1K2P,3GEN,3PIX


Conserved Protein Domain Family
PTKc_Btk_Bmx

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cd05113: PTKc_Btk_Bmx 
Click on image for an interactive view with Cn3D
Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow kinase on the X chromosome
PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Btk and Bmx (also named Etk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Btk contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor, leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. Bmx is primarily expressed in bone marrow and the arterial endothelium, and plays an important role in ischemia-induced angiogenesis. It facilitates arterial growth, capillary formation, vessel maturation, and bone marrow-derived endothelial progenitor cell mobilization. The Btk/Bmx subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.
Statistics
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PSSM-Id: 173657
Aligned: 6 rows
Threshold Bit Score: 512.503
Created: 12-Jun-2007
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 16 residues -Click on image for an interactive view with Cn3D
Feature 1:ATP binding site [chemical binding site]
Evidence:
  • Structure:3GEN; Human Btk tyr kinase binds Pyrrolopyrimidine-containing inhibitor; contacts at 4A.
  • Structure:3PIX; Human Btk tyr kinase binds inhibitor, Compound 1; contacts at 4A.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                #       #           # #                  #                      # ###
1K2P_B      1 IDPKDLTFLKELGTGQFGVVKYGKWrgqYDVAIKMIKEGSmsEDEFIEEAKVMMNLSHEKLVQLYGVCTkqrPIFIITEY 80  human
P51813    412 LKREEITLLKELGSGQFGVVQLGKWkgqYDVAVKMIKEGSmsEDEFFQEAQTMMKLSHPKLVKFYGVCSkeyPIYIVTEY 491 human
Q8JH64    395 IDPKDLTFLKELGTGQFGVVKYGKWrgqYNVAIKMIREGSmsEDEFIDEAKVMMNLSHEKLVQLYGVCTkqrPIFIITEY 474 chicken
CAC44628  372 IDPRHLTFIKDLGTGQFGVVKYGKWqgkHDVAIKMIKEGSmsEDDFIEEAKIMMKLHHENLVQLYGVCTtqrPIYIVTEF 451 torafugu
3GEN_A     21 IDPKDLTFLKELGTGQFGVVKYGKWrgqYDVAIKMIKEGSmsEDEFIEEAKVMMNLSHEKLVQLYGVCTkqrPIFIITEY 100 human
3PIX_A     12 IDPKDLTFLKELGTGQFGVVKYGKWrgqYDVAIKMIKEGSmsEDEFIEEAKVMMNLSHEKLVQLYGVCTkqrPIFIITEY 91  human
Feature 1     ## #                                                #         ##  #             
1K2P_B     81 MANGCLLNYLREMrh-rFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDqGVVKVSDFGLSRYVLDDEYTSSV 159 human
P51813    492 ISNGCLLNYLRSHgk-gLEPSQLLEMCYDVCEGMAFLESHQFIHRDLAARNCLVDRdLCVKVSDFGMTRYVLDDQYVSSV 570 human
Q8JH64    475 MANGCLLNFLRETqr-rFQPAELLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDqGIVKVSDFGLSRYVLDDEYTSSM 553 chicken
CAC44628  452 LSNGCLLTYLREGlkqhPTMVQLLEMCKDVSEGMAYLESKQYIHRDLAARNCLVDSnGTVKVTDFGLSRYVLDDEYTSSV 531 torafugu
3GEN_A    101 MANGCLLNYLREMrh-rFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDqGVVKVSDFGLSRYVLDDEYTSSV 179 human
3PIX_A     92 MANGCLLNYLREMrh-rFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDqGVVKVSDFGLSRYVLDDEYTSSV 170 human
Feature 1                                                                                     
1K2P_B    160 GSKFPVRWSPPEVLMYsKFSSKSDIWAFGVLMWEIYSLGKMPYERFTNSETAEHIAQGLRLYRPHLASEKVYTIMYSCWH 239 human
P51813    571 GTKFPVKWSAPEVFHYfKYSSKSDVWAFGILMWEVFSLGKQPYDLYDNSQVVLKVSQGHRLYRPHLASDTIYQIMYSCWH 650 human
Q8JH64    554 GSKFPVRWSPPEVLLYsKFSSKSDVWSFGVLMWEVYSLGKMPYERFNNSETTEHVIQGLRLYRPQQASERVYAIMYSCWH 633 chicken
CAC44628  532 GAKFPVRWSPPEVLLYcKFSSKSDVWAYGVLLWEVYTLGKLPYERLNNQEIVDKVSSGRRLYRPQLASEKVYAVMTSCWH 611 torafugu
3GEN_A    180 GSKFPVRWSPPEVLMYsKFSSKSDIWAFGVLMWEIYSLGKMPYERFTNSETAEHIAQGLRLYRPHLASEKVYTIMYSCWH 259 human
3PIX_A    171 GSKFPVRWSPPEVLMYsKFSSKSDIWAFGVLMWEIYSLGKMPYERFTNSETAEHIAQGLRLYRPHLASEKVYTIMYSCWH 250 human
Feature 1                      
1K2P_B    240 EkADERPTFKILLSNIL 256 human
P51813    651 ElPEKRPTFQQLLSSIE 667 human
Q8JH64    634 EkAEERPTFSALLGSIV 650 chicken
CAC44628  612 EkADERPTFEELVLTVQ 628 torafugu
3GEN_A    260 EkADERPTFKILLSNIL 276 human
3PIX_A    251 EkADERPTFKILLSNIL 267 human

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