Tyrosine-protein kinase Blk

UniProt P51451 Organism Homo sapiens Gene BLK EC 2.7.10.2

Also known as: BLK

Function

Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling (By similarity). B-cell receptor (BCR) signaling requires a tight regulation of several protein tyrosine kinases and phosphatases, and associated coreceptors (By similarity). Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation (By similarity). Signaling through BLK plays an important role in transmitting signals through surface immunoglobulins and supports the pro-B to pre-B transition, as well as the signaling for growth arrest and apoptosis downstream of B-cell receptor (By similarity). Specifically binds and phosphorylates CD79A at 'Tyr-188'and 'Tyr-199', as well as CD79B at 'Tyr-196' and 'Tyr-207' (By similarity). Also phosphorylates the immunoglobulin G receptors FCGR2A, FCGR2B and FCGR2C. With FYN and LYN, plays an essential role in pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation (By similarity). Also contributes to BTK activation by indirectly stimulating BTK intramolecular autophosphorylation (By similarity). In pancreatic islets, acts as a modulator of beta-cells function through the up-regulation of PDX1 and NKX6-1 and consequent stimulation of insulin secretion in response to glucose. Phosphorylates CGAS, promoting retention of CGAS in the cytosol.

Classification

Family (Pfam): PF07714 PK_Tyr_Ser-Thr, PF00017 SH2, PF00018 SH3_1
InterPro: Blk_SH2, Kinase-like_dom_sf, Non-receptor_tyrosine_kinases, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser-Thr/Tyr_kinase_cat_dom, SH2, SH2_dom_sf, SH3-like_dom_sf, SH3_domain, Tyr_kinase_cat_dom
Functional cluster: Serine/Threonine Protein Kinases

Gene Ontology · 12

Disease associations

maturity-onset diabetes of the young type 11 MONDO:0013242

Drugs targeting this protein · 5

DASATINIB ANHYDROUS inhibitor
ILORASERTIB inhibitor
XL-228 inhibitor
TG100-801 inhibitor
ENMD-981693 inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Low affinity immunoglobulin gamma Fc region receptor II-c 1 shared papers
E3 ubiquitin-protein ligase CBL 1 shared papers
Low affinity immunoglobulin gamma Fc region receptor II-a 1 shared papers
Low affinity immunoglobulin gamma Fc region receptor II-b 1 shared papers
Protein timeless homolog 1 shared papers
Cyclic GMP-AMP synthase 1 shared papers
Poly [ADP-ribose] polymerase 1 1 shared papers
Cyclic GMP-AMP synthase 1 shared papers

Literature · 12 cited papers

Nuclear cGAS suppresses DNA repair and promotes tumorigenesis. Nature · 2018
Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
Mutations at the BLK locus linked to maturity onset diabetes of the young and beta-cell dysfunction. Proc. Natl. Acad. Sci. U.S.A. · 2009
Patterns of somatic mutation in human cancer genomes. Nature · 2007
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
IgA Fc receptor (FcalphaR) cross-linking recruits tyrosine kinases, phosphoinositide kinases and serine/threonine kinases to glycolipid rafts. Biochem. J. · 2002
Early B cell factor is an activator of the B lymphoid kinase promoter in early B cell development. J. Immunol. · 1999
In vivo and in vitro specificity of protein tyrosine kinases for immunoglobulin G receptor (FcgammaRII) phosphorylation. Mol. Cell. Biol. · 1996
The protein product of the c-cbl protooncogene is the 120-kDa tyrosine-phosphorylated protein in Jurkat cells activated via the T cell antigen receptor. J. Biol. Chem. · 1994
Molecular cloning and chromosomal localization of the human homologue of a B-lymphocyte specific protein tyrosine kinase (blk). Oncogene · 1995
Molecular cloning, characterization, and chromosomal localization of a human lymphoid tyrosine kinase related to murine Blk. J. Immunol. · 1995

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