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Reviewed, UniProtKB/Swiss-Prot Q06187 (BTK_HUMAN)

Last modified November 25, 2008. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended 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
Name: BTK
Synonyms: AGMX1, ATK, BPK
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length659 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed
Chain2 – 659658Tyrosine-protein kinase BTK
PRO_0000088065

Regions

Domain3 – 133131PH
Domain214 – 27461SH3
Domain281 – 37797SH2
Domain402 – 655254Protein kinase
Zinc finger135 – 17137Btk-type
Nucleotide binding408 – 4169ATP By similarity

Sites

Active site5211Proton acceptor By similarity
Metal binding1431Zinc
Metal binding1541Zinc
Metal binding1551Zinc
Metal binding1651Zinc
Binding site4301ATP By similarity

Amino acid modifications

Modified residue21N-acetylalanine
Modified residue401Phosphotyrosine By similarity
Modified residue2231Phosphotyrosine; by autocatalysis
Modified residue3441Phosphotyrosine By similarity
Modified residue5511Phosphotyrosine; by autocatalysis

Natural variations

Natural variant111L → P in XLA.
VAR_006216
Natural variant121K → R in XLA.
VAR_006217
Natural variant141S → F in XLA.
VAR_006218
Natural variant191K → E in XLA.
VAR_008291
Natural variant251F → S in XLA.
VAR_006219
Natural variant271K → R in XLA.
VAR_008292
Natural variant281R → C in XLA; no effect on phosphorylation of GTF2I.
VAR_008293
Natural variant281R → H in XLA; moderate.
VAR_006220
Natural variant281R → P in XLA.
VAR_006221
Natural variant331T → P in XLA; severe.
VAR_006222
Natural variant391Y → S in XLA.
VAR_008960
Natural variant401Y → C in XLA.
VAR_008294
Natural variant401Y → N in XLA.
VAR_008295
Natural variant611I → N in XLA.
VAR_008296
Natural variant641V → D in XLA.
VAR_008297
Natural variant641V → F in XLA.
VAR_006223
Natural variant821R → K
VAR_041676
Natural variant1031Q → QSVFSSTR in XLA.
VAR_006224
Natural variant1131V → D in XLA.
VAR_006225
Natural variant1151S → F in XLA.
VAR_008298
Natural variant1171T → P in XLA.
VAR_008299
Natural variant1271Q → H in XLA.
VAR_008300
Natural variant1541C → S in XLA.
VAR_008301
Natural variant1551C → G in XLA.
VAR_008302
Natural variant1551C → R in XLA.
VAR_008303
Natural variant1841T → P in XLA.
VAR_008304
Natural variant1901P → K in a lung large cell carcinoma sample; somatic mutation; requires 2 nucleotide substitutions.
VAR_041677
Natural variant260 – 28021Missing in XLA; severe.
VAR_006226
Natural variant2881R → Q in XLA.
VAR_008305
Natural variant2881R → W in XLA.
VAR_006227
Natural variant2951L → P in XLA.
VAR_006228
Natural variant3021G → E in XLA.
VAR_006230
Natural variant3021G → R in XLA.
VAR_008306
Natural variant3021Missing in XLA.
VAR_006229
Natural variant3071R → G in XLA; loss of activity.
VAR_006231
Natural variant3071R → T in XLA.
VAR_008307
Natural variant3081D → E in XLA.
VAR_008308
Natural variant3191V → A in XLA; moderate.
VAR_008309
Natural variant3341Y → S in XLA.
VAR_006232
Natural variant3581L → F in XLA.
VAR_006233
Natural variant3611Y → C in XLA; mild. dbSNP rs28935478.
VAR_006234
Natural variant3621H → Q in XLA.
VAR_006235
Natural variant3641H → P in XLA.
VAR_006236
Natural variant3651N → Y in XLA.
VAR_006237
Natural variant3661S → F in XLA.
VAR_008310
Natural variant3691L → F in XLA.
VAR_008311
Natural variant3701I → M in XLA.
VAR_006238
Natural variant3721R → G in XLA.
VAR_008312
Natural variant4081L → P in XLA; moderate.
VAR_006239
Natural variant4141G → R in XLA.
VAR_008313
Natural variant4181Y → H in XLA.
VAR_006240
Natural variant4291I → N in XLA.
VAR_006241
Natural variant4301K → E in XLA; loss of phosphorylation of GTF2I.
VAR_006242
Natural variant4301K → R in XLA.
VAR_008314
Natural variant4451E → D in XLA.
VAR_008315
Natural variant4621G → D in XLA.
VAR_008316
Natural variant4621G → V in XLA.
VAR_008317
Natural variant4761Y → D in XLA.
VAR_006243
Natural variant4771M → R in XLA.
VAR_006244
Natural variant5021C → F in XLA.
VAR_006245
Natural variant5021C → W in XLA.
VAR_006246
Natural variant5061C → R in XLA.
VAR_006247
Natural variant5061C → Y in XLA.
VAR_006248
Natural variant5081A → D in XLA.
VAR_008318
Natural variant5091M → I in XLA.
VAR_008319
Natural variant5091M → V in XLA.
VAR_006249
Natural variant5121L → P in XLA.
VAR_008961
Natural variant5121L → Q in XLA.
VAR_008962