Descriptions

Bruton’s tyrosine kinase (BTK) is a non-receptor tyrosine kinase belonging to the TEC family, and is expressed primarily in B cells and myeloid cells, where it functions downstream of receptors including the B-cell receptor, Fc receptors, and toll-like receptors. BTK is autoinhibited by its SH3 and SH2 domains, forming a compact autoinhibitory conformation on the distal surface of the kinase domain. Additionally, there exists another autoinhibitory interface on the activation loop face of the kinase domain, which is occupied by the Pleckstrin homology and Tec homology (PHTH) domain. B-cell receptor engagement lead to BTK activation (via phosphorylation on Y551 in the activation loop), which results in the direct phosphorylation and activation of phospholipase C gamma 2 triggering calcium flux and subsequent regulation of gene transcription.

Autoinhibitory domains (AIDs)

Target domain

364-619 (Protein kinase domain)

Relief mechanism

PTM

Assay

Target domain

364-619 (Protein kinase domain)

Relief mechanism

PTM

Assay

Target domain

369-622 (Kinase domain)

Relief mechanism

Assay

Accessory elements

505-529 (Activation loop from InterPro)

Target domain

369-622 (Protein kinase domain)

Relief mechanism

Assay

Autoinhibited structure

Activated structure

2 structures for P24604

Entry ID Method Resolution Chain Position Source
1GL5 NMR - A 181-244 PDB
AF-P24604-F1 Predicted AlphaFoldDB

No variants for P24604

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for P24604

No associated diseases with P24604

10 regional properties for P24604

Type Name Position InterPro Accession
domain Protein kinase domain 369 - 622 IPR000719
domain SH2 domain 244 - 344 IPR000980
domain Serine-threonine/tyrosine-protein kinase, catalytic domain 369 - 617 IPR001245
domain SH3 domain 178 - 238 IPR001452
conserved_site Zinc finger, Btk motif 102 - 149 IPR001562
domain Pleckstrin homology domain 4 - 113 IPR001849
active_site Tyrosine-protein kinase, active site 484 - 496 IPR008266
binding_site Protein kinase, ATP binding site 375 - 397 IPR017441
domain Tyrosine-protein kinase, catalytic domain 369 - 618 IPR020635
domain Tyrosine-protein kinase Tec, SH3 domain 182 - 236 IPR035572

Functions

Description
EC Number 2.7.10.2 Protein-tyrosine kinases
Subcellular Localization
  • Cytoplasm
  • Cell membrane; Peripheral membrane protein
  • Cytoplasm, cytoskeleton
  • Following B-cell or T-cell receptors activation by antigen, translocates to the plasma membrane through its PH domain
  • Thrombin and integrin engagement induces translocation of TEC to the cytoskeleton during platelet activation
  • In cardiac myocytes, assumes a diffuse intracellular localization under basal conditions but is recruited to striated structures upon various stimuli, including ATP (By similarity)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

4 GO annotations of cellular component

Name Definition
cell-cell junction A cell junction that forms a connection between two or more cells of an organism; excludes direct cytoplasmic intercellular bridges, such as ring canals in insects.
cytoskeleton A cellular structure that forms the internal framework of eukaryotic and prokaryotic cells. The cytoskeleton includes intermediate filaments, microfilaments, microtubules, the microtrabecular lattice, and other structures characterized by a polymeric filamentous nature and long-range order within the cell. The various elements of the cytoskeleton not only serve in the maintenance of cellular shape but also have roles in other cellular functions, including cellular movement, cell division, endocytosis, and movement of organelles.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.

4 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
lipid binding Binding to a lipid.
metal ion binding Binding to a metal ion.
non-membrane spanning protein tyrosine kinase activity Catalysis of the reaction

8 GO annotations of biological process

Name Definition
adaptive immune response An immune response mediated by cells expressing specific receptors for antigens produced through a somatic diversification process, and allowing for an enhanced secondary response to subsequent exposures to the same antigen (immunological memory).
B cell receptor signaling pathway The series of molecular signals initiated by the cross-linking of an antigen receptor on a B cell.
integrin-mediated signaling pathway The series of molecular signals initiated by an extracellular ligand binding to an integrin on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
intracellular signal transduction The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell.
phosphorylation The process of introducing a phosphate group into a molecule, usually with the formation of a phosphoric ester, a phosphoric anhydride or a phosphoric amide.
regulation of platelet activation Any process that modulates the rate or frequency of platelet activation. Platelet activation is a series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue.
T cell receptor signaling pathway The series of molecular signals initiated by the cross-linking of an antigen receptor on a T cell.
tissue regeneration The regrowth of lost or destroyed tissues.

86 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
A0JNB0 FYN Tyrosine-protein kinase Fyn Bos taurus (Bovine) SS
Q0VBZ0 CSK Tyrosine-protein kinase CSK Bos taurus (Bovine) SS
Q3ZC95 BTK Tyrosine-protein kinase Bos taurus (Bovine) EV SS
P42683 LCK Proto-oncogene tyrosine-protein kinase LCK Gallus gallus (Chicken) SS
P41239 CSK Tyrosine-protein kinase CSK Gallus gallus (Chicken) SS
P00523 SRC Proto-oncogene tyrosine-protein kinase Src Gallus gallus (Chicken) EV
Q02977 YRK Proto-oncogene tyrosine-protein kinase Yrk Gallus gallus (Chicken) SS
Q8JH64 BTK Tyrosine-protein kinase BTK Gallus gallus (Chicken) SS
P09324 YES1 Tyrosine-protein kinase Yes Gallus gallus (Chicken) SS
Q05876 FYN Tyrosine-protein kinase Fyn Gallus gallus (Chicken) SS
Q75R65 JAK2 Tyrosine-protein kinase JAK2 Gallus gallus (Chicken) SS
Q24592 hop Tyrosine-protein kinase hopscotch Drosophila melanogaster (Fruit fly) PR
Q9V9J3 Src42A Tyrosine-protein kinase Src42A Drosophila melanogaster (Fruit fly) SS
P00528 Src64B Tyrosine-protein kinase Src64B Drosophila melanogaster (Fruit fly) SS
P08630 Btk Tyrosine-protein kinase Btk Drosophila melanogaster (Fruit fly) SS
P41240 CSK Tyrosine-protein kinase CSK Homo sapiens (Human) SS
P51451 BLK Tyrosine-protein kinase Blk Homo sapiens (Human) SS
P06239 LCK Tyrosine-protein kinase Lck Homo sapiens (Human) EV
P23458 JAK1 Tyrosine-protein kinase JAK1 Homo sapiens (Human) SS
P06241 FYN Tyrosine-protein kinase Fyn Homo sapiens (Human) SS
P51813 BMX Cytoplasmic tyrosine-protein kinase BMX Homo sapiens (Human) SS
P12931 SRC Proto-oncogene tyrosine-protein kinase Src Homo sapiens (Human) EV
P09769 FGR Tyrosine-protein kinase Fgr Homo sapiens (Human) SS
O60674 JAK2 Tyrosine-protein kinase JAK2 Homo sapiens (Human) EV
P42679 MATK Megakaryocyte-associated tyrosine-protein kinase Homo sapiens (Human) SS
P52333 JAK3 Tyrosine-protein kinase JAK3 Homo sapiens (Human) SS
Q08881 ITK Tyrosine-protein kinase ITK/TSK Homo sapiens (Human) EV
P07948 LYN Tyrosine-protein kinase Lyn Homo sapiens (Human) SS
P29597 TYK2 Non-receptor tyrosine-protein kinase TYK2 Homo sapiens (Human) EV
Q13882 PTK6 Protein-tyrosine kinase 6 Homo sapiens (Human) EV
P08631 HCK Tyrosine-protein kinase HCK Homo sapiens (Human) EV
P07947 YES1 Tyrosine-protein kinase Yes Homo sapiens (Human) SS
P42685 FRK Tyrosine-protein kinase FRK Homo sapiens (Human) EV
Q06187 BTK Tyrosine-protein kinase BTK Homo sapiens (Human) EV
P42680 TEC Tyrosine-protein kinase Tec Homo sapiens (Human) SS
Q9R117 Tyk2 Non-receptor tyrosine-protein kinase TYK2 Mus musculus (Mouse) SS
Q62137 Jak3 Tyrosine-protein kinase JAK3 Mus musculus (Mouse) SS
Q62120 Jak2 Tyrosine-protein kinase JAK2 Mus musculus (Mouse) EV
P52332 Jak1 Tyrosine-protein kinase JAK1 Mus musculus (Mouse) SS
P48025 Syk Tyrosine-protein kinase SYK Mus musculus (Mouse) SS
P43404 Zap70 Tyrosine-protein kinase ZAP-70 Mus musculus (Mouse) SS
Q64434 Ptk6 Protein-tyrosine kinase 6 Mus musculus (Mouse) SS
P14234 Fgr Tyrosine-protein kinase Fgr Mus musculus (Mouse) SS
P25911 Lyn Tyrosine-protein kinase Lyn Mus musculus (Mouse) EV
P39688 Fyn Tyrosine-protein kinase Fyn Mus musculus (Mouse) SS
P05480 Src Proto-oncogene tyrosine-protein kinase Src Mus musculus (Mouse) EV
P06240 Lck Proto-oncogene tyrosine-protein kinase LCK Mus musculus (Mouse) SS
P16277 Blk Tyrosine-protein kinase Blk Mus musculus (Mouse) SS
P08103 Hck Tyrosine-protein kinase HCK Mus musculus (Mouse) SS
Q04736 Yes1 Tyrosine-protein kinase Yes Mus musculus (Mouse) SS
Q922K9 Frk Tyrosine-protein kinase FRK Mus musculus (Mouse) SS
Q03526 Itk Tyrosine-protein kinase ITK/TSK Mus musculus (Mouse) SS
P35991 Btk Tyrosine-protein kinase BTK Mus musculus (Mouse) EV
P41242 Matk Megakaryocyte-associated tyrosine-protein kinase Mus musculus (Mouse) SS
P41241 Csk Tyrosine-protein kinase CSK Mus musculus (Mouse) EV
Q9QVP9 Ptk2b Protein-tyrosine kinase 2-beta Mus musculus (Mouse) PR
P34152 Ptk2 Focal adhesion kinase 1 Mus musculus (Mouse) SS
Q99ML2 Tnk1 Non-receptor tyrosine-protein kinase TNK1 Mus musculus (Mouse) PR
O54967 Tnk2 Activated CDC42 kinase 1 Mus musculus (Mouse) SS
P70451 Fer Tyrosine-protein kinase Fer Mus musculus (Mouse) PR
Q6J9G1 Styk1 Tyrosine-protein kinase STYK1 Mus musculus (Mouse) PR
P00520 Abl1 Tyrosine-protein kinase ABL1 Mus musculus (Mouse) EV
Q62270 Srms Tyrosine-protein kinase Srms Mus musculus (Mouse) SS
Q4JIM5 Abl2 Tyrosine-protein kinase ABL2 Mus musculus (Mouse) SS
A1Y2K1 FYN Tyrosine-protein kinase Fyn Sus scrofa (Pig) SS
O19064 JAK2 Tyrosine-protein kinase JAK2 Sus scrofa (Pig) SS
Q62662 Frk Tyrosine-protein kinase FRK Rattus norvegicus (Rat) SS
Q62844 Fyn Tyrosine-protein kinase Fyn Rattus norvegicus (Rat) SS
Q07014 Lyn Tyrosine-protein kinase Lyn Rattus norvegicus (Rat) SS
P50545 Hck Tyrosine-protein kinase HCK Rattus norvegicus (Rat) SS
Q9WUD9 Src Proto-oncogene tyrosine-protein kinase Src Rattus norvegicus (Rat) SS
Q01621 Lck Proto-oncogene tyrosine-protein kinase LCK Rattus norvegicus (Rat) SS
Q6P6U0 Fgr Tyrosine-protein kinase Fgr Rattus norvegicus (Rat) SS
Q62689 Jak2 Tyrosine-protein kinase JAK2 Rattus norvegicus (Rat) SS
Q63272 Jak3 Tyrosine-protein kinase JAK3 Rattus norvegicus (Rat) SS
P32577 Csk Tyrosine-protein kinase CSK Rattus norvegicus (Rat) SS
P41243 Matk Megakaryocyte-associated tyrosine-protein kinase Rattus norvegicus (Rat) SS
F1LM93 Yes1 Tyrosine-protein kinase Yes Rattus norvegicus (Rat) SS
O45539 src-2 Tyrosine protein-kinase src-2 Caenorhabditis elegans SS
G5ECJ6 csk-1 Tyrosine-protein kinase csk-1 Caenorhabditis elegans SS
G5EE56 src-1 Tyrosine protein-kinase src-1 Caenorhabditis elegans SS
A1A5H8 yes1 Tyrosine-protein kinase yes Danio rerio (Zebrafish) (Brachydanio rerio) SS
F1RDG9 fynb Tyrosine-protein kinase fynb Danio rerio (Zebrafish) (Brachydanio rerio) SS
O12990 jak1 Tyrosine-protein kinase JAK1 Danio rerio (Zebrafish) (Brachydanio rerio) PR
Q1JPZ3 src Proto-oncogene tyrosine-protein kinase Src Danio rerio (Zebrafish) (Brachydanio rerio) SS
Q6EWH2 fyna Tyrosine-protein kinase fyna Danio rerio (Zebrafish) (Brachydanio rerio) SS
10 20 30 40 50 60
MNFNTILEEI LIKRSQQKKK TSLLNYKERL CVLPKSVLSY YEGRAEKKYR KGVIDISKIK
70 80 90 100 110 120
CVEIVKNDDG VIPCQNKFPF QVVHDANTLY IFAPSPQSRD RWVKKLKEEI KNNNNIMIKY
130 140 150 160 170 180
HPKFWADGSY QCCRQTEKLA PGCEKYNLFE SSIRKTLPPA PEIKKRRPPP PIPPEEENTE
190 200 210 220 230 240
EIVVAMYDFQ ATEAHDLRLE RGQEYIILEK NDLHWWRARD KYGSEGYIPS NYVTGKKSNN
250 260 270 280 290 300
LDQYEWYCRN TNRSKAEQLL RTEDKEGGFM VRDSSQPGLY TVSLYTKFGG EGSSGFRHYH
310 320 330 340 350 360
IKETATSPKK YYLAEKHAFG SIPEIIEYHK HNAAGLVTRL RYPVSTKGKN APTTAGFSYD
370 380 390 400 410 420
KWEINPSELT FMRELGSGLF GVVRLGKWRA QYKVAIKAIR EGAMCEEDFI EEAKVMMKLT
430 440 450 460 470 480
HPKLVQLYGV CTQQKPIYIV TEFMERGCLL NFLRQRQGHF SRDMLLSMCQ DVCEGMEYLE
490 500 510 520 530 540
RNSFIHRDLA ARNCLVNEAG VVKVSDFGMA RYVLDDQYTS SSGAKFPVKW CPPEVFNYSR
550 560 570 580 590 600
FSSKSDVWSF GVLMWEIFTE GRMPFEKNTN YEVVTMVTRG HRLHRPKLAT KYLYEVMLRC
610 620
WQERPEGRPS LEDLLRTIDE LVECEETFGR