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Q9QUN3

- BLNK_MOUSE

UniProt

Q9QUN3 - BLNK_MOUSE

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Protein
B-cell linker protein
Gene
Blnk, Bash, Ly57, Slp65
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.3 Publications

GO - Molecular functioni

  1. protein binding Source: UniProtKB

GO - Biological processi

  1. B cell activation Source: UniProtKB-KW
  2. intracellular signal transduction Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

B-cell activation

Enzyme and pathway databases

ReactomeiREACT_188194. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
REACT_198634. Regulation of signaling by CBL.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Blnk
Synonyms:Bash, Ly57, Slp65
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 19

Organism-specific databases

MGIiMGI:96878. Blnk.

Subcellular locationi

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

GO - Cellular componenti

  1. cytoplasm Source: MGI
  2. plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi52 – 521Y → F: No effect on pre-BCR down-regulation. 1 Publication
Mutagenesisi96 – 961Y → F: Fails to induce pre-BCR down-regulation, leading to splenomegaly and leukemia. 1 Publication
Mutagenesisi373 – 3731R → L: Abolishes binding to CD79A and SYK. 2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 457457B-cell linker protein
PRO_0000064941Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei72 – 721Phosphotyrosine; by SYK By similarity
Modified residuei84 – 841Phosphotyrosine; by SYK By similarity
Modified residuei96 – 961Phosphotyrosine; by SYK By similarity
Modified residuei178 – 1781Phosphotyrosine; by SYK By similarity
Modified residuei189 – 1891Phosphotyrosine; by SYK By similarity

Post-translational modificationi

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.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9QUN3.
PRIDEiQ9QUN3.

PTM databases

PhosphoSiteiQ9QUN3.

Expressioni

Tissue specificityi

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.1 Publication

Gene expression databases

ArrayExpressiQ9QUN3.
BgeeiQ9QUN3.
CleanExiMM_BLNK.
GenevestigatoriQ9QUN3.

Interactioni

Subunit structurei

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.6 Publications

Protein-protein interaction databases

BioGridi201236. 5 interactions.
IntActiQ9QUN3. 6 interactions.
MINTiMINT-110328.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi334 – 3407
Turni341 – 3444
Beta strandi346 – 3516
Helixi354 – 36411
Beta strandi372 – 3743
Beta strandi383 – 3908
Beta strandi393 – 3997
Turni403 – 4064
Beta strandi410 – 4123
Beta strandi420 – 4223
Helixi423 – 43210
Beta strandi440 – 4423

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2EO6NMR-A330-457[»]
ProteinModelPortaliQ9QUN3.
SMRiQ9QUN3. Positions 328-457.

Miscellaneous databases

EvolutionaryTraceiQ9QUN3.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini347 – 454108SH2
Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi130 – 330201Pro-rich
Add
BLAST

Sequence similaritiesi

Contains 1 SH2 domain.

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiNOG44661.
GeneTreeiENSGT00530000063094.
HOGENOMiHOG000088646.
HOVERGENiHBG053147.
InParanoidiQ9QUN3.
KOiK07371.
OMAiHRQENMQ.
PhylomeDBiQ9QUN3.
TreeFamiTF326567.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
[Graphical view]
PfamiPF00017. SH2. 1 hit.
[Graphical view]
SMARTiSM00252. SH2. 1 hit.
[Graphical view]
SUPFAMiSSF55550. SSF55550. 1 hit.
PROSITEiPS50001. SH2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9QUN3-1 [UniParc]FASTAAdd to Basket

« Hide

MDKLNKITVP ASQKLRQLQK MVHDIKNNEG GIMDKIKKLK VKGPPSVPRR    50
DYALDSPADE EEQWSDDFDS DYENPDEHSD SEMYVMPAEE TGDDSYEPPP 100
AEQQTRVVHP ALPFTRGEYV DNRSSQRHSP PFSKTLPSKP SWPSAKARLA 150
STLPAPNSLQ KPQVPPKPKD LLEDEADYVV PVEDNDENYI HPRESSPPPA 200
EKAPMVNRST KPNSSSKHMS PPGTVAGRNS GVWDSKSSLP AAPSPLPRAG 250
KKPATPLKTT PVPPLPNASN VCEEKPVPAE RHRGSSHRQD TVQSPVFPPT 300
QKPVHQKPVP LPRFPEAGSP AADGPFHSFP FNSTFADQEA ELLGKPWYAG 350
ACDRKSAEEA LHRSNKDGSF LIRKSSGHDS KQPYTLVAFF NKRVYNIPVR 400
FIEATKQYAL GKKKNGEEYF GSVVEIVNSH QHNPLVLIDS QNNTKDSTRL 450
KYAVKVS 457
Length:457
Mass (Da):50,671
Last modified:May 1, 2000 - v1
Checksum:i66C93D4FDDF9D260
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti333 – 3331S → L in AAC40206. 1 Publication
Sequence conflicti340 – 3401A → G in AAC40206. 1 Publication
Sequence conflicti356 – 3561S → F in AAC40206. 1 Publication
Sequence conflicti376 – 3761S → F in AAC40206. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS37983.1.
RefSeqiNP_032554.2. NM_008528.4.
UniGeneiMm.9749.

Genome annotation databases

EnsembliENSMUST00000054769; ENSMUSP00000057844; ENSMUSG00000061132.
GeneIDi17060.
KEGGimmu:17060.
UCSCiuc008hll.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS37983.1.
RefSeqi NP_032554.2. NM_008528.4.
UniGenei Mm.9749.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2EO6 NMR - A 330-457 [» ]
ProteinModelPortali Q9QUN3.
SMRi Q9QUN3. Positions 328-457.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 201236. 5 interactions.
IntActi Q9QUN3. 6 interactions.
MINTi MINT-110328.

PTM databases

PhosphoSitei Q9QUN3.

Proteomic databases

PaxDbi Q9QUN3.
PRIDEi Q9QUN3.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000054769 ; ENSMUSP00000057844 ; ENSMUSG00000061132 .
GeneIDi 17060.
KEGGi mmu:17060.
UCSCi uc008hll.1. mouse.

Organism-specific databases

CTDi 29760.
MGIi MGI:96878. Blnk.

Phylogenomic databases

eggNOGi NOG44661.
GeneTreei ENSGT00530000063094.
HOGENOMi HOG000088646.
HOVERGENi HBG053147.
InParanoidi Q9QUN3.
KOi K07371.
OMAi HRQENMQ.
PhylomeDBi Q9QUN3.
TreeFami TF326567.

Enzyme and pathway databases

Reactomei REACT_188194. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
REACT_198634. Regulation of signaling by CBL.

Miscellaneous databases

EvolutionaryTracei Q9QUN3.
NextBioi 291162.
PROi Q9QUN3.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q9QUN3.
Bgeei Q9QUN3.
CleanExi MM_BLNK.
Genevestigatori Q9QUN3.

Family and domain databases

Gene3Di 3.30.505.10. 1 hit.
InterProi IPR000980. SH2.
[Graphical view ]
Pfami PF00017. SH2. 1 hit.
[Graphical view ]
SMARTi SM00252. SH2. 1 hit.
[Graphical view ]
SUPFAMi SSF55550. SSF55550. 1 hit.
PROSITEi PS50001. SH2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.

Entry informationi

Entry nameiBLNK_MOUSE
AccessioniPrimary (citable) accession number: Q9QUN3
Secondary accession number(s): O88504
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 22, 2005
Last sequence update: May 1, 2000
Last modified: September 3, 2014
This is version 106 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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