P11912 (CD79A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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, MB1

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	226 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.13 Ref.14
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-210, 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 By similarity. Ref.18
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 By similarity.
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 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. Phosphorylated by LYN. Phosphorylation of serine and threonine residues may prevent subsequent tyrosine phosphorylation. Ref.16 Ref.18 Arginine methylation in the ITAM domain may interfere with the binding of SYK. It promotes signals leading to B cell differentiation By similarity.
Involvement in disease	Agammaglobulinemia 3 (AGM3) [MIM:613501]: A primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B cells due to an early block of B-cell development. Affected individuals develop severe infections in the first years of life. Note: The disease is caused by mutations affecting the gene represented in this entry. Two different mutations, one at the splice donor site of intron 2 and the other at the splice acceptor site for exon 3, have been identified. Both mutations give rise to a truncated protein. Ref.15 Ref.17
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
Coding sequence diversity	Alternative splicing
Domain	Immunoglobulin domain Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein Methylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	B cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB B cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB B cell receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	B cell receptor complex Inferred from sequence or structural similarity. Source: UniProtKB external side of plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW membrane raft Inferred from sequence or structural similarity. Source: UniProtKB multivesicular body Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	transmembrane signaling receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P11912-1)

Also known as: Long;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P11912-2)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     89-127: GTLIIQNVNKSHGGIYVCRVQEGNESYQQSCGTYLRVRQ → E

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 32	32	Ref.11
	Chain	33 – 226	194	B-cell antigen receptor complex-associated protein alpha chain		PRO_0000014558
Regions
	Topological domain	33 – 143	111	Extracellular Potential
	Transmembrane	144 – 165	22	Helical; Potential
	Topological domain	166 – 226	61	Cytoplasmic Potential
	Domain	33 – 116	84	Ig-like C2-type
	Domain	177 – 205	29	ITAM
Sites
	Site	210	1	Required for binding to BLNK By similarity
Amino acid modifications
	Modified residue	188	1	Phosphotyrosine; by SRC-type Tyr-kinases By similarity
	Modified residue	199	1	Phosphotyrosine; by SRC-type Tyr-kinases By similarity
	Modified residue	204	1	Asymmetric dimethylarginine; by PRMT1 By similarity
	Modified residue	210	1	Phosphotyrosine; by Tyr-kinases By similarity
	Glycosylation	57	1	N-linked (GlcNAc...) Potential
	Glycosylation	63	1	N-linked (GlcNAc...) Potential
	Glycosylation	73	1	N-linked (GlcNAc...) Potential
	Glycosylation	88	1	N-linked (GlcNAc...) Potential
	Glycosylation	97	1	N-linked (GlcNAc...) Potential
	Glycosylation	112	1	N-linked (GlcNAc...) Potential
	Disulfide bond	54 ↔ 106		Potential
	Disulfide bond	119		Interchain (with C-136 in beta chain) Potential
Natural variations
	Alternative sequence	89 – 127	39	GTLII…LRVRQ → E in isoform 2.		VSP_002476
Experimental info
	Mutagenesis	197	1	S → A: Increased phosphorylation of Y-188; when associated with A-203 and V-209. Ref.16
	Mutagenesis	203	1	S → A: Increased phosphorylation of Y-188; when associated with A-197 and V-209. Ref.16
	Mutagenesis	209	1	T → V: Increased phosphorylation of Y-188; when associated with A-197 and A-203. Ref.16
	Sequence conflict	47	1	G → V in BAD97091. Ref.10
	Sequence conflict	69	1	V → I in AAA60270. Ref.3
	Sequence conflict	189	1	E → G in BAD97091. Ref.10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Long) [UniParc]. Last modified June 1, 1994. Version 2. Checksum: 6E5B837409969292	FASTA	226	25,038
	10 20 30 40 50 60 MPGGPGVLQA LPATIFLLFL LSAVYLGPGC QALWMHKVPA SLMVSLGEDA HFQCPHNSSN 70 80 90 100 110 120 NANVTWWRVL HGNYTWPPEF LGPGEDPNGT LIIQNVNKSH GGIYVCRVQE GNESYQQSCG 130 140 150 160 170 180 TYLRVRQPPP RPFLDMGEGT KNRIITAEGI ILLFCAVVPG TLLLFRKRWQ NEKLGLDAGD 190 200 210 220 EYEDENLYEG LNLDDCSMYE DISRGLQGTY QDVGSLNIGD VQLEKP
	Isoform 2 (Short) [UniParc]. Checksum: 176B170B710E6EEB	FASTA	188	20,786
	10 20 30 40 50 60 MPGGPGVLQA LPATIFLLFL LSAVYLGPGC QALWMHKVPA SLMVSLGEDA HFQCPHNSSN 70 80 90 100 110 120 NANVTWWRVL HGNYTWPPEF LGPGEDPNEP PPRPFLDMGE GTKNRIITAE GIILLFCAVV 130 140 150 160 170 180 PGTLLLFRKR WQNEKLGLDA GDEYEDENLY EGLNLDDCSM YEDISRGLQG TYQDVGSLNI GDVQLEKP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure and expression of the mb-1 transcript in human lymphoid cells." Leduc I., Preud'Homme J.L., Cogne M. Clin. Exp. Immunol. 90:141-146(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Cloning and sequencing of the cDNA encoding the human homologue of the murine immunoglobulin-associated protein B29." Mueller B.S., Cooper L., Terhorst C. Eur. J. Immunol. 22:1621-1625(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Tonsil.
[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 [MRNA] (ISOFORM 1).
[4]	"Human mb-1 gene: complete cDNA sequence and its expression in B cells bearing membrane Ig of various isotypes." Yu L.M., Chang T.W. J. Immunol. 148:633-637(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[5]	"Molecular cloning and expression pattern of a human gene homologous to the murine mb-1 gene." Ha H.J., Kubagawa H., Burrows P.D. J. Immunol. 148:1526-1531(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
[6]	"Chromosomal localization, genomic structure, and allelic polymorphism of the human CD79 alpha (Ig-alpha/mb-1) gene." Hashimoto S., Mohrenweiser H.W., Gregersen P.K., Chiorazzi N. Immunogenetics 40:287-295(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[7]	"Structure, chromosomal localization, and methylation pattern of the human mb-1 gene." Ha H., Barnoski B.L., Sun L., Emanuel B.S., Burrows P.D. J. Immunol. 152:5749-5757(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[8]	"Alternative splicing of CD79a (Ig-alpha/mb-1) and CD79b (Ig-beta/B29) RNA transcripts in human B cells." Hashimoto S., Chiorazzi N., Gregersen P.K. Mol. Immunol. 32:651-659(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[9]	Koyama M., Nakamura T. Submitted (DEC-1994) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[10]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Small intestine.
[11]	"Isolation and chemical characterization of the human B29 and mb-1 proteins of the B cell antigen receptor complex." Vasile S., Coligan J.E., Yoshida M., Seon B.K. Mol. Immunol. 31:419-427(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 33-52.
[12]	"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: PRELIMINARY NUCLEOTIDE SEQUENCE [MRNA] OF 190-226 (ISOFORM 1).
[13]	"Cooperativity and segregation of function within the Ig-alpha/beta heterodimer of the B cell antigen receptor complex." Luisiri P., Lee Y.J., Eisfelder B.J., Clark M.R. J. Biol. Chem. 271:5158-5163(1996) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[14]	"B-cell antigen receptor-induced apoptosis requires both Ig alpha and Ig beta." Tseng J., Eisfelder B.J., Clark M.R. Blood 89:1513-1520(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[15]	"Mutations in Igalpha (CD79a) result in a complete block in B-cell development." Minegishi Y., Coustan-Smith E., Rapalus L., Ersoy F., Campana D., Conley M.E. J. Clin. Invest. 104:1115-1121(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN AGM3.
[16]	"The serine and threonine residues in the Ig-alpha cytoplasmic tail negatively regulate immunoreceptor tyrosine-based activation motif-mediated signal transduction." Mueller R., Wienands J., Reth M. Proc. Natl. Acad. Sci. U.S.A. 97:8451-8454(2000) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION, MUTAGENESIS OF SER-197; SER-203 AND THR-209.
[17]	"Novel Igalpha (CD79a) gene mutation in a Turkish patient with B cell-deficient agammaglobulinemia." Wang Y., Kanegane H., Sanal O., Tezcan I., Ersoy F., Futatani T., Miyawaki T. Am. J. Med. Genet. 108:333-336(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN AGM3.
[18]	"Substrate recognition by the Lyn protein-tyrosine kinase. NMR structure of the immunoreceptor tyrosine-based activation motif signaling region of the B cell antigen receptor." Gaul B.S., Harrison M.L., Geahlen R.L., Burton R.A., Post C.B. J. Biol. Chem. 275:16174-16182(2000) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 184-195, PHOSPHORYLATION, INTERACTION WITH LYN.
+	Additional computationally mapped references.

