EKS-MUM-00109

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-MUM-00109

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TK/Tec	488.9	6.4E-147	402	652	251

Status

Reviewed

Ensembl Protein

ENSMUSP00000033617

UniProt Accession

P35991; Q61365;

Protein Name

Tyrosine-protein kinase BTK

Protein Synonyms/Alias

Agammaglobulinaemia tyrosine kinase; ATK; B-cell progenitor kinase; BPK; Bruton tyrosine kinase; Kinase EMB;

Gene Name

Btk

Gene Synonyms/Alias

Btk; Bpk;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSMUSG00000031264	ENSMUSP00000033617	ENSMUST00000033617
ENSMUSG00000031264	ENSMUSP00000108839	ENSMUST00000113213

Organism

Mus musculus

Functional Description

Non-receptor tyrosine kinase indispensable for Blymphocyte 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.

Protein Length

659

Protein Sequence
(FASTA)

MAAVILESIF LKRSQQKKKT SPLNFKKRLF LLTVHKLSYY EYDFERGRRG SKKGSIDVEK 60

ITCVETVIPE KNPPPERQIP RRGEESSEME QISIIERFPY PFQVVYDEGP LYVFSPTEEL 120

RKRWIHQLKN VIRYNSDLVQ KYHPCFWIDG QYLCCSQTAK NAMGCQILEN RNGSLKPGSS 180

HRKTKKPLPP TPEEDQILKK PLPPEPTAAP ISTTELKKVV ALYDYMPMNA NDLQLRKGEE 240

YFILEESNLP WWRARDKNGQ EGYIPSNYIT EAEDSIEMYE WYSKHMTRSQ AEQLLKQEGK 300

EGGFIVRDSS KAGKYTVSVF AKSTGEPQGV IRHYVVCSTP QSQYYLAEKH LFSTIPELIN 360

YHQHNSAGLI SRLKYPVSKQ NKNAPSTAGL GYGSWEIDPK DLTFLKELGT GQFGVVKYGK 420

WRGQYDVAIK MIREGSMSED EFIEEAKVMM NLSHEKLVQL YGVCTKQRPI FIITEYMANG 480

CLLNYLREMR HRFQTQQLLE MCKDVCEAME YLESKQFLHR DLAARNCLVN DQGVVKVSDF 540

GLSRYVLDDE YTSSVGSKFP VRWSPPEVLM YSKFSSKSDI WAFGVLMWEI YSLGKMPYER 600

FTNSETAEHI AQGLRLYRPH LASERVYTIM YSCWHEKADE RPSFKILLSN ILDVMDEES 659

Nucleotide Sequence
(FASTA)

ATGGCTGCAG TGATACTGGA GAGCATCTTT CTGAAGCGCT CCCAGCAGAA AAAGAAAACA 60

TCACCTTTAA ACTTCAAGAA GCGCCTGTTT CTCTTGACTG TACACAAACT TTCATACTAT 120

GAATATGACT TTGAACGTGG GAGAAGAGGC AGTAAGAAAG GTTCAATAGA TGTTGAGAAG 180

ATCACCTGTG TTGAAACAGT AATTCCTGAA AAAAATCCCC CACCAGAAAG ACAGATTCCG 240

AGGAGAGGTG AGGAGTCTAG TGAAATGGAA CAGATTTCAA TCATTGAAAG GTTCCCGTAC 300

CCATTCCAGG TTGTATATGA TGAAGGACCT CTCTATGTTT TCTCCCCAAC TGAAGAGCTG 360

AGAAAGCGCT GGATTCACCA GCTCAAAAAT GTAATCCGGT ACAATAGTGA CCTGGTACAG 420

AAATACCATC CTTGCTTCTG GATTGATGGA CAGTATCTCT GCTGCTCTCA GACAGCCAAG 480

AATGCTATGG GCTGCCAAAT TTTGGAGAAC AGGAATGGAA GCTTAAAACC TGGGAGTTCT 540

CATCGAAAAA CGAAAAAGCC TCTTCCCCCT ACCCCAGAGG AAGATCAGAT CTTGAAAAAA 600

CCGCTTCCCC CGGAGCCAAC AGCAGCACCA ATCTCCACAA CCGAGCTGAA AAAGGTCGTG 660

GCCCTTTATG ATTACATGCC AATGAACGCA AATGACTTAC AATTGCGAAA GGGCGAGGAG 720

TATTTTATCC TGGAGGAGAG CAACCTACCG TGGTGGCGAG CACGAGATAA AAATGGGCAG 780

GAAGGCTACA TCCCAAGTAA CTATATCACT GAAGCTGAGG ACTCCATAGA GATGTATGAG 840

TGGTATTCCA AGCACATGAC TCGAAGTCAA GCTGAGCAAC TGCTAAAGCA AGAGGGGAAA 900

GAAGGAGGTT TCATTGTCAG AGACTCCAGC AAAGCTGGAA AATACACCGT GTCTGTGTTT 960

GCTAAATCTA CTGGGGAGCC TCAAGGGGTG ATCCGCCATT ACGTTGTGTG TTCCACGCCA 1020

CAGAGCCAGT ATTACCTGGC TGAGAAACAC CTCTTCAGCA CCATCCCTGA GCTCATTAAC 1080

TACCATCAAC ACAACTCTGC AGGCCTCATA TCCAGGCTGA AATATCCTGT GTCTAAACAA 1140

AACAAAAACG CGCCTTCTAC TGCAGGCCTG GGCTATGGAT CATGGGAAAT TGATCCAAAG 1200

GACCTCACCT TCTTGAAGGA GCTTGGGACT GGACAATTCG GTGTCGTGAA ATATGGGAAG 1260

TGGAGGGGCC AATATGATGT GGCCATCAAG ATGATCAGAG AAGGTTCCAT GTCGGAGGAT 1320

GAATTCATTG AAGAAGCCAA AGTCATGATG AATCTTTCCC ATGAGAAGCT GGTGCAGTTG 1380

TATGGCGTCT GCACCAAACA ACGCCCCATC TTCATCATCA CCGAGTACAT GGCTAATGGC 1440

TGCCTCTTGA ACTACCTGAG GGAGATGCGG CACCGCTTCC AGACACAGCA GCTGCTTGAG 1500

ATGTGCAAAG ATGTCTGTGA AGCAATGGAA TACTTGGAGT CGAAGCAGTT CCTTCACAGA 1560

GACCTGGCAG CTCGAAACTG TTTGGTAAAC GATCAAGGAG TTGTGAAAGT ATCTGACTTT 1620

GGCCTGTCTA GGTATGTCCT TGATGATGAG TACACCAGCT CTGTAGGCTC CAAGTTTCCA 1680

GTCCGGTGGT CTCCACCAGA AGTGCTTATG TATAGCAAGT TCAGCAGCAA ATCTGACATC 1740

TGGGCTTTTG GGGTTTTAAT GTGGGAGATC TACTCCCTGG GGAAGATGCC GTATGAGAGA 1800

TTTACTAACA GTGAGACAGC AGAACACATT GCTCAAGGCT TACGTCTCTA CAGGCCTCAT 1860

CTGGCATCAG AGAGGGTATA TACCATCATG TACAGCTGCT GGCACGAGAA AGCAGATGAA 1920

CGTCCTAGTT TCAAAATTCT CTTGAGTAAC ATTCTAGATG TGATGGATGA AGAATCCTGA 1980

Domain Profile

S: 1     ltllkelgsgqfgvvklgkwrakidvaikaikegamseedfieeakvmmklshpklvqly  60

         lt+lkelg+gqfgvvk+gkwr+++dvaik+i+eg+mse++fieeakvmm+lsh+klvqly

Q: 402   LTFLKELGTGQFGVVKYGKWRGQYDVAIKMIREGSMSEDEFIEEAKVMMNLSHEKLVQLY  461

         79**********************************************************

S: 61    gvclkqkpiyivteylengcllnylrekkkklekelllemckdvcegmeylerksfihrd  120

         gvc+kq+pi+i+tey++ngcllnylre+++++++++llemckdvce+meyle+k+f+hrd

Q: 462   GVCTKQRPIFIITEYMANGCLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRD  521

         ************************************************************

S: 121   laarnclvdeelvvkvsdfglaryvlddqyvssvgakfpvkwsppevlsyskyssksdvw  180

         laarnclv+++ vvkvsdfgl+ryvldd+y+ssvg+kfpv+wsppevl+ysk+ssksd+w

Q: 522   LAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSSVGSKFPVRWSPPEVLMYSKFSSKSDIW  581

         ************************************************************

S: 181   afgvlmwevfsegklpyekksnsevvekvsrglrlyrpklaskkvyevmkscwkekpeer  240

         afgvlmwe++s+gk+pye+++nse++e++++glrlyrp+las++vy++m+scw+ek++er

Q: 582   AFGVLMWEIYSLGKMPYERFTNSETAEHIAQGLRLYRPHLASERVYTIMYSCWHEKADER  641

         ************************************************************

S: 241   ptfkellsale  251

         p+fk lls++

Q: 642   PSFKILLSNIL  652

         ********996

Domain Sequence
(FASTA)

LTFLKELGTG QFGVVKYGKW RGQYDVAIKM IREGSMSEDE FIEEAKVMMN LSHEKLVQLY 60

GVCTKQRPIF IITEYMANGC LLNYLREMRH RFQTQQLLEM CKDVCEAMEY LESKQFLHRD 120

LAARNCLVND QGVVKVSDFG LSRYVLDDEY TSSVGSKFPV RWSPPEVLMY SKFSSKSDIW 180

AFGVLMWEIY SLGKMPYERF TNSETAEHIA QGLRLYRPHL ASERVYTIMY SCWHEKADER 240

PSFKILLSNI L 251

Keyword

Acetylation; Adaptive immunity; Apoptosis; ATP-binding; Cell membrane; Complete proteome; Cytoplasm; Direct protein sequencing; Disease mutation; Immunity; Innate immunity; Kinase; Lipid-binding; Membrane; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; SH2 domain; SH3 domain; Transcription; Transcription regulation; Transferase; Tyrosine-protein kinase; Zinc; Zinc-finger.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Ciona savignyi"; ?>Danio rerio"; ?>Drosophila melanogaster"; ?>Equus caballus"; ?>Felis catus"; ?>Gadus morhua"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Homo sapiens"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Oreochromis niloticus"; ?>Ornithorhynchus anatinus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Petromyzon marinus"; ?>Pongo abelii"; ?>Pteropus vampyrus"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sorex araneus"; ?>Sus scrofa"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0031410	; C:cytoplasmic vesicle
GO:0005829	; C:cytosol
GO:0045121	; C:membrane raft
GO:0005634	; C:nucleus
GO:0005886	; C:plasma membrane
GO:0005524	; F:ATP binding
GO:0046872	; F:metal ion binding
GO:0004715	; F:non-membrane spanning protein tyrosine kinase activity
GO:0005547	; F:phosphatidylinositol-3,4,5-trisphosphate binding
GO:0004713	; F:protein tyrosine kinase activity
GO:0006915	; P:apoptotic process
GO:0048469	; P:cell maturation
GO:0007249	; P:I-kappaB kinase/NF-kappaB cascade
GO:0045087	; P:innate immune response
GO:0018108	; P:peptidyl-tyrosine phosphorylation
GO:0006355	; P:regulation of transcription, DNA-dependent
GO:0006351	; P:transcription, DNA-dependent

KEGG

mmu:12229

;

InterPros

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.

Pfam

PF00779	; BTK; 1.
PF00169	; PH; 1.
PF07714	; Pkinase_Tyr; 1.
PF00017	; SH2; 1.
PF00018	; SH3_1; 1.

SMARTs

SM00107	; BTK; 1.
SM00233	; PH; 1.
SM00252	; SH2; 1.
SM00326	; SH3; 1.
SM00219	; TyrKc; 1.

Prosites

PS50003	; PH_DOMAIN; 1.
PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00109	; PROTEIN_KINASE_TYR; 1.
PS50001	; SH2; 1.
PS50002	; SH3; 1.
PS51113	; ZF_BTK; 1.

Prints

PR00401	; SH2DOMAIN.
PR00452	; SH3DOMAIN.
PR00402	; TECBTKDOMAIN.
PR00109	; TYRKINASE.

Created Date

20-Feb-2013