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Q9YGC1 (BLNK_CHICK) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 79. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·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 SH2 domain-containing protein
Cytoplasmic adapter protein
Src homology 2 domain-containing leukocyte protein of 65 kDa
Short name=SLP-65
Gene names
Name:BLNK
Synonyms:BASH
OrganismGallus gallus (Chicken) [Reference proteome]
Taxonomic identifier9031 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiTestudines + Archosauria groupArchosauriaDinosauriaSaurischiaTheropodaCoelurosauriaAvesNeognathaeGalliformesPhasianidaePhasianinaeGallus

Protein attributes

Sequence length552 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 By similarity. Plays a critical role in B-cell development in the bursa. Plays an important role in BCR-induced apoptosis. Ref.1 Ref.2 Ref.4 Ref.5

Subunit structure

Associates with PLCG1, VAV1 and NCK1 in a B-cell antigen receptor-dependent fashion. Interacts through its SH2 domain with CD79A By similarity. Interacts with VAV3, PLCG2 and GRB2. Ref.4

Subcellular location

Cytoplasm. Cell membrane. Note: BCR activation results in the translocation to membrane fraction. Ref.5

Tissue specificity

Highly expressed in the bursa, very low expression in ovary and spleen. Expression was variable among B-cell lines. Highly expressed in immature B-cell lines such as DT40 and CL18, low expression was seen in relatively mature B-cell lines, such as 293B9 and 249L4. No expression was seen in T-cell lines.

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 is required for both Ca2+ and MAPK signaling pathways By similarity. Phosphorylation of Tyr-103, Tyr-194 and Tyr-205 facilitates PLCG1 binding. Phosphorylation of Tyr-115 facilitates BTK binding. Phosphorylation of Tyr-91 facilitates VAV1 and NCK1 binding. Ref.1 Ref.3 Ref.4 Ref.5

Sequence similarities

Contains 1 SH2 domain.

Ontologies

Keywords
   Biological processB-cell activation
   Cellular componentCell membrane
Cytoplasm
Membrane
   Coding sequence diversityAlternative splicing
   DomainSH2 domain
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processB cell activation

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9YGC1-1)

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: Q9YGC1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     40-58: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 552552B-cell linker protein
PRO_0000064939

Regions

Domain442 – 549108SH2
Compositional bias149 – 271123Pro-rich

Amino acid modifications

Modified residue911Phosphotyrosine; by SYK Ref.3
Modified residue1031Phosphotyrosine; by SYK Ref.3
Modified residue1151Phosphotyrosine; by SYK Ref.3
Modified residue1941Phosphotyrosine; by SYK Ref.3
Modified residue2051Phosphotyrosine; by SYK Ref.3
Modified residue2491Phosphotyrosine; by SYK Ref.3

Natural variations

Alternative sequence40 – 5819Missing in isoform 2.
VSP_016179

Experimental info

Mutagenesis911Y → F: Significant phosphorylation reduction; when associated with F-103; F-115; F-194 and F-205. Loss of phosphorylation; when associated with F-103; F-115; F-194; F-205 and F-249. Ref.3
Mutagenesis1031Y → F: Significant reduction of Ca(2+) mobilization; when associated with F-194. Loss of Ca(2+) mobilization; when associated with F-194 and F-205. Significant phosphorylation reduction; when associated with F-91; F-115; F-194 and F-205. Loss of phosphorylation; when associated with F-91; F-115; F-194; F-205 and F-249. Ref.3
Mutagenesis1151Y → F: Significant phosphorylation reduction; when associated with F-91; F-103; F-194 and F-205. Loss of phosphorylation; when associated with F-91; F-103; F-194; F-205 and F-249. Ref.3
Mutagenesis1941Y → F: Reduction in Ca(2+) mobilization. Significant reduction of Ca(2+) mobilization; when associated with F-103. Loss of Ca(2+) mobilization; when associated with F-103 and F-205. Significant phosphorylation reduction; when associated with F-91; F-103; F-115 and F-205. Loss of phosphorylation; when associated with F-91; F-103; F-115; F-205 and F-249. Ref.3
Mutagenesis2051Y → F: Loss of Ca(2+) mobilization; when associated with F-194 and F-205. Significant phosphorylation reduction; when associated with F-91; F-103; F-115 and F-194. Loss of phosphorylation; when associated with F-91; F-103; F-115; F-194 and F-249. Ref.3
Mutagenesis2491Y → F: Loss of phosphorylation; when associated with F-91; F-103; F-115; F-194 and F-205. Ref.3
Mutagenesis4681R → L: Strongly reduced tyrosine phosphorylation. Strongly reduced activation of NFAT. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: FB232179BE38D072

FASTA55261,823
        10         20         30         40         50         60 
MDKLNKLAVP AGEKFRKLQK MVHDIKKNES GIINKFKKFQ NEQVALICKT GKDTWDRLKK 

        70         80         90        100        110        120 
KPPPSLPRRD YASEHADNEE EQWSDDFDSD YENPDGHSDS EMYVVPSEEN PDDSYEPPPS 

       130        140        150        160        170        180 
EQEKKKIPSS FPISRGEYAD NRTSHHQLPP INKPLPSTPS SALPRPKKPS LPSPAAKPKL 

       190        200        210        220        230        240 
PLKPRECSDD EDNYIVPVDN DDDNYIEPTE SSTPPPAKPP VNRFMKPPAK SALPTPPKPS 

       250        260        270        280        290        300 
LASDMQEVYE VPEEEEELSP PPVTRFTKPL PATRAQNAEH SHMHSMTRES PKLDASRNIL 

       310        320        330        340        350        360 
PLPRNRLHPK TDHEANNNDE NHSFSNTQES KFPPGAAPSP LPRALKKTSN AVNPAKPCLP 

       370        380        390        400        410        420 
SRDTFTVNED KPTAADRRRG SSHEFPLPPL PSGTPKSSLQ KPLVLPKVPE APSRALGTSP 

       430        440        450        460        470        480 
HSSISSISST ADQDAGVHSK AWYAATCDRK TAEDALYRSN KDGSFLIRKS SGQDSRQPYT 

       490        500        510        520        530        540 
LVVFYNRRVY NIPIRFIEST RQYALGREKC GEERFDSVAE IVENHQHTSL VLIDSQNNTK 

       550 
DSTKLKYIVR VS 

« Hide

Isoform 2 [UniParc].

Checksum: 97208F0B7267FC8E
Show »

FASTA53359,623

References

[1]"BASH, a novel signaling molecule preferentially expressed in B cells of the bursa of Fabricius."
Goitsuka R., Fujimura Y., Mamada H., Umeda A., Morimura T., Uetsuka K., Doi K., Tsuji S., Kitamura D.
J. Immunol. 161:5804-5808(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION IN BCR-MEDIATED SIGNAL TRANSDUCTION, ALTERNATIVE SPLICING, PHOSPHORYLATION BY SYK AND LYN.
[2]"BLNK required for coupling Syk to PLC gamma 2 and Rac1-JNK in B cells."
Ishiai M., Kurosaki M., Pappu R., Okawa K., Ronko I., Fu C., Shibata M., Iwamatsu A., Chan A.C., Kurosaki T.
Immunity 10:117-125(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION IN REGULATING THE RAC1-JNK PATHWAY.
[3]"BLNK: molecular scaffolding through 'cis'-mediated organization of signaling proteins."
Chiu C.W., Dalton M., Ishiai M., Kurosaki T., Chan A.C.
EMBO J. 21:6461-6472(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-91; TYR-103; TYR-115; TYR-194; TYR-205 AND TYR-249 BY SYK, MUTAGENESIS OF TYR-91; TYR-103; TYR-115; TYR-194; TYR-205 AND TYR-249.
[4]"Human SLP-65 isoforms contribute differently to activation and apoptosis of B lymphocytes."
Grabbe A., Wienands J.
Blood 108:3761-3768(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TYROSINE PHOSPHORYLATION, INTERACTION WITH GRB2; PLCG2 AND VAV3.
[5]"SLP-65 signal transduction requires Src homology 2 domain-mediated membrane anchoring and a kinase-independent adaptor function of Syk."
Abudula A., Grabbe A., Brechmann M., Polaschegg C., Herrmann N., Goldbeck I., Dittmann K., Wienands J.
J. Biol. Chem. 282:29059-29066(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TYROSINE PHOSPHORYLATION, MUTAGENESIS OF ARG-468, SUBCELLULAR LOCATION.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB015289 mRNA. Translation: BAA36275.1.
AF089727 mRNA. Translation: AAD12783.1.
RefSeqNP_990239.1. NM_204908.1.
UniGeneGga.3738.

3D structure databases

ProteinModelPortalQ9YGC1.
SMRQ9YGC1. Positions 428-552.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid676007. 2 interactions.
IntActQ9YGC1. 1 interaction.
STRING9031.ENSGALP00000011282.

Proteomic databases

PaxDbQ9YGC1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSGALT00000011296; ENSGALP00000011282; ENSGALG00000006973. [Q9YGC1-1]
GeneID395733.
KEGGgga:395733.

Organism-specific databases

CTD29760.

Phylogenomic databases

eggNOGNOG44661.
GeneTreeENSGT00530000063094.
HOGENOMHOG000088646.
HOVERGENHBG053147.
InParanoidQ9YGC1.
KOK07371.
OrthoDBEOG7WMCKM.
PhylomeDBQ9YGC1.
TreeFamTF326567.

Enzyme and pathway databases

ReactomeREACT_102124. Immune System.

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

NextBio20815801.
PROQ9YGC1.

Entry information

Entry nameBLNK_CHICK
AccessionPrimary (citable) accession number: Q9YGC1
Entry history
Integrated into UniProtKB/Swiss-Prot: November 22, 2005
Last sequence update: May 1, 1999
Last modified: April 16, 2014
This is version 79 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