BLK_HUMAN
ID BLK_HUMAN Reviewed; 505 AA.
AC P51451; Q16291; Q96IN1;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 21-AUG-2007, sequence version 3.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=Tyrosine-protein kinase Blk;
DE EC=2.7.10.2 {ECO:0000269|PubMed:30356214};
DE AltName: Full=B lymphocyte kinase;
DE AltName: Full=p55-Blk;
GN Name=BLK;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7822795;
RA Islam K.B., Rabbani H., Larsson C., Sanders R., Smith C.I.;
RT "Molecular cloning, characterization, and chromosomal localization of a
RT human lymphoid tyrosine kinase related to murine Blk.";
RL J. Immunol. 154:1265-1272(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7845672;
RA Drebin J.A., Hartzell S.W., Griffin C., Campbell M.J., Niederhuber J.E.;
RT "Molecular cloning and chromosomal localization of the human homologue of a
RT B-lymphocyte specific protein tyrosine kinase (blk).";
RL Oncogene 10:477-486(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Spleen;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Blood, and Lymph;
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 INTERACTION WITH CBL.
RX PubMed=8083187; DOI=10.1016/s0021-9258(17)31595-8;
RA Donovan J.A., Wange R.L., Langdon W.Y., Samelson L.E.;
RT "The protein product of the c-cbl protooncogene is the 120-kDa tyrosine-
RT phosphorylated protein in Jurkat cells activated via the T cell antigen
RT receptor.";
RL J. Biol. Chem. 269:22921-22924(1994).
RN [7]
RP FUNCTION IN PHOSPHORYLATION OF FCGR2A; FCGR2B AND FCGR2C.
RX PubMed=8756631; DOI=10.1128/mcb.16.9.4735;
RA Bewarder N., Weinrich V., Budde P., Hartmann D., Flaswinkel H., Reth M.,
RA Frey J.;
RT "In vivo and in vitro specificity of protein tyrosine kinases for
RT immunoglobulin G receptor (FcgammaRII) phosphorylation.";
RL Mol. Cell. Biol. 16:4735-4743(1996).
RN [8]
RP INDUCTION.
RX PubMed=10553071;
RA Akerblad P., Sigvardsson M.;
RT "Early B cell factor is an activator of the B lymphoid kinase promoter in
RT early B cell development.";
RL J. Immunol. 163:5453-5461(1999).
RN [9]
RP PHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=12023895; DOI=10.1042/bj20011696;
RA Lang M.L., Chen Y.W., Shen L., Gao H., Lang G.A., Wade T.K., Wade W.F.;
RT "IgA Fc receptor (FcalphaR) cross-linking recruits tyrosine kinases,
RT phosphoinositide kinases and serine/threonine kinases to glycolipid
RT rafts.";
RL Biochem. J. 364:517-525(2002).
RN [10]
RP FUNCTION AS REGULATOR OF INSULIN SECRETION, TISSUE SPECIFICITY, INVOLVEMENT
RP IN MODY11, VARIANT THR-71, AND CHARACTERIZATION OF VARIANT THR-71.
RX PubMed=19667185; DOI=10.1073/pnas.0906474106;
RA Borowiec M., Liew C.W., Thompson R., Boonyasrisawat W., Hu J.,
RA Mlynarski W.M., El Khattabi I., Kim S.H., Marselli L., Rich S.S.,
RA Krolewski A.S., Bonner-Weir S., Sharma A., Sale M., Mychaleckyj J.C.,
RA Kulkarni R.N., Doria A.;
RT "Mutations at the BLK locus linked to maturity onset diabetes of the young
RT and beta-cell dysfunction.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:14460-14465(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=30356214; DOI=10.1038/s41586-018-0629-6;
RA Liu H., Zhang H., Wu X., Ma D., Wu J., Wang L., Jiang Y., Fei Y., Zhu C.,
RA Tan R., Jungblut P., Pei G., Dorhoi A., Yan Q., Zhang F., Zheng R., Liu S.,
RA Liang H., Liu Z., Yang H., Chen J., Wang P., Tang T., Peng W., Hu Z.,
RA Xu Z., Huang X., Wang J., Li H., Zhou Y., Liu F., Yan D., Kaufmann S.H.E.,
RA Chen C., Mao Z., Ge B.;
RT "Nuclear cGAS suppresses DNA repair and promotes tumorigenesis.";
RL Nature 563:131-136(2018).
RN [13]
RP VARIANTS [LARGE SCALE ANALYSIS] ILE-48; THR-71 AND THR-71.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Non-receptor tyrosine kinase involved in B-lymphocyte
CC development, differentiation and signaling (By similarity). B-cell
CC receptor (BCR) signaling requires a tight regulation of several protein
CC tyrosine kinases and phosphatases, and associated coreceptors (By
CC similarity). Binding of antigen to the B-cell antigen receptor (BCR)
CC triggers signaling that ultimately leads to B-cell activation (By
CC similarity). 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 (By similarity).
CC Specifically binds and phosphorylates CD79A at 'Tyr-188'and 'Tyr-199',
CC as well as CD79B at 'Tyr-196' and 'Tyr-207' (By similarity).
CC Phosphorylates also the immunoglobulin G receptors FCGR2A, FCGR2B and
CC FCGR2C (PubMed:8756631). With FYN and LYN, plays an essential role in
CC pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation (By
CC similarity). Contributes also to BTK activation by indirectly
CC stimulating BTK intramolecular autophosphorylation (By similarity). In
CC pancreatic islets, acts as a modulator of beta-cells function through
CC the up-regulation of PDX1 and NKX6-1 and consequent stimulation of
CC insulin secretion in response to glucose (PubMed:19667185).
CC Phosphorylates CGAS, promoting retention of CGAS in the cytosol
CC (PubMed:30356214). {ECO:0000250|UniProtKB:P16277,
CC ECO:0000269|PubMed:19667185, ECO:0000269|PubMed:30356214,
CC ECO:0000269|PubMed:8756631}.
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 Evidence={ECO:0000269|PubMed:30356214};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10597;
CC Evidence={ECO:0000269|PubMed:30356214};
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. {ECO:0000250}.
CC -!- SUBUNIT: Interacts with CBL (via SH2 domain). Interacts with CD79A and
CC CD79B (via SH2 domain) (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC P51451; P10275: AR; NbExp=3; IntAct=EBI-2105445, EBI-608057;
CC P51451; Q8NDB2: BANK1; NbExp=6; IntAct=EBI-2105445, EBI-2837677;
CC P51451; Q13490: BIRC2; NbExp=3; IntAct=EBI-2105445, EBI-514538;
CC P51451; P46109: CRKL; NbExp=3; IntAct=EBI-2105445, EBI-910;
CC P51451; O43281: EFS; NbExp=5; IntAct=EBI-2105445, EBI-718488;
CC P51451; O43281-2: EFS; NbExp=3; IntAct=EBI-2105445, EBI-11525448;
CC P51451; P00533: EGFR; NbExp=3; IntAct=EBI-2105445, EBI-297353;
CC P51451; Q96Q35-2: FLACC1; NbExp=5; IntAct=EBI-2105445, EBI-11533409;
CC P51451; P51114-2: FXR1; NbExp=3; IntAct=EBI-2105445, EBI-11022345;
CC P51451; P51116: FXR2; NbExp=3; IntAct=EBI-2105445, EBI-740459;
CC P51451; Q13480: GAB1; NbExp=3; IntAct=EBI-2105445, EBI-517684;
CC P51451; Q13322-4: GRB10; NbExp=3; IntAct=EBI-2105445, EBI-12353035;
CC P51451; O75031: HSF2BP; NbExp=3; IntAct=EBI-2105445, EBI-7116203;
CC P51451; P08238: HSP90AB1; NbExp=3; IntAct=EBI-2105445, EBI-352572;
CC P51451; Q9UKT9: IKZF3; NbExp=3; IntAct=EBI-2105445, EBI-747204;
CC P51451; Q96N16: JAKMIP1; NbExp=3; IntAct=EBI-2105445, EBI-2680803;
CC P51451; P10721: KIT; NbExp=5; IntAct=EBI-2105445, EBI-1379503;
CC P51451; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-2105445, EBI-10172526;
CC P51451; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-2105445, EBI-79165;
CC P51451; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-2105445, EBI-9090282;
CC P51451; Q92569: PIK3R3; NbExp=3; IntAct=EBI-2105445, EBI-79893;
CC P51451; P49023-2: PXN; NbExp=3; IntAct=EBI-2105445, EBI-11954250;
CC P51451; O14796: SH2D1B; NbExp=3; IntAct=EBI-2105445, EBI-3923013;
CC P51451; Q13239-3: SLA; NbExp=3; IntAct=EBI-2105445, EBI-17630587;
CC P51451; O14543: SOCS3; NbExp=3; IntAct=EBI-2105445, EBI-714146;
CC P51451; Q9BWW4: SSBP3; NbExp=3; IntAct=EBI-2105445, EBI-2902395;
CC P51451; Q9UGK3: STAP2; NbExp=3; IntAct=EBI-2105445, EBI-1553984;
CC P51451; P40763: STAT3; NbExp=9; IntAct=EBI-2105445, EBI-518675;
CC P51451; O95551: TDP2; NbExp=3; IntAct=EBI-2105445, EBI-2819865;
CC P51451; P08670: VIM; NbExp=3; IntAct=EBI-2105445, EBI-353844;
CC P51451; A0A0C4DGF1: ZBTB32; NbExp=3; IntAct=EBI-2105445, EBI-10188476;
CC P51451; B2RXF5: ZBTB42; NbExp=3; IntAct=EBI-2105445, EBI-12287587;
CC P51451; Q96BR9: ZBTB8A; NbExp=3; IntAct=EBI-2105445, EBI-742740;
CC P51451; Q6NX45: ZNF774; NbExp=3; IntAct=EBI-2105445, EBI-10251462;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Lipid-anchor
CC {ECO:0000250}. Note=Present and active in lipid rafts. Membrane
CC location is required for the phosphorylation of CD79A and CD79B (By
CC similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in lymphatic organs, pancreatic islets,
CC Leydig cells, striate ducts of salivary glands and hair follicles.
CC {ECO:0000269|PubMed:19667185}.
CC -!- INDUCTION: Expression is under the control of NF-kappa-B as well as the
CC B-cell specific transcription factors PAX5 and EBF1.
CC {ECO:0000269|PubMed:10553071}.
CC -!- PTM: Phosphorylated on tyrosine residues after antibody-mediated
CC surface engagement of the B-cell antigen receptor (BCR). {ECO:0000250}.
CC -!- PTM: Ubiquitination of activated BLK by the UBE3A ubiquitin protein
CC ligase leads to its degradation by the ubiquitin-proteasome pathway.
CC {ECO:0000250}.
CC -!- DISEASE: Maturity-onset diabetes of the young 11 (MODY11) [MIM:613375]:
CC A form of diabetes that is characterized by an autosomal dominant mode
CC of inheritance, onset in childhood or early adulthood (usually before
CC 25 years of age), a primary defect in insulin secretion and frequent
CC insulin-independence at the beginning of the disease.
CC {ECO:0000269|PubMed:19667185}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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; Z33998; CAA83965.1; -; mRNA.
DR EMBL; S76617; AAB33265.1; -; mRNA.
DR EMBL; AK313751; BAG36491.1; -; mRNA.
DR EMBL; CH471157; EAW65617.1; -; Genomic_DNA.
DR EMBL; BC007371; AAH07371.1; -; mRNA.
DR EMBL; BC032413; AAH32413.1; -; mRNA.
DR CCDS; CCDS5982.1; -.
DR PIR; I37206; I37206.
DR RefSeq; NP_001706.2; NM_001715.2.
DR AlphaFoldDB; P51451; -.
DR SMR; P51451; -.
DR BioGRID; 107109; 168.
DR ELM; P51451; -.
DR IntAct; P51451; 108.
DR MINT; P51451; -.
DR STRING; 9606.ENSP00000259089; -.
DR BindingDB; P51451; -.
DR ChEMBL; CHEMBL2250; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB15035; Zanubrutinib.
DR DrugCentral; P51451; -.
DR GuidetoPHARMACOLOGY; 1940; -.
DR CarbonylDB; P51451; -.
DR iPTMnet; P51451; -.
DR PhosphoSitePlus; P51451; -.
DR BioMuta; BLK; -.
DR DMDM; 158936749; -.
DR CPTAC; CPTAC-1777; -.
DR jPOST; P51451; -.
DR MassIVE; P51451; -.
DR PaxDb; P51451; -.
DR PeptideAtlas; P51451; -.
DR PRIDE; P51451; -.
DR ProteomicsDB; 56307; -.
DR Antibodypedia; 3914; 610 antibodies from 39 providers.
DR DNASU; 640; -.
DR Ensembl; ENST00000259089.9; ENSP00000259089.4; ENSG00000136573.14.
DR GeneID; 640; -.
DR KEGG; hsa:640; -.
DR MANE-Select; ENST00000259089.9; ENSP00000259089.4; NM_001715.3; NP_001706.2.
DR UCSC; uc003wty.4; human.
DR CTD; 640; -.
DR DisGeNET; 640; -.
DR GeneCards; BLK; -.
DR GeneReviews; BLK; -.
DR HGNC; HGNC:1057; BLK.
DR HPA; ENSG00000136573; Group enriched (intestine, lymphoid tissue).
DR MalaCards; BLK; -.
DR MIM; 191305; gene.
DR MIM; 613375; phenotype.
DR neXtProt; NX_P51451; -.
DR OpenTargets; ENSG00000136573; -.
DR Orphanet; 552; MODY.
DR Orphanet; 536; Systemic lupus erythematosus.
DR PharmGKB; PA25368; -.
DR VEuPathDB; HostDB:ENSG00000136573; -.
DR eggNOG; KOG0197; Eukaryota.
DR GeneTree; ENSGT00940000159864; -.
DR InParanoid; P51451; -.
DR OMA; FYTATEQ; -.
DR OrthoDB; 539311at2759; -.
DR PhylomeDB; P51451; -.
DR TreeFam; TF351634; -.
DR BRENDA; 2.7.10.2; 2681.
DR PathwayCommons; P51451; -.
DR Reactome; R-HSA-8939245; RUNX1 regulates transcription of genes involved in BCR signaling.
DR Reactome; R-HSA-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR SignaLink; P51451; -.
DR SIGNOR; P51451; -.
DR BioGRID-ORCS; 640; 9 hits in 1097 CRISPR screens.
DR ChiTaRS; BLK; human.
DR GeneWiki; Tyrosine-protein_kinase_BLK; -.
DR GenomeRNAi; 640; -.
DR Pharos; P51451; Tchem.
DR PRO; PR:P51451; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; P51451; protein.
DR Bgee; ENSG00000136573; Expressed in spleen and 93 other tissues.
DR ExpressionAtlas; P51451; baseline and differential.
DR Genevisible; P51451; HS.
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; IDA:UniProtKB.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0050853; P:B cell receptor signaling pathway; IDA:UniProtKB.
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:0035556; P:intracellular signal transduction; TAS:ProtInc.
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; IDA: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; IMP:UniProtKB.
DR GO; GO:0032092; P:positive regulation of protein binding; IMP:ARUK-UCL.
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 ATP-binding; Cell membrane; Diabetes mellitus; Kinase; Lipoprotein;
KW Membrane; Myristate; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; SH2 domain; SH3 domain; Transferase;
KW Tyrosine-protein kinase; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..505
FT /note="Tyrosine-protein kinase Blk"
FT /id="PRO_0000088061"
FT DOMAIN 58..118
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 124..220
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 241..494
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..23
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 360
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 247..255
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 269
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 389
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250"
FT VARIANT 48
FT /note="T -> I (in dbSNP:rs35339715)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041672"
FT VARIANT 71
FT /note="A -> T (associated with MODY11; reduces the
FT enhancing effect of BLK on insulin secretion; reduces the
FT inducing effect of BLK on the expression of PDX1 and NKX6-
FT 1; found as somatic mutation in a colorectal adenocarcinoma
FT sample; dbSNP:rs55758736)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:19667185"
FT /id="VAR_041673"
FT CONFLICT 287
FT /note="V -> M (in Ref. 1; CAA83965)"
FT /evidence="ECO:0000305"
FT CONFLICT 407
FT /note="I -> Y (in Ref. 2; AAB33265)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 505 AA; 57706 MW; B5F739BEF8389176 CRC64;
MGLVSSKKPD KEKPIKEKDK GQWSPLKVSA QDKDAPPLPP LVVFNHLTPP PPDEHLDEDK
HFVVALYDYT AMNDRDLQML KGEKLQVLKG TGDWWLARSL VTGREGYVPS NFVARVESLE
MERWFFRSQG RKEAERQLLA PINKAGSFLI RESETNKGAF SLSVKDVTTQ GELIKHYKIR
CLDEGGYYIS PRITFPSLQA LVQHYSKKGD GLCQRLTLPC VRPAPQNPWA QDEWEIPRQS
LRLVRKLGSG QFGEVWMGYY KNNMKVAIKT LKEGTMSPEA FLGEANVMKA LQHERLVRLY
AVVTKEPIYI VTEYMARGCL LDFLKTDEGS RLSLPRLIDM SAQIAEGMAY IERMNSIHRD
LRAANILVSE ALCCKIADFG LARIIDSEYT AQEGAKFPIK WTAPEAIHFG VFTIKADVWS
FGVLLMEVVT YGRVPYPGMS NPEVIRNLER GYRMPRPDTC PPELYRGVIA ECWRSRPEER
PTFEFLQSVL EDFYTATERQ YELQP