Web resources

CD79Abase

CD79A mutation db

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

S46706 mRNA. Translation: AAB23558.1.
M80462 mRNA. Translation: AAA59556.1.
M74721 mRNA. Translation: AAA60270.1.
S75217 mRNA. Translation: AAB20812.1.
M86921 mRNA. Translation: AAA59557.1.
U05259 Genomic DNA. Translation: AAA20495.1.
S79248 mRNA. Translation: AAC60653.1.
X83540 mRNA. Translation: CAA58523.1.
AK223371 mRNA. Translation: BAD97091.1.
X13451 mRNA. Translation: CAA31802.1. Sequence problems.

IPI

IPI00008473.
IPI00218322.

PIR

A46477. I54539.
S12504.

RefSeq

NP_001774.1. NM_001783.3.
NP_067612.1. NM_021601.3.

UniGene

Hs.631567.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CV9	NMR	-	A	184-195	[»]

DisProt

DP00502.

ProteinModelPortal

P11912.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-6491159.

STRING

9606.ENSP00000221972.

PTM databases

PhosphoSite

P11912.

Polymorphism databases

DMDM

547896.

Proteomic databases

PaxDb

P11912.

PeptideAtlas

P11912.

PRIDE

P11912.

Protocols and materials databases

DNASU

973.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000221972; ENSP00000221972; ENSG00000105369.
ENST00000444740; ENSP00000400605; ENSG00000105369.

GeneID

973.

KEGG

hsa:973.

UCSC

uc002orv.3. human.

Organism-specific databases

CTD

973.

GeneCards

GC19P042381.

HGNC

HGNC:1698. CD79A.

HPA

CAB000019.
HPA017748.

MIM

112205. gene.
613501. phenotype.

neXtProt

NX_P11912.

Orphanet

33110. Autosomal agammaglobulinemia.

PharmGKB

PA26237.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG41728.

HOGENOM

HOG000074307.

HOVERGEN

HBG050854.

InParanoid

P11912.

KO

K06506.

OMA

PFLDMGE.

OrthoDB

EOG4H464J.

PhylomeDB

P11912.

Enzyme and pathway databases

Pathway_Interaction_DB

bcr_5pathway. BCR signaling pathway.

Reactome

REACT_6900. Immune System.

Gene expression databases

Bgee

P11912.

CleanEx

HS_CD79A.

Genevestigator

P11912.

GermOnline

ENSG00000105369. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 1 hit.

InterPro

IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003598. Ig_sub2.
IPR013106. Ig_V-set.
IPR003110. Phos_immunorcpt_sig_ITAM.
[Graphical view]

Pfam

PF02189. ITAM. 1 hit.
PF07686. V-set. 1 hit.
[Graphical view]

SMART

SM00408. IGc2. 1 hit.
SM00077. ITAM. 1 hit.
[Graphical view]

PROSITE

PS50835. IG_LIKE. 1 hit.
PS51055. ITAM_1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P11912.

GenomeRNAi

973.

NextBio

4076.

SOURCE

Search...

Entry information

Entry name

CD79A_HUMAN

Accession

Primary (citable) accession number: P11912
Secondary accession number(s): A0N775, Q53FB8

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	June 1, 1994
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

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.