Tyrosine-protein kinase BTK - Mus musculus (Mouse)

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Reviewed, UniProtKB/Swiss-Prot P35991 (BTK_MOUSE)

Last modified February 9, 2010. Version 112. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Tyrosine-protein kinase BTK
    EC=2.7.10.2
Alternative name(s):
    Bruton tyrosine kinase
    Agammaglobulinaemia tyrosine kinase
      Short name=ATK
    B-cell progenitor kinase
      Short name=BPK
    Kinase EMB

Gene names

Name:	Btk
Synonyms:	Bpk

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

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Protein attributes

Sequence length	659 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Plays a crucial role in B-cell ontogeny. Transiently phosphorylates GTF2I on tyrosine residues in response to B-cell receptor cross-linking. Required for the formation of functional ARID3A DNA-binding complexes. Ref.6 Ref.7 Ref.9 Ref.10
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Enzyme regulation	Inhibited by IBTK By similarity. Activated by phosphorylation.
Subunit structure	Binds GTF2I through the PH domain. Interacts with SH3BP5 via the SH3 domain. Interacts with IBTK via its PH domain By similarity. Interacts with GTF2I and ARID3A. Ref.9 Ref.10
Subcellular location	Cytoplasm. Membrane; Peripheral membrane protein. Nucleus Ref.9.
Domain	The PH domain mediates the binding to inositol polyphosphate and phosphoinositides. Ref.8
Post-translational modification	Autophosphorylated on Tyr-223 and Tyr-551. Phosphorylation of Tyr-223 may create a docking site for a SH2 containing protein. Ref.7 Ref.5 Ref.11
Involvement in disease	Defects in Btk are the cause of murine X-linked immunodeficiency (XID). Ref.9 Ref.12
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.

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Ontologies

Keywords
Cellular component	Cytoplasm Membrane Nucleus
Disease	Disease mutation
Domain	SH2 domain SH3 domain Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Acetylation Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	I-kappaB kinase/NF-kappaB cascade Inferred from mutant phenotype. Source: MGI cell maturation Inferred from mutant phenotype. Source: MGI peptidyl-tyrosine phosphorylation Inferred from direct assay. Source: MGI
Cellular component	cytoplasmic vesicle Inferred from direct assay. Source: MGI extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay. Source: MGI
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
Blnk	Q9QUN3	1	EBI-625119,EBI-642145
Grb2	Q60631	2	EBI-625119,EBI-1688
GTF2I	P78347	1	EBI-625119,EBI-359622	From a different organism.

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

Removed By similarity

Chain

2 – 659

658

Tyrosine-protein kinase BTK

PRO_0000088066

Regions

Domain

3 – 133

131

Domain

214 – 274

SH3

Domain

281 – 377

SH2

Domain

402 – 655

254

Protein kinase

Zinc finger

135 – 171

Btk-type

Nucleotide binding

408 – 416

ATP By similarity

Sites

Active site

521

Proton acceptor By similarity

Metal binding

143

Zinc By similarity

Metal binding

154

Zinc By similarity

Metal binding

155

Zinc By similarity

Metal binding

165

Zinc By similarity

Binding site

430

ATP By similarity

Amino acid modifications

Modified residue

N-acetylalanine By similarity

Modified residue

Phosphothreonine By similarity

Modified residue

Phosphoserine By similarity

Modified residue

Phosphotyrosine Ref.11

Modified residue

Phosphoserine By similarity

Modified residue

179

Phosphoserine By similarity

Modified residue

180

Phosphoserine By similarity

Modified residue

191

Phosphothreonine By similarity

Modified residue

223

Phosphotyrosine; by autocatalysis Ref.5

Modified residue

309

Phosphoserine By similarity

Modified residue

323

Phosphoserine By similarity

Modified residue

342

Phosphoserine By similarity

Modified residue

344

Phosphotyrosine Ref.11

Modified residue

361

Phosphotyrosine By similarity

Modified residue

375

Phosphotyrosine By similarity

Modified residue

551

Phosphotyrosine; by autocatalysis Ref.7 Ref.11

Modified residue

602

Phosphothreonine By similarity

Modified residue

604

Phosphoserine By similarity

Modified residue

659

Phosphoserine By similarity

Natural variations

Natural variant

R → C in XID; prevents interaction with ARID3A. Ref.9 Ref.12

Experimental info

Mutagenesis

E → K: Constitutive activation. Ref.6

Mutagenesis

223

Y → F: No autophosphorylation. Ref.5

Mutagenesis

430

K → R: Loss of activity and no phosphorylation. Ref.6 Ref.5

Sequence conflict

V → A in L10627. Ref.2

Sequence conflict

123

R → P in AAA37316. Ref.1

Sequence conflict

197

I → IWI Ref.2

Sequence conflict

450

Missing in L10627. Ref.2

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Sequences

Sequence

Length

Mass (Da)

Tools

P35991-1 [UniParc].

Last modified January 23, 2007. Version 4.
Checksum: E502B798BC36E223
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FASTA

659

76,437

        10         20         30         40         50         60 
MAAVILESIF LKRSQQKKKT SPLNFKKRLF LLTVHKLSYY EYDFERGRRG SKKGSIDVEK 

        70         80         90        100        110        120 
ITCVETVIPE KNPPPERQIP RRGEESSEME QISIIERFPY PFQVVYDEGP LYVFSPTEEL 

       130        140        150        160        170        180 
RKRWIHQLKN VIRYNSDLVQ KYHPCFWIDG QYLCCSQTAK NAMGCQILEN RNGSLKPGSS 

       190        200        210        220        230        240 
HRKTKKPLPP TPEEDQILKK PLPPEPTAAP ISTTELKKVV ALYDYMPMNA NDLQLRKGEE 

       250        260        270        280        290        300 
YFILEESNLP WWRARDKNGQ EGYIPSNYIT EAEDSIEMYE WYSKHMTRSQ AEQLLKQEGK 

       310        320        330        340        350        360 
EGGFIVRDSS KAGKYTVSVF AKSTGEPQGV IRHYVVCSTP QSQYYLAEKH LFSTIPELIN 

       370        380        390        400        410        420 
YHQHNSAGLI SRLKYPVSKQ NKNAPSTAGL GYGSWEIDPK DLTFLKELGT GQFGVVKYGK 

       430        440        450        460        470        480 
WRGQYDVAIK MIREGSMSED EFIEEAKVMM NLSHEKLVQL YGVCTKQRPI FIITEYMANG 

       490        500        510        520        530        540 
CLLNYLREMR HRFQTQQLLE MCKDVCEAME YLESKQFLHR DLAARNCLVN DQGVVKVSDF 

       550        560        570        580        590        600 
GLSRYVLDDE YTSSVGSKFP VRWSPPEVLM YSKFSSKSDI WAFGVLMWEI YSLGKMPYER 

       610        620        630        640        650 
FTNSETAEHI AQGLRLYRPH LASERVYTIM YSCWHEKADE RPSFKILLSN ILDVMDEES

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia." Tsukada S., Saffran D.C., Rawlings D.J., Parolini O., Allen R.C., Klisak I., Sparkes R.S., Kubagawa H., Mohandas T., Quan S., Belmont J.W., Cooper M.D., Conley M.E., Witte O.N. Cell 72:279-290(1993) [PubMed: 8425221] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Structure and expression of novel protein-tyrosine kinases, Emb and Emt, in hematopoietic cells." Yamada N., Kawakami Y., Kimura H., Fukamachi H., Baier G., Altman A., Kato T., Inagaki Y., Kawakami T. Biochem. Biophys. Res. Commun. 192:231-240(1993) [PubMed: 8476425] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Genomic organization of mouse and human Bruton's agammaglobulinemia tyrosine kinase (Btk) loci." Sideras P., Mueller S., Shiels H., Jin H., Khan W.N., Nilsson L., Parkinson E., Thomas J.D., Branden L., Larsson I., Paul W.E., Rosen F.S., Alt F.W., Vetrie D., Smith C.I.E., Xanthopoulos K.G. J. Immunol. 153:5607-5617(1994) [PubMed: 7989760] [Abstract] Cited for: NUCLEOTIDE SEQUENCE.
[4]	"Sixty-nine kilobases of contiguous human genomic sequence containing the alpha-galactosidase A and Bruton's tyrosine kinase loci." Oeltjen J.C., Liu X., Lu J., Allen R.C., Muzny D.M., Belmont J.W., Gibbs R.A. Mamm. Genome 6:334-338(1995) [PubMed: 7626884] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: C129.
[5]	"Regulation of Btk function by a major autophosphorylation site within the 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) [PubMed: 8630736] [Abstract] Cited for: PROTEIN SEQUENCE OF 219-233, PHOSPHORYLATION AT TYR-223, MUTAGENESIS OF TYR-223 AND LYS-430.
[6]	"Activation of Bruton's tyrosine kinase (BTK) by a point mutation in its pleckstrin homology (PH) domain." Li T., Tsukada S., Satterthwaite A., Havlik M.H., Park H., Takatsu K., Witte O.N. Immunity 2:451-460(1995) [PubMed: 7538439] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF GLU-41 AND LYS-430.
[7]	"Activation of BTK by a phosphorylation mechanism initiated by SRC family 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) [PubMed: 8629002] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT TYR-551.
[8]	"Characterization of the pleckstrin homology domain of Btk as an inositol polyphosphate and phosphoinositide binding domain." Kojima T., Fukuda M., Watanabe Y., Hamazato F., Mikoshiba K. Biochem. Biophys. Res. Commun. 236:333-339(1997) [PubMed: 9240435] [Abstract] Cited for: DOMAIN.
[9]	"The transcription factor Bright associates with Bruton's tyrosine kinase, the defective protein in immunodeficiency disease." Webb C.F., Yamashita Y., Ayers N., Evetts S., Paulin Y., Conley M.E., Smith E.A. J. Immunol. 165:6956-6965(2000) [PubMed: 11120822] [Abstract] Cited for: FUNCTION, INTERACTION WITH ARID3A, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT XID CYS-28.
[10]	"Induction of immunoglobulin heavy-chain transcription through the transcription factor Bright requires TFII-I." Rajaiya J., Nixon J.C., Ayers N., Desgranges Z.P., Roy A.L., Webb C.F. Mol. Cell. Biol. 26:4758-4768(2006) [PubMed: 16738337] [Abstract] Cited for: INTERACTION WITH GTF2I AND ARID3A, FUNCTION.
[11]	"Quantitative time-resolved phosphoproteomic analysis of mast cell signaling." 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) [PubMed: 17947660] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-40; TYR-344 AND TYR-551, MASS SPECTROMETRY. Tissue: Mast cell.
[12]	"Mutation of unique region of Bruton's tyrosine kinase in immunodeficient XID mice." Rawlings D.J., Saffran D.C., Tsukada S., Largaespada D.A., Grimaldi J.C., Cohen L., Mohr R.N., Bazan J.F., Howard M., Copeland N.G., Jenkins N.A., Witte O.N. Science 261:358-361(1993) [PubMed: 8332901] [Abstract] Cited for: VARIANT XID CYS-28.
+	Additional computationally mapped references.

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Cross-references

Sequence databases
EMBL GenBank DDBJ	L08967 mRNA. Translation: AAA37316.1. L10627 mRNA. No translation available. L29788 mRNA. Translation: AAA66943.1. U58105 Genomic DNA. Translation: AAB47246.1.
IPI	IPI00312116.
PIR	I49553.
RefSeq	NP_038510.2.
UniGene	Mm.4475
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	P35991. 27 interactions.
STRING	P35991.
PTM databases
PhosphoSite	P35991.
Proteomic databases
PRIDE	P35991.
Genome annotation databases
Ensembl	ENSMUST00000033617; ENSMUSP00000033617; ENSMUSG00000031264; Mus musculus. [Genome view]
GeneID	12229.
KEGG	mmu:12229.
UCSC	uc009uge.1. mouse.
Organism-specific databases
CTD	12229.
MGI	MGI:88216. Btk.
Phylogenomic databases
eggNOG	roNOG13677.
HOGENOM	HBG755340.
HOVERGEN	P35991.
InParanoid	P35991.
OMA	WEIDPKD.
OrthoDB	EOG97WR7S.
PhylomeDB	P35991.
Enzyme and pathway databases
BRENDA	2.7.10.2. 244.
Gene expression databases
ArrayExpress	P35991.
Bgee	P35991.
CleanEx	MM_BTK.
Genevestigator	P35991.
GermOnline	ENSMUSG00000031264. Mus musculus.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR011993. PH_type. IPR001849. Pleckstrin_homology. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR000980. SH2. IPR001452. SH3_domain. IPR020473. SH3_region. IPR020635. Tyr_Pkinase_cat_dom. IPR020685. Tyr_prot_kinase. IPR008266. Tyr_prot_kinase_AS. IPR001562. Znf_Btk_motif. [Graphical view]
Gene3D	G3DSA:2.30.29.30. PH_type. 1 hit. G3DSA:3.30.505.10. SH2. 1 hit.
PANTHER	PTHR23256. Tyr_prot_kinase. 1 hit.
Pfam	PF00779. BTK. 1 hit. PF00169. PH. 1 hit. PF00017. SH2. 1 hit. PF00018. SH3_1. 1 hit. [Graphical view]
PRINTS	PR00401. SH2DOMAIN. PR00452. SH3DOMAIN. PR00402. TECBTKDOMAIN.
SMART	SM00107. BTK. 1 hit. SM00233. PH. 1 hit. SM00252. SH2. 1 hit. SM00326. SH3. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
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...
Other Resources
NextBio	280647.
SOURCE	Search...

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Entry information

Entry name

BTK_MOUSE

Accession

Primary (citable) accession number: P35991
Secondary accession number(s): Q61365

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	January 23, 2007
Last modified:	February 9, 2010
This is version 112 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents