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   27-MAR-2024, entry version 207.
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 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; 199.
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   CPTAC; CPTAC-2895; -.
DR   CPTAC; CPTAC-2896; -.
DR   jPOST; P51451; -.
DR   MassIVE; P51451; -.
DR   PaxDb; 9606-ENSP00000259089; -.
DR   PeptideAtlas; P51451; -.
DR   ProteomicsDB; 56307; -.
DR   Antibodypedia; 3914; 643 antibodies from 39 providers.
DR   DNASU; 640; -.
DR   Ensembl; ENST00000259089.9; ENSP00000259089.4; ENSG00000136573.16.
DR   Ensembl; ENST00000646615.3; ENSP00000494522.3; ENSG00000285369.3.
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   AGR; HGNC:1057; -.
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; PMNKAGS; -.
DR   OrthoDB; 1614410at2759; -.
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 1175 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 cell types or tissues.
DR   ExpressionAtlas; P51451; baseline and differential.
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:0045087; P:innate immune response; IBA:GO_Central.
DR   GO; GO:0035556; P:intracellular signal transduction; TAS:ProtInc.
DR   GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
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:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR   CDD; cd10371; SH2_Src_Blk; 1.
DR   CDD; cd12009; SH3_Blk; 1.
DR   Gene3D; 3.30.505.10; SH2 domain; 1.
DR   Gene3D; 2.30.30.40; SH3 Domains; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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   PANTHER; PTHR24418; TYROSINE-PROTEIN KINASE; 1.
DR   PANTHER; PTHR24418:SF181; TYROSINE-PROTEIN KINASE BLK; 1.
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; SSF56112; Protein kinase-like (PK-like); 1.
DR   SUPFAM; SSF55550; SH2 domain; 1.
DR   SUPFAM; SSF50044; SH3-domain; 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.
DR   Genevisible; P51451; HS.
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 (reduces the enhancing effect of BLK on
FT                   insulin secretion; reduces the inducing effect of BLK on
FT                   the expression of PDX1 and NKX6-1; 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
//