InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: BLK

Summary

InnateDB Protein

IDBP-7349.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

BLK

Protein Name

B lymphoid tyrosine kinase

Synonyms

MODY11;

Species

Homo sapiens

Ensembl Protein

ENSP00000259089

InnateDB Gene

IDBG-7345 (BLK)

Protein Structure

UniProt Annotation

Function

Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling. B-cell receptor (BCR) signaling requires a tight regulation of several protein tyrosine kinases and phosphatases, and associated coreceptors. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. 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. Specifically binds and phosphorylates CD79A at 'Tyr-188'and 'Tyr-199', as well as CD79B at 'Tyr-196' and 'Tyr- 207'. Phosphorylates also 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. Contributes also to BTK activation by indirectly stimulating BTK intramolecular autophosphorylation. 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. {ECO:0000269PubMed:19667185, ECO:0000269PubMed:8756631}.

Subcellular Localization

Cell membrane {ECO:0000250}; Lipid-anchor {ECO:0000250}. Note=Present and active in lipid rafts. Membrane location is required for the phosphorylation of CD79A and CD79B (By similarity). {ECO:0000250}.

Disease Associations

Maturity-onset diabetes of the young 11 (MODY11) [MIM:613375]: A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease. {ECO:0000269PubMed:19667185}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Expressed in lymphatic organs, pancreatic islets, Leydig cells, striate ducts of salivary glands and hair follicles. {ECO:0000269PubMed:19667185}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 23 experimentally validated interaction(s) in this database.
They are also associated with 4 interaction(s) predicted by orthology.

Experimentally validated
Total	23 [view]
Protein-Protein	20 [view]
Protein-DNA	3 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	4 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004715	non-membrane spanning protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups

Biological Process

GO:0006468	protein phosphorylation
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0032024	positive regulation of insulin secretion
GO:0035556	intracellular signal transduction
GO:0050853	B cell receptor signaling pathway

Cellular Component

GO:0005886

plasma membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR000980 SH2 domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR001452 SH3 domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR011511 Variant SH3 domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM