BTK_HUMAN
Source:
PM19886704
PM23856902
Marked as 'Membrane associated protein'
Confidence:
low (only semi-automatic identification from reviews)
Search PubMed for
(RBC AND this entry)
Gene names:
BTK
, AGMX1, ATK, BPK
Protein names and data:
BTK_HUMAN
, Tyrosine-protein kinase BTK; 2.7.10.2
, Agammaglobulinemia tyrosine kinase; ATK; B-cell progenitor kinase; BPK; Bruton tyrosine kinase
Lenght: 659 a.a.
Mass: 76281 Da
fasta formatted sequence
Function:
Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. After BCR engagement and activation at the plasma membrane, phosphorylates PLCG2 at several sites, igniting the downstream signaling pathway through calcium mobilization, followed by activation of the protein kinase C (PKC) family members. PLCG2 phosphorylation is performed in close cooperation with the adapter protein B-cell linker protein BLNK. BTK acts as a platform to bring together a diverse array of signaling proteins and is implicated in cytokine receptor signaling pathways. Plays an important role in the function of immune cells of innate as well as adaptive immunity, as a component of the Toll-like receptors (TLR) pathway. The TLR pathway acts as a primary surveillance system for the detection of pathogens and are crucial to the activation of host defense. Especially, is a critical molecule in regulating TLR9 activation in splenic B-cells. Within the TLR pathway, induces tyrosine phosphorylation of TIRAP which leads to TIRAP degradation. BTK plays also a critical role in transcription regulation. Induces the activity of NF-kappa-B, which is involved in regulating the expression of hundreds of genes. BTK is involved on the signaling pathway linking TLR8 and TLR9 to NF-kappa-B. Transiently phosphorylates transcription factor GTF2I on tyrosine residues in response to BCR. GTF2I then translocates to the nucleus to bind regulatory enhancer elements to modulate gene expression. ARID3A and NFAT are other transcriptional target of BTK. BTK is required for the formation of functional ARID3A DNA-binding complexes. There is however no evidence that BTK itself binds directly to DNA. BTK has a dual role in the regulation of apoptosis.
Catalytic activity:
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Disease:
( OMIM:
300300
300755
307200
)
X-linked agammaglobulinemia (XLA) [MIM:300755]: 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. Note=The disease is caused by mutations affecting the gene represented in this entry. X-linked hypogammaglobulinemia and isolated growth hormone deficiency (XLA-IGHD) [MIM:307200]: In rare cases XLA is inherited together with isolated growth hormone deficiency (IGHD). Note=The disease may be caused by mutations affecting the gene represented in this entry.
Cellular location:
Cytoplasm. Cell membrane; Peripheral membrane protein. Nucleus. Note=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.
Tissue specificity:
Predominantly expressed in B-lymphocytes.
Genetic variants
11 - 11
L -> P (in XLA). VAR_006216
12 - 12
K -> R (in XLA). VAR_006217
14 - 14
S -> F (in XLA). VAR_006218
19 - 19
K -> E (in XLA). VAR_008291
25 - 25
F -> S (in XLA). VAR_006219
27 - 27
K -> R (in XLA). VAR_008292
28 - 28
R -> C (in XLA; no effect on phosphorylation of GTF2I). VAR_008293
28 - 28
R -> H (in XLA; moderate). VAR_006220
28 - 28
R -> P (in XLA). VAR_006221
33 - 33
T -> P (in XLA; severe). VAR_006222
39 - 39
Y -> S (in XLA). VAR_008960
40 - 40
Y -> C (in XLA). VAR_008294
40 - 40
Y -> N (in XLA). VAR_008295
61 - 61
I -> N (in XLA). VAR_008296
64 - 64
V -> D (in XLA). VAR_008297
64 - 64
V -> F (in XLA). VAR_006223
82 - 82
R -> K (in dbSNP:rs56035945). VAR_041676
56035945
103 - 103
Q -> QSVFSSTR (in XLA). VAR_006224
113 - 113
V -> D (in XLA). VAR_006225
115 - 115
S -> F (in XLA). VAR_008298
117 - 117
T -> P (in XLA). VAR_008299
127 - 127
Q -> H (in XLA). VAR_008300
154 - 154
C -> S (in XLA). VAR_008301
155 - 155
C -> G (in XLA). VAR_008302
155 - 155
C -> R (in XLA). VAR_008303
184 - 184
T -> P (in XLA). VAR_008304
190 - 190
P -> K (in a lung large cell carcinoma sample; somatic mutation; requires 2 nucleotide substitutions). VAR_041677
260 - 280
Missing (in XLA; severe). VAR_006226
288 - 288
R -> Q (in XLA). VAR_008305
288 - 288
R -> W (in XLA). VAR_006227
295 - 295
L -> P (in XLA). VAR_006228
302 - 302
G -> E (in XLA). VAR_006230
302 - 302
G -> R (in XLA). VAR_008306
302 - 302
Missing (in XLA). VAR_006229
307 - 307
R -> G (in XLA; loss of activity). VAR_006231
307 - 307
R -> T (in XLA). VAR_008307
308 - 308
D -> E (in XLA). VAR_008308
319 - 319
V -> A (in XLA; moderate). VAR_008309
334 - 334
Y -> S (in XLA). VAR_006232
358 - 358
L -> F (in XLA). VAR_006233
361 - 361
Y -> C (in XLA; mild; dbSNP:rs28935478). VAR_006234
28935478
362 - 362
H -> Q (in XLA). VAR_006235
364 - 364
H -> P (in XLA). VAR_006236
365 - 365
N -> Y (in XLA). VAR_006237
366 - 366
S -> F (in XLA). VAR_008310
369 - 369
L -> F (in XLA). VAR_008311
370 - 370
I -> M (in XLA). VAR_006238
372 - 372
R -> G (in XLA). VAR_008312
408 - 408
L -> P (in XLA; moderate). VAR_006239
414 - 414
G -> R (in XLA). VAR_008313
418 - 418
Y -> H (in XLA). VAR_006240
429 - 429
I -> N (in XLA). VAR_006241
430 - 430
K -> E (in XLA; loss of phosphorylation of GTF2I). VAR_006242
430 - 430
K -> R (in XLA). VAR_008314
445 - 445
E -> D (in XLA). VAR_008315
462 - 462
G -> D (in XLA). VAR_008316
462 - 462
G -> V (in XLA). VAR_008317
476 - 476
Y -> D (in XLA). VAR_006243
477 - 477
M -> R (in XLA). VAR_006244
502 - 502
C -> F (in XLA). VAR_006245
502 - 502
C -> W (in XLA). VAR_006246
506 - 506
C -> R (in XLA). VAR_006247
506 - 506
C -> Y (in XLA). VAR_006248
508 - 508
A -> D (in XLA). VAR_008318
509 - 509
M -> I (in XLA). VAR_008319
509 - 509
M -> V (in XLA). VAR_006249
512 - 512
L -> P (in XLA). VAR_008961
512 - 512
L -> Q (in XLA). VAR_008962
518 - 518
L -> R (in XLA). VAR_008320
520 - 520
R -> Q (in XLA; severe; prevents activation due to absence of contact between the catalytic loop and the regulatory phosphorylated residue). VAR_006251
521 - 521
D -> G (in XLA). VAR_008321
521 - 521
D -> H (in XLA; severe). VAR_006252
521 - 521
D -> N (in XLA; severe). VAR_006253
523 - 523
A -> E (in XLA). VAR_008322
525 - 525
R -> G (in XLA). VAR_008323
525 - 525
R -> P (in XLA). VAR_006254
525 - 525
R -> Q (in XLA; severe; disturbs ATP- binding). VAR_006255
526 - 526
N -> K (in XLA). VAR_006256
535 - 535
V -> F (in XLA). VAR_008324
542 - 542
L -> P (in XLA; growth hormone deficiency). VAR_006257
544 - 544
R -> G (in XLA). VAR_008963
544 - 544
R -> K (in XLA). VAR_006258
559 - 559
F -> S (in XLA). VAR_008325
562 - 562
R -> P (in XLA; dbSNP:rs28935176). VAR_006259
28935176
562 - 562
R -> W (in XLA). VAR_006260
563 - 563
W -> L (in XLA). VAR_008326
567 - 567
E -> K (in XLA; severe). VAR_006261
578 - 578
S -> Y (in XLA). VAR_008964
581 - 581
W -> R (in XLA). VAR_006262
582 - 582
A -> V (in XLA). VAR_006263
583 - 583
F -> S (in XLA). VAR_008327
587 - 587
M -> L (in XLA; mild). VAR_006264
589 - 589
E -> D (in XLA). VAR_008328
589 - 589
E -> G (in XLA; moderate; interferes with substrate binding). VAR_006265
589 - 589
E -> K (in XLA). VAR_008965
592 - 592
S -> P (in XLA). VAR_006267
594 - 594
G -> E (in XLA; mild; interferes with substrate binding). VAR_006268
594 - 594
G -> R (in XLA). VAR_006269
598 - 598
Y -> C (in XLA). VAR_006270
607 - 607
A -> D (in XLA; mild). VAR_006271
613 - 613
G -> D (in XLA; mild; interferes with substrate binding and/or domain interactions). VAR_006272
619 - 619
P -> A (in XLA). VAR_008330
619 - 619
P -> S (in XLA). VAR_006273
619 - 619
P -> T (in XLA). VAR_008331
622 - 622
A -> P (in XLA). VAR_008332
626 - 626
V -> G (in XLA). VAR_008333
630 - 630
M -> I (polymorphism, 35%). VAR_006274
630 - 630
M -> K (in XLA). VAR_006275
630 - 630
M -> T (in XLA). VAR_008334
633 - 633
C -> Y (in XLA). VAR_006276
641 - 641
R -> C (in XLA). VAR_006277
641 - 641
R -> H (in XLA; severe). VAR_006278
644 - 644
F -> L (in XLA). VAR_008335
644 - 644
F -> S (in XLA). VAR_006279
647 - 647
L -> P (in XLA). VAR_006280
652 - 652
L -> P (in XLA). VAR_006281
Database cross-references
UniProt:
Q06187
Ensembl:
ENST00000308731
Ensembl:
ENST00000593575
MIM:
300300
MIM:
300755
MIM:
307200
neXtProt:
NX_Q06187
Antibodypedia:
Q06187
(may not find the protein thus also not any antibody)
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