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Q9QUN3 (BLNK_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
B-cell linker protein
Alternative name(s):
B-cell adapter containing a SH2 domain protein
B-cell adapter containing a Src homology 2 domain protein
Cytoplasmic adapter protein
Lymphocyte antigen 57
Src homology 2 domain-containing leukocyte protein of 65 kDa
Short name=Slp-65
Gene names
Name:Blnk
Synonyms:Bash, Ly57, Slp65
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length457 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Functions as a central linker protein, downstream of the B-cell receptor (BCR), bridging the SYK kinase to a multitude of signaling pathways and regulating biological outcomes of B-cell function and development. Plays a role in the activation of ERK/EPHB2, MAP kinase p38 and JNK. Modulates AP1 activation. Important for the activation of NF-kappa-B and NFAT. Plays an important role in BCR-mediated PLCG1 and PLCG2 activation and Ca2+ mobilization and is required for trafficking of the BCR to late endosomes. However, does not seem to be required for pre-BCR-mediated activation of MAP kinase and phosphatidyl-inositol 3 (PI3) kinase signaling. May be required for the RAC1-JNK pathway. Plays a critical role in orchestrating the pro-B cell to pre-B cell transition. May play an important role in BCR-induced B-cell apoptosis. Ref.2 Ref.9 Ref.10

Subunit structure

Associates with PLCG1, VAV1 and NCK1 in a B-cell antigen receptor-dependent fashion. Interacts with VAV3, PLCG2 and GRB2 By similarity. Interacts through its SH2 domain with CD79A. Interacts (via SH2 domain) with SYK; phosphorylated and activated by SYK. Interacts with SCIMP. Ref.2 Ref.6 Ref.7 Ref.8 Ref.10 Ref.11

Subcellular location

Cytoplasm By similarity. Cell membrane By similarity. Note: BCR activation results in the translocation to membrane fraction By similarity.

Tissue specificity

Expressed in the spleen and weakly in thymus, no expression was seen in liver, testis, or brain. Expressed in B-cell lines representing different developmental stages from the pre-B to the plasma cell stage, but not in a T-cell or a fibroblast cell line. Ref.2

Post-translational modification

Following BCR activation, phosphorylated on tyrosine residues by SYK and LYN. When phosphorylated, serves as a scaffold to assemble downstream targets of antigen activation, including PLCG1, VAV1, GRB2 and NCK1. Phosphorylation of Tyr-84, Tyr-178 and Tyr-189 facilitates PLCG1 binding. Phosphorylation of Tyr-72 facilitates VAV1 and NCK1 binding. Phosphorylation is required for both Ca2+ and MAPK signaling pathways By similarity. Phosphorylation of Tyr-96 is required for the binding of BTK. Ref.2

Sequence similarities

Contains 1 SH2 domain.

Ontologies

Keywords
   Biological processB-cell activation
   Cellular componentCell membrane
Cytoplasm
Membrane
   DomainSH2 domain
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processB cell activation

Inferred from electronic annotation. Source: UniProtKB-KW

intracellular signal transduction

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 457457B-cell linker protein
PRO_0000064941

Regions

Domain347 – 454108SH2
Compositional bias130 – 330201Pro-rich

Amino acid modifications

Modified residue721Phosphotyrosine; by SYK By similarity
Modified residue841Phosphotyrosine; by SYK By similarity
Modified residue961Phosphotyrosine; by SYK By similarity
Modified residue1781Phosphotyrosine; by SYK By similarity
Modified residue1891Phosphotyrosine; by SYK By similarity

Experimental info

Mutagenesis521Y → F: No effect on pre-BCR down-regulation. Ref.9
Mutagenesis961Y → F: Fails to induce pre-BCR down-regulation, leading to splenomegaly and leukemia. Ref.9
Mutagenesis3731R → L: Abolishes binding to CD79A and SYK. Ref.6 Ref.10
Sequence conflict3331S → L in AAC40206. Ref.1
Sequence conflict3401A → G in AAC40206. Ref.1
Sequence conflict3561S → F in AAC40206. Ref.1
Sequence conflict3761S → F in AAC40206. Ref.1

Secondary structure

....................... 457
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9QUN3 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: 66C93D4FDDF9D260

FASTA45750,671
        10         20         30         40         50         60 
MDKLNKITVP ASQKLRQLQK MVHDIKNNEG GIMDKIKKLK VKGPPSVPRR DYALDSPADE 

        70         80         90        100        110        120 
EEQWSDDFDS DYENPDEHSD SEMYVMPAEE TGDDSYEPPP AEQQTRVVHP ALPFTRGEYV 

       130        140        150        160        170        180 
DNRSSQRHSP PFSKTLPSKP SWPSAKARLA STLPAPNSLQ KPQVPPKPKD LLEDEADYVV 

       190        200        210        220        230        240 
PVEDNDENYI HPRESSPPPA EKAPMVNRST KPNSSSKHMS PPGTVAGRNS GVWDSKSSLP 

       250        260        270        280        290        300 
AAPSPLPRAG KKPATPLKTT PVPPLPNASN VCEEKPVPAE RHRGSSHRQD TVQSPVFPPT 

       310        320        330        340        350        360 
QKPVHQKPVP LPRFPEAGSP AADGPFHSFP FNSTFADQEA ELLGKPWYAG ACDRKSAEEA 

       370        380        390        400        410        420 
LHRSNKDGSF LIRKSSGHDS KQPYTLVAFF NKRVYNIPVR FIEATKQYAL GKKKNGEEYF 

       430        440        450 
GSVVEIVNSH QHNPLVLIDS QNNTKDSTRL KYAVKVS 

« Hide

References

« Hide 'large scale' references
[1]"BLNK: a central linker protein in B cell activation."
Fu C., Turck C.W., Kurosaki T., Chan A.C.
Immunity 9:93-103(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"SLP-65: a new signaling component in B lymphocytes which requires expression of the antigen receptor for phosphorylation."
Wienands J., Schweikert J., Wollschied B., Jumaa H., Nielsen P.J., Reth M.
J. Exp. Med. 188:791-795(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 7-20; 147-161; 170-186; 356-366 AND 393-412, FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION, INTERACTION WITH VAV1 AND GRB2.
Strain: BALB/c.
Tissue: Lymphoid tissue.
[3]"BASH: B lymphocyte adaptor protein containing SH2 domain."
Okamoto N., Hayashi K., Tsuji S., Goitsuka R., Kitamura D.
Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"The murine SLP-65 gene."
Nielsen P.J., Guenet J.-L.
Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"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: 129.
Tissue: Mammary tumor.
[6]"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 CD79A, MUTAGENESIS OF ARG-373.
[7]"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: INTERACTION WITH CD79A.
[8]"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 CD79A.
[9]"Deficiency of the adaptor SLP-65 in pre-B-cell acute lymphoblastic leukaemia."
Jumaa H., Bossaller L., Portugal K., Storch B., Lotz M., Flemming A., Schrappe M., Postila V., Riikonen P., Pelkonen J., Niemeyer C.M., Reth M.
Nature 423:452-456(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PRO-B CELL TO PRE-B CELL TRANSITION, MUTAGENESIS OF TYR-52 AND TYR-96.
[10]"The kinase Syk as an adaptor controlling sustained calcium signalling and B-cell development."
Kulathu Y., Hobeika E., Turchinovich G., Reth M.
EMBO J. 27:1333-1344(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN SYK ACTIVATION, INTERACTION WITH SYK, MUTAGENESIS OF ARG-373.
[11]"SCIMP, a transmembrane adapter protein involved in major histocompatibility complex class II signaling."
Draber P., Vonkova I., Stepanek O., Hrdinka M., Kucova M., Skopcova T., Otahal P., Angelisova P., Horejsi V., Yeung M., Weiss A., Brdicka T.
Mol. Cell. Biol. 31:4550-4562(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SCIMP.
[12]"Solution structure of the SH2 domain from mouse B-cell linker protein BLNK."
RIKEN structural genomics initiative (RSGI)
Submitted (APR-2008) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 328-457.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF068182 mRNA. Translation: AAC40206.1.
Y17159 mRNA. Translation: CAA76666.1.
AB015290 mRNA. Translation: BAA34944.1.
AJ298054 Genomic DNA. Translation: CAC18565.1.
BC059785 mRNA. Translation: AAH59785.1.
RefSeqNP_032554.2. NM_008528.4.
UniGeneMm.9749.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2EO6NMR-A330-457[»]
ProteinModelPortalQ9QUN3.
SMRQ9QUN3. Positions 1-42, 328-457.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201236. 5 interactions.
IntActQ9QUN3. 6 interactions.
MINTMINT-110328.

PTM databases

PhosphoSiteQ9QUN3.

Proteomic databases

PaxDbQ9QUN3.
PRIDEQ9QUN3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000054769; ENSMUSP00000057844; ENSMUSG00000061132.
GeneID17060.
KEGGmmu:17060.
UCSCuc008hll.1. mouse.

Organism-specific databases

CTD29760.
MGIMGI:96878. Blnk.

Phylogenomic databases

eggNOGNOG44661.
GeneTreeENSGT00530000063094.
HOGENOMHOG000088646.
HOVERGENHBG053147.
InParanoidQ9QUN3.
KOK07371.
OMAHRQENMQ.
PhylomeDBQ9QUN3.
TreeFamTF326567.

Gene expression databases

ArrayExpressQ9QUN3.
BgeeQ9QUN3.
CleanExMM_BLNK.
GenevestigatorQ9QUN3.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR000980. SH2.
[Graphical view]
PfamPF00017. SH2. 1 hit.
[Graphical view]
SMARTSM00252. SH2. 1 hit.
[Graphical view]
SUPFAMSSF55550. SSF55550. 1 hit.
PROSITEPS50001. SH2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9QUN3.
NextBio291162.
PROQ9QUN3.
SOURCESearch...

Entry information

Entry nameBLNK_MOUSE
AccessionPrimary (citable) accession number: Q9QUN3
Secondary accession number(s): O88504
Entry history
Integrated into UniProtKB/Swiss-Prot: November 22, 2005
Last sequence update: May 1, 2000
Last modified: April 16, 2014
This is version 103 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

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