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P16277 (BLK_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tyrosine-protein kinase Blk

EC=2.7.10.2
Alternative name(s):
B lymphocyte kinase
p55-Blk
Gene names
Name:Blk
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length499 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling. B-cell receptor (BCR) signaling requires a tight regulation of several protein tyrosine kinases and phosphatases, and associated coreceptors. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. Signaling through BLK plays an important role in transmitting signals through surface immunoglobulins and supports the pro-B to pre-B transition, as well as the signaling for growth arrest and apoptosis downstream of B-cell receptor. Specifically binds and phosphorylates CD79A at 'Tyr-188'and 'Tyr-199', as well as CD79B at 'Tyr-196' and 'Tyr-207'. Phosphorylates also the immunoglobulin G receptor FCGR2. With FYN and LYN, plays an essential role in pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation. Contributes also to BTK activation by indirectly stimulating BTK intramolecular autophosphorylation. In pancreatic islets, acts as a modulator of beta-cells function through the up-regulation of PDX1 and NKX6-1 and consequent stimulation of insulin secretion in response to glucose. Ref.1 Ref.9 Ref.12 Ref.13 Ref.14 Ref.15 Ref.17 Ref.19 Ref.20

Catalytic activity

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

Enzyme regulation

Antibody-mediated surface engagement of the B-cell antigen receptor (BCR) which results in the phosphorylation of BLK on tyrosine residues, stimulates the enzymatic activity. Ref.6 Ref.11

Subunit structure

Interacts with CBL (via SH2 domain) By similarity. Interacts with CD79A and CD79B (via SH2 domain). Ref.8 Ref.13

Subcellular location

Cell membrane; Lipid-anchor By similarity. Note: Present and active in lipid rafts By similarity. Membrane location is required for the phosphorylation of CD79A and CD79B. Ref.13

Tissue specificity

Specifically expressed in the B-cell lineage. Ref.1 Ref.7

Induction

Expression increases during B-cell differentiation and is under the control of the B-cell specific transcription factors PAX5 and NF-kappa-B. Ref.6 Ref.10 Ref.11 Ref.12 Ref.16

Post-translational modification

Phosphorylated on tyrosine residues after antibody-mediated surface engagement of the B-cell antigen receptor (BCR).

Ubiquitination of activated BLK by the UBE3A ubiquitin protein ligase leads to its degradation by the ubiquitin-proteasome pathway.

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.

Contains 1 protein kinase domain.

Contains 1 SH2 domain.

Contains 1 SH3 domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 499498Tyrosine-protein kinase Blk
PRO_0000088062

Regions

Domain52 – 11261SH3
Domain118 – 21497SH2
Domain235 – 488254Protein kinase
Nucleotide binding241 – 2499ATP By similarity

Sites

Active site3541Proton acceptor By similarity
Binding site2631ATP By similarity

Amino acid modifications

Modified residue3831Phosphotyrosine; by autocatalysis By similarity
Lipidation21N-myristoyl glycine By similarity

Experimental info

Mutagenesis1451R → K: Impairs the interaction with CD79A and CD79B. Ref.13
Mutagenesis4951Y → F: Leads to constitutive activation of BLK. Ref.17 Ref.19
Sequence conflict4211E → V in AAA40453. Ref.1

Secondary structure

....................... 499
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P16277 [UniParc].

Last modified July 27, 2011. Version 4.
Checksum: 14C607564BB4E66D

FASTA49956,674
        10         20         30         40         50         60 
MGLLSSKRQV SEKGKGWSPV KIRTQDKAPP PLPPLVVFNH LAPPSPNQDP DEEERFVVAL 

        70         80         90        100        110        120 
FDYAAVNDRD LQVLKGEKLQ VLRSTGDWWL ARSLVTGREG YVPSNFVAPV ETLEVEKWFF 

       130        140        150        160        170        180 
RTISRKDAER QLLAPMNKAG SFLIRESESN KGAFSLSVKD ITTQGEVVKH YKIRSLDNGG 

       190        200        210        220        230        240 
YYISPRITFP TLQALVQHYS KKGDGLCQKL TLPCVNLAPK NLWAQDEWEI PRQSLKLVRK 

       250        260        270        280        290        300 
LGSGQFGEVW MGYYKNNMKV AIKTLKEGTM SPEAFLGEAN VMKTLQHERL VRLYAVVTRE 

       310        320        330        340        350        360 
PIYIVTEYMA RGCLLDFLKT DEGSRLSLPR LIDMSAQVAE GMAYIERMNS IHRDLRAANI 

       370        380        390        400        410        420 
LVSETLCCKI ADFGLARIID SEYTAQEGAK FPIKWTAPEA IHFGVFTIKA DVWSFGVLLM 

       430        440        450        460        470        480 
EIVTYGRVPY PGMSNPEVIR SLEHGYRMPC PETCPPELYN DIITECWRGR PEERPTFEFL 

       490 
QSVLEDFYTA TEGQYELQP 

« Hide

References

« Hide 'large scale' references
[1]"Specific expression of a tyrosine kinase gene, blk, in B lymphoid cells."
Dymecki S.M., Niederhuber J.E., Desiderio S.V.
Science 247:332-336(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
Tissue: B-cell.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: NOD.
[3]"Cloning of mouse full open reading frames in Gateway(R) system entry vector (pDONR201)."
Ebert L., Muenstermann E., Schatten R., Henze S., Bohn E., Mollenhauer J., Wiemann S., Schick M., Korn B.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Mammary gland.
[6]"Anti-immunoglobulin stimulation of B lymphocytes activates src-related protein-tyrosine kinases."
Burkhardt A.L., Brunswick M., Bolen J.B., Mond J.J.
Proc. Natl. Acad. Sci. U.S.A. 88:7410-7414(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[7]"Structure and developmental regulation of the B-lymphoid tyrosine kinase gene blk."
Dymecki S.M., Zwollo P., Zeller K., Kuhajda F.P., Desiderio S.V.
J. Biol. Chem. 267:4815-4823(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[8]"The MB-1/B29 heterodimer couples the B cell antigen receptor to multiple src family protein tyrosine kinases."
Lin J., Justement L.B.
J. Immunol. 149:1548-1555(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CD79A AND CD79B.
[9]"Antisense oligodeoxynucleotides to the blk tyrosine kinase prevent anti-mu-chain-mediated growth inhibition and apoptosis in a B-cell lymphoma."
Yao X.R., Scott D.W.
Proc. Natl. Acad. Sci. U.S.A. 90:7946-7950(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Specific recognition of the blk promoter by the B-lymphoid transcription factor B-cell-specific activator protein."
Zwollo P., Desiderio S.
J. Biol. Chem. 269:15310-15317(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION BY PAX5.
[11]"Temporal differences in the activation of three classes of non-transmembrane protein tyrosine kinases following B-cell antigen receptor surface engagement."
Saouaf S.J., Mahajan S., Rowley R.B., Kut S.A., Fargnoli J., Burkhardt A.L., Tsukada S., Witte O.N., Bolen J.B.
Proc. Natl. Acad. Sci. U.S.A. 91:9524-9528(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[12]"Differential expression of the blk and ret tyrosine kinases during B lineage development is dependent on Ig rearrangement."
Wasserman R., Li Y.S., Hardy R.R.
J. Immunol. 155:644-651(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION.
[13]"Reconstitution of the B cell antigen receptor signaling components in COS cells."
Saouaf S.J., Kut S.A., Fargnoli J., Rowley R.B., Bolen J.B., Mahajan S.
J. Biol. Chem. 270:27072-27078(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CD79A AND CD79B, INTERACTION WITH CD79A AND CD79B, SUBCELLULAR LOCATION, MUTAGENESIS OF ARG-145.
[14]"Src family protein tyrosine kinases induce autoactivation of Bruton's tyrosine kinase."
Mahajan S., Fargnoli J., Burkhardt A.L., Kut S.A., Saouaf S.J., Bolen J.B.
Mol. Cell. Biol. 15:5304-5311(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN REGULATION OF BTK ACTIVITY.
[15]"Palmitylation of Src family tyrosine kinases regulates functional interaction with a B cell substrate."
Saouaf S.J., Wolven A., Resh M.D., Bolen J.B.
Biochem. Biophys. Res. Commun. 234:325-329(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CD79A.
[16]"The transcription factor NF-kappaB/p50 interacts with the blk gene during B cell activation."
Zwollo P., Rao S., Wallin J.J., Gackstetter E.R., Koshland M.E.
J. Biol. Chem. 273:18647-18655(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[17]"Malignant transformation of early lymphoid progenitors in mice expressing an activated Blk tyrosine kinase."
Malek S.N., Dordai D.I., Reim J., Dintzis H., Desiderio S.
Proc. Natl. Acad. Sci. U.S.A. 95:7351-7356(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF TYR-495.
[18]"Regulation of the Src family tyrosine kinase Blk through E6AP-mediated ubiquitination."
Oda H., Kumar S., Howley P.M.
Proc. Natl. Acad. Sci. U.S.A. 96:9557-9562(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION.
[19]"Mimicry of pre-B-cell receptor signaling by activation of the tyrosine kinase Blk."
Tretter T., Ross A.E., Dordai D.I., Desiderio S.
J. Exp. Med. 198:1863-1873(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF TYR-495.
[20]"Essential role of Src-family protein tyrosine kinases in NF-kappaB activation during B cell development."
Saijo K., Schmedt C., Su I.H., Karasuyama H., Lowell C.A., Reth M., Adachi T., Patke A., Santana A., Tarakhovsky A.
Nat. Immunol. 4:274-279(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[21]"The three-dimensional solution structure of the SH2 domain from p55blk kinase."
Metzler W.J., Leiting B., Pryor K., Mueller L., Farmer B.T. II
Biochemistry 35:6201-6211(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF SH2 DOMAIN.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M30903 mRNA. Translation: AAA40453.1.
AK089888 mRNA. Translation: BAC40986.1.
CT010240 mRNA. Translation: CAJ18448.1.
AC090496 Genomic DNA. No translation available.
BC030668 mRNA. Translation: AAH30668.1.
CCDSCCDS27200.1.
PIRA40092.
RefSeqNP_031575.2. NM_007549.2.
UniGeneMm.3962.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1BLJNMR-A107-218[»]
1BLKNMR-A107-218[»]
ProteinModelPortalP16277.
SMRP16277. Positions 57-499.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP16277. 3 interactions.
STRING10090.ENSMUSP00000014597.

Chemistry

BindingDBP16277.
ChEMBLCHEMBL3343.

PTM databases

PhosphoSiteP16277.

Proteomic databases

PaxDbP16277.
PRIDEP16277.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000014597; ENSMUSP00000014597; ENSMUSG00000014453.
GeneID12143.
KEGGmmu:12143.
UCSCuc007uhq.1. mouse.

Organism-specific databases

CTD640.
MGIMGI:88169. Blk.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00620000087866.
HOGENOMHOG000233858.
HOVERGENHBG008761.
InParanoidQ8K2M8.
KOK08890.
OMAKNNMKVA.
OrthoDBEOG7GTT2V.
TreeFamTF351634.

Enzyme and pathway databases

BRENDA2.7.10.2. 3474.

Gene expression databases

BgeeP16277.
CleanExMM_BLK.
GenevestigatorP16277.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR000980. SH2.
IPR001452. SH3_domain.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PfamPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS50001. SH2. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP16277.
NextBio280469.
PROP16277.
SOURCESearch...

Entry information

Entry nameBLK_MOUSE
AccessionPrimary (citable) accession number: P16277
Secondary accession number(s): Q8K2M8
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 144 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

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