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Protein

B-cell linker protein

Gene

Blnk

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

B-cell activation

Enzyme and pathway databases

ReactomeiR-MMU-983695. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.

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
Proteomesi
  • UP000000589 Componenti: 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

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

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi52Y → F: No effect on pre-BCR down-regulation. 1 Publication1
Mutagenesisi96Y → F: Fails to induce pre-BCR down-regulation, leading to splenomegaly and leukemia. 1 Publication1
Mutagenesisi373R → L: Abolishes binding to CD79A and SYK. 2 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000649411 – 457B-cell linker proteinAdd BLAST457

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei72Phosphotyrosine; by SYKBy similarity1
Modified residuei84Phosphotyrosine; by SYKBy similarity1
Modified residuei96Phosphotyrosine; by SYKBy similarity1
Modified residuei178Phosphotyrosine; by SYKBy similarity1
Modified residuei189Phosphotyrosine; by SYKBy similarity1

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.By similarity1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9QUN3.
PeptideAtlasiQ9QUN3.
PRIDEiQ9QUN3.

PTM databases

iPTMnetiQ9QUN3.
PhosphoSitePlusiQ9QUN3.

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

BgeeiENSMUSG00000061132.
CleanExiMM_BLNK.
ExpressionAtlasiQ9QUN3. baseline and differential.
GenevisibleiQ9QUN3. MM.

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.By similarity6 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi201236. 5 interactors.
IntActiQ9QUN3. 6 interactors.
MINTiMINT-110328.
STRINGi10090.ENSMUSP00000057844.

Structurei

Secondary structure

1457
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi334 – 340Combined sources7
Turni341 – 344Combined sources4
Beta strandi346 – 351Combined sources6
Helixi354 – 364Combined sources11
Beta strandi372 – 374Combined sources3
Beta strandi383 – 390Combined sources8
Beta strandi393 – 399Combined sources7
Turni403 – 406Combined sources4
Beta strandi410 – 412Combined sources3
Beta strandi420 – 422Combined sources3
Helixi423 – 432Combined sources10
Beta strandi440 – 442Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EO6NMR-A330-457[»]
ProteinModelPortaliQ9QUN3.
SMRiQ9QUN3.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9QUN3.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini347 – 454SH2PROSITE-ProRule annotationAdd BLAST108

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi130 – 330Pro-richAdd BLAST201

Sequence similaritiesi

Contains 1 SH2 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiENOG410IGWN. Eukaryota.
ENOG410XYB6. LUCA.
GeneTreeiENSGT00530000063094.
HOGENOMiHOG000088646.
HOVERGENiHBG053147.
InParanoidiQ9QUN3.
KOiK07371.
OMAiHRQENMQ.
OrthoDBiEOG091G053I.
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

        10         20         30         40         50
MDKLNKITVP ASQKLRQLQK MVHDIKNNEG GIMDKIKKLK VKGPPSVPRR
60 70 80 90 100
DYALDSPADE EEQWSDDFDS DYENPDEHSD SEMYVMPAEE TGDDSYEPPP
110 120 130 140 150
AEQQTRVVHP ALPFTRGEYV DNRSSQRHSP PFSKTLPSKP SWPSAKARLA
160 170 180 190 200
STLPAPNSLQ KPQVPPKPKD LLEDEADYVV PVEDNDENYI HPRESSPPPA
210 220 230 240 250
EKAPMVNRST KPNSSSKHMS PPGTVAGRNS GVWDSKSSLP AAPSPLPRAG
260 270 280 290 300
KKPATPLKTT PVPPLPNASN VCEEKPVPAE RHRGSSHRQD TVQSPVFPPT
310 320 330 340 350
QKPVHQKPVP LPRFPEAGSP AADGPFHSFP FNSTFADQEA ELLGKPWYAG
360 370 380 390 400
ACDRKSAEEA LHRSNKDGSF LIRKSSGHDS KQPYTLVAFF NKRVYNIPVR
410 420 430 440 450
FIEATKQYAL GKKKNGEEYF GSVVEIVNSH QHNPLVLIDS QNNTKDSTRL

KYAVKVS
Length:457
Mass (Da):50,671
Last modified:May 1, 2000 - v1
Checksum:i66C93D4FDDF9D260
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti333S → L in AAC40206 (PubMed:9697839).Curated1
Sequence conflicti340A → G in AAC40206 (PubMed:9697839).Curated1
Sequence conflicti356S → F in AAC40206 (PubMed:9697839).Curated1
Sequence conflicti376S → F in AAC40206 (PubMed:9697839).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EO6NMR-A330-457[»]
ProteinModelPortaliQ9QUN3.
SMRiQ9QUN3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201236. 5 interactors.
IntActiQ9QUN3. 6 interactors.
MINTiMINT-110328.
STRINGi10090.ENSMUSP00000057844.

PTM databases

iPTMnetiQ9QUN3.
PhosphoSitePlusiQ9QUN3.

Proteomic databases

PaxDbiQ9QUN3.
PeptideAtlasiQ9QUN3.
PRIDEiQ9QUN3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi29760.
MGIiMGI:96878. Blnk.

Phylogenomic databases

eggNOGiENOG410IGWN. Eukaryota.
ENOG410XYB6. LUCA.
GeneTreeiENSGT00530000063094.
HOGENOMiHOG000088646.
HOVERGENiHBG053147.
InParanoidiQ9QUN3.
KOiK07371.
OMAiHRQENMQ.
OrthoDBiEOG091G053I.
PhylomeDBiQ9QUN3.
TreeFamiTF326567.

Enzyme and pathway databases

ReactomeiR-MMU-983695. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.

Miscellaneous databases

EvolutionaryTraceiQ9QUN3.
PROiQ9QUN3.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000061132.
CleanExiMM_BLNK.
ExpressionAtlasiQ9QUN3. baseline and differential.
GenevisibleiQ9QUN3. MM.

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]
ProtoNetiSearch...

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: November 2, 2016
This is version 126 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.