Bioinformatics study on Bruton's Tyrosine Kinase (BTK)

Introduction

Bruton's agammaglobulinemia tyrosine kinase (Btk) is a cytoplasmic tyrosine kinase important in B-lymphocyte development, differentiation, and signaling. Btk is a member of the Tec family of kinases. Mutations in the Btk gene lead to X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (Xid) in mice. Activation of Btk triggers a cascade of signaling events that culminates in the generation of calcium mobilization and fluxes, cytoskeletal rearrangements, and transcriptional regulation involving nuclear factor-κB (NF-κB) and nuclear factor of activated T cells (NFAT). In B cells, NF-κB was shown to bind to the Btk promoter and induce transcription, whereas the B-cell receptor-dependent NF-κB signaling pathway requires functional Btk.

Gene Overview

The BTK gene consists of 19 exons and spans approximately 37.5 kb on the human X chromosome.

Gene tree

Signaling Pathway

Over 800 mutations affecting Btk have been reported to the international mutation database designated BTKbase

BTKbase

BTK mRNA

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Splicing prediction (GENSCAN)

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BTK promoter

Regulation of expression

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Regulation of expression (zoomed to upstream region)

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mRNA Secondary Structure ( Vienna RNA Package)

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BTK expression in tissues ( BioGPS)

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BTK expression in cell lines ( BioGPS)

Protein stucture

Protein name: Tyrosine-protein kinase BTK

Organism: Homo sapiens (Human)

Sequence length: 659 AA.

Subcellular location: Cytoplasm, Membrane, Nucleus

Catalytic activity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate

Belongs to the protein kinase superfamily

Domains: Contains 1 Btk-type zinc finger.

Contains 1 PH domain.

Contains 1 protein kinase domain.

Contains 1 SH2 domain.

Contains 1 SH3 domain.

The 3D structure of BTK is still unknown.

Some of the domain of BTK:

Crystal structure of PH domain and BTK motif of Bruton's tyrosine kinase

Single crystal X-ray diffraction, resolution 1.60Å

protein kinase domain.

SH2 domain

Sh3 domain

Protein similarity

Alignments

Protein Interactors