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Protein

Tyrosine-protein kinase Blk

Gene

BLK

Organism
Homo sapiens (Human)
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 receptors FCGR2A, FCGR2B and FCGR2C. 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.2 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.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei269ATPPROSITE-ProRule annotation1
Active sitei360Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi247 – 255ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • non-membrane spanning protein tyrosine kinase activity Source: UniProtKB
  • protein tyrosine kinase activity Source: ProtInc
  • receptor binding Source: GO_Central

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS06184-MONOMER.
BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-983695. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
SignaLinkiP51451.
SIGNORiP51451.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:1057. BLK.

Subcellular locationi

  • Cell membrane By similarity; Lipid-anchor By similarity

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

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Maturity-onset diabetes of the young 11 (MODY11)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.
See also OMIM:613375
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04167371A → T Associated with MODY11; reduces the enhancing effect of BLK on insulin secretion; reduces the inducing effect of BLK on the expression of PDX1 and NKX6-1; found as somatic mutation in a colorectal adenocarcinoma sample. 2 PublicationsCorresponds to variant rs55758736dbSNPEnsembl.1

Keywords - Diseasei

Diabetes mellitus

Organism-specific databases

DisGeNETi640.
MalaCardsiBLK.
MIMi613375. phenotype.
OpenTargetsiENSG00000136573.
Orphaneti552. MODY.
536. Systemic lupus erythematosus.
PharmGKBiPA25368.

Chemistry databases

ChEMBLiCHEMBL2250.
GuidetoPHARMACOLOGYi1940.

Polymorphism and mutation databases

BioMutaiBLK.
DMDMi158936749.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved
ChainiPRO_00000880612 – 505Tyrosine-protein kinase BlkAdd BLAST504

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineBy similarity1
Modified residuei389Phosphotyrosine; by autocatalysisBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP51451.
PeptideAtlasiP51451.
PRIDEiP51451.

PTM databases

iPTMnetiP51451.
PhosphoSitePlusiP51451.

Expressioni

Tissue specificityi

Expressed in lymphatic organs, pancreatic islets, Leydig cells, striate ducts of salivary glands and hair follicles.1 Publication

Inductioni

Expression is under the control of NF-kappa-B as well as the B-cell specific transcription factors PAX5 and EBF1.1 Publication

Gene expression databases

BgeeiENSG00000136573.
CleanExiHS_BLK.
ExpressionAtlasiP51451. baseline and differential.
GenevisibleiP51451. HS.

Organism-specific databases

HPAiCAB005093.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
ARP102753EBI-2105445,EBI-608057
EGFRP005332EBI-2105445,EBI-297353
GAB1Q134803EBI-2105445,EBI-517684
KITP107215EBI-2105445,EBI-1379503
STAT3P407635EBI-2105445,EBI-518675

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107109. 52 interactors.
IntActiP51451. 49 interactors.
MINTiMINT-1494192.
STRINGi9606.ENSP00000259089.

Chemistry databases

BindingDBiP51451.

Structurei

3D structure databases

ProteinModelPortaliP51451.
SMRiP51451.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini58 – 118SH3PROSITE-ProRule annotationAdd BLAST61
Domaini124 – 220SH2PROSITE-ProRule annotationAdd BLAST97
Domaini241 – 494Protein 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.
InParanoidiP51451.
KOiK08890.
OMAiGYYKNNM.
OrthoDBiEOG091G0D46.
PhylomeDBiP51451.
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.

P51451-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGLVSSKKPD KEKPIKEKDK GQWSPLKVSA QDKDAPPLPP LVVFNHLTPP
60 70 80 90 100
PPDEHLDEDK HFVVALYDYT AMNDRDLQML KGEKLQVLKG TGDWWLARSL
110 120 130 140 150
VTGREGYVPS NFVARVESLE MERWFFRSQG RKEAERQLLA PINKAGSFLI
160 170 180 190 200
RESETNKGAF SLSVKDVTTQ GELIKHYKIR CLDEGGYYIS PRITFPSLQA
210 220 230 240 250
LVQHYSKKGD GLCQRLTLPC VRPAPQNPWA QDEWEIPRQS LRLVRKLGSG
260 270 280 290 300
QFGEVWMGYY KNNMKVAIKT LKEGTMSPEA FLGEANVMKA LQHERLVRLY
310 320 330 340 350
AVVTKEPIYI VTEYMARGCL LDFLKTDEGS RLSLPRLIDM SAQIAEGMAY
360 370 380 390 400
IERMNSIHRD LRAANILVSE ALCCKIADFG LARIIDSEYT AQEGAKFPIK
410 420 430 440 450
WTAPEAIHFG VFTIKADVWS FGVLLMEVVT YGRVPYPGMS NPEVIRNLER
460 470 480 490 500
GYRMPRPDTC PPELYRGVIA ECWRSRPEER PTFEFLQSVL EDFYTATERQ

YELQP
Length:505
Mass (Da):57,706
Last modified:August 21, 2007 - v3
Checksum:iB5F739BEF8389176
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti287V → M in CAA83965 (PubMed:7822795).Curated1
Sequence conflicti407I → Y in AAB33265 (PubMed:7845672).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04167248T → I.1 PublicationCorresponds to variant rs35339715dbSNPEnsembl.1
Natural variantiVAR_04167371A → T Associated with MODY11; reduces the enhancing effect of BLK on insulin secretion; reduces the inducing effect of BLK on the expression of PDX1 and NKX6-1; found as somatic mutation in a colorectal adenocarcinoma sample. 2 PublicationsCorresponds to variant rs55758736dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z33998 mRNA. Translation: CAA83965.1.
S76617 mRNA. Translation: AAB33265.1.
AK313751 mRNA. Translation: BAG36491.1.
CH471157 Genomic DNA. Translation: EAW65617.1.
BC007371 mRNA. Translation: AAH07371.1.
BC032413 mRNA. Translation: AAH32413.1.
CCDSiCCDS5982.1.
PIRiI37206.
RefSeqiNP_001706.2. NM_001715.2.
UniGeneiHs.146591.

Genome annotation databases

EnsembliENST00000259089; ENSP00000259089; ENSG00000136573.
GeneIDi640.
KEGGihsa:640.
UCSCiuc003wty.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z33998 mRNA. Translation: CAA83965.1.
S76617 mRNA. Translation: AAB33265.1.
AK313751 mRNA. Translation: BAG36491.1.
CH471157 Genomic DNA. Translation: EAW65617.1.
BC007371 mRNA. Translation: AAH07371.1.
BC032413 mRNA. Translation: AAH32413.1.
CCDSiCCDS5982.1.
PIRiI37206.
RefSeqiNP_001706.2. NM_001715.2.
UniGeneiHs.146591.

3D structure databases

ProteinModelPortaliP51451.
SMRiP51451.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107109. 52 interactors.
IntActiP51451. 49 interactors.
MINTiMINT-1494192.
STRINGi9606.ENSP00000259089.

Chemistry databases

BindingDBiP51451.
ChEMBLiCHEMBL2250.
GuidetoPHARMACOLOGYi1940.

PTM databases

iPTMnetiP51451.
PhosphoSitePlusiP51451.

Polymorphism and mutation databases

BioMutaiBLK.
DMDMi158936749.

Proteomic databases

PaxDbiP51451.
PeptideAtlasiP51451.
PRIDEiP51451.

Protocols and materials databases

DNASUi640.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000259089; ENSP00000259089; ENSG00000136573.
GeneIDi640.
KEGGihsa:640.
UCSCiuc003wty.4. human.

Organism-specific databases

CTDi640.
DisGeNETi640.
GeneCardsiBLK.
H-InvDBHIX0007315.
HIX0168887.
HGNCiHGNC:1057. BLK.
HPAiCAB005093.
MalaCardsiBLK.
MIMi191305. gene.
613375. phenotype.
neXtProtiNX_P51451.
OpenTargetsiENSG00000136573.
Orphaneti552. MODY.
536. Systemic lupus erythematosus.
PharmGKBiPA25368.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118938.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiP51451.
KOiK08890.
OMAiGYYKNNM.
OrthoDBiEOG091G0D46.
PhylomeDBiP51451.
TreeFamiTF351634.

Enzyme and pathway databases

BioCyciZFISH:HS06184-MONOMER.
BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-983695. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
SignaLinkiP51451.
SIGNORiP51451.

Miscellaneous databases

ChiTaRSiBLK. human.
GeneWikiiTyrosine-protein_kinase_BLK.
GenomeRNAii640.
PROiP51451.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000136573.
CleanExiHS_BLK.
ExpressionAtlasiP51451. baseline and differential.
GenevisibleiP51451. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: P51451
Secondary accession number(s): Q16291, Q96IN1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: August 21, 2007
Last modified: November 30, 2016
This is version 164 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. 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.