Protein detail
BTK
Tyrosine-protein kinase BTK (EC 2.7.10.2) (Agammaglobulinemia tyrosine kinase) (ATK) (B-cell progenitor kinase) (BPK) (Bruton tyrosine kinase)
Protein symbol BTK | UniProt ID | EVMP score 0.63 |
Frequency 9 | Transmembrane count | Protein classification Cancer-related genesDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPlasma proteinsPredicted intracellular proteins |
Basic Information
Protein Names
Tyrosine-protein kinase BTK (EC 2.7.10.2) (Agammaglobulinemia tyrosine kinase) (ATK) (B-cell progenitor kinase) (BPK) (Bruton tyrosine kinase)
Protein Class
Cancer-related genesDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPlasma proteinsPredicted intracellular proteins
Protein Function
- Predicted intracellular proteins
- ENZYME proteins:Transferases
- Human disease related genes:Endocrine and metabolic diseases:Hypothalamus and pituitary gland diseases
- Human disease related genes:Immune system diseases:Primary immunodeficiency
- Enzymes
- Cancer-related genes
- Kinases:Tyr protein kinases
- Disease related genes
- FDA approved drug targets:Small molecule drugs
Ensembl
Entrez Gene Symbol
Gene Synonym
AGMX1ATKIMD1PSCTK1XLA
Gene Description
Bruton tyrosine kinase
Chromosome
X
Position
101349338-101390796
Frequency
9
EVMP Score
0.63
Fluorescence & Localization
Tissue SpecificbrainCell SpecificNeutrophil progenitorsSingle-Nuclei Brain Specificcommitted oligodendrocyte precursor
Function & Pathway
Protein Function
- Predicted intracellular proteins
- ENZYME proteins:Transferases
- Human disease related genes:Endocrine and metabolic diseases:Hypothalamus and pituitary gland diseases
- Human disease related genes:Immune system diseases:Primary immunodeficiency
- Enzymes
- Cancer-related genes
- Kinases:Tyr protein kinases
- Disease related genes
- FDA approved drug targets:Small molecule drugs
Cellular Component
Molecular Function
- GO:0004713 protein tyrosine kinase activity
- GO:0004715 non-membrane spanning protein tyrosine kinase activity
- GO:0005515 protein binding
- GO:0005524 ATP binding
- GO:0005547 phosphatidylinositol-3,4,5-trisphosphate binding
- GO:0016004 phospholipase activator activity
- GO:0042802 identical protein binding
- GO:0043274 phospholipase binding
- GO:0046872 metal ion binding
Biological Process
KEGG
Reactome
- R-hsa-1280218 adaptive immune system
- R-hsa-983695 antigen activates b cell receptor bcr leading to generation of second messengers
- R-hsa-1236975 antigen processing cross presentation
- R-hsa-983169 class i mhc mediated antigen processing presentation
- R-hsa-2172127 dap12 interactions
- R-hsa-2424491 dap12 signaling
- R-hsa-5260271 diseases of immune system
- R-hsa-2871809 fceri mediated ca 2 mobilization
- R-hsa-2029480 fcgamma receptor fcgr dependent phagocytosis
- R-hsa-2454202 fc epsilon receptor fceri signaling
- R-hsa-416482 g alpha 12 13 signalling events
- R-hsa-416476 g alpha q signalling events
- R-hsa-397795 g protein beta gamma signalling
- R-hsa-5663205 infectious disease
- R-hsa-168249 innate immune system
- R-hsa-5603041 irak4 deficiency tlr2 4
- R-hsa-9658195 leishmania infection
- R-hsa-9664407 parasite infection
- R-hsa-9679191 potential therapeutics for sars
- R-hsa-5663213 rho gtpases activate wasps and waves
- R-hsa-195258 rho gtpase effectors
- R-hsa-9679506 sars cov infections
- R-hsa-372790 signaling by gpcr
- R-hsa-9716542 signaling by rho gtpases miro gtpases and rhobtb3
- R-hsa-983705 signaling by the b cell receptor bcr
- R-hsa-168898 toll like receptor cascades
- R-hsa-168179 toll like receptor tlr1 tlr2 cascade
- R-hsa-9824446 viral infection pathways
Canonical Pathways
- M83 Pid cdc42 reg pathway
- M241 Pid rac1 reg pathway
- M68 Pid rhoa reg pathway
Mediation Categories
Clinical-translation mediationFusion and delivery mediationImmune mediationReceptor-signaling mediation
Relations & Evidence
Enzyme-Mediated Modification
23 records.
| Substrate Gene Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| BTK | TLR9 | Q9NR96 | Y | 551 | phosphorylation | REACH_ProtMapperProtMapper | ProtMapper:26478008 |
| BTK | CSK | P41240 | Y | 551 | phosphorylation | Sparser_ProtMapperProtMapper | ProtMapper:10196129 |
| BTK | PRKCA | P17252 | S | 179 | phosphorylation | KEA | KEA:11598012 |
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Ligand-Receptor Signaling
12 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| receptor | receptor | OmniPath | No | Yes | No | No | No |
| intracellular | intracellular | ComPPI | No | No | No | No | No |
| intracellular | intracellular | GO_Intercell | No | No | No | No | No |
| intracellular | intracellular | UniProt_location | No | No | No | No | No |
| intracellular | intracellular | OmniPath | No | No | No | No | No |
| cell_adhesion | cell_adhesion | Cellinker | Yes | Yes | No | No | No |
| adhesion | adhesion | OmniPath | Yes | Yes | No | No | No |
| cell_adhesion | cell_adhesion | OmniPath | Yes | Yes | No | No | No |
| plasma_membrane | plasma_membrane | UniProt_location | No | No | No | No | No |
| plasma_membrane | plasma_membrane | Cellinker | No | No | No | No | No |
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Regulatory Interaction Network
30 records.
| Source Protein Symbol | Source UniProt ID | Target Protein Symbol | Target UniProt ID | Is Directed | Is Stimulation | Is Inhibition | Database | References |
|---|---|---|---|---|---|---|---|---|
| BTK | Q06187 | BMX | P51813 | Yes | Yes | No | HPRD_MIMPSIGNORProtMapperPhosphoSite_KEAphosphoELM_KEAPhosphoNetworksHPRDWangPhosphoSite_ProtMapperphosphoELM_MIMPPhosphoSite_MIMPMIMPiPTMnetPhosphoPointKEAHPRD_KEAphosphoELMSIGNOR_ProtMapperPhosphoSite | ProtMapper:12573241PhosphoSite:12573241phosphoELM:12573241KEA:12573241SIGNOR:12573241HPRD:12573241 |
| BTK | Q06187 | DAPP1 | Q9UN19 | Yes | Yes | No | phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetPhosphoPointSIGNORProtMapperHPRDPhosphoSite_KEAKEAHPRD_KEASIGNOR_ProtMapperHPRD-phos | ProtMapper:17389395HPRD-phos:17389395ProtMapper:19901323ProtMapper:11524430KEA:10880360SIGNOR:10880360SIGNOR:11524430HPRD:11524430KEA:11524430ProtMapper:10880360HPRD-phos:19901323HPRD-phos:10880360 |
| AKT1 | P31749 | BTK | Q06187 | Yes | No | Yes | PhosphoSite_norefSIGNORiPTMnetProtMapperPhosphoSitePhosphoSite_ProtMapper | SIGNOR:23754751PhosphoSite:23754751 |
| BTK | Q06187 | MDM2 | Q00987 | Yes | Yes | Yes | WangSIGNOR | SIGNOR:29290977 |
| GNAQ | P50148 | BTK | Q06187 | Yes | Yes | No | HPRDSIGNOR | HPRD:9770463SIGNOR:9305846 |
| COMPLEX:P27986_P42336 | BTK | Q06187 | Yes | Yes | No | SIGNOR | SIGNOR:10201980 | |
| PTPRG | P23470 | BTK | Q06187 | Yes | No | Yes | SIGNOR_ProtMapperSIGNORProtMapper | SIGNOR:25624455ProtMapper:25624455 |
| BTK | Q06187 | ITK | Q08881 | Yes | Yes | No | PhosphoNetworksphosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetPhosphoPointSIGNORProtMapperHPRDPhosphoSite_KEAKEAKinexus_KEAphosphoELM_KEAphosphoELMSIGNOR_ProtMapperPhosphoSite_ProtMapper | ProtMapper:12573241HPRD:8630736phosphoELM:12573241KEA:12573241SIGNOR:12573241HPRD:12445832HPRD:12573241HPRD:11598012HPRD:8629002 |
| ITK | Q08881 | BTK | Q06187 | Yes | No | Yes | phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetPhosphoPointSIGNORProtMapperHPRDPhosphoSite_KEAKEAKinexus_KEAHPRD_KEASIGNOR_ProtMapperHPRD-phosPhosphoSite_ProtMapper | HPRD-phos:11598012KEA:11598012ProtMapper:8629002HPRD-phos:12573241ProtMapper:8630736ProtMapper:12445832KEA:8630736KEA:12573241HPRD:12445832HPRD:8629002ProtMapper:11598012ProtMapper:12573241HPRD:8630736SIGNOR:12573241KEA:12445832HPRD:12573241HPRD:11598012KEA:8629002HPRD-phos:8629002ProtMapper:16497976HPRD-phos:8630736HPRD-phos:16497976HPRD-phos:12445832 |
| BTK | Q06187 | IKBA | P25963 | Yes | Yes | No | PhosphoNetworksPhosphoSite_norefProtMapperWangREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper | PhosphoSite:12167702PhosphoSite:12909638PhosphoSite:30887112ProtMapper:30887112 |
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Protein Complex Composition
7 records.
| Component Name | Component Gene Symbols | Component UniProt ID | Stoichiometry | Database | Database IDs | References |
|---|---|---|---|---|---|---|
| HT_SC_Cluster107 | IBTKRANRANGRFRCC1 | P18754P62826Q9HD47Q9P2D0 | 1:1:1:1 | Compleat | Compleat:HC2468 | |
| CSE1LIBTKKPNA4KPNB1NUP153NUTF2RANRANBP1RANBP3RCC1SNRPNUBCXPO1 | O00629O14980P0CG48P18754P43487P49790P55060P61970P62826P63162Q14974Q9H6Z4Q9P2D0 | 1:1:1:1:1:1:1:1:1:1:1:1:1 | NetworkBlastCompleat | Compleat:HC9631 | ||
| IBTKPOP7RPP25L | O75817Q8N5L8Q9P2D0 | 0:0:0 | hu.MAP | |||
| BTK | Q06187 | 2 | PDB | PDB:1k2pPDB:6yyfPDB:6yykPDB:6nzmPDB:6yygPDB:5zz4PDB:6tfpPDB:4nwmPDB:5bpyPDB:7l5pPDB:6tt2PDB:6x3oPDB:1btkPDB:8yvvPDB:1bwnPDB:6tsePDB:5fbnPDB:2z0pPDB:3p08PDB:4yhfPDB:6s90PDB:5jrsPDB:6tvnPDB:5xyzPDB:1b55PDB:6tuhPDB:5j87 | ||
| BIRC2BTK | Q06187Q13490 | 2:2 | PDB | PDB:6w8iPDB:8dsoPDB:6w7o | ||
| ANKRD54BTK | Q06187Q6NXT1 | 0:0 | hu.MAP2 | |||
| IBTKRPP25L | Q8N5L8Q9P2D0 | 0:0 | hu.MAP2 |
Isolation & Detection Technology
1 record.
| EV Isolation Method | Detection Method | Number of References | References |
|---|---|---|---|
| Protein Organic Solvent Precipitation | Mass Spectrometry | 1 | 32384937 |
Sequence, Structure & Domains
Sequences
Length
659
Mass
76,281
Sequence
MAAVILESIFLKRSQQKKKTSPLNFKKRLFLLTVHKLSYYEYDFERGRRGSKKGSIDVEKITCVETVVPEKNPPPERQIPRRGEESSEMEQISIIERFPYPFQVVYDEGPLYVFSPTEELRKRWIHQLKNVIRYNSDLVQKYHPCFWIDGQYLCCSQTAKNAMGCQILENRNGSLKPGSSHRKTKKPLPPTPEEDQILKKPLPPEPAAAPVSTSELKKVVALYDYMPMNANDLQLRKGDEYFILEESNLPWWRARDKNGQEGYIPSNYVTEAEDSIEMYEWYSKHMTRSQAEQLLKQEGKEGGFIVRDSSKAGKYTVSVFAKSTGDPQGVIRHYVVCSTPQSQYYLAEKHLFSTIPELINYHQHNSAGLISRLKYPVSQQNKNAPSTAGLGYGSWEIDPKDLTFLKELGTGQFGVVKYGKWRGQYDVAIKMIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANGCLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSSVGSKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKMPYERFTNSETAEHIAQGLRLYRPHLASEKVYTIMYSCWHEKADERPTFKILLSNILDVMDEES
Alternative Products
Event=Alternative promoter usage; Named isoforms=2; Name=BTK-A; IsoId=Q06187-1; Sequence=Displayed; Name=BTK-C; IsoId=Q06187-2; Sequence=VSP_053838
Alternative Sequence
1; M -> MASWSIQQMVIGCPLCGRHCSGGEHTGELQKEEAM (in isoform BTK-C)
3D Structural Models
Turn
44..47; 153..155; 212..215; 257..259; 266..268; 340..342; 422..424; 434..436; 524..526; 592..594; 597..600
Helix
58..60; 75..77; 93..96; 118..132; 288..298; 355..362; 393..395; 399..401; 439..450; 482..487; 489..491; 495..514; 542..545; 549..551; 561..563; 566..571; 576..591; 603..611; 624..632; 638..640; 644..657
Beta Strand
5..13; 15..17; 19..21; 25..32; 34..43; 48..57; 63..66; 82..85; 100..106; 109..117; 140..142; 149..152; 165..167; 218..223; 228..232; 240..242; 248..252; 261..265; 279..282; 303..308; 310..313; 315..321; 330..335; 337..339; 344..347; 352..354; 369..371; 373..376; 402..410; 412..414; 415..421; 425..431; 460..464; 466..469; 471..474; 527..529; 535..537; 556..559
3D Structure
NMR spectroscopy (4); X-ray crystallography (129)
Domain & Motif Annotations
Motif
581..588; CAV1-binding
Zinc Finger
135..171; Btk-type
Domain (CC)
The PH domain mediates the binding to inositol polyphosphate and phosphoinositides, leading to its targeting to the plasma membrane. It is extended in the BTK kinase family by a region designated the TH (Tec homology) domain, which consists of about 80 residues preceding the SH3 domain.
Domain (FT)
3..133; PH; 214..274; SH3; 281..377; SH2; 402..655; Protein kinase
Region
12..24; Inositol-(1,3,4,5)-tetrakisphosphate 1-binding; 171..210; Disordered
Protein Families
- Protein kinase superfamily
- Tyr protein kinase family
- TEC subfamily
Sequence Similarities
Belongs to the protein kinase superfamily. Tyr protein kinase family. TEC subfamily.
Clinical Relevance
Disease Involvement
Cancer-related genesDisease variantDwarfismFDA approved drug targets
Biomarker
Phase 2; Approved
Drug Targets
FDA approved drug targets
Drugs
IBRUTINIBEDRALBRUTINIBNULLBRANEBRUTINIBZANUBRUTINIBCENISERTIBACALABRUTINIBPF-06651600HG2+VANDETANIBVECABRUTINIBRILZABRUTINIBPIRTOBRUTINIBALISERTIBBARASERTIB-HQPAFENEBRUTINIBSPEBRUTINIBZM447439POSELTINIBELSUBRUTINIBABIVERTINIBPD-0166285DOVITINIBMSC-2364447BTK INHIBITOR DTRMWXHS-12EVOBRUTINIBBMS-986142TIRABRUTINIBPP2MLN-8054SPEBRUTINIB BESYLATENVP-TAE684NEMTABRUTINIBTOLEBRUTINIBENTRECTINIBILORASERTIBDASATINIB ANHYDROUSBTK INHIBITORRG-1530TAK-020ABIVERTINIB MALEATEBIIB068TAMATINIBHESPERADINBTK INHIBITOR TL-895ORELABRUTINIBACALABRUTINIB MALEATECHEMBL:CHEMBL1997335PI3K-DELTA INHIBITOR AMG 319PF-562271TOZASERTIBREMIBRUTINIB
Interaction Protein
ENSG00000005700ENSG00000095585ENSG00000100124ENSG00000131370ENSG00000177885ENSG00000263001
Interaction Count
6
Interaction Dataset
intact_biogridbiogrid_bioplex