[1]
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NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PROTEIN SEQUENCE OF 7-20; 140-146; 237-248; 250-257; 366-373 AND 392-405, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PLCG1; VAV1; GRB2 AND NCK1, ALTERNATIVE SPLICING, PHOSPHORYLATION, AND MUTAGENESIS OF TYR-72; TYR-84; TYR-96 AND TYR-178.
DOI=10.1016/S1074-7613(00)80591-9; PubMed=9697839 [NCBI, ExPASy, EBI, Israel, Japan]
Fu C.,
Turck C.W.,
Kurosaki T.,
Chan A.C.;
"BLNK: a central linker protein in B cell activation.";
Immunity 9:93-103(1998).
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[2]
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NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2), AND FUNCTION IN B-CELL DEVELOPMENT.
DOI=10.1126/science.286.5446.1954; PubMed=10583958 [NCBI, ExPASy, EBI, Israel, Japan]
Minegishi Y.,
Rohrer J.,
Coustan-Smith E.,
Lederman H.M.,
Pappu R.,
Campana D.,
Chan A.C.,
Conley M.E.;
"An essential role for BLNK in human B cell development.";
Science 286:1954-1957(1999).
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[3]
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NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=B-cell;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
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[4]
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INTERACTION WITH PLCG1; VAV1; GRB2 AND NCK1.
DOI=10.1074/jbc.272.43.27362; PubMed=9341187 [NCBI, ExPASy, EBI, Israel, Japan]
Fu C.,
Chan A.C.;
"Identification of two tyrosine phosphoproteins, pp70 and pp68, which interact with phospholipase Cgamma, Grb2, and Vav after B cell antigen receptor activation.";
J. Biol. Chem. 272:27362-27368(1997).
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[5]
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PHOSPHORYLATION AT TYR-72; TYR-84; TYR-96; TYR-178 AND TYR-189, AND MUTAGENESIS OF TYR-72; TYR-84 AND TYR-96.
DOI=10.1093/emboj/cdf658; PubMed=12456653 [NCBI, ExPASy, EBI, Israel, Japan]
Chiu C.W.,
Dalton M.,
Ishiai M.,
Kurosaki T.,
Chan A.C.;
"BLNK: molecular scaffolding through 'cis'-mediated organization of signaling proteins.";
EMBO J. 21:6461-6472(2002).
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[6]
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INVOLVEMENT IN ACUTE LYMPHOBLASTIC LEUKEMIA.
DOI=10.1038/nature01608; PubMed=12761551 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"Deficiency of the adaptor SLP-65 in pre-B-cell acute lymphoblastic leukaemia.";
Nature 423:452-456(2003).
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[7]
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FUNCTION IN PLCG1 ACTIVATION AND CALCIUM MOBILIZATION.
DOI=10.1111/j.1365-2567.2004.01918.x; PubMed=15270728 [NCBI, ExPASy, EBI, Israel, Japan]
Taguchi T.,
Kiyokawa N.,
Takenouch H.,
Matsui J.,
Tang W.-R.,
Nakajima H.,
Suzuki K.,
Shiozawa Y.,
Saito M.,
Katagiri Y.U.,
Takahashi T.,
Karasuyama H.,
Matsuo Y.,
Okita H.,
Fujimoto J.;
"Deficiency of BLNK hampers PLC-gamma2 phosphorylation and Ca2+ influx induced by the pre-B-cell receptor in human pre-B cells.";
Immunology 112:575-582(2004).
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[8]
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FUNCTION, AND INTERACTION WITH GRB2.
DOI=10.1182/blood-2006-02-005397; PubMed=16912232 [NCBI, ExPASy, EBI, Israel, Japan]
Grabbe A.,
Wienands J.;
"Human SLP-65 isoforms contribute differently to activation and apoptosis of B lymphocytes.";
Blood 108:3761-3768(2006).
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- FUNCTION: Functions as a central linker protein that bridges kinases associated with the B-cell receptor (BCR) with a multitude of signaling pathways, 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 Ca(2+) 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 an important role in BCR-induced B-cell apoptosis.
- SUBUNIT: Associates with PLCG1, VAV1 and NCK1 in a B-cell antigen receptor-dependent fashion. Interacts with VAV3, PLCG2 and GRB2. Interacts through its SH2 domain with CD79A.
- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Note=BCR activation results in the translocation to membrane fraction.
- ALTERNATIVE PRODUCTS:
2 named isoforms [FASTA] produced by alternative splicing.
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| Name | 2 |
| Isoform ID | Q8WV28-2 |
| Features which should be applied to build the isoform sequence: VSP_016178. |
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- TISSUE SPECIFICITY: Expressed in B-cell lineage and fibroblast cell lines (at protein level). Highest levels of expression in the spleen, with lower levels in the liver, kidney, pancreas, small intestines and colon.
- PTM: 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-96 facilitates BTK binding. Phosphorylation of Tyr-72 facilitates VAV1 and NCK1 binding. Phosphorylation is required for both Ca(2+) and MAPK signaling pathways.
- DISEASE: Defects in BLNK are the cause of hypoglobulinemia and absent B-cells [MIM:604515]. This is a developmental blockage at the pro- to pre-B-cell transition.
- DISEASE: In 6 of 34 childhood pre-B acute lymphoblastic leukemia (ALL) samples that were tested showed a complete loss or drastic reduction of BLNK expression.
- SIMILARITY: Contains 1 SH2 domain.
- WEB RESOURCE: Name=BLNKbase; Note=BLNK mutation db; URL="http://bioinf.uta.fi/BLNKbase/";.
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