dbPTM

BTK_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	BTK_MOUSE
UniProt AC	P35991
Protein Name	Tyrosine-protein kinase BTK
Gene Name	Btk
Organism	Mus musculus (Mouse).
Sequence Length	659
Subcellular Localization	Cytoplasm . Cell membrane Peripheral membrane protein . Nucleus . In steady state, BTK is predominantly cytosolic. Following B-cell receptor (BCR) engagement by antigen, translocates to the plasma membrane through its PH domain. Plasma membrane loc
Protein Description	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..
Protein Sequence	MAAVILESIFLKRSQQKKKTSPLNFKKRLFLLTVHKLSYYEYDFERGRRGSKKGSIDVEKITCVETVIPEKNPPPERQIPRRGEESSEMEQISIIERFPYPFQVVYDEGPLYVFSPTEELRKRWIHQLKNVIRYNSDLVQKYHPCFWIDGQYLCCSQTAKNAMGCQILENRNGSLKPGSSHRKTKKPLPPTPEEDQILKKPLPPEPTAAPISTTELKKVVALYDYMPMNANDLQLRKGEEYFILEESNLPWWRARDKNGQEGYIPSNYITEAEDSIEMYEWYSKHMTRSQAEQLLKQEGKEGGFIVRDSSKAGKYTVSVFAKSTGEPQGVIRHYVVCSTPQSQYYLAEKHLFSTIPELINYHQHNSAGLISRLKYPVSKQNKNAPSTAGLGYGSWEIDPKDLTFLKELGTGQFGVVKYGKWRGQYDVAIKMIREGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANGCLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSSVGSKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKMPYERFTNSETAEHIAQGLRLYRPHLASERVYTIMYSCWHEKADERPSFKILLSNILDVMDEES

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Acetylation	------MAAVILESI ------CCCHHHHHH	15.50	-
8	Phosphorylation	MAAVILESIFLKRSQ CCCHHHHHHHHHHHH	18.39	28542873
21	Phosphorylation	SQQKKKTSPLNFKKR HHCCCCCCCCCHHHH	35.95	22817900
40	Phosphorylation	TVHKLSYYEYDFERG EHHHCCEEEECCCCC	12.49	22817900
55	Phosphorylation	RRGSKKGSIDVEKIT CCCCCCCCCCCEEEE	25.21	-
115	Phosphorylation	EGPLYVFSPTEELRK CCCEEEECCCHHHHH	22.37	22817900
134	Phosphorylation	QLKNVIRYNSDLVQK HHHHHHHCCHHHHHH	14.11	25367039
174	Phosphorylation	ILENRNGSLKPGSSH CCCCCCCCCCCCCCC	36.45	25367039
179	Phosphorylation	NGSLKPGSSHRKTKK CCCCCCCCCCCCCCC	31.34	25367039
180	Phosphorylation	GSLKPGSSHRKTKKP CCCCCCCCCCCCCCC	32.97	22817900
191	Phosphorylation	TKKPLPPTPEEDQIL CCCCCCCCCHHHCCC	41.20	27180971
207	Phosphorylation	KPLPPEPTAAPISTT CCCCCCCCCCCCCHH	33.51	21454597
214	Phosphorylation	TAAPISTTELKKVVA CCCCCCHHHHHHHHH	32.31	21454597
223	Phosphorylation	LKKVVALYDYMPMNA HHHHHHHHHCCCCCH	8.69	12023340
225	Phosphorylation	KVVALYDYMPMNAND HHHHHHHCCCCCHHH	6.91	26745281
309	Phosphorylation	GGFIVRDSSKAGKYT CCEEEECCCCCCCEE	24.15	29176673
310	Phosphorylation	GFIVRDSSKAGKYTV CEEEECCCCCCCEEE	30.71	29176673
315	Phosphorylation	DSSKAGKYTVSVFAK CCCCCCCEEEEEEEE	16.08	15879432
334	Phosphorylation	PQGVIRHYVVCSTPQ CCCEEEEEEEECCCH	5.68	-
342	Phosphorylation	VVCSTPQSQYYLAEK EEECCCHHHHHHHHH	22.73	25367039
344	Phosphorylation	CSTPQSQYYLAEKHL ECCCHHHHHHHHHHH	12.99	22817900
345	Phosphorylation	STPQSQYYLAEKHLF CCCHHHHHHHHHHHH	7.56	25367039
353	Phosphorylation	LAEKHLFSTIPELIN HHHHHHHCCHHHHHH	31.61	25367039
354	Phosphorylation	AEKHLFSTIPELINY HHHHHHCCHHHHHHH	32.96	25367039
361	Phosphorylation	TIPELINYHQHNSAG CHHHHHHHHHCCCCH	8.89	22817900
366	Phosphorylation	INYHQHNSAGLISRL HHHHHCCCCHHHHHC	22.91	25367039
371	Phosphorylation	HNSAGLISRLKYPVS CCCCHHHHHCCCCCC	36.28	25367039
375	Phosphorylation	GLISRLKYPVSKQNK HHHHHCCCCCCCCCC	17.29	16291652
425	Phosphorylation	YGKWRGQYDVAIKMI ECCCCCCEEHHHHHH	18.40	-
436	Phosphorylation	IKMIREGSMSEDEFI HHHHHCCCCCHHHHH	17.87	-
461	Phosphorylation	HEKLVQLYGVCTKQR HHHHHHHHCHHCCCC	7.16	-
485	Phosphorylation	ANGCLLNYLREMRHR CCCHHHHHHHHHHHH	13.70	29109428
543	Phosphorylation	KVSDFGLSRYVLDDE EECCCCCCEEEECCC	23.19	22817900
545	Phosphorylation	SDFGLSRYVLDDEYT CCCCCCEEEECCCCC	11.29	15879432
551	Phosphorylation	RYVLDDEYTSSVGSK EEEECCCCCCCCCCC	20.93	12023340
552	Phosphorylation	YVLDDEYTSSVGSKF EEECCCCCCCCCCCC	16.69	30635358
553	Phosphorylation	VLDDEYTSSVGSKFP EECCCCCCCCCCCCC	23.33	25367039
604	Phosphorylation	PYERFTNSETAEHIA CHHHCCCHHHHHHHH	33.01	-
617	Phosphorylation	IAQGLRLYRPHLASE HHHHHHHHCHHHCHH	18.70	22817900
623	Phosphorylation	LYRPHLASERVYTIM HHCHHHCHHHEEEEH	32.09	22817900
659	Phosphorylation	LDVMDEES------- HHHHCCCC-------	43.40	-

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
180	S	Phosphorylation	Kinase	PKCB	P68404	PSP
223	Y	Phosphorylation	Kinase	BTK	P35991	GPS
223	Y	Phosphorylation	Kinase	PIK3CD	O35904	PSP
375	Y	Phosphorylation	Kinase	BTK	P35991	PSP
551	Y	Phosphorylation	Kinase	BTK	P35991	PSP
551	Y	Phosphorylation	Kinase	SYK	P48025	Uniprot
551	Y	Phosphorylation	Kinase	LYN	P07948	PSP
551	Y	Phosphorylation	Kinase	LYN	P25911	Uniprot
551	Y	Phosphorylation	Kinase	PIK3CD	O35904	PSP
617	Y	Phosphorylation	Kinase	BTK	P35991	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
21	S	Phosphorylation	-
Phosphorylation at Ser-21 and Ser-115 creates a binding site for PIN1 at these Ser-Pro motifs, and promotes it's recruitment (By similarity).
115	S	Phosphorylation	-
Phosphorylation at Ser-21 and Ser-115 creates a binding site for PIN1 at these Ser-Pro motifs, and promotes it's recruitment (By similarity).
180	S	Phosphorylation	-
Phosphorylation at Ser-180 by PRKCB, leads in translocation of BTK back to the cytoplasmic fraction.

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of BTK_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference	Domain-Domain Interactions
GBB1_MOUSE	Gnb1	physical	7972043
GBG2_MOUSE	Gng2	physical	7972043

Drug and Disease Associations

Kegg Drug
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of BTK_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Quantitative time-resolved phosphoproteomic analysis of mast cellsignaling."; Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,Kawakami T., Salomon A.R.; J. Immunol. 179:5864-5876(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-40; TYR-344 AND TYR-551,AND MASS SPECTROMETRY.	17947660 [Abstract]
"Activation of BTK by a phosphorylation mechanism initiated by SRCfamily kinases."; Rawlings D.J., Scharenberg A.M., Park H., Wahl M.I., Lin S.,Kato R.M., Fluckiger A.C., Witte O.N., Kinet J.P.; Science 271:822-825(1996). Cited for: FUNCTION, AND PHOSPHORYLATION AT TYR-551.	8629002 [Abstract]
"Regulation of Btk function by a major autophosphorylation site withinthe SH3 domain."; Park H., Wahl M.I., Afar D.E., Turck C.W., Rawlings D.J., Tam C.,Scharenberg A.M., Kinet J.P., Witte O.N.; Immunity 4:515-525(1996). Cited for: PROTEIN SEQUENCE OF 219-233, PHOSPHORYLATION AT TYR-223, ANDMUTAGENESIS OF TYR-223 AND LYS-430.	8630736 [Abstract]

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