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Protein

Tyrosine-protein kinase Blk

Gene

Blk

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. 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. Specifically binds and phosphorylates CD79A at 'Tyr-188'and 'Tyr-199', as well as CD79B at 'Tyr-196' and 'Tyr-207'. Phosphorylates also the immunoglobulin G receptor FCGR2. With FYN and LYN, plays an essential role in pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation. Contributes also to BTK activation by indirectly stimulating BTK intramolecular autophosphorylation. 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.9 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Activity regulationi

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.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei263ATPPROSITE-ProRule annotation1
Active sitei354Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi241 – 249ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Transferase, Tyrosine-protein kinase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2 3474

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase Blk (EC:2.7.10.2)
Alternative name(s):
B lymphocyte kinase
p55-Blk
Gene namesi
Name:Blk
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:88169 Blk

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi145R → K: Impairs the interaction with CD79A and CD79B. 1 Publication1
Mutagenesisi495Y → F: Leads to constitutive activation of BLK. 2 Publications1

Chemistry databases

ChEMBLiCHEMBL3343

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved
ChainiPRO_00000880622 – 499Tyrosine-protein kinase BlkAdd BLAST498

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineBy similarity1
Modified residuei383Phosphotyrosine; by autocatalysisBy similarity1

Post-translational modificationi

Phosphorylated on tyrosine residues after antibody-mediated surface engagement of the B-cell antigen receptor (BCR).
Ubiquitination of activated BLK by the UBE3A ubiquitin protein ligase leads to its degradation by the ubiquitin-proteasome pathway.1 Publication

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP16277
PaxDbiP16277
PeptideAtlasiP16277
PRIDEiP16277

PTM databases

iPTMnetiP16277
PhosphoSitePlusiP16277

Expressioni

Tissue specificityi

Specifically expressed in the B-cell lineage.2 Publications

Inductioni

Expression increases during B-cell differentiation and is under the control of the B-cell specific transcription factors PAX5 and NF-kappa-B.3 Publications

Gene expression databases

BgeeiENSMUSG00000014453 Expressed in 52 organ(s), highest expression level in spleen
CleanExiMM_BLK
GenevisibleiP16277 MM

Interactioni

Subunit structurei

Interacts with CBL (via SH2 domain) (By similarity). Interacts with CD79A and CD79B (via SH2 domain).By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198356, 1 interactor
IntActiP16277, 3 interactors
MINTiP16277
STRINGi10090.ENSMUSP00000014597

Chemistry databases

BindingDBiP16277

Structurei

Secondary structure

1499
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP16277
SMRiP16277
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP16277

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini52 – 112SH3PROSITE-ProRule annotationAdd BLAST61
Domaini118 – 214SH2PROSITE-ProRule annotationAdd BLAST97
Domaini235 – 488Protein kinasePROSITE-ProRule annotationAdd BLAST254

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG0197 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000118938
HOGENOMiHOG000233858
HOVERGENiHBG008761
InParanoidiP16277
KOiK08890
OMAiVLEDFHT
OrthoDBiEOG091G0D46
TreeFamiTF351634

Family and domain databases

CDDicd10371 SH2_Src_Blk, 1 hit
Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR035853 Blk_SH2
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
IPR020635 Tyr_kinase_cat_dom
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 1 hit
PF00017 SH2, 1 hit
PF00018 SH3_1, 1 hit
PRINTSiPR00401 SH2DOMAIN
PR00452 SH3DOMAIN
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00252 SH2, 1 hit
SM00326 SH3, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF50044 SSF50044, 1 hit
SSF55550 SSF55550, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS50001 SH2, 1 hit
PS50002 SH3, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P16277-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGLLSSKRQV SEKGKGWSPV KIRTQDKAPP PLPPLVVFNH LAPPSPNQDP
60 70 80 90 100
DEEERFVVAL FDYAAVNDRD LQVLKGEKLQ VLRSTGDWWL ARSLVTGREG
110 120 130 140 150
YVPSNFVAPV ETLEVEKWFF RTISRKDAER QLLAPMNKAG SFLIRESESN
160 170 180 190 200
KGAFSLSVKD ITTQGEVVKH YKIRSLDNGG YYISPRITFP TLQALVQHYS
210 220 230 240 250
KKGDGLCQKL TLPCVNLAPK NLWAQDEWEI PRQSLKLVRK LGSGQFGEVW
260 270 280 290 300
MGYYKNNMKV AIKTLKEGTM SPEAFLGEAN VMKTLQHERL VRLYAVVTRE
310 320 330 340 350
PIYIVTEYMA RGCLLDFLKT DEGSRLSLPR LIDMSAQVAE GMAYIERMNS
360 370 380 390 400
IHRDLRAANI LVSETLCCKI ADFGLARIID SEYTAQEGAK FPIKWTAPEA
410 420 430 440 450
IHFGVFTIKA DVWSFGVLLM EIVTYGRVPY PGMSNPEVIR SLEHGYRMPC
460 470 480 490
PETCPPELYN DIITECWRGR PEERPTFEFL QSVLEDFYTA TEGQYELQP
Length:499
Mass (Da):56,674
Last modified:July 27, 2011 - v4
Checksum:i14C607564BB4E66D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti421E → V in AAA40453 (PubMed:2404338).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M30903 mRNA Translation: AAA40453.1
AK089888 mRNA Translation: BAC40986.1
CT010240 mRNA Translation: CAJ18448.1
AC090496 Genomic DNA No translation available.
BC030668 mRNA Translation: AAH30668.1
CCDSiCCDS27200.1
PIRiA40092
RefSeqiNP_031575.2, NM_007549.2
UniGeneiMm.3962

Genome annotation databases

EnsembliENSMUST00000014597; ENSMUSP00000014597; ENSMUSG00000014453
GeneIDi12143
KEGGimmu:12143
UCSCiuc007uhq.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M30903 mRNA Translation: AAA40453.1
AK089888 mRNA Translation: BAC40986.1
CT010240 mRNA Translation: CAJ18448.1
AC090496 Genomic DNA No translation available.
BC030668 mRNA Translation: AAH30668.1
CCDSiCCDS27200.1
PIRiA40092
RefSeqiNP_031575.2, NM_007549.2
UniGeneiMm.3962

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BLJNMR-A107-218[»]
1BLKNMR-A107-218[»]
ProteinModelPortaliP16277
SMRiP16277
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198356, 1 interactor
IntActiP16277, 3 interactors
MINTiP16277
STRINGi10090.ENSMUSP00000014597

Chemistry databases

BindingDBiP16277
ChEMBLiCHEMBL3343

PTM databases

iPTMnetiP16277
PhosphoSitePlusiP16277

Proteomic databases

MaxQBiP16277
PaxDbiP16277
PeptideAtlasiP16277
PRIDEiP16277

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000014597; ENSMUSP00000014597; ENSMUSG00000014453
GeneIDi12143
KEGGimmu:12143
UCSCiuc007uhq.1 mouse

Organism-specific databases

CTDi640
MGIiMGI:88169 Blk

Phylogenomic databases

eggNOGiKOG0197 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000118938
HOGENOMiHOG000233858
HOVERGENiHBG008761
InParanoidiP16277
KOiK08890
OMAiVLEDFHT
OrthoDBiEOG091G0D46
TreeFamiTF351634

Enzyme and pathway databases

BRENDAi2.7.10.2 3474

Miscellaneous databases

ChiTaRSiBik mouse
EvolutionaryTraceiP16277
PROiPR:P16277
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000014453 Expressed in 52 organ(s), highest expression level in spleen
CleanExiMM_BLK
GenevisibleiP16277 MM

Family and domain databases

CDDicd10371 SH2_Src_Blk, 1 hit
Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR035853 Blk_SH2
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
IPR020635 Tyr_kinase_cat_dom
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 1 hit
PF00017 SH2, 1 hit
PF00018 SH3_1, 1 hit
PRINTSiPR00401 SH2DOMAIN
PR00452 SH3DOMAIN
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00252 SH2, 1 hit
SM00326 SH3, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF50044 SSF50044, 1 hit
SSF55550 SSF55550, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS50001 SH2, 1 hit
PS50002 SH3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiBLK_MOUSE
AccessioniPrimary (citable) accession number: P16277
Secondary accession number(s): Q8K2M8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: July 27, 2011
Last modified: November 7, 2018
This is version 177 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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Main funding by: National Institutes of Health

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