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Protein

Tyrosine-protein kinase Blk

Gene

Blk

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.

Enzyme 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

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2. 3474.
ReactomeiR-MMU-983695. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:88169. Blk.

Subcellular locationi

  • Cell membrane By similarity; Lipid-anchor By similarity

  • Note: Present and active in lipid rafts (By similarity). Membrane location is required for the phosphorylation of CD79A and CD79B.By similarity1 Publication

GO - Cellular componenti

Complete GO annotation...

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.
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

IntActiP16277. 3 interactors.
STRINGi10090.ENSMUSP00000014597.

Chemistry databases

BindingDBiP16277.

Structurei

Secondary structure

1499
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi116 – 119Combined sources4
Helixi125 – 132Combined sources8
Beta strandi142 – 144Combined sources3
Beta strandi150 – 152Combined sources3
Beta strandi154 – 158Combined sources5
Beta strandi160 – 162Combined sources3
Turni163 – 165Combined sources3
Beta strandi171 – 176Combined sources6
Turni177 – 179Combined sources3
Beta strandi180 – 184Combined sources5
Beta strandi187 – 191Combined sources5
Helixi192 – 201Combined sources10
Beta strandi204 – 208Combined sources5

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...

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
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 SH2 domain.PROSITE-ProRule annotation
Contains 1 SH3 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118938.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiP16277.
KOiK08890.
OMAiGYYKNNM.
OrthoDBiEOG091G0D46.
TreeFamiTF351634.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR000980. SH2.
IPR001452. SH3_domain.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTiSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS50001. SH2. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

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.

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

IntActiP16277. 3 interactors.
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.
OMAiGYYKNNM.
OrthoDBiEOG091G0D46.
TreeFamiTF351634.

Enzyme and pathway databases

BRENDAi2.7.10.2. 3474.
ReactomeiR-MMU-983695. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.

Miscellaneous databases

EvolutionaryTraceiP16277.
PROiP16277.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000014453.
CleanExiMM_BLK.
GenevisibleiP16277. MM.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR000980. SH2.
IPR001452. SH3_domain.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTiSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS50001. SH2. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiBLK_MOUSE
AccessioniPrimary (citable) accession number: P16277
Secondary accession number(s): Q8K2M8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: July 27, 2011
Last modified: November 2, 2016
This is version 166 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.