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Q8JH64 (BTK_CHICK) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 93. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tyrosine-protein kinase BTK

EC=2.7.10.2
Alternative name(s):
Bruton tyrosine kinase
Gene names
Name:BTK
OrganismGallus gallus (Chicken) [Reference proteome]
Taxonomic identifier9031 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiTestudines + Archosauria groupArchosauriaDinosauriaSaurischiaTheropodaCoelurosauriaAvesNeognathaeGalliformesPhasianidaePhasianinaeGallus

Protein attributes

Sequence length657 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.2 Ref.4 Ref.5

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Cofactor

Binds 1 zinc ion per subunit By similarity. UniProtKB Q06187

Enzyme regulation

Activated by phosphorylation By similarity. Ref.3

Subunit structure

Binds GTF2I through the PH domain. Interacts with SH3BP5 via the SH3 domain By similarity. Interacts with IBTK via its PH domain By similarity. Interacts with ARID3A, CAV1, FASLG, PIN1, TLR8 and TLR9 By similarity.

Subcellular location

Cytoplasm By similarity. Cell membrane; Peripheral membrane protein By similarity. Nucleus By similarity. Note: In steady state, BTK is predominantly cytosolic By similarity. Following B-cell receptor (BCR) engagement by antigen, translocates to the plasma membrane through its PH domain By similarity. Plasma membrane localization is a critical step in the activation of BTK By similarity. A fraction of BTK also shuttles between the nucleus and the cytoplasm By similarity.

Domain

The PH domain mediates the binding to inositol polyphosphate and phosphoinositides, leading to its targeting to the plasma membrane By similarity. 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.

Post-translational modification

Following B-cell receptor (BCR) engagement, translocates to the plasma membrane where it gets phosphorylated at Tyr-549 by LYN and SYK. Phosphorylation at Tyr-549 is followed by autophosphorylation of Tyr-220 which may create a docking site for a SH2 containing protein By similarity. Phosphorylation at Ser-179 by PRKCB, leads in translocation of BTK back to the cytoplasmic fraction By similarity.

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 By similarity
Chain2 – 657656Tyrosine-protein kinase BTK
PRO_0000088067

Regions

Domain3 – 132130PH
Domain214 – 27057SH3
Domain276 – 36691SH2
Domain400 – 653254Protein kinase
Zinc finger134 – 17037Btk-type
Nucleotide binding406 – 4149ATP By similarity UniProtKB P08631
Region12 – 2413Inositol-(1,3,4,5)-tetrakisphosphate 1-binding By similarity
Region472 – 4776Inhibitor-binding By similarity
Motif579 – 5868CAV1-binding By similarity

Sites

Active site5191Proton acceptor By similarity UniProtKB P08631
Metal binding1421Zinc By similarity UniProtKB Q06187
Metal binding1531Zinc By similarity UniProtKB Q06187
Metal binding1541Zinc By similarity UniProtKB Q06187
Metal binding1641Zinc By similarity UniProtKB Q06187
Binding site261Inositol-(1,3,4,5)-tetrakisphosphate By similarity
Binding site281Inositol-(1,3,4,5)-tetrakisphosphate By similarity
Binding site391Inositol-(1,3,4,5)-tetrakisphosphate By similarity
Binding site531Inositol-(1,3,4,5)-tetrakisphosphate; via carbonyl oxygen By similarity
Binding site4281ATP By similarity UniProtKB P08631
Binding site4431Inhibitor By similarity
Binding site4591Inhibitor By similarity
Binding site4751Inhibitor By similarity
Binding site5361Inhibitor By similarity
Binding site5371Inhibitor; via amide nitrogen By similarity
Binding site5401Inhibitor; via carbonyl oxygen By similarity

Amino acid modifications

Modified residue21N-acetylalanine By similarity
Modified residue201Phosphothreonine By similarity
Modified residue211Phosphoserine By similarity
Modified residue401Phosphotyrosine By similarity
Modified residue551Phosphoserine By similarity
Modified residue1791Phosphoserine; by PKC/PRKCB By similarity
Modified residue1901Phosphothreonine By similarity
Modified residue2201Phosphotyrosine; by autocatalysis By similarity UniProtKB P35991
Modified residue3061Phosphoserine By similarity
Modified residue3211Phosphoserine By similarity
Modified residue3421Phosphotyrosine By similarity
Modified residue3591Phosphotyrosine By similarity
Modified residue3731Phosphotyrosine By similarity
Modified residue5491Phosphotyrosine; by autocatalysis By similarity UniProtKB P35991
Modified residue5491Phosphotyrosine; by LYN and SYK By similarity
Modified residue6021Phosphoserine By similarity

Sequences

Sequence LengthMass (Da)Tools
Q8JH64 [UniParc].

Last modified October 1, 2002. Version 1.
Checksum: FE5217E8E6195F6A

FASTA65775,879
        10         20         30         40         50         60 
MASIILESIF LKRSQQKKKT SPLNFKKRLF LLTESKLSYY EYDFERGRRG SKKGSVDIEK 

        70         80         90        100        110        120 
ITCVETVVPE NNPPPERQVP KKGEDYNMEQ ISIIERFPYP FQVVYDEGPL YVFSPTEELR 

       130        140        150        160        170        180 
KRWIHQLKSV IRYNSDLVQK YHPCFWIDGQ YLCCSQTAKN AMGCKILESR NGSLKAGRSH 

       190        200        210        220        230        240 
RKTKKPLPPT PEEDTMVMKP LPPEPAPSAA GEMKKVVALY NYVPMNVQDL QLQKGEDYLI 

       250        260        270        280        290        300 
LEESHLPWWK ARDKNGREGY IPSNYVTATS NSLEIYEWYS KNITRSQAEQ LLKQEGKEGG 

       310        320        330        340        350        360 
FIVRDSTSKT GKYTVSVYAK SAVDPQGMIR HYVVCCTPQN QYYLAEKHLF NTIPELITYH 

       370        380        390        400        410        420 
QHNSAGLISR LKYPVSRHQK SAPSTAGLGY GSWEIDPKDL TFLKELGTGQ FGVVKYGKWR 

       430        440        450        460        470        480 
GQYNVAIKMI REGSMSEDEF IDEAKVMMNL SHEKLVQLYG VCTKQRPIFI ITEYMANGCL 

       490        500        510        520        530        540 
LNFLRETQRR FQPAELLEMC KDVCEAMEYL ESKQFLHRDL AARNCLVNDQ GIVKVSDFGL 

       550        560        570        580        590        600 
SRYVLDDEYT SSMGSKFPVR WSPPEVLLYS KFSSKSDVWS FGVLMWEVYS LGKMPYERFN 

       610        620        630        640        650 
NSETTEHVIQ GLRLYRPQQA SERVYAIMYS CWHEKAEERP TFSALLGSIV DITDEEP 

« Hide

References

[1]"Btk expressed in primary chicken erythroblasts."
Schmidt U., Haubenwallner S., Beug H., Nimpf J.
Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"A role for Bruton's tyrosine kinase in B cell antigen receptor-mediated activation of phospholipase C-gamma 2."
Takata M., Kurosaki T.
J. Exp. Med. 184:31-40(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF PLCG2.
[3]"Bruton's tyrosine kinase activity is negatively regulated by Sab, the Btk-SH3 domain-binding protein."
Yamadori T., Baba Y., Mastushita M., Hashimoto S., Kurosaki M., Kurosaki T., Kishimoto T., Tsukada S.
Proc. Natl. Acad. Sci. U.S.A. 96:6341-6346(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[4]"Bruton's tyrosine kinase links the B cell receptor to nuclear factor kappaB activation."
Bajpai U.D., Zhang K., Teutsch M., Sen R., Wortis H.H.
J. Exp. Med. 191:1735-1744(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN REGULATION OF THE ACTIVITY OF NF-KAPPA-B.
[5]"Differential regulation of NFAT and SRF by the B cell receptor via a PLCgamma-Ca(2+)-dependent pathway."
Hao S., Kurosaki T., August A.
EMBO J. 22:4166-4177(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"Bruton's tyrosine kinase (BTK) as a dual-function regulator of apoptosis."
Uckun F.M.
Biochem. Pharmacol. 56:683-691(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION IN REGULATION OF APOPTOSIS.
[7]"Bruton's tyrosine kinase (Btk): function, regulation, and transformation with special emphasis on the PH domain."
Mohamed A.J., Yu L., Backesjo C.M., Vargas L., Faryal R., Aints A., Christensson B., Berglof A., Vihinen M., Nore B.F., Smith C.I.
Immunol. Rev. 228:58-73(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION, REVIEW ON ENZYME REGULATION.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF535118 mRNA. Translation: AAN04043.2.
UniGeneGga.1305.

3D structure databases

ProteinModelPortalQ8JH64.
SMRQ8JH64. Positions 2-169, 209-385, 395-652.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233859.
HOVERGENHBG008761.
InParanoidQ8JH64.

Family and domain databases

Gene3D2.30.29.30. 1 hit.
3.30.505.10. 1 hit.
InterProIPR011009. Kinase-like_dom.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR000980. SH2.
IPR001452. SH3_domain.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR001562. Znf_Btk_motif.
[Graphical view]
PfamPF00779. BTK. 1 hit.
PF00169. PH. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00402. TECBTKDOMAIN.
PR00109. TYRKINASE.
SMARTSM00107. BTK. 1 hit.
SM00233. PH. 1 hit.
SM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS50003. PH_DOMAIN. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50001. SH2. 1 hit.
PS50002. SH3. 1 hit.
PS51113. ZF_BTK. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

PROQ8JH64.

Entry information

Entry nameBTK_CHICK
AccessionPrimary (citable) accession number: Q8JH64
Entry history
Integrated into UniProtKB/Swiss-Prot: February 16, 2004
Last sequence update: October 1, 2002
Last modified: April 16, 2014
This is version 93 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families