Reactome | UniProt:P51451 BLK

chain	initiator methionine:1 chain:2-505
checksum	B5F739BEF8389176
comment	FUNCTION Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling (By similarity). B-cell receptor (BCR) signaling requires a tight regulation of several protein tyrosine kinases and phosphatases, and associated coreceptors (By similarity). Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation (By similarity). 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 (By similarity). Specifically binds and phosphorylates CD79A at 'Tyr-188'and 'Tyr-199', as well as CD79B at 'Tyr-196' and 'Tyr-207' (By similarity). Also phosphorylates the immunoglobulin G receptors FCGR2A, FCGR2B and FCGR2C (PubMed:8756631). With FYN and LYN, plays an essential role in pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation (By similarity). Also contributes to BTK activation by indirectly stimulating BTK intramolecular autophosphorylation (By similarity). 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 (PubMed:19667185). Phosphorylates CGAS, promoting retention of CGAS in the cytosol (PubMed:30356214).CATALYTIC ACTIVITY L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)ACTIVITY 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.SUBUNIT Interacts with CBL (via SH2 domain). Interacts with CD79A and CD79B (via SH2 domain) (By similarity).INTERACTION Present and active in lipid rafts. Membrane location is required for the phosphorylation of CD79A and CD79B (By similarity).TISSUE SPECIFICITY Expressed in lymphatic organs, pancreatic islets, Leydig cells, striate ducts of salivary glands and hair follicles.INDUCTION Expression is under the control of NF-kappa-B as well as the B-cell specific transcription factors PAX5 and EBF1.PTM Phosphorylated on tyrosine residues after antibody-mediated surface engagement of the B-cell antigen receptor (BCR).PTM Ubiquitination of activated BLK by the UBE3A ubiquitin protein ligase leads to its degradation by the ubiquitin-proteasome pathway.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.
crossReference	[DatabaseIdentifier:11488007] ENSEMBL:ENSG00000136573 [DatabaseIdentifier:12818337] ZINC - World Drugs:BLK_HUMAN [DatabaseIdentifier:12816476] ZINC target:P51451 [DatabaseIdentifier:12813078] ZINC - Substances:BLK_HUMAN [DatabaseIdentifier:12808844] ZINC - Predictions - Purchasable:BLK_HUMAN [DatabaseIdentifier:12806824] ZINC - Investigational:BLK_HUMAN [DatabaseIdentifier:12805743] ZINC - FDA approved:BLK_HUMAN [DatabaseIdentifier:12804625] ZINC - Biogenic:BLK_HUMAN [DatabaseIdentifier:12403932] RefSeq:XP_054216945.1 [DatabaseIdentifier:12403928] RefSeq:XP_047278038.1 [DatabaseIdentifier:12403926] RefSeq:XP_054188229.1 [DatabaseIdentifier:12403927] RefSeq:NP_001706.2 [DatabaseIdentifier:12403930] RefSeq:XP_054216946.1 [DatabaseIdentifier:12403925] RefSeq:XP_054188228.1 [DatabaseIdentifier:12403931] RefSeq:XP_047278039.1 [DatabaseIdentifier:12403929] RefSeq:XP_054216944.1 [DatabaseIdentifier:12282661] Pharos - Targets:P51451 [DatabaseIdentifier:12240643] PRO:P51451 [DatabaseIdentifier:12137042] Orphanet:BLK [DatabaseIdentifier:12122341] OpenTargets:ENSG00000136573 [DatabaseIdentifier:11837841] HPA:ENSG00000136573-BLK [DatabaseIdentifier:11832613] HMDB Protein:HMDBP01438 [DatabaseIdentifier:11784749] GeneCards:BLK [DatabaseIdentifier:11779361] Guide to Pharmacology - Targets:1940 [DatabaseIdentifier:11715835] ENSEMBL:ENST00000259089 [DatabaseIdentifier:11715836] ENSEMBL:ENST00000646615 [DatabaseIdentifier:11593136] ENSEMBL:ENSP00000259089 [DatabaseIdentifier:11593137] ENSEMBL:ENSP00000494522 [DatabaseIdentifier:11488008] ENSEMBL:ENSG00000285369
databaseName	UniProt
dbId	50860
description	recommendedName: Tyrosine-protein kinase Blk ecNumber evidence="10"2.7.10.2 alternativeName: B lymphocyte kinase alternativeName: p55-Blk
displayName	UniProt:P51451 BLK
geneName	BLK
identifier	P51451
isSequenceChanged	false
keyword	ATP-binding Cell membrane Diabetes mellitus Kinase Lipoprotein Membrane Myristate Nucleotide-binding Phosphoprotein Proteomics identification Reference proteome SH2 domain SH3 domain Transferase Tyrosine-protein kinase Ubl conjugation
modified	[InstanceEdit:9963647] Weiser, Joel, 2025-08-15
moleculeType	Protein
name	BLK
otherIdentifier	11727346_a_at 11756075_x_at 17065750 206255_3p_at 206255_PM_at 206255_at 210934_PM_at 210934_at 3085991 3085997 3085998 3085999 3086008 3086009 3086010 3086011 3086012 3086013 3086014 3086016 3086017 3086019 3086020 3086021 3086023 3086024 3086025 3086026 3086028 3086029 3086033 3086034 3086035 3086036 640 8144625 854_at A_14_P126180 A_23_P31725 GE81061 GO:0000166 GO:0002376 GO:0002429 GO:0003824 GO:0004672 GO:0004713 GO:0004715 GO:0005102 GO:0005515 GO:0005524 GO:0005829 GO:0005886 GO:0006468 GO:0007169 GO:0016020 GO:0016301 GO:0016740 GO:0018108 GO:0030154 GO:0032024 GO:0035556 GO:0050853 GO:0140096 HMNXSV003027574 ILMN_1668277 S76617_at TC08000087.hg TC08001801.hg g13325324_3p_at g4502412_3p_s_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-9606871] MyrG2-BLK [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-983580] BLK [cytosol] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:11353288] BioGPS Gene:640 BLK [ReferenceDNASequence:12697091] UCSC:P51451 BLK [ReferenceDNASequence:12107954] OMIM:191305 BLK [ReferenceDNASequence:12067170] NCBI Gene:640 BLK [ReferenceDNASequence:11983077] Monarch:640 BLK [ReferenceDNASequence:11892935] KEGG:hsa:640 BLK [ReferenceDNASequence:11816374] HGNC:1057 BLK [ReferenceDNASequence:11429958] dbSNP Gene:640 BLK [ReferenceDNASequence:11408857] CTD Gene:640 BLK [ReferenceDNASequence:11393933] COSMIC - genes:BLK BLK [ReferenceDNASequence:ensembl:ENSG00000136573] ENSEMBL:ENSG00000136573 BLK
referenceTranscript	[ReferenceRNASequence:12585644] RefSeq:XM_054332253.1 BLK [ReferenceRNASequence:12585650] RefSeq:XM_054360970.1 BLK [ReferenceRNASequence:12585645] RefSeq:XM_054332254.1 BLK [ReferenceRNASequence:12585649] RefSeq:XM_047422083.1 BLK [ReferenceRNASequence:12585646] RefSeq:NM_001715.2 BLK [ReferenceRNASequence:12585647] RefSeq:XM_054360969.1 BLK [ReferenceRNASequence:12585648] RefSeq:XM_047422082.1 BLK [ReferenceRNASequence:12585651] RefSeq:XM_054360971.1 BLK
schemaClass	ReferenceGeneProduct
secondaryIdentifier	BLK_HUMAN Q16291 Q96IN1
sequenceLength	505
species	[Species:48887] Homo sapiens
stId	uniprot:P51451
url	http://purl.uniprot.org/uniprot/P51451

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-9606871] MyrG2-BLK [plasma membrane] [EntityWithAccessionedSequence:R-HSA-983580] BLK [cytosol]
(referenceSequence)	[ModifiedResidue:9606874] N-myristoylglycine at 2
(interactor)	[UndirectedInteraction:11134019] UniProt:P08670 <-> UniProt:P51451 (IntAct) [UndirectedInteraction:11143063] UniProt:P40763 <-> UniProt:P51451 (IntAct) [UndirectedInteraction:11155609] UniProt:P51451 <-> UniProt:O43281 (IntAct) [UndirectedInteraction:11155611] UniProt:P51451 <-> UniProt:P00533 (IntAct) [UndirectedInteraction:11155613] UniProt:P51451 <-> UniProt:P08238 (IntAct) [UndirectedInteraction:11155615] UniProt:P51451 <-> UniProt:Q8IZU3 (IntAct) [UndirectedInteraction:11155617] UniProt:P51451 <-> UniProt:Q6NX45 (IntAct) [UndirectedInteraction:11155619] UniProt:P51451 <-> UniProt:Q9UGK3 (IntAct) [UndirectedInteraction:11155623] UniProt:P51451 <-> IntAct:EBI-22620261 (IntAct) [UndirectedInteraction:11155625] UniProt:P51451 <-> IntAct:EBI-10171584 (IntAct) [UndirectedInteraction:11155627] UniProt:P51451 <-> UniProt:P46109 (IntAct) [UndirectedInteraction:11155629] UniProt:P51451 <-> UniProt:Q8NDB2 (IntAct) [UndirectedInteraction:11155633] UniProt:P51451 <-> UniProt:A0A0C4DGF1 (IntAct) [UndirectedInteraction:11155635] UniProt:P51451 <-> UniProt:B2RXF5 (IntAct) [UndirectedInteraction:11155637] UniProt:P51451 <-> UniProt:O14543 (IntAct) [UndirectedInteraction:11155639] UniProt:P51451 <-> UniProt:Q13239-3 (IntAct) [UndirectedInteraction:11155641] UniProt:P51451 <-> UniProt:Q96BR9 (IntAct) [UndirectedInteraction:11155643] UniProt:P51451 <-> IntAct:EBI-16439879 (IntAct) [UndirectedInteraction:11155645] UniProt:P51451 <-> UniProt:P27986-2 (IntAct) [UndirectedInteraction:11155647] UniProt:P51451 <-> UniProt:P51116 (IntAct) [UndirectedInteraction:11155649] UniProt:P51451 <-> UniProt:O95551 (IntAct) [UndirectedInteraction:11155653] UniProt:P51451 <-> UniProt:P49023-2 (IntAct) [UndirectedInteraction:11155655] UniProt:P51451 <-> UniProt:Q13322-4 (IntAct) [UndirectedInteraction:11155657] UniProt:P51451 <-> UniProt:Q13490 (IntAct) [UndirectedInteraction:11155659] UniProt:P51451 <-> UniProt:Q9UKT9 (IntAct) [UndirectedInteraction:11155661] UniProt:P51451 <-> UniProt:Q92569 (IntAct) [UndirectedInteraction:11155663] UniProt:P51451 <-> UniProt:Q9NRD5 (IntAct) [UndirectedInteraction:11155667] UniProt:P51451 <-> UniProt:O43281-2 (IntAct) [UndirectedInteraction:11155669] UniProt:P51451 <-> UniProt:O14796 (IntAct) [UndirectedInteraction:11155671] UniProt:P51451 <-> UniProt:Q9UJV3-2 (IntAct) [UndirectedInteraction:11155675] UniProt:P51451 <-> UniProt:Q9BWW4 (IntAct) [UndirectedInteraction:11155679] UniProt:P51451 <-> UniProt:Q96Q35-2 (IntAct) [UndirectedInteraction:11155681] UniProt:P51451 <-> UniProt:P51114-2 (IntAct) [UndirectedInteraction:11155685] UniProt:P51451 <-> UniProt:Q96N16 (IntAct) [UndirectedInteraction:11155687] UniProt:P51451 <-> UniProt:O75031 (IntAct) [UndirectedInteraction:11155689] UniProt:P51451 <-> UniProt:P24539 (IntAct) [UndirectedInteraction:11155691] UniProt:P51451 <-> UniProt:P48047 (IntAct) [UndirectedInteraction:11155695] UniProt:P51451 <-> UniProt:Q9NTX9 (IntAct) [UndirectedInteraction:11155697] UniProt:P51451 <-> UniProt:Q16543 (IntAct) [UndirectedInteraction:11155699] UniProt:P51451 <-> UniProt:P07900 (IntAct) [UndirectedInteraction:11155701] UniProt:P51451 <-> UniProt:P06576 (IntAct) [UndirectedInteraction:11155703] UniProt:P51451 <-> UniProt:P12724 (IntAct) [UndirectedInteraction:11155705] UniProt:P51451 <-> UniProt:Q6NXT1 (IntAct)

UniProt:P51451 BLK Show undefined attributes

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