Q9YGC1 (BLNK_CHICK) Reviewed, UniProtKB/Swiss-Prot
Last modified April 16, 2014. Version 79. History...
Names and origin
|Protein names||Recommended name:|
B-cell linker protein
B-cell adapter SH2 domain-containing protein
Cytoplasmic adapter protein
Src homology 2 domain-containing leukocyte protein of 65 kDa
|Organism||Gallus gallus (Chicken) [Reference proteome]|
|Taxonomic identifier||9031 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Testudines + Archosauria group › Archosauria › Dinosauria › Saurischia › Theropoda › Coelurosauria › Aves › Neognathae › Galliformes › Phasianidae › Phasianinae › Gallus|
|Sequence length||552 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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
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
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.
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
Contains 1 SH2 domain.
|Biological process||B-cell activation|
|Cellular component||Cell membrane|
|Coding sequence diversity||Alternative splicing|
|Technical term||Complete proteome|
|Gene Ontology (GO)|
|Biological_process||B cell activation|
Inferred from electronic annotation. Source: UniProtKB-KW
Traceable author statement. Source: Reactomeplasma membrane
Inferred from electronic annotation. Source: UniProtKB-SubCell
|Complete GO annotation...|
|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:
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 552||552||B-cell linker protein||PRO_0000064939|
|Domain||442 – 549||108||SH2|
|Compositional bias||149 – 271||123||Pro-rich|
Amino acid modifications
|Modified residue||91||1||Phosphotyrosine; by SYK Ref.3|
|Modified residue||103||1||Phosphotyrosine; by SYK Ref.3|
|Modified residue||115||1||Phosphotyrosine; by SYK Ref.3|
|Modified residue||194||1||Phosphotyrosine; by SYK Ref.3|
|Modified residue||205||1||Phosphotyrosine; by SYK Ref.3|
|Modified residue||249||1||Phosphotyrosine; by SYK Ref.3|
|Alternative sequence||40 – 58||19||Missing in isoform 2.||VSP_016179|
|Mutagenesis||91||1||Y → 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|
|Mutagenesis||103||1||Y → 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|
|Mutagenesis||115||1||Y → 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|
|Mutagenesis||194||1||Y → 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|
|Mutagenesis||205||1||Y → 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|
|Mutagenesis||249||1||Y → F: Loss of phosphorylation; when associated with F-91; F-103; F-115; F-194 and F-205. Ref.3|
|Mutagenesis||468||1||R → L: Strongly reduced tyrosine phosphorylation. Strongly reduced activation of NFAT. Ref.5|
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|AB015289 mRNA. Translation: BAA36275.1.|
AF089727 mRNA. Translation: AAD12783.1.
|RefSeq||NP_990239.1. NM_204908.1. |
3D structure databases
|SMR||Q9YGC1. Positions 428-552. |
Protein-protein interaction databases
|BioGrid||676007. 2 interactions.|
|IntAct||Q9YGC1. 1 interaction.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSGALT00000011296; ENSGALP00000011282; ENSGALG00000006973. [Q9YGC1-1]|
Enzyme and pathway databases
|Reactome||REACT_102124. Immune System. |
Family and domain databases
|Gene3D||3.30.505.10. 1 hit. |
|InterPro||IPR000980. SH2. |
|Pfam||PF00017. SH2. 1 hit. |
|SMART||SM00252. SH2. 1 hit. |
|SUPFAM||SSF55550. SSF55550. 1 hit. |
|PROSITE||PS50001. SH2. 1 hit. |
|Accession||Primary (citable) accession number: Q9YGC1|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families