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P51451 (BLK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length505 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 receptors FCGR2A, FCGR2B and FCGR2C. 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.7 Ref.10

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 By similarity.

Subunit structure

Interacts with CBL (via SH2 domain). Interacts with CD79A and CD79B (via SH2 domain) By similarity. Ref.6

Subcellular location

Cell membrane; Lipid-anchor By similarity. Note: Present and active in lipid rafts. Membrane location is required for the phosphorylation of CD79A and CD79B By similarity. Ref.9

Tissue specificity

Expressed in lymphatic organs, pancreatic islets, Leydig cells, striate ducts of salivary glands and hair follicles. Ref.10

Induction

Expression is under the control of NF-kappa-B as well as the B-cell specific transcription factors PAX5 and EBF1. Ref.8

Post-translational modification

Phosphorylated on tyrosine residues after antibody-mediated surface engagement of the B-cell antigen receptor (BCR) By similarity. Ref.9

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

Involvement in disease

Maturity-onset diabetes of the young 11 (MODY11) [MIM:613375]: A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

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 – 505504Tyrosine-protein kinase Blk
PRO_0000088061

Regions

Domain58 – 11861SH3
Domain124 – 22097SH2
Domain241 – 494254Protein kinase
Nucleotide binding247 – 2559ATP By similarity

Sites

Active site3601Proton acceptor By similarity
Binding site2691ATP By similarity

Amino acid modifications

Modified residue3891Phosphotyrosine; by autocatalysis By similarity
Lipidation21N-myristoyl glycine By similarity

Natural variations

Natural variant481T → I. Ref.12
Corresponds to variant rs35339715 [ dbSNP | Ensembl ].
VAR_041672
Natural variant711A → T Associated with MODY11; reduces the enhancing effect of BLK on insulin secretion; reduces the inducing effect of BLK on the expression of PDX1 and NKX6-1; found as somatic mutation in a colorectal adenocarcinoma sample. Ref.10 Ref.12
Corresponds to variant rs55758736 [ dbSNP | Ensembl ].
VAR_041673

Experimental info

Sequence conflict2871V → M in CAA83965. Ref.1
Sequence conflict4071I → Y in AAB33265. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P51451 [UniParc].

Last modified August 21, 2007. Version 3.
Checksum: B5F739BEF8389176

FASTA50557,706
        10         20         30         40         50         60 
MGLVSSKKPD KEKPIKEKDK GQWSPLKVSA QDKDAPPLPP LVVFNHLTPP PPDEHLDEDK 

        70         80         90        100        110        120 
HFVVALYDYT AMNDRDLQML KGEKLQVLKG TGDWWLARSL VTGREGYVPS NFVARVESLE 

       130        140        150        160        170        180 
MERWFFRSQG RKEAERQLLA PINKAGSFLI RESETNKGAF SLSVKDVTTQ GELIKHYKIR 

       190        200        210        220        230        240 
CLDEGGYYIS PRITFPSLQA LVQHYSKKGD GLCQRLTLPC VRPAPQNPWA QDEWEIPRQS 

       250        260        270        280        290        300 
LRLVRKLGSG QFGEVWMGYY KNNMKVAIKT LKEGTMSPEA FLGEANVMKA LQHERLVRLY 

       310        320        330        340        350        360 
AVVTKEPIYI VTEYMARGCL LDFLKTDEGS RLSLPRLIDM SAQIAEGMAY IERMNSIHRD 

       370        380        390        400        410        420 
LRAANILVSE ALCCKIADFG LARIIDSEYT AQEGAKFPIK WTAPEAIHFG VFTIKADVWS 

       430        440        450        460        470        480 
FGVLLMEVVT YGRVPYPGMS NPEVIRNLER GYRMPRPDTC PPELYRGVIA ECWRSRPEER 

       490        500 
PTFEFLQSVL EDFYTATERQ YELQP 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning, characterization, and chromosomal localization of a human lymphoid tyrosine kinase related to murine Blk."
Islam K.B., Rabbani H., Larsson C., Sanders R., Smith C.I.
J. Immunol. 154:1265-1272(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Molecular cloning and chromosomal localization of the human homologue of a B-lymphocyte specific protein tyrosine kinase (blk)."
Drebin J.A., Hartzell S.W., Griffin C., Campbell M.J., Niederhuber J.E.
Oncogene 10:477-486(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Spleen.
[4]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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].
Tissue: Blood and Lymph.
[6]"The protein product of the c-cbl protooncogene is the 120-kDa tyrosine-phosphorylated protein in Jurkat cells activated via the T cell antigen receptor."
Donovan J.A., Wange R.L., Langdon W.Y., Samelson L.E.
J. Biol. Chem. 269:22921-22924(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CBL.
[7]"In vivo and in vitro specificity of protein tyrosine kinases for immunoglobulin G receptor (FcgammaRII) phosphorylation."
Bewarder N., Weinrich V., Budde P., Hartmann D., Flaswinkel H., Reth M., Frey J.
Mol. Cell. Biol. 16:4735-4743(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF FCGR2A; FCGR2B AND FCGR2C.
[8]"Early B cell factor is an activator of the B lymphoid kinase promoter in early B cell development."
Akerblad P., Sigvardsson M.
J. Immunol. 163:5453-5461(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[9]"IgA Fc receptor (FcalphaR) cross-linking recruits tyrosine kinases, phosphoinositide kinases and serine/threonine kinases to glycolipid rafts."
Lang M.L., Chen Y.W., Shen L., Gao H., Lang G.A., Wade T.K., Wade W.F.
Biochem. J. 364:517-525(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, SUBCELLULAR LOCATION.
[10]"Mutations at the BLK locus linked to maturity onset diabetes of the young and beta-cell dysfunction."
Borowiec M., Liew C.W., Thompson R., Boonyasrisawat W., Hu J., Mlynarski W.M., El Khattabi I., Kim S.H., Marselli L., Rich S.S., Krolewski A.S., Bonner-Weir S., Sharma A., Sale M., Mychaleckyj J.C., Kulkarni R.N., Doria A.
Proc. Natl. Acad. Sci. U.S.A. 106:14460-14465(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS REGULATOR OF INSULIN SECRETION, TISSUE SPECIFICITY, INVOLVEMENT IN MODY11, VARIANT THR-71, CHARACTERIZATION OF VARIANT THR-71.
[11]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] ILE-48; THR-71 AND THR-71.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z33998 mRNA. Translation: CAA83965.1.
S76617 mRNA. Translation: AAB33265.1.
AK313751 mRNA. Translation: BAG36491.1.
CH471157 Genomic DNA. Translation: EAW65617.1.
BC007371 mRNA. Translation: AAH07371.1.
BC032413 mRNA. Translation: AAH32413.1.
PIRI37206.
RefSeqNP_001706.2. NM_001715.2.
UniGeneHs.146591.

3D structure databases

ProteinModelPortalP51451.
SMRP51451. Positions 33-505.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107109. 13 interactions.
IntActP51451. 5 interactions.
MINTMINT-1494192.
STRING9606.ENSP00000259089.

Chemistry

BindingDBP51451.
ChEMBLCHEMBL2363074.
GuidetoPHARMACOLOGY1940.

PTM databases

PhosphoSiteP51451.

Polymorphism databases

DMDM158936749.

Proteomic databases

PaxDbP51451.
PRIDEP51451.

Protocols and materials databases

DNASU640.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000259089; ENSP00000259089; ENSG00000136573.
GeneID640.
KEGGhsa:640.
UCSCuc003wty.3. human.

Organism-specific databases

CTD640.
GeneCardsGC08P011388.
H-InvDBHIX0007315.
HIX0168887.
HGNCHGNC:1057. BLK.
HPACAB005093.
MIM191305. gene.
613375. phenotype.
neXtProtNX_P51451.
Orphanet552. MODY syndrome.
536. Systemic lupus erythematosus.
PharmGKBPA25368.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233858.
HOVERGENHBG008761.
InParanoidP51451.
KOK08890.
OMAKNNMKVA.
OrthoDBEOG7GTT2V.
PhylomeDBP51451.
TreeFamTF351634.

Enzyme and pathway databases

BRENDA2.7.10.2. 2681.
ReactomeREACT_6900. Immune System.
SignaLinkP51451.

Gene expression databases

ArrayExpressP51451.
BgeeP51451.
CleanExHS_BLK.
GenevestigatorP51451.

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

ChiTaRSBLK. human.
GeneWikiTyrosine-protein_kinase_BLK.
GenomeRNAi640.
NextBio2596.
PROP51451.
SOURCESearch...

Entry information

Entry nameBLK_HUMAN
AccessionPrimary (citable) accession number: P51451
Secondary accession number(s): Q16291, Q96IN1
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: August 21, 2007
Last modified: April 16, 2014
This is version 136 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM