Tyrosine-protein kinase BTK - Gallus gallus (Chicken)

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Q8JH64 (BTK_CHICK) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 85. History...

Clusters with 100%, 90%, 50% identity |

Documents (1) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Tyrosine-protein kinase BTK
EC=2.7.10.2

Alternative name(s):
Bruton tyrosine kinase

Gene names

Name:

BTK

Organism

Gallus gallus (Chicken) [Reference proteome]

Taxonomic identifier

9031 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Archosauria › Dinosauria › Saurischia › Theropoda › Coelurosauria › Aves › Neognathae › Galliformes › Phasianidae › Phasianinae › Gallus

Protein attributes

Sequence length	657 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	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.

Ontologies

Keywords
Biological process	Adaptive immunity Immunity Innate immunity Transcription Transcription regulation
Cellular component	Cell membrane Cytoplasm Membrane Nucleus
Domain	SH2 domain SH3 domain Zinc-finger
Ligand	ATP-binding Lipid-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	innate immune response Inferred from electronic annotation. Source: UniProtKB-KW intracellular signal transduction Inferred from electronic annotation. Source: InterPro regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC phospholipid binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

Removed By similarity

Chain

2 – 657

656

Tyrosine-protein kinase BTK

PRO_0000088067

Regions

Domain

3 – 132

130

Domain

214 – 270

SH3

Domain

276 – 366

SH2

Domain

400 – 653

254

Protein kinase

Zinc finger

134 – 170

Btk-type

Nucleotide binding

406 – 414

ATP By similarity UniProtKB P08631

Region

12 – 24

Inositol-(1,3,4,5)-tetrakisphosphate 1-binding By similarity

Region

472 – 477

Inhibitor-binding By similarity

Motif

579 – 586

CAV1-binding By similarity

Sites

Active site

519

Proton acceptor By similarity UniProtKB P08631

Metal binding

142

Zinc By similarity UniProtKB Q06187

Metal binding

153

Zinc By similarity UniProtKB Q06187

Metal binding

154

Zinc By similarity UniProtKB Q06187

Metal binding

164

Zinc By similarity UniProtKB Q06187

Binding site

Inositol-(1,3,4,5)-tetrakisphosphate By similarity

Binding site

Inositol-(1,3,4,5)-tetrakisphosphate By similarity

Binding site

Inositol-(1,3,4,5)-tetrakisphosphate By similarity

Binding site

Inositol-(1,3,4,5)-tetrakisphosphate; via carbonyl oxygen By similarity

Binding site

428

ATP By similarity UniProtKB P08631

Binding site

443

Inhibitor By similarity

Binding site

459

Inhibitor By similarity

Binding site

475

Inhibitor By similarity

Binding site

536

Inhibitor By similarity

Binding site

537

Inhibitor; via amide nitrogen By similarity

Binding site

540

Inhibitor; via carbonyl oxygen By similarity

Amino acid modifications

Modified residue

N-acetylalanine By similarity

Modified residue

Phosphothreonine By similarity

Modified residue

Phosphoserine By similarity

Modified residue

Phosphotyrosine By similarity

Modified residue

Phosphoserine By similarity

Modified residue

179

Phosphoserine; by PKC/PRKCB By similarity

Modified residue

190

Phosphothreonine By similarity

Modified residue

220

Phosphotyrosine; by autocatalysis By similarity UniProtKB P35991

Modified residue

306

Phosphoserine By similarity

Modified residue

321

Phosphoserine By similarity

Modified residue

342

Phosphotyrosine By similarity

Modified residue

359

Phosphotyrosine By similarity

Modified residue

373

Phosphotyrosine By similarity

Modified residue

549

Phosphotyrosine; by autocatalysis By similarity UniProtKB P35991

Modified residue

549

Phosphotyrosine; by LYN and SYK By similarity

Modified residue

602

Phosphoserine By similarity

Sequences

Sequence

Length

Mass (Da)

Tools

Q8JH64 [UniParc].

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

657

75,879

        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

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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.
IPI	IPI00595247.
UniGene	Gga.1305.
3D structure databases
ProteinModelPortal	Q8JH64.
SMR	Q8JH64. Positions 2-169, 209-385, 395-652.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000233859.
HOVERGEN	HBG008761.
InParanoid	Q8JH64.
OrthoDB	EOG4DR9BX.
Family and domain databases
Gene3D	2.30.29.30. 1 hit. 3.30.505.10. 1 hit.
InterPro	IPR011009. Kinase-like_dom. IPR011993. PH_like_dom. IPR001849. Pleckstrin_homology. IPR000719. Prot_kinase_cat_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]
Pfam	PF00779. BTK. 1 hit. PF00169. PH. 1 hit. PF07714. Pkinase_Tyr. 1 hit. PF00017. SH2. 1 hit. PF00018. SH3_1. 1 hit. [Graphical view]
PRINTS	PR00401. SH2DOMAIN. PR00452. SH3DOMAIN. PR00402. TECBTKDOMAIN. PR00109. TYRKINASE.
SMART	SM00107. BTK. 1 hit. SM00233. PH. 1 hit. SM00252. SH2. 1 hit. SM00326. SH3. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit. SSF50044. SH3. 1 hit.
PROSITE	PS50003. 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]
ProtoNet	Search...

Entry information

Entry name

BTK_CHICK

Accession

Primary (citable) accession number: Q8JH64

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 16, 2004
Last sequence update:	October 1, 2002
Last modified:	April 3, 2013
This is version 85 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protocols and materials databases

Phylogenomic databases

Family and domain databases

Entry information

Relevant documents