2463161 [NCBI, ExPASy, EBI, Israel, Japan] Sakaguchi N., Kashiwamura S., Kimoto M., Thalmann P., Melchers F.; "B lymphocyte lineage-restricted expression of mb-1, a gene with CD3-like structural properties."; EMBO J. 7:3457-3464(1988).
[2]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. STRAIN=BALB/c; TISSUE=Liver; PubMed=2358676 [NCBI, ExPASy, EBI, Israel, Japan] Kashiwamura S., Koyama T., Matsuo T., Steinmetz M., Kimoto M., Sakaguchi N.; "Structure of the murine mb-1 gene encoding a putative sIgM-associated molecule."; J. Immunol. 145:337-343(1990).
[3]	NUCLEOTIDE SEQUENCE. DOI=10.1007/BF00215058; PubMed=1639443 [NCBI, ExPASy, EBI, Israel, Japan] Flaswinkel H., Reth M.; "Molecular cloning of the Ig-alpha subunit of the human B-cell antigen receptor complex."; Immunogenetics 36:266-269(1992).
[4]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. STRAIN=C57BL/6J; TISSUE=Mammary gland; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[5]	NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-15. PubMed=1922076 [NCBI, ExPASy, EBI, Israel, Japan] Travis A., Hagman J., Grosschedl R.; "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."; Mol. Cell. Biol. 11:5756-5766(1991).
[6]	PROTEIN SEQUENCE OF 29-38. DOI=10.1002/eji.1830201239; PubMed=2269334 [NCBI, ExPASy, EBI, Israel, Japan] Hombach J., Lottspeich F., Reth M.; "Identification of the genes encoding the IgM-alpha and Ig-beta components of the IgM antigen receptor complex by amino-terminal sequencing."; Eur. J. Immunol. 20:2795-2799(1990).
[7]	PROTEIN SEQUENCE OF 29-38. DOI=10.1073/pnas.88.9.3982; PubMed=2023945 [NCBI, ExPASy, EBI, Israel, Japan] Campbell K.S., Hager E.J., Friedrich R.J., Cambier J.C.; "IgM antigen receptor complex contains phosphoprotein products of B29 and mb-1 genes."; Proc. Natl. Acad. Sci. U.S.A. 88:3982-3986(1991).
[8]	PHOSPHORYLATION AT TYR-182, AND MUTAGENESIS OF TYR-176; TYR-182 AND TYR-193. PubMed=8306975 [NCBI, ExPASy, EBI, Israel, Japan] Flaswinkel H., Reth M.; "Dual role of the tyrosine activation motif of the Ig-alpha protein during signal transduction via the B cell antigen receptor."; EMBO J. 13:83-89(1994).
[9]	INTERACTION WITH FYN AND LYN. PubMed=8168489 [NCBI, ExPASy, EBI, Israel, Japan] Clark M.R., Johnson S.A., Cambier J.C.; "Analysis of Ig-alpha-tyrosine kinase interaction reveals two levels of binding specificity and tyrosine phosphorylated Ig-alpha stimulation of Fyn activity."; EMBO J. 13:1911-1919(1994).
[10]	FUNCTION. PubMed=8175787 [NCBI, ExPASy, EBI, Israel, Japan] Taddie J.A., Hurley T.R., Hardwick B.S., Sefton B.M.; "Activation of B- and T-cells by the cytoplasmic domains of the B-cell antigen receptor proteins Ig-alpha and Ig-beta."; J. Biol. Chem. 269:13529-13535(1994).
[11]	INTERACTION WITH SYK. DOI=10.1074/jbc.270.19.11590; PubMed=7538118 [NCBI, ExPASy, EBI, Israel, Japan] Rowley R.B., Burkhardt A.L., Chao H.-G., Matsueda G.R., Bolen J.B.; "Syk protein-tyrosine kinase is regulated by tyrosine-phosphorylated Ig alpha/Ig beta immunoreceptor tyrosine activation motif binding and autophosphorylation."; J. Biol. Chem. 270:11590-11594(1995).
[12]	FUNCTION, AND MUTAGENESIS OF TYR-182 AND TYR-193. PubMed=9469435 [NCBI, ExPASy, EBI, Israel, Japan] Cassard S., Salamero J., Hanau D., Spehner D., Davoust J., Fridman W.H., Bonnerot C.; "A tyrosine-based signal present in Ig alpha mediates B cell receptor constitutive internalization."; J. Immunol. 160:1767-1773(1998).
[13]	FUNCTION. DOI=10.1016/S1074-7613(00)80128-4; PubMed=10591178 [NCBI, ExPASy, EBI, Israel, Japan] Torres R.M., Hafen K.; "A negative regulatory role for Ig-alpha during B cell development."; Immunity 11:527-536(1999).
[14]	SUBCELLULAR LOCATION. DOI=10.1084/jem.190.11.1549; PubMed=10587346 [NCBI, ExPASy, EBI, Israel, Japan] Cheng P.C., Dykstra M.L., Mitchell R.N., Pierce S.K.; "A role for lipid rafts in B cell antigen receptor signaling and antigen targeting."; J. Exp. Med. 190:1549-1560(1999).
[15]	FUNCTION. PubMed=10352267 [NCBI, ExPASy, EBI, Israel, Japan] Siemasko K., Eisfelder B.J., Stebbins C., Kabak S., Sant A.J., Song W., Clark M.R.; "Ig alpha and Ig beta are required for efficient trafficking to late endosomes and to enhance antigen presentation."; J. Immunol. 162:6518-6525(1999).
[16]	INTERACTION WITH BLNK, PHOSPHORYLATION AT TYR-204, AND MUTAGENESIS OF TYR-204. DOI=10.1002/1521-4141(200107)31:7<2126::AID-IMMU2126>3.0.CO;2-O; PubMed=11449366 [NCBI, ExPASy, EBI, Israel, Japan] Engels N., Wollscheid B., Wienands J.; "Association of SLP-65/BLNK with the B cell antigen receptor through a non-ITAM tyrosine of Ig-alpha."; Eur. J. Immunol. 31:2126-2134(2001).
[17]	FUNCTION, AND MUTAGENESIS OF TYR-182 AND TYR-193. DOI=10.1084/jem.194.4.455; PubMed=11514602 [NCBI, ExPASy, EBI, Israel, Japan] Kraus M., Pao L.I., Reichlin A., Hu Y., Canono B., Cambier J.C., Nussenzweig M.C., Rajewsky K.; "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."; J. Exp. Med. 194:455-469(2001).
[18]	SUBCELLULAR LOCATION. PubMed=11238609 [NCBI, ExPASy, EBI, Israel, Japan] Cheng P.C., Brown B.K., Song W., Pierce S.K.; "Translocation of the B cell antigen receptor into lipid rafts reveals a novel step in signaling."; J. Immunol. 166:3693-3701(2001).
[19]	FUNCTION. DOI=10.1093/intimm/dxf083; PubMed=12356683 [NCBI, ExPASy, EBI, Israel, Japan] Li C., Siemasko K., Clark M.R., Song W.; "Cooperative interaction of Ig(alpha) and Ig(beta) of the BCR regulates the kinetics and specificity of antigen targeting."; Int. Immunol. 14:1179-1191(2002).
[20]	FUNCTION, INTERACTION WITH BLNK, AND MUTAGENESIS OF TYR-176 AND TYR-204. PubMed=11859098 [NCBI, ExPASy, EBI, Israel, Japan] Siemasko K., Skaggs B.J., Kabak S., Williamson E., Brown B.K., Song W., Clark M.R.; "Receptor-facilitated antigen presentation requires the recruitment of B cell linker protein to Igalpha."; J. Immunol. 168:2127-2138(2002).
[21]	FUNCTION, AND DISRUPTION PHENOTYPE. PubMed=12097390 [NCBI, ExPASy, EBI, Israel, Japan] Pelanda R., Braun U., Hobeika E., Nussenzweig M.C., Reth M.; "B cell progenitors are arrested in maturation but have intact VDJ recombination in the absence of Ig-alpha and Ig-beta."; J. Immunol. 169:865-872(2002).
[22]	INTERACTION WITH BLNK, AND MUTAGENESIS OF TYR-176 AND TYR-204. DOI=10.1128/MCB.22.8.2524-2535.2002; PubMed=11909947 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "The direct recruitment of BLNK to immunoglobulin alpha couples the B-cell antigen receptor to distal signaling pathways."; Mol. Cell. Biol. 22:2524-2535(2002).
[23]	FUNCTION, AND SUBCELLULAR LOCATION. PubMed=15661879 [NCBI, ExPASy, EBI, Israel, Japan] Fuentes-Panana E.M., Bannish G., van der Voort D., King L.B., Monroe J.G.; "Ig alpha/Ig beta complexes generate signals for B cell development independent of selective plasma membrane compartmentalization."; J. Immunol. 174:1245-1252(2005).
[24]	FUNCTION, AND MUTAGENESIS OF TYR-176 AND TYR-204. DOI=10.1016/j.immuni.2006.04.014; PubMed=16860757 [NCBI, ExPASy, EBI, Israel, Japan] Patterson H.C.K., Kraus M., Kim Y.-M., Ploegh H., Rajewsky K.; "The B cell receptor promotes B cell activation and proliferation through a non-ITAM tyrosine in the Igalpha cytoplasmic domain."; Immunity 25:55-65(2006).
[25]	FUNCTION, AND MUTAGENESIS OF TYR-176; TYR-182; TYR-193 AND TYR-204. DOI=10.1002/eji.200636667; PubMed=17163454 [NCBI, ExPASy, EBI, Israel, Japan] Storch B., Meixlsperger S., Jumaa H.; "The Ig-alpha ITAM is required for efficient differentiation but not proliferation of pre-B cells."; Eur. J. Immunol. 37:252-260(2007).

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.
SUBUNIT: 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.
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.
TISSUE SPECIFICITY: B-cells.
PTM: Phosphorylated on tyrosine, serine and threonine residues upon B-cell activation. Phosphorylation of tyrosine residues by Src-family kinases 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.
DISRUPTION PHENOTYPE: Mice display impaired B-cell development which does not progress pass the progenitor stage.
SIMILARITY: Contains 1 Ig-like C2-type (immunoglobulin-like) domain.
SIMILARITY: Contains 1 ITAM domain.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

X13450; CAA31801.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M31773; AAA39494.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC027633; AAH27633.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
S59359; -; NOT_ANNOTATED_CDS; Genomic_DNA.	[EMBL / GenBank / DDBJ]

IPI00118409; -.

A43540; A43540.

NP_031681.2; -.

3D structure databases

ModBase

P11911.

PTM databases

PhosphoSite

P11911; -.

Organism-specific databases

MGI

MGI:101774; Cd79a.

Gene expression databases

P11911; -.

P11911; -.

MM_CD79A; -.

ENSMUSG00000003379; Mus musculus.

Ontologies

GO:0019815;	Cellular component: B cell receptor complex (inferred from direct assay from MGI).
GO:0009897;	Cellular component: external side of plasma membrane (inferred from direct assay from MGI).
GO:0016021;	Cellular component: integral to membrane (inferred from electronic annotation from UniProtKB-KW).
GO:0045121;	Cellular component: membrane raft (inferred from direct assay from UniProtKB).
GO:0005771;	Cellular component: multivesicular body (inferred from direct assay from MGI).
GO:0005515;	Molecular function: protein binding (inferred from physical interaction from MGI).
GO:0004888;	Molecular function: transmembrane receptor activity (inferred from electronic annotation from InterPro).
GO:0030183;	Biological process: B cell differentiation (inferred from mutant phenotype from UniProtKB).
GO:0042100;	Biological process: B cell proliferation (inferred from mutant phenotype from UniProtKB).
GO:0050853;	Biological process: B cell receptor signaling pathway (inferred from direct assay from MGI).
GO:0006955;	Biological process: immune response (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.

Family and domain databases

InterPro

IPR013151; Ig.
IPR007110; Ig-like.
IPR003599; Ig_sub.
IPR003110; Phos_immunorcpt_sig_ITAM.
Graphical view of domain structure.

Pfam

PF00047; ig; 1.
PF02189; ITAM; 1.
Pfam graphical view of domain structure.

SMART

SM00409; IG; 1.
SM00077; ITAM; 1.
SMART graphical view of domain structure.

PROSITE

PS50835; IG_LIKE; 1.
PS51055; ITAM_1; 1.
PROSITE graphical view of domain structure (profiles).

Genome annotation databases

Ensembl

ENSMUSG00000003379; Mus musculus. [Contig view]

GeneID

12518; -.

KEGG

mmu:12518; -.

Phylogenomic databases

HOGENOM

P11911; -.

HOVERGEN

P11911; -.

OMA

P11911; LLFRKRW.

Other

281518; -.

Cd79a; Mus musculus.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Cell membrane; Direct protein sequencing; Disulfide bond; Glycoprotein; Immune response; Immunoglobulin domain; Membrane; Phosphoprotein; Signal; Transmembrane.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`SIGNAL`	`1 28`	`28`
`CHAIN`	`29 220`	`192`	`B-cell antigen receptor complex-associated protein alpha chain.`	`PRO_0000014559`
`TOPO_DOM`	`29 137`	`109`	`Extracellular (Potential).`
`TRANSMEM`	`138 159`	`22`	`Potential.`
`TOPO_DOM`	`160 220`	`61`	`Cytoplasmic (Potential).`
`DOMAIN`	`29 117`	`89`	`Ig-like C2-type.`
`DOMAIN`	`171 199`	`29`	`ITAM.`
`SITE`	`204 204`	`1`	`Required for binding to BLNK.`
`MOD_RES`	`182 182`		`Phosphotyrosine; by SRC-type Tyr-kinases.`
`MOD_RES`	`204 204`		`Phosphotyrosine; by Tyr-kinases.`
`CARBOHYD`	`58 58`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`68 68`		`N-linked (GlcNAc...) (Potential).`
`DISULFID`	`50 101`		`Potential.`
`DISULFID`	`113 113`		`Interchain (with C-135 in beta chain) (Potential).`
`MUTAGEN`	`176 176`		`Y->F: Increases tyrosine phosphorylation. Inhibits phosphorylation of BLNK. Impaired antigen presentation; when associated with F-204.`
`MUTAGEN`	`182 182`		`Y->F: Strongly reduces tyrosine phosphorylation and pre-B-cell differentiation; when associated with F-193. Abolishes constitutive internalization of BCR.`
`MUTAGEN`	`193 193`		`Y->F: Strongly reduces tyrosine phosphorylation and pre-B-cell differentiation; when associated with F-182. No effect on constitutive internalization of BCR.`
`MUTAGEN`	`204 204`		`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.`
`CONFLICT`	`95 100`		`HRGLYW -> TGACTG (in Ref. 1; CAA31801 and 2; AAA39494).`

Sequence information

Length: 220 AA [This is the length of the unprocessed precursor]

Molecular weight: 24583 Da [This is the MW of the unprocessed precursor]

CRC64: A4C648C2BE6D3E38 [This is a checksum on the sequence]

        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

P11911 in FASTA format

View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools