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Protein

B-cell linker protein

Gene

BLNK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Functions as a central linker protein, downstream of the B-cell receptor (BCR), bridging the SYK kinase to a multitude of signaling pathways and regulating biological outcomes of B-cell function and development. Plays a role in the activation of ERK/EPHB2, MAP kinase p38 and JNK. Modulates AP1 activation. Important for the activation of NF-kappa-B and NFAT. Plays an important role in BCR-mediated PLCG1 and PLCG2 activation and Ca2+ mobilization and is required for trafficking of the BCR to late endosomes. However, does not seem to be required for pre-BCR-mediated activation of MAP kinase and phosphatidyl-inositol 3 (PI3) kinase signaling. May be required for the RAC1-JNK pathway. Plays a critical role in orchestrating the pro-B cell to pre-B cell transition. May play an important role in BCR-induced B-cell apoptosis.4 Publications

GO - Molecular functioni

  • SH3/SH2 adaptor activity Source: UniProtKB
  • transmembrane receptor protein tyrosine kinase adaptor activity Source: ProtInc

GO - Biological processi

  • B cell differentiation Source: UniProtKB
  • humoral immune response Source: ProtInc
  • inflammatory response Source: ProtInc
  • intracellular signal transduction Source: UniProtKB
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central

Keywordsi

Biological processB-cell activation

Enzyme and pathway databases

ReactomeiR-HSA-912631 Regulation of signaling by CBL
R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
SignaLinkiQ8WV28
SIGNORiQ8WV28

Names & Taxonomyi

Protein namesi
Recommended name:
B-cell linker protein
Alternative name(s):
B-cell adapter containing a SH2 domain protein
B-cell adapter containing a Src homology 2 domain protein
Cytoplasmic adapter protein
Src homology 2 domain-containing leukocyte protein of 65 kDa
Short name:
SLP-65
Gene namesi
Name:BLNK
Synonyms:BASH, SLP65
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000095585.16
HGNCiHGNC:14211 BLNK
MIMi604515 gene
neXtProtiNX_Q8WV28

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, Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Agammaglobulinemia 4, autosomal recessive (AGM4)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B-cells due to an early block of B-cell development. Affected individuals develop severe infections in the first years of life.
See also OMIM:613502

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi72Y → F: Significant phosphorylation reduction; when associated with F-84; F-96 and F-178. 2 Publications1
Mutagenesisi84Y → F: Significant phosphorylation reduction; when associated with F-72; F-96 and F-178. 2 Publications1
Mutagenesisi96Y → F: Significant phosphorylation reduction; when associated with F-72; F-84 and F-178. 2 Publications1
Mutagenesisi178Y → F: Significant phosphorylation reduction; when associated with F-72; F-84 and F-96. 1 Publication1

Organism-specific databases

DisGeNETi29760
MalaCardsiBLNK
MIMi613502 phenotype
OpenTargetsiENSG00000095585
Orphaneti33110 Autosomal agammaglobulinemia
PharmGKBiPA25371

Polymorphism and mutation databases

BioMutaiBLNK
DMDMi82592659

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000649401 – 456B-cell linker proteinAdd BLAST456

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei72Phosphotyrosine; by SYK1 Publication1
Modified residuei84Phosphotyrosine; by SYK1 Publication1
Modified residuei96Phosphotyrosine; by SYK1 Publication1
Modified residuei178Phosphotyrosine; by SYK1 Publication1
Modified residuei189Phosphotyrosine; by SYK1 Publication1

Post-translational modificationi

Following BCR activation, phosphorylated on tyrosine residues by SYK and LYN. When phosphorylated, serves as a scaffold to assemble downstream targets of antigen activation, including PLCG1, VAV1, GRB2 and NCK1. Phosphorylation of Tyr-84, Tyr-178 and Tyr-189 facilitates PLCG1 binding. Phosphorylation of Tyr-96 facilitates BTK binding. Phosphorylation of Tyr-72 facilitates VAV1 and NCK1 binding. Phosphorylation is required for both Ca2+ and MAPK signaling pathways.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ8WV28
PaxDbiQ8WV28
PeptideAtlasiQ8WV28
PRIDEiQ8WV28
ProteomicsDBi74740
74741 [Q8WV28-2]

PTM databases

iPTMnetiQ8WV28
PhosphoSitePlusiQ8WV28

Expressioni

Tissue specificityi

Expressed in B-cell lineage and fibroblast cell lines (at protein level). Highest levels of expression in the spleen, with lower levels in the liver, kidney, pancreas, small intestines and colon.

Gene expression databases

BgeeiENSG00000095585 Expressed in 193 organ(s), highest expression level in mouth mucosa
CleanExiHS_BLNK
ExpressionAtlasiQ8WV28 baseline and differential
GenevisibleiQ8WV28 HS

Organism-specific databases

HPAiCAB009333
CAB016291
HPA038309
HPA038310

Interactioni

Subunit structurei

Associates with PLCG1, VAV1 and NCK1 in a B-cell antigen receptor-dependent fashion. Interacts with VAV3, PLCG2 and GRB2. Interacts through its SH2 domain with CD79A. Interacts (via SH2 domain) with SYK; phosphorylated and activated by SYK. Interacts with SCIMP.5 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi118894, 34 interactors
CORUMiQ8WV28
IntActiQ8WV28, 22 interactors
MINTiQ8WV28
STRINGi9606.ENSP00000224337

Structurei

3D structure databases

ProteinModelPortaliQ8WV28
SMRiQ8WV28
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini346 – 453SH2PROSITE-ProRule annotationAdd BLAST108

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi98 – 260Pro-richAdd BLAST163

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiENOG410IGWN Eukaryota
ENOG410XYB6 LUCA
GeneTreeiENSGT00530000063094
HOGENOMiHOG000088646
HOVERGENiHBG053147
InParanoidiQ8WV28
KOiK07371
OMAiDSEMYVL
OrthoDBiEOG091G053I
PhylomeDBiQ8WV28
TreeFamiTF326567

Family and domain databases

Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR000980 SH2
IPR036860 SH2_dom_sf
PfamiView protein in Pfam
PF00017 SH2, 1 hit
SMARTiView protein in SMART
SM00252 SH2, 1 hit
SUPFAMiSSF55550 SSF55550, 1 hit
PROSITEiView protein in PROSITE
PS50001 SH2, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q8WV28-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MDKLNKITVP ASQKLRQLQK MVHDIKNNEG GIMNKIKKLK VKAPPSVPRR
60 70 80 90 100
DYASESPADE EEQWSDDFDS DYENPDEHSD SEMYVMPAEE NADDSYEPPP
110 120 130 140 150
VEQETRPVHP ALPFARGEYI DNRSSQRHSP PFSKTLPSKP SWPSEKARLT
160 170 180 190 200
STLPALTALQ KPQVPPKPKG LLEDEADYVV PVEDNDENYI HPTESSSPPP
210 220 230 240 250
EKAPMVNRST KPNSSTPASP PGTASGRNSG AWETKSPPPA APSPLPRAGK
260 270 280 290 300
KPTTPLKTTP VASQQNASSV CEEKPIPAER HRGSSHRQEA VQSPVFPPAQ
310 320 330 340 350
KQIHQKPIPL PRFTEGGNPT VDGPLPSFSS NSTISEQEAG VLCKPWYAGA
360 370 380 390 400
CDRKSAEEAL HRSNKDGSFL IRKSSGHDSK QPYTLVVFFN KRVYNIPVRF
410 420 430 440 450
IEATKQYALG RKKNGEEYFG SVAEIIRNHQ HSPLVLIDSQ NNTKDSTRLK

YAVKVS
Length:456
Mass (Da):50,466
Last modified:November 22, 2005 - v2
Checksum:i95F1D5485D03D397
GO
Isoform 2 (identifier: Q8WV28-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     203-225: Missing.

Show »
Length:433
Mass (Da):48,229
Checksum:i0B36FE9FCF5DC7DC
GO
Isoform 3 (identifier: Q8WV28-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     366-417: Missing.

Show »
Length:404
Mass (Da):44,451
Checksum:i2288B35E399683F4
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q2MD59Q2MD59_HUMAN
B-cell linker protein
BLNK BASH, SLP65
299Annotation score:
Q2MD47Q2MD47_HUMAN
B-cell linker protein
BLNK BASH, SLP65
121Annotation score:
K7EKR2K7EKR2_HUMAN
B-cell linker protein
BLNK
65Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti62E → Q in AAH18906 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_016178203 – 225Missing in isoform 2. 1 PublicationAdd BLAST23
Alternative sequenceiVSP_045324366 – 417Missing in isoform 3. 1 PublicationAdd BLAST52

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF068180 mRNA Translation: AAC39936.1
AF068181 mRNA Translation: AAC39937.1
AF180756
, AF180740, AF180741, AF180742, AF180743, AF180744, AF180745, AF180746, AF180747, AF180748, AF180749, AF180750, AF180751, AF180752, AF180753, AF180754, AF180755 Genomic DNA Translation: AAF20382.1
AF180756
, AF180740, AF180741, AF180742, AF180743, AF180744, AF180745, AF180746, AF180748, AF180749, AF180750, AF180751, AF180752, AF180753, AF180754, AF180755 Genomic DNA Translation: AAF20383.1
AM180337 mRNA Translation: CAJ55331.1
AC021037 Genomic DNA No translation available.
BC018906 mRNA Translation: AAH18906.1
CCDSiCCDS44464.1 [Q8WV28-2]
CCDS58091.1 [Q8WV28-3]
CCDS7446.1 [Q8WV28-1]
RefSeqiNP_001107566.1, NM_001114094.1 [Q8WV28-2]
NP_001245369.1, NM_001258440.1 [Q8WV28-3]
NP_037446.1, NM_013314.3 [Q8WV28-1]
UniGeneiHs.665244

Genome annotation databases

EnsembliENST00000224337; ENSP00000224337; ENSG00000095585 [Q8WV28-1]
ENST00000371176; ENSP00000360218; ENSG00000095585 [Q8WV28-2]
ENST00000413476; ENSP00000397487; ENSG00000095585 [Q8WV28-3]
GeneIDi29760
KEGGihsa:29760
UCSCiