P16277 (BLK_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tyrosine-protein kinase Blk
EC=2.7.10.2

Alternative name(s):
B lymphocyte kinase
p55-Blk

Gene names

Name:

Blk

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	499 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Domain	SH2 domain SH3 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Lipoprotein Myristate Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell receptor signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of insulin secretion Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Traceable author statement. Source: Reactome plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 499

499

Tyrosine-protein kinase Blk

PRO_0000088062

Regions

Domain

52 – 112

61

SH3

Domain

118 – 214

97

SH2

Domain

235 – 488

254

Protein kinase

Nucleotide binding

241 – 249

9

ATP By similarity

Sites

Active site

354

1

Proton acceptor By similarity

Binding site

263

1

ATP By similarity

Amino acid modifications

Modified residue

383

1

Phosphotyrosine; by autocatalysis By similarity

Lipidation

2

1

N-myristoyl glycine By similarity

Experimental info

Mutagenesis

145

1

R → K: Impairs the interaction with CD79A and CD79B. Ref.13

Mutagenesis

495

1

Y → F: Leads to constitutive activation of BLK. Ref.17 Ref.19

Sequence conflict

421

1

E → V in AAA40453. Ref.1

Secondary structure

1

.

.

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.

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499

Helix Strand Turn

Details...

Beta strand

116 – 119

4

Helix

125 – 132

8

Beta strand

142 – 144

3

Beta strand

150 – 152

3

Beta strand

154 – 158

5

Beta strand

160 – 162

3

Turn

163 – 165

3

Beta strand

171 – 176

6

Turn

177 – 179

3

Beta strand

180 – 184

5

Beta strand

187 – 191

5

Helix

192 – 201

10

Beta strand

204 – 208

5

Sequences

	Sequence		Length	Mass (Da)
	P16277 [UniParc]. Last modified July 27, 2011. Version 4. Checksum: 14C607564BB4E66D	FASTA	499	56,674
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.

IPI

IPI00555003.

PIR

A40092.

RefSeq

NP_031575.2. NM_007549.2.

UniGene

Mm.3962.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BLJ	NMR	-	A	107-218	[»]
1BLK	NMR	-	A	107-218	[»]

ProteinModelPortal

P16277.

SMR

P16277. Positions 57-499.

ModBase

Search...

Protein-protein interaction databases

STRING

10090.ENSMUSP00000014597.

PTM databases

PhosphoSite

P16277.

Proteomic databases

PaxDb

P16277.

PRIDE

P16277.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000014597; ENSMUSP00000014597; ENSMUSG00000014453.

GeneID

12143.

KEGG

mmu:12143.

Organism-specific databases

CTD

640.

MGI

MGI:88169. Blk.

Phylogenomic databases

eggNOG

COG0515.

GeneTree

ENSGT00620000087866.

HOGENOM

HOG000233858.

HOVERGEN

HBG008761.

InParanoid

Q8K2M8.

KO

K08890.

OMA

VVFNHLT.

OrthoDB

EOG4Q84XM.

Enzyme and pathway databases

BRENDA

2.7.10.2. 3474.

Reactome

REACT_107772. Immune System.

Gene expression databases

Bgee

P16277.

CleanEx

MM_BLK.

Genevestigator

P16277.

GermOnline

ENSMUSG00000014453. Mus musculus.

Family and domain databases

Gene3D

3.30.505.10. 1 hit.

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_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]

Pfam

PF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]

PRINTS

PR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.

SMART

SM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.
SSF50044. SH3. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. False negative.
PS50001. SH2. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P16277.

ChEMBL

CHEMBL3343.

EvolutionaryTrace

P16277.

NextBio

280469.

SOURCE

Search...

Entry information

Entry name

BLK_MOUSE

Accession

Primary (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:	May 1, 2013
This is version 130 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program