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Q8JH64

- BTK_CHICK

UniProt

Q8JH64 - BTK_CHICK

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Protein
Tyrosine-protein kinase BTK
Gene
BTK
Organism
Gallus gallus (Chicken)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.3 Publications

Catalytic activityi

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

Cofactori

Binds 1 zinc ion per subunit By similarity.By similarity

Enzyme regulationi

Activated by phosphorylation By similarity.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei26 – 261Inositol-(1,3,4,5)-tetrakisphosphate By similarity
Binding sitei28 – 281Inositol-(1,3,4,5)-tetrakisphosphate By similarity
Binding sitei39 – 391Inositol-(1,3,4,5)-tetrakisphosphate By similarity
Binding sitei53 – 531Inositol-(1,3,4,5)-tetrakisphosphate; via carbonyl oxygen By similarity
Metal bindingi142 – 1421Zinc By similarityBy similarity
Metal bindingi153 – 1531Zinc By similarityBy similarity
Metal bindingi154 – 1541Zinc By similarityBy similarity
Metal bindingi164 – 1641Zinc By similarityBy similarity
Binding sitei428 – 4281ATP By similarityBy similarity
Binding sitei443 – 4431Inhibitor By similarity
Binding sitei459 – 4591Inhibitor By similarity
Binding sitei475 – 4751Inhibitor By similarity
Active sitei519 – 5191Proton acceptor By similarityBy similarity
Binding sitei536 – 5361Inhibitor By similarity
Binding sitei537 – 5371Inhibitor; via amide nitrogen By similarity
Binding sitei540 – 5401Inhibitor; via carbonyl oxygen By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri134 – 17037Btk-type
Add
BLAST
Nucleotide bindingi406 – 4149ATP By similarityBy similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. lipid binding Source: UniProtKB-KW
  3. metal ion binding Source: UniProtKB-KW
  4. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC
Complete GO annotation...

GO - Biological processi

  1. innate immune response Source: UniProtKB-KW
  2. intracellular signal transduction Source: InterPro
  3. regulation of transcription, DNA-templated Source: UniProtKB-KW
  4. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Adaptive immunity, Immunity, Innate immunity, Transcription, Transcription regulation

Keywords - Ligandi

ATP-binding, Lipid-binding, Metal-binding, Nucleotide-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase BTK (EC:2.7.10.2)
Alternative name(s):
Bruton tyrosine kinase
Gene namesi
Name:BTK
OrganismiGallus gallus (Chicken)
Taxonomic identifieri9031 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiTestudines + Archosauria groupArchosauriaDinosauriaSaurischiaTheropodaCoelurosauriaAvesNeognathaeGalliformesPhasianidaePhasianinaeGallus
ProteomesiUP000000539: Unplaced

Subcellular locationi

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.

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-SubCell
  2. nucleus Source: UniProtKB-SubCell
  3. plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed By similarity
Chaini2 – 657656Tyrosine-protein kinase BTK
PRO_0000088067Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine By similarity
Modified residuei20 – 201Phosphothreonine By similarity
Modified residuei21 – 211Phosphoserine By similarity
Modified residuei40 – 401Phosphotyrosine By similarity
Modified residuei55 – 551Phosphoserine By similarity
Modified residuei179 – 1791Phosphoserine; by PKC/PRKCB By similarity
Modified residuei190 – 1901Phosphothreonine By similarity
Modified residuei220 – 2201Phosphotyrosine; by autocatalysis By similarityBy similarity
Modified residuei306 – 3061Phosphoserine By similarity
Modified residuei321 – 3211Phosphoserine By similarity
Modified residuei342 – 3421Phosphotyrosine By similarity
Modified residuei359 – 3591Phosphotyrosine By similarity
Modified residuei373 – 3731Phosphotyrosine By similarity
Modified residuei549 – 5491Phosphotyrosine; by autocatalysis By similarityBy similarity
Modified residuei549 – 5491Phosphotyrosine; by LYN and SYK By similarity
Modified residuei602 – 6021Phosphoserine By similarity

Post-translational modificationi

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.

Keywords - PTMi

Acetylation, Phosphoprotein

Interactioni

Subunit structurei

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.

Structurei

3D structure databases

ProteinModelPortaliQ8JH64.
SMRiQ8JH64. Positions 2-169, 209-385, 395-652.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini3 – 132130PH
Add
BLAST
Domaini214 – 27057SH3
Add
BLAST
Domaini276 – 36691SH2
Add
BLAST
Domaini400 – 653254Protein kinase
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni12 – 2413Inositol-(1,3,4,5)-tetrakisphosphate 1-binding By similarity
Add
BLAST
Regioni472 – 4776Inhibitor-binding By similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi579 – 5868CAV1-binding By similarity

Domaini

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.

Sequence similaritiesi

Contains 1 PH domain.
Contains 1 SH2 domain.
Contains 1 SH3 domain.

Keywords - Domaini

SH2 domain, SH3 domain, Zinc-finger

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000233859.
HOVERGENiHBG008761.
InParanoidiQ8JH64.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
3.30.505.10. 1 hit.
InterProiIPR011009. Kinase-like_dom.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
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]
PfamiPF00779. BTK. 1 hit.
PF00169. PH. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00402. TECBTKDOMAIN.
PR00109. TYRKINASE.
SMARTiSM00107. BTK. 1 hit.
SM00233. PH. 1 hit.
SM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50003. 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]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q8JH64-1 [UniParc]FASTAAdd to Basket

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MASIILESIF LKRSQQKKKT SPLNFKKRLF LLTESKLSYY EYDFERGRRG    50
SKKGSVDIEK ITCVETVVPE NNPPPERQVP KKGEDYNMEQ ISIIERFPYP 100
FQVVYDEGPL YVFSPTEELR KRWIHQLKSV IRYNSDLVQK YHPCFWIDGQ 150
YLCCSQTAKN AMGCKILESR NGSLKAGRSH RKTKKPLPPT PEEDTMVMKP 200
LPPEPAPSAA GEMKKVVALY NYVPMNVQDL QLQKGEDYLI LEESHLPWWK 250
ARDKNGREGY IPSNYVTATS NSLEIYEWYS KNITRSQAEQ LLKQEGKEGG 300
FIVRDSTSKT GKYTVSVYAK SAVDPQGMIR HYVVCCTPQN QYYLAEKHLF 350
NTIPELITYH QHNSAGLISR LKYPVSRHQK SAPSTAGLGY GSWEIDPKDL 400
TFLKELGTGQ FGVVKYGKWR GQYNVAIKMI REGSMSEDEF IDEAKVMMNL 450
SHEKLVQLYG VCTKQRPIFI ITEYMANGCL LNFLRETQRR FQPAELLEMC 500
KDVCEAMEYL ESKQFLHRDL AARNCLVNDQ GIVKVSDFGL SRYVLDDEYT 550
SSMGSKFPVR WSPPEVLLYS KFSSKSDVWS FGVLMWEVYS LGKMPYERFN 600
NSETTEHVIQ GLRLYRPQQA SERVYAIMYS CWHEKAEERP TFSALLGSIV 650
DITDEEP 657
Length:657
Mass (Da):75,879
Last modified:October 1, 2002 - v1
Checksum:iFE5217E8E6195F6A
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF535118 mRNA. Translation: AAN04043.2.
UniGeneiGga.1305.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF535118 mRNA. Translation: AAN04043.2 .
UniGenei Gga.1305.

3D structure databases

ProteinModelPortali Q8JH64.
SMRi Q8JH64. Positions 2-169, 209-385, 395-652.
ModBasei Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000233859.
HOVERGENi HBG008761.
InParanoidi Q8JH64.

Miscellaneous databases

PROi Q8JH64.

Family and domain databases

Gene3Di 2.30.29.30. 1 hit.
3.30.505.10. 1 hit.
InterProi IPR011009. Kinase-like_dom.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
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 ]
Pfami PF00779. BTK. 1 hit.
PF00169. PH. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view ]
PRINTSi PR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00402. TECBTKDOMAIN.
PR00109. TYRKINASE.
SMARTi SM00107. BTK. 1 hit.
SM00233. PH. 1 hit.
SM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view ]
SUPFAMi SSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEi 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 ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiBTK_CHICK
AccessioniPrimary (citable) accession number: Q8JH64
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 16, 2004
Last sequence update: October 1, 2002
Last modified: September 3, 2014
This is version 94 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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