BLK_MOUSE
ID BLK_MOUSE Reviewed; 499 AA.
AC P16277; Q8K2M8;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 4.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Tyrosine-protein kinase Blk;
DE EC=2.7.10.2;
DE AltName: Full=B lymphocyte kinase;
DE AltName: Full=p55-Blk;
GN Name=Blk;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=B-cell;
RX PubMed=2404338; DOI=10.1126/science.2404338;
RA Dymecki S.M., Niederhuber J.E., Desiderio S.V.;
RT "Specific expression of a tyrosine kinase gene, blk, in B lymphoid cells.";
RL Science 247:332-336(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NOD;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Muenstermann E., Schatten R., Henze S., Bohn E., Mollenhauer J.,
RA Wiemann S., Schick M., Korn B.;
RT "Cloning of mouse full open reading frames in Gateway(R) system entry
RT vector (pDONR201).";
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP ACTIVITY REGULATION.
RX PubMed=1714601; DOI=10.1073/pnas.88.16.7410;
RA Burkhardt A.L., Brunswick M., Bolen J.B., Mond J.J.;
RT "Anti-immunoglobulin stimulation of B lymphocytes activates src-related
RT protein-tyrosine kinases.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:7410-7414(1991).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=1537861; DOI=10.1016/s0021-9258(18)42905-5;
RA Dymecki S.M., Zwollo P., Zeller K., Kuhajda F.P., Desiderio S.V.;
RT "Structure and developmental regulation of the B-lymphoid tyrosine kinase
RT gene blk.";
RL J. Biol. Chem. 267:4815-4823(1992).
RN [8]
RP INTERACTION WITH CD79A AND CD79B.
RX PubMed=1506682;
RA Lin J., Justement L.B.;
RT "The MB-1/B29 heterodimer couples the B cell antigen receptor to multiple
RT src family protein tyrosine kinases.";
RL J. Immunol. 149:1548-1555(1992).
RN [9]
RP FUNCTION.
RX PubMed=7690139; DOI=10.1073/pnas.90.17.7946;
RA Yao X.R., Scott D.W.;
RT "Antisense oligodeoxynucleotides to the blk tyrosine kinase prevent anti-
RT mu-chain-mediated growth inhibition and apoptosis in a B-cell lymphoma.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:7946-7950(1993).
RN [10]
RP INDUCTION BY PAX5.
RX PubMed=8195169; DOI=10.1016/s0021-9258(17)36607-3;
RA Zwollo P., Desiderio S.;
RT "Specific recognition of the blk promoter by the B-lymphoid transcription
RT factor B-cell-specific activator protein.";
RL J. Biol. Chem. 269:15310-15317(1994).
RN [11]
RP ACTIVITY REGULATION.
RX PubMed=7524079; DOI=10.1073/pnas.91.20.9524;
RA Saouaf S.J., Mahajan S., Rowley R.B., Kut S.A., Fargnoli J.,
RA Burkhardt A.L., Tsukada S., Witte O.N., Bolen J.B.;
RT "Temporal differences in the activation of three classes of non-
RT transmembrane protein tyrosine kinases following B-cell antigen receptor
RT surface engagement.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:9524-9528(1994).
RN [12]
RP FUNCTION, AND INDUCTION.
RX PubMed=7608542;
RA Wasserman R., Li Y.S., Hardy R.R.;
RT "Differential expression of the blk and ret tyrosine kinases during B
RT lineage development is dependent on Ig rearrangement.";
RL J. Immunol. 155:644-651(1995).
RN [13]
RP FUNCTION IN PHOSPHORYLATION OF CD79A AND CD79B, INTERACTION WITH CD79A AND
RP CD79B, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ARG-145.
RX PubMed=7592958; DOI=10.1074/jbc.270.45.27072;
RA Saouaf S.J., Kut S.A., Fargnoli J., Rowley R.B., Bolen J.B., Mahajan S.;
RT "Reconstitution of the B cell antigen receptor signaling components in COS
RT cells.";
RL J. Biol. Chem. 270:27072-27078(1995).
RN [14]
RP FUNCTION IN REGULATION OF BTK ACTIVITY.
RX PubMed=7565679; DOI=10.1128/mcb.15.10.5304;
RA Mahajan S., Fargnoli J., Burkhardt A.L., Kut S.A., Saouaf S.J., Bolen J.B.;
RT "Src family protein tyrosine kinases induce autoactivation of Bruton's
RT tyrosine kinase.";
RL Mol. Cell. Biol. 15:5304-5311(1995).
RN [15]
RP FUNCTION IN PHOSPHORYLATION OF CD79A.
RX PubMed=9177269; DOI=10.1006/bbrc.1997.6638;
RA Saouaf S.J., Wolven A., Resh M.D., Bolen J.B.;
RT "Palmitylation of Src family tyrosine kinases regulates functional
RT interaction with a B cell substrate.";
RL Biochem. Biophys. Res. Commun. 234:325-329(1997).
RN [16]
RP INDUCTION.
RX PubMed=9660839; DOI=10.1074/jbc.273.29.18647;
RA Zwollo P., Rao S., Wallin J.J., Gackstetter E.R., Koshland M.E.;
RT "The transcription factor NF-kappaB/p50 interacts with the blk gene during
RT B cell activation.";
RL J. Biol. Chem. 273:18647-18655(1998).
RN [17]
RP FUNCTION, AND MUTAGENESIS OF TYR-495.
RX PubMed=9636152; DOI=10.1073/pnas.95.13.7351;
RA Malek S.N., Dordai D.I., Reim J., Dintzis H., Desiderio S.;
RT "Malignant transformation of early lymphoid progenitors in mice expressing
RT an activated Blk tyrosine kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:7351-7356(1998).
RN [18]
RP UBIQUITINATION.
RX PubMed=10449731; DOI=10.1073/pnas.96.17.9557;
RA Oda H., Kumar S., Howley P.M.;
RT "Regulation of the Src family tyrosine kinase Blk through E6AP-mediated
RT ubiquitination.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:9557-9562(1999).
RN [19]
RP FUNCTION, AND MUTAGENESIS OF TYR-495.
RX PubMed=14662906; DOI=10.1084/jem.20030729;
RA Tretter T., Ross A.E., Dordai D.I., Desiderio S.;
RT "Mimicry of pre-B-cell receptor signaling by activation of the tyrosine
RT kinase Blk.";
RL J. Exp. Med. 198:1863-1873(2003).
RN [20]
RP FUNCTION.
RX PubMed=12563261; DOI=10.1038/ni893;
RA Saijo K., Schmedt C., Su I.H., Karasuyama H., Lowell C.A., Reth M.,
RA Adachi T., Patke A., Santana A., Tarakhovsky A.;
RT "Essential role of Src-family protein tyrosine kinases in NF-kappaB
RT activation during B cell development.";
RL Nat. Immunol. 4:274-279(2003).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [22]
RP TISSUE SPECIFICITY.
RX PubMed=23562159; DOI=10.1016/j.immuni.2013.01.010;
RG Immunological Genome Project Consortium;
RA Malhotra N., Narayan K., Cho O.H., Sylvia K.E., Yin C., Melichar H.,
RA Rashighi M., Lefebvre V., Harris J.E., Berg L.J., Kang J.;
RT "A network of high-mobility group box transcription factors programs innate
RT interleukin-17 production.";
RL Immunity 38:681-693(2013).
RN [23]
RP STRUCTURE BY NMR OF SH2 DOMAIN.
RX PubMed=8639560; DOI=10.1021/bi960157x;
RA Metzler W.J., Leiting B., Pryor K., Mueller L., Farmer B.T. II;
RT "The three-dimensional solution structure of the SH2 domain from p55blk
RT kinase.";
RL Biochemistry 35:6201-6211(1996).
CC -!- FUNCTION: Non-receptor tyrosine kinase involved in B-lymphocyte
CC development, differentiation and signaling. B-cell receptor (BCR)
CC signaling requires a tight regulation of several protein tyrosine
CC kinases and phosphatases, and associated coreceptors (PubMed:2404338,
CC PubMed:7690139, PubMed:7608542, PubMed:9636152, PubMed:14662906,
CC PubMed:12563261). Binding of antigen to the B-cell antigen receptor
CC (BCR) triggers signaling that ultimately leads to B-cell activation
CC (PubMed:2404338, PubMed:7690139, PubMed:7608542, PubMed:14662906,
CC PubMed:12563261). Signaling through BLK plays an important role in
CC transmitting signals through surface immunoglobulins and supports the
CC pro-B to pre-B transition, as well as the signaling for growth arrest
CC and apoptosis downstream of B-cell receptor (PubMed:2404338,
CC PubMed:7690139, PubMed:7608542, PubMed:14662906, PubMed:12563261).
CC Specifically binds and phosphorylates CD79A at 'Tyr-188'and 'Tyr-199',
CC as well as CD79B at 'Tyr-196' and 'Tyr-207' (PubMed:7592958,
CC PubMed:9177269). Phosphorylates also the immunoglobulin G receptor
CC FCGR2 (By similarity). With FYN and LYN, plays an essential role in
CC pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation
CC (PubMed:14662906, PubMed:12563261). Contributes also to BTK activation
CC by indirectly stimulating BTK intramolecular autophosphorylation
CC (PubMed:7565679). In pancreatic islets, acts as a modulator of beta-
CC cells function through the up-regulation of PDX1 and NKX6-1 and
CC consequent stimulation of insulin secretion in response to glucose (By
CC similarity). Phosphorylates CGAS, promoting retention of CGAS in the
CC cytosol (By similarity). {ECO:0000250|UniProtKB:P51451,
CC ECO:0000269|PubMed:12563261, ECO:0000269|PubMed:14662906,
CC ECO:0000269|PubMed:2404338, ECO:0000269|PubMed:7565679,
CC ECO:0000269|PubMed:7592958, ECO:0000269|PubMed:7608542,
CC ECO:0000269|PubMed:7690139, ECO:0000269|PubMed:9177269,
CC ECO:0000269|PubMed:9636152}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC -!- ACTIVITY REGULATION: Antibody-mediated surface engagement of the B-cell
CC antigen receptor (BCR) which results in the phosphorylation of BLK on
CC tyrosine residues, stimulates the enzymatic activity.
CC {ECO:0000269|PubMed:1714601, ECO:0000269|PubMed:7524079}.
CC -!- SUBUNIT: Interacts with CBL (via SH2 domain) (By similarity). Interacts
CC with CD79A and CD79B (via SH2 domain). {ECO:0000250,
CC ECO:0000269|PubMed:1506682, ECO:0000269|PubMed:7592958}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Lipid-anchor
CC {ECO:0000250}. Note=Present and active in lipid rafts (By similarity).
CC Membrane location is required for the phosphorylation of CD79A and
CC CD79B. {ECO:0000250, ECO:0000269|PubMed:7592958}.
CC -!- TISSUE SPECIFICITY: Expressed in immature Vgamma2 gamma-delta T-cells
CC (at protein level) (PubMed:23562159). Expressed in the B-cell lineage
CC (PubMed:2404338, PubMed:1537861). {ECO:0000269|PubMed:1537861,
CC ECO:0000269|PubMed:23562159, ECO:0000269|PubMed:2404338}.
CC -!- INDUCTION: Expression increases during B-cell differentiation and is
CC under the control of the B-cell specific transcription factors PAX5 and
CC NF-kappa-B. {ECO:0000269|PubMed:7608542, ECO:0000269|PubMed:8195169,
CC ECO:0000269|PubMed:9660839}.
CC -!- PTM: Phosphorylated on tyrosine residues after antibody-mediated
CC surface engagement of the B-cell antigen receptor (BCR).
CC -!- PTM: Ubiquitination of activated BLK by the UBE3A ubiquitin protein
CC ligase leads to its degradation by the ubiquitin-proteasome pathway.
CC {ECO:0000269|PubMed:10449731}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. SRC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; M30903; AAA40453.1; -; mRNA.
DR EMBL; AK089888; BAC40986.1; -; mRNA.
DR EMBL; CT010240; CAJ18448.1; -; mRNA.
DR EMBL; AC090496; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC030668; AAH30668.1; -; mRNA.
DR CCDS; CCDS27200.1; -.
DR PIR; A40092; A40092.
DR RefSeq; NP_031575.2; NM_007549.2.
DR PDB; 1BLJ; NMR; -; A=107-218.
DR PDB; 1BLK; NMR; -; A=107-218.
DR PDBsum; 1BLJ; -.
DR PDBsum; 1BLK; -.
DR AlphaFoldDB; P16277; -.
DR SMR; P16277; -.
DR BioGRID; 198356; 1.
DR IntAct; P16277; 3.
DR MINT; P16277; -.
DR STRING; 10090.ENSMUSP00000014597; -.
DR BindingDB; P16277; -.
DR ChEMBL; CHEMBL3343; -.
DR DrugCentral; P16277; -.
DR iPTMnet; P16277; -.
DR PhosphoSitePlus; P16277; -.
DR jPOST; P16277; -.
DR MaxQB; P16277; -.
DR PaxDb; P16277; -.
DR PeptideAtlas; P16277; -.
DR PRIDE; P16277; -.
DR ProteomicsDB; 273498; -.
DR Antibodypedia; 3914; 610 antibodies from 39 providers.
DR DNASU; 12143; -.
DR Ensembl; ENSMUST00000014597; ENSMUSP00000014597; ENSMUSG00000014453.
DR GeneID; 12143; -.
DR KEGG; mmu:12143; -.
DR UCSC; uc007uhq.1; mouse.
DR CTD; 640; -.
DR MGI; MGI:88169; Blk.
DR VEuPathDB; HostDB:ENSMUSG00000014453; -.
DR eggNOG; KOG0197; Eukaryota.
DR GeneTree; ENSGT00940000159864; -.
DR HOGENOM; CLU_000288_7_2_1; -.
DR InParanoid; P16277; -.
DR OMA; FYTATEQ; -.
DR OrthoDB; 539311at2759; -.
DR PhylomeDB; P16277; -.
DR TreeFam; TF351634; -.
DR BRENDA; 2.7.10.2; 3474.
DR BioGRID-ORCS; 12143; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Bik; mouse.
DR EvolutionaryTrace; P16277; -.
DR PRO; PR:P16277; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; P16277; protein.
DR Bgee; ENSMUSG00000014453; Expressed in spleen and 52 other tissues.
DR Genevisible; P16277; MM.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; ISO:MGI.
DR GO; GO:0004713; F:protein tyrosine kinase activity; ISS:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0050853; P:B cell receptor signaling pathway; ISO:MGI.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IBA:GO_Central.
DR GO; GO:0097028; P:dendritic cell differentiation; IBA:GO_Central.
DR GO; GO:0002431; P:Fc receptor mediated stimulatory signaling pathway; IBA:GO_Central.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0030889; P:negative regulation of B cell proliferation; IBA:GO_Central.
DR GO; GO:0070667; P:negative regulation of mast cell proliferation; IBA:GO_Central.
DR GO; GO:0031175; P:neuron projection development; IBA:GO_Central.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:0002576; P:platelet degranulation; IBA:GO_Central.
DR GO; GO:2000670; P:positive regulation of dendritic cell apoptotic process; IBA:GO_Central.
DR GO; GO:0032024; P:positive regulation of insulin secretion; ISO:MGI.
DR GO; GO:0032092; P:positive regulation of protein binding; ISO:MGI.
DR GO; GO:0002902; P:regulation of B cell apoptotic process; IBA:GO_Central.
DR GO; GO:0050855; P:regulation of B cell receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0043304; P:regulation of mast cell degranulation; IBA:GO_Central.
DR GO; GO:0090330; P:regulation of platelet aggregation; IBA:GO_Central.
DR GO; GO:0002513; P:tolerance induction to self antigen; IBA:GO_Central.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd10371; SH2_Src_Blk; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR035853; Blk_SH2.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF00018; SH3_1; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00452; SH3DOMAIN.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00326; SH3; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell membrane; Kinase; Lipoprotein; Membrane;
KW Myristate; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW SH2 domain; SH3 domain; Transferase; Tyrosine-protein kinase;
KW Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..499
FT /note="Tyrosine-protein kinase Blk"
FT /id="PRO_0000088062"
FT DOMAIN 52..112
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 118..214
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 235..488
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 354
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 241..249
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 263
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 383
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250"
FT MUTAGEN 145
FT /note="R->K: Impairs the interaction with CD79A and CD79B."
FT /evidence="ECO:0000269|PubMed:7592958"
FT MUTAGEN 495
FT /note="Y->F: Leads to constitutive activation of BLK."
FT /evidence="ECO:0000269|PubMed:14662906,
FT ECO:0000269|PubMed:9636152"
FT CONFLICT 421
FT /note="E -> V (in Ref. 1; AAA40453)"
FT /evidence="ECO:0000305"
FT STRAND 116..119
FT /evidence="ECO:0007829|PDB:1BLJ"
FT HELIX 125..132
FT /evidence="ECO:0007829|PDB:1BLJ"
FT STRAND 142..144
FT /evidence="ECO:0007829|PDB:1BLJ"
FT STRAND 150..152
FT /evidence="ECO:0007829|PDB:1BLK"
FT STRAND 154..158
FT /evidence="ECO:0007829|PDB:1BLJ"
FT STRAND 160..162
FT /evidence="ECO:0007829|PDB:1BLK"
FT TURN 163..165
FT /evidence="ECO:0007829|PDB:1BLJ"
FT STRAND 171..176
FT /evidence="ECO:0007829|PDB:1BLJ"
FT TURN 177..179
FT /evidence="ECO:0007829|PDB:1BLJ"
FT STRAND 180..184
FT /evidence="ECO:0007829|PDB:1BLJ"
FT STRAND 187..191
FT /evidence="ECO:0007829|PDB:1BLJ"
FT HELIX 192..201
FT /evidence="ECO:0007829|PDB:1BLJ"
FT STRAND 204..208
FT /evidence="ECO:0007829|PDB:1BLJ"
SQ SEQUENCE 499 AA; 56674 MW; 14C607564BB4E66D CRC64;
MGLLSSKRQV SEKGKGWSPV KIRTQDKAPP PLPPLVVFNH LAPPSPNQDP DEEERFVVAL
FDYAAVNDRD LQVLKGEKLQ VLRSTGDWWL ARSLVTGREG YVPSNFVAPV ETLEVEKWFF
RTISRKDAER QLLAPMNKAG SFLIRESESN KGAFSLSVKD ITTQGEVVKH YKIRSLDNGG
YYISPRITFP TLQALVQHYS KKGDGLCQKL TLPCVNLAPK NLWAQDEWEI PRQSLKLVRK
LGSGQFGEVW MGYYKNNMKV AIKTLKEGTM SPEAFLGEAN VMKTLQHERL VRLYAVVTRE
PIYIVTEYMA RGCLLDFLKT DEGSRLSLPR LIDMSAQVAE GMAYIERMNS IHRDLRAANI
LVSETLCCKI ADFGLARIID SEYTAQEGAK FPIKWTAPEA IHFGVFTIKA DVWSFGVLLM
EIVTYGRVPY PGMSNPEVIR SLEHGYRMPC PETCPPELYN DIITECWRGR PEERPTFEFL
QSVLEDFYTA TEGQYELQP
