Reviewed,
UniProtKB/Swiss-Prot Q06187 (BTK_HUMAN)
Last modified
November 25, 2008.
Version 117.
History...
Clusters with 100%,
90%,
50% identity |
 Documents (7) |
 Third-party data |
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Names and origin
| Protein names | Recommended name: Tyrosine-protein kinase BTK EC=2.7.10.2 Alternative name(s): Bruton tyrosine kinase Agammaglobulinaemia tyrosine kinase Short name=ATK B-cell progenitor kinase Short name=BPK | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 659 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Plays a crucial role in B-cell ontogeny. Transiently phosphorylates GTF2I on tyrosine residues in response to B-cell receptor cross-linking. Required for the formation of functional ARID3A DNA-binding complexes. |
| Catalytic activity | ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. |
| Cofactor | Binds 1 zinc ion per subunit. |
| Enzyme regulation | Inhibited by IBTK. Activated by phosphorylation. |
| Subunit structure | Binds GTF2I through the PH domain. Interacts with SH3BP5 via the SH3 domain. Interacts with IBTK via its PH domain. Interacts with GTF2I and ARID3A. |
| Subcellular location | CytoplasmBy similarity. Membrane; Peripheral membrane proteinBy similarity. NucleusBy similarity. |
| Post-translational modification | Autophosphorylated on Tyr-223 and Tyr-551. Phosphorylation of Tyr-223 may create a docking site for a SH2 containing protein By similarity. |
| Involvement in disease | Defects in BTK are the cause of X-linked agammaglobulinemia type 1 (XLA) [MIM:300300]. XLA is a humoral immunodeficiency disease which results in developmental defects in the maturation pathway of B-cells. Affected boys have normal levels of pre-B-cells in their bone marrow but virtually no circulating mature B-lymphocytes. This results in a lack of immunoglobulins of all classes and leads to recurrent bacterial infections like otitis, conjunctivitis, dermatitis, sinusitis in the first few years of life, or even some patients present overwhelming sepsis or meningitis, resulting in death in a few hours. Treatment in most cases is by infusion of intravenous immunoglobulin. Defects in BTK may be the cause of X-linked hypogammaglobulinemia and isolated growth hormone deficiency (XLA-IGHD) [MIM:307200]; also known as agammaglobulinemia and isolated growth hormone deficiency or Fleisher syndrome or isolated growth hormone deficiency type 3 (IGHD3). In rare cases XLA is inherited together with isolated growth hormone deficiency (IGHD). |
| Sequence similarities | Belongs to the protein kinase superfamily. Tyr protein kinase family. TEC subfamily. Contains 1 Btk-type zinc finger. Contains 1 PH domain. Contains 1 protein kinase domain. Contains 1 SH2 domain. Contains 1 SH3 domain. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| itself | 1 | EBI-624835,EBI-624835 | ||
| FCER1G | P30273 | 1 | EBI-624835,EBI-515289 | |
| GTF2I | P78347 | 4 | EBI-624835,EBI-359622 | |
| IBTK | Q9P2D0 | 1 | EBI-624835,EBI-1052017 | |
| IBTK | Q9P2D0-4 | 3 | EBI-624835,EBI-1521221 | |
| PRKCQ | Q04759 | 2 | EBI-624835,EBI-374762 | |
| SH3BP5 | O60239 | 3 | EBI-624835,EBI-624860 |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Initiator methionine | 1 | 1 | Removed | ||||||
| Chain | 2 – 659 | 658 | Tyrosine-protein kinase BTK | PRO_0000088065 | |||||
Regions | |||||||||
| Domain | 3 – 133 | 131 | PH | ||||||
| Domain | 214 – 274 | 61 | SH3 | ||||||
| Domain | 281 – 377 | 97 | SH2 | ||||||
| Domain | 402 – 655 | 254 | Protein kinase | ||||||
| Zinc finger | 135 – 171 | 37 | Btk-type | ||||||
| Nucleotide binding | 408 – 416 | 9 | ATP By similarity | ||||||
Sites | |||||||||
| Active site | 521 | 1 | Proton acceptor By similarity | ||||||
| Metal binding | 143 | 1 | Zinc | ||||||
| Metal binding | 154 | 1 | Zinc | ||||||
| Metal binding | 155 | 1 | Zinc | ||||||
| Metal binding | 165 | 1 | Zinc | ||||||
| Binding site | 430 | 1 | ATP By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 2 | 1 | N-acetylalanine | ||||||
| Modified residue | 40 | 1 | Phosphotyrosine By similarity | ||||||
| Modified residue | 223 | 1 | Phosphotyrosine; by autocatalysis | ||||||
| Modified residue | 344 | 1 | Phosphotyrosine By similarity | ||||||
| Modified residue | 551 | 1 | Phosphotyrosine; by autocatalysis | ||||||
Natural variations | |||||||||
| Natural variant | 11 | 1 | L → P in XLA. | VAR_006216 | |||||
| Natural variant | 12 | 1 | K → R in XLA. | VAR_006217 | |||||
| Natural variant | 14 | 1 | S → F in XLA. | VAR_006218 | |||||
| Natural variant | 19 | 1 | K → E in XLA. | VAR_008291 | |||||
| Natural variant | 25 | 1 | F → S in XLA. | VAR_006219 | |||||
| Natural variant | 27 | 1 | K → R in XLA. | VAR_008292 | |||||
| Natural variant | 28 | 1 | R → C in XLA; no effect on phosphorylation of GTF2I. | VAR_008293 | |||||
| Natural variant | 28 | 1 | R → H in XLA; moderate. | VAR_006220 | |||||
| Natural variant | 28 | 1 | R → P in XLA. | VAR_006221 | |||||
| Natural variant | 33 | 1 | T → P in XLA; severe. | VAR_006222 | |||||
| Natural variant | 39 | 1 | Y → S in XLA. | VAR_008960 | |||||
| Natural variant | 40 | 1 | Y → C in XLA. | VAR_008294 | |||||
| Natural variant | 40 | 1 | Y → N in XLA. | VAR_008295 | |||||
| Natural variant | 61 | 1 | I → N in XLA. | VAR_008296 | |||||
| Natural variant | 64 | 1 | V → D in XLA. | VAR_008297 | |||||
| Natural variant | 64 | 1 | V → F in XLA. | VAR_006223 | |||||
| Natural variant | 82 | 1 | R → K | VAR_041676 | |||||
| Natural variant | 103 | 1 | Q → QSVFSSTR in XLA. | VAR_006224 | |||||
| Natural variant | 113 | 1 | V → D in XLA. | VAR_006225 | |||||
| Natural variant | 115 | 1 | S → F in XLA. | VAR_008298 | |||||
| Natural variant | 117 | 1 | T → P in XLA. | VAR_008299 | |||||
| Natural variant | 127 | 1 | Q → H in XLA. | VAR_008300 | |||||
| Natural variant | 154 | 1 | C → S in XLA. | VAR_008301 | |||||
| Natural variant | 155 | 1 | C → G in XLA. | VAR_008302 | |||||
| Natural variant | 155 | 1 | C → R in XLA. | VAR_008303 | |||||
| Natural variant | 184 | 1 | T → P in XLA. | VAR_008304 | |||||
| Natural variant | 190 | 1 | P → K in a lung large cell carcinoma sample; somatic mutation; requires 2 nucleotide substitutions. | VAR_041677 | |||||
| Natural variant | 260 – 280 | 21 | Missing in XLA; severe. | VAR_006226 | |||||
| Natural variant | 288 | 1 | R → Q in XLA. | VAR_008305 | |||||
| Natural variant | 288 | 1 | R → W in XLA. | VAR_006227 | |||||
| Natural variant | 295 | 1 | L → P in XLA. | VAR_006228 | |||||
| Natural variant | 302 | 1 | G → E in XLA. | VAR_006230 | |||||
| Natural variant | 302 | 1 | G → R in XLA. | VAR_008306 | |||||
| Natural variant | 302 | 1 | Missing in XLA. | VAR_006229 | |||||
| Natural variant | 307 | 1 | R → G in XLA; loss of activity. | VAR_006231 | |||||
| Natural variant | 307 | 1 | R → T in XLA. | VAR_008307 | |||||
| Natural variant | 308 | 1 | D → E in XLA. | VAR_008308 | |||||
| Natural variant | 319 | 1 | V → A in XLA; moderate. | VAR_008309 | |||||
| Natural variant | 334 | 1 | Y → S in XLA. | VAR_006232 | |||||
| Natural variant | 358 | 1 | L → F in XLA. | VAR_006233 | |||||
| Natural variant | 361 | 1 | Y → C in XLA; mild. dbSNP rs28935478. | VAR_006234 | |||||
| Natural variant | 362 | 1 | H → Q in XLA. | VAR_006235 | |||||
| Natural variant | 364 | 1 | H → P in XLA. | VAR_006236 | |||||
| Natural variant | 365 | 1 | N → Y in XLA. | VAR_006237 | |||||
| Natural variant | 366 | 1 | S → F in XLA. | VAR_008310 | |||||
| Natural variant | 369 | 1 | L → F in XLA. | VAR_008311 | |||||
| Natural variant | 370 | 1 | I → M in XLA. | VAR_006238 | |||||
| Natural variant | 372 | 1 | R → G in XLA. | VAR_008312 | |||||
| Natural variant | 408 | 1 | L → P in XLA; moderate. | VAR_006239 | |||||
| Natural variant | 414 | 1 | G → R in XLA. | VAR_008313 | |||||
| Natural variant | 418 | 1 | Y → H in XLA. | VAR_006240 | |||||
| Natural variant | 429 | 1 | I → N in XLA. | VAR_006241 | |||||
| Natural variant | 430 | 1 | K → E in XLA; loss of phosphorylation of GTF2I. | VAR_006242 | |||||
| Natural variant | 430 | 1 | K → R in XLA. | VAR_008314 | |||||
| Natural variant | 445 | 1 | E → D in XLA. | VAR_008315 | |||||
| Natural variant | 462 | 1 | G → D in XLA. | VAR_008316 | |||||
| Natural variant | 462 | 1 | G → V in XLA. | VAR_008317 | |||||
| Natural variant | 476 | 1 | Y → D in XLA. | VAR_006243 | |||||
| Natural variant | 477 | 1 | M → R in XLA. | VAR_006244 | |||||
| Natural variant | 502 | 1 | C → F in XLA. | VAR_006245 | |||||
| Natural variant | 502 | 1 | C → W in XLA. | VAR_006246 | |||||
| Natural variant | 506 | 1 | C → R in XLA. | VAR_006247 | |||||
| Natural variant | 506 | 1 | C → Y in XLA. | VAR_006248 | |||||
| Natural variant | 508 | 1 | A → D in XLA. | VAR_008318 | |||||
| Natural variant | 509 | 1 | M → I in XLA. | VAR_008319 | |||||
| Natural variant | 509 | 1 | M → V in XLA. | VAR_006249 | |||||
| Natural variant | 512 | 1 | L → P in XLA. | VAR_008961 | |||||
| Natural variant | 512 | 1 | L → Q in XLA. | VAR_008962 | |||||