UniProt functional annotation for P16277



	UniProt functional annotation for P16277

UniProt code: P16277.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

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 (PubMed:2404338, PubMed:7690139, PubMed:7608542, PubMed:9636152, PubMed:14662906, PubMed:12563261). Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation (PubMed:2404338, PubMed:7690139, PubMed:7608542, PubMed:14662906, PubMed:12563261). 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 (PubMed:2404338, PubMed:7690139, PubMed:7608542, PubMed:14662906, PubMed:12563261). Specifically binds and phosphorylates CD79A at 'Tyr-188'and 'Tyr-199', as well as CD79B at 'Tyr-196' and 'Tyr-207' (PubMed:7592958, PubMed:9177269). Phosphorylates also the immunoglobulin G receptor FCGR2 (By similarity). With FYN and LYN, plays an essential role in pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation (PubMed:14662906, PubMed:12563261). Contributes also to BTK activation by indirectly stimulating BTK intramolecular autophosphorylation (PubMed:7565679). 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 (By similarity). Phosphorylates CGAS, promoting retention of CGAS in the cytosol (By similarity). {ECO:0000250|UniProtKB:P51451, ECO:0000269|PubMed:12563261, ECO:0000269|PubMed:14662906, ECO:0000269|PubMed:2404338, ECO:0000269|PubMed:7565679, ECO:0000269|PubMed:7592958, ECO:0000269|PubMed:7608542, ECO:0000269|PubMed:7690139, ECO:0000269|PubMed:9177269, ECO:0000269|PubMed:9636152}.

Catalytic activity: Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;

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. {ECO:0000269|PubMed:1714601, ECO:0000269|PubMed:7524079}.

Subunit: Interacts with CBL (via SH2 domain) (By similarity). Interacts with CD79A and CD79B (via SH2 domain). {ECO:0000250, ECO:0000269|PubMed:1506682, ECO:0000269|PubMed:7592958}.

Subcellular location: Cell membrane {ECO:0000250}; Lipid-anchor {ECO:0000250}. Note=Present and active in lipid rafts (By similarity). Membrane location is required for the phosphorylation of CD79A and CD79B. {ECO:0000250, ECO:0000269|PubMed:7592958}.

Tissue specificity: Expressed in immature Vgamma2 gamma-delta T-cells (at protein level) (PubMed:23562159). Expressed in the B-cell lineage (PubMed:2404338, PubMed:1537861). {ECO:0000269|PubMed:1537861, ECO:0000269|PubMed:23562159, ECO:0000269|PubMed:2404338}.

Induction: Expression increases during B-cell differentiation and is under the control of the B-cell specific transcription factors PAX5 and NF-kappa-B. {ECO:0000269|PubMed:7608542, ECO:0000269|PubMed:8195169, ECO:0000269|PubMed:9660839}.

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. {ECO:0000269|PubMed:10449731}.

Similarity: Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



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 (PubMed:2404338, PubMed:7690139, PubMed:7608542, PubMed:9636152, PubMed:14662906, PubMed:12563261). Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation (PubMed:2404338, PubMed:7690139, PubMed:7608542, PubMed:14662906, PubMed:12563261). 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 (PubMed:2404338, PubMed:7690139, PubMed:7608542, PubMed:14662906, PubMed:12563261). Specifically binds and phosphorylates CD79A at 'Tyr-188'and 'Tyr-199', as well as CD79B at 'Tyr-196' and 'Tyr-207' (PubMed:7592958, PubMed:9177269). Phosphorylates also the immunoglobulin G receptor FCGR2 (By similarity). With FYN and LYN, plays an essential role in pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation (PubMed:14662906, PubMed:12563261). Contributes also to BTK activation by indirectly stimulating BTK intramolecular autophosphorylation (PubMed:7565679). 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 (By similarity). Phosphorylates CGAS, promoting retention of CGAS in the cytosol (By similarity). {ECO:0000250\|UniProtKB:P51451, ECO:0000269\|PubMed:12563261, ECO:0000269\|PubMed:14662906, ECO:0000269\|PubMed:2404338, ECO:0000269\|PubMed:7565679, ECO:0000269\|PubMed:7592958, ECO:0000269\|PubMed:7608542, ECO:0000269\|PubMed:7690139, ECO:0000269\|PubMed:9177269, ECO:0000269\|PubMed:9636152}.


Catalytic activity:		Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
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. {ECO:0000269\|PubMed:1714601, ECO:0000269\|PubMed:7524079}.
Subunit:		Interacts with CBL (via SH2 domain) (By similarity). Interacts with CD79A and CD79B (via SH2 domain). {ECO:0000250, ECO:0000269\|PubMed:1506682, ECO:0000269\|PubMed:7592958}.
Subcellular location:		Cell membrane {ECO:0000250}; Lipid-anchor {ECO:0000250}. Note=Present and active in lipid rafts (By similarity). Membrane location is required for the phosphorylation of CD79A and CD79B. {ECO:0000250, ECO:0000269\|PubMed:7592958}.
Tissue specificity:		Expressed in immature Vgamma2 gamma-delta T-cells (at protein level) (PubMed:23562159). Expressed in the B-cell lineage (PubMed:2404338, PubMed:1537861). {ECO:0000269\|PubMed:1537861, ECO:0000269\|PubMed:23562159, ECO:0000269\|PubMed:2404338}.
Induction:		Expression increases during B-cell differentiation and is under the control of the B-cell specific transcription factors PAX5 and NF-kappa-B. {ECO:0000269\|PubMed:7608542, ECO:0000269\|PubMed:8195169, ECO:0000269\|PubMed:9660839}.
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. {ECO:0000269\|PubMed:10449731}.
Similarity:		Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. {ECO:0000255\|PROSITE-ProRule:PRU00159}.