P35991

EV
Gene name
Btk (Bpk)
Protein name
Tyrosine-protein kinase BTK
Names
EC 2.7.10.2 , Agammaglobulinemia tyrosine kinase , ATK , B-cell progenitor kinase , BPK , Bruton tyrosine kinase , Kinase EMB
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:12229
EC number
2.7.10.2: Protein-tyrosine kinases
Protein Class
TYROSINE-PROTEIN KINASE (PTHR24418)

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)

214-378 (SH3 and SH2 domain) EV

Target domain

397-652 (Protein kinase domain)

Relief mechanism

PTM

Assay

Structural analysis

4-171 (Pleckstrin homology and Tec homology domain) EV

Target domain

397-652 (Protein kinase domain)

Relief mechanism

PTM

Assay

Structural analysis

Accessory elements

538-562 (Activation loop from InterPro)

Target domain

397-652 (Protein kinase domain)

Relief mechanism

Assay

References

Autoinhibited structure

Activated structure

8 structures for P35991

Entry ID Method Resolution Chain Position Source
4XI2 X-ray 260 A A 214-659 PDB
6MNY X-ray 280 A A/B 384-659 PDB
8FD9 X-ray 170 A A 396-659 PDB
8FF0 X-ray 260 A A 396-659 PDB
8GMB X-ray 340 A A 1-659 PDB
8S93 X-ray 210 A PDB
8S9F X-ray 260 A A/B 382-659 PDB
AF-P35991-F1 Predicted AlphaFoldDB

32 variants for P35991

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3389541818 25 F>L No EVA
28 R>C XID; prevents interaction with ARID3A [UniProt] No
rs3389573169 36 K>Q No EVA
rs3411955871 44 F>SFGKLTPRSKSYS* No EVA
rs3389584353 91 Q>* No EVA
rs3389587595 138 L>Q No EVA
rs3389568336 218 K>M No EVA
rs3389576101 227 P>L No EVA
rs3389541792 262 G>R No EVA
rs3389576158 277 E>K No EVA
rs3411996247 290 Q>H No EVA
rs3411177996 308 D>V No EVA
rs3412197297 308 D>Y No EVA
rs3412064298 311 K>* No EVA
rs3410567339 311 K>I No EVA
rs3412191238 311 K>N No EVA
rs3412282049 334 Y>F No EVA
rs3389573118 341 Q>* No EVA
rs3411996267 344 Y>* No EVA
rs3389573103 346 L>M No EVA
rs263268603 353 S>N No EVA
rs3389573164 375 Y>* No EVA
rs3409324223 405 L>* No EVA
rs3412092431 405 L>M No EVA
rs3412197316 466 K>I No EVA
rs3412092432 469 P>T No EVA
rs3411616507 470 I>S No EVA
rs3389541786 471 F>S No EVA
rs3389587714 524 A>V No EVA
rs3389541846 553 S>N No EVA
rs229428789 580 I>V No EVA
rs3389531712 633 C>W No EVA

No associated diseases with P35991

4 regional properties for P35991

Type Name Position InterPro Accession
domain Protein kinase domain 14 - 272 IPR000719
active_site Serine/threonine-protein kinase, active site 132 - 144 IPR008271
domain Calcium/calmodulin-dependent protein kinase II, association-domain 380 - 507 IPR013543
binding_site Protein kinase, ATP binding site 20 - 43 IPR017441

Functions

Description
EC Number 2.7.10.2 Protein-tyrosine kinases
Subcellular Localization
  • Cytoplasm
  • Cell membrane ; Peripheral membrane protein
  • Nucleus
  • Membrane raft
  • In steady state, BTK is predominantly cytosolic
  • Following B-cell receptor (BCR) engagement by antigen, translocates to the plasma membrane through its PH domain
  • Plasma membrane localization is a critical step in the activation of BTK
  • A fraction of BTK also shuttles between the nucleus and the cytoplasm, and nuclear export is mediated by the nuclear export receptor CRM1
PANTHER Family PTHR24418 TYROSINE-PROTEIN KINASE
PANTHER Subfamily PTHR24418:SF92 TYROSINE-PROTEIN KINASE BTK
PANTHER Protein Class non-receptor tyrosine protein kinase
PANTHER Pathway Category B cell activation
Btk

7 GO annotations of cellular component

Name Definition
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytoplasmic vesicle A vesicle found in the cytoplasm of a cell.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
membrane raft Any of the small (10-200 nm), heterogeneous, highly dynamic, sterol- and sphingolipid-enriched membrane domains that compartmentalize cellular processes. Small rafts can sometimes be stabilized to form larger platforms through protein-protein and protein-lipid interactions.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
perinuclear region of cytoplasm Cytoplasm situated near, or occurring around, the nucleus.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.

8 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
identical protein binding Binding to an identical protein or proteins.
metal ion binding Binding to a metal ion.
non-membrane spanning protein tyrosine kinase activity Catalysis of the reaction
phosphatidylinositol-3,4,5-trisphosphate binding Binding to phosphatidylinositol-3,4,5-trisphosphate, a derivative of phosphatidylinositol in which the inositol ring is phosphorylated at the 3', 4' and 5' positions.
phospholipase activator activity Binds to and increases the activity of a phospholipase, an enzyme that catalyzes of the hydrolysis of a glycerophospholipid.
phospholipase binding Binding to a phospholipase.
protein tyrosine kinase activity Catalysis of the reaction

34 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).
apoptotic process A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died.
B cell affinity maturation The process in which B cells produce antibodies with increased antigen affinity. This is accomplished by somatic hypermutation and selection for B cells which produce higher affinity antibodies to antigen.
B cell receptor signaling pathway The series of molecular signals initiated by the cross-linking of an antigen receptor on a B cell.
cell maturation The cellular developmental process, independent of morphogenetic (shape) change, that is required for a specific cell to attain its fully functional state.
cellular response to interleukin-7 Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interleukin-7 stimulus.
cellular response to molecule of fungal origin Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus by molecules of fungal origin such as chito-octamer oligosaccharide.
cellular response to reactive oxygen species Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a reactive oxygen species stimulus. Reactive oxygen species include singlet oxygen, superoxide, and oxygen free radicals.
eosinophil homeostasis The process of regulating the proliferation and elimination of eosinophils such that the total number of eosinophils within a whole or part of an organism is stable over time in the absence of an outside stimulus.
histamine secretion by mast cell The regulated release of histamine by a mast cell or group of mast cells.
innate immune response Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens.
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.
monocyte proliferation The expansion of a monocyte population by cell division.
negative regulation of B cell activation Any process that stops, prevents, or reduces the frequency, rate or extent of B cell activation.
negative regulation of B cell proliferation Any process that stops, prevents or reduces the rate or extent of B cell proliferation.
negative regulation of cytokine production Any process that stops, prevents, or reduces the rate of production of a cytokine.
negative regulation of interleukin-10 production Any process that stops, prevents, or reduces the frequency, rate, or extent of interleukin-10 production.
negative regulation of leukocyte proliferation Any process that stops, prevents, or reduces the frequency, rate or extent of leukocyte proliferation.
neutrophil homeostasis The process of regulating the proliferation and elimination of neutrophils such that the total number of neutrophils within a whole or part of an organism is stable over time in the absence of an outside stimulus.
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.
positive regulation of B cell proliferation Any process that activates or increases the rate or extent of B cell proliferation.
positive regulation of immunoglobulin production Any process that activates or increases the frequency, rate, or extent of immunoglobulin production.
positive regulation of interleukin-17A production Any process that activates or increases the frequency, rate or extent of interleukin-17A production.
positive regulation of interleukin-6 production Any process that activates or increases the frequency, rate, or extent of interleukin-6 production.
positive regulation of NLRP3 inflammasome complex assembly Any process that activates or increases the frequency, rate or extent of NLRP3 inflammasome complex assembly.
positive regulation of phagocytosis Any process that activates or increases the frequency, rate or extent of phagocytosis.
positive regulation of synoviocyte proliferation Any process that activates or increases the frequency, rate or extent of synoviocyte proliferation.
positive regulation of tumor necrosis factor production Any process that activates or increases the frequency, rate or extent of tumor necrosis factor production.
positive regulation of type I hypersensitivity Any process that activates or increases the frequency, rate or extent of type I hypersensitivity, a type of inflammatory response.
positive regulation of type III hypersensitivity Any process that activates or increases the frequency, rate or extent of type III hypersensitivity, a type of inflammatory response.
proteoglycan catabolic process The chemical reactions and pathways resulting in the breakdown of proteoglycans, any glycoprotein in which the carbohydrate units are glycosaminoglycans.
response to lipopolysaccharide Any process that results in a change in state or activity of an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria.
response to organic substance Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an organic substance stimulus.
T cell receptor signaling pathway The series of molecular signals initiated by the cross-linking of an antigen receptor on a T cell.

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
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
Q8JH64 BTK Tyrosine-protein kinase BTK 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
P42680 TEC Tyrosine-protein kinase Tec 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
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
P05480 Src Proto-oncogene tyrosine-protein kinase Src Mus musculus (Mouse) EV
P06240 Lck Proto-oncogene tyrosine-protein kinase LCK Mus musculus (Mouse) SS
P14234 Fgr Tyrosine-protein kinase Fgr Mus musculus (Mouse) SS
P16277 Blk Tyrosine-protein kinase Blk Mus musculus (Mouse) SS
P41241 Csk Tyrosine-protein kinase CSK Mus musculus (Mouse) EV
Q03526 Itk Tyrosine-protein kinase ITK/TSK Mus musculus (Mouse) SS
Q04736 Yes1 Tyrosine-protein kinase Yes Mus musculus (Mouse) SS
Q64434 Ptk6 Protein-tyrosine kinase 6 Mus musculus (Mouse) SS
Q922K9 Frk Tyrosine-protein kinase FRK 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
P25911 Lyn Tyrosine-protein kinase Lyn Mus musculus (Mouse) EV
P39688 Fyn Tyrosine-protein kinase Fyn Mus musculus (Mouse) SS
P08103 Hck Tyrosine-protein kinase HCK Mus musculus (Mouse) SS
P24604 Tec Tyrosine-protein kinase Tec Mus musculus (Mouse) SS
P41242 Matk Megakaryocyte-associated tyrosine-protein kinase Mus musculus (Mouse) SS
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
MAAVILESIF LKRSQQKKKT SPLNFKKRLF LLTVHKLSYY EYDFERGRRG SKKGSIDVEK
70 80 90 100 110 120
ITCVETVIPE KNPPPERQIP RRGEESSEME QISIIERFPY PFQVVYDEGP LYVFSPTEEL
130 140 150 160 170 180
RKRWIHQLKN VIRYNSDLVQ KYHPCFWIDG QYLCCSQTAK NAMGCQILEN RNGSLKPGSS
190 200 210 220 230 240
HRKTKKPLPP TPEEDQILKK PLPPEPTAAP ISTTELKKVV ALYDYMPMNA NDLQLRKGEE
250 260 270 280 290 300
YFILEESNLP WWRARDKNGQ EGYIPSNYIT EAEDSIEMYE WYSKHMTRSQ AEQLLKQEGK
310 320 330 340 350 360
EGGFIVRDSS KAGKYTVSVF AKSTGEPQGV IRHYVVCSTP QSQYYLAEKH LFSTIPELIN
370 380 390 400 410 420
YHQHNSAGLI SRLKYPVSKQ NKNAPSTAGL GYGSWEIDPK DLTFLKELGT GQFGVVKYGK
430 440 450 460 470 480
WRGQYDVAIK MIREGSMSED EFIEEAKVMM NLSHEKLVQL YGVCTKQRPI FIITEYMANG
490 500 510 520 530 540
CLLNYLREMR HRFQTQQLLE MCKDVCEAME YLESKQFLHR DLAARNCLVN DQGVVKVSDF
550 560 570 580 590 600
GLSRYVLDDE YTSSVGSKFP VRWSPPEVLM YSKFSSKSDI WAFGVLMWEI YSLGKMPYER
610 620 630 640 650
FTNSETAEHI AQGLRLYRPH LASERVYTIM YSCWHEKADE RPSFKILLSN ILDVMDEES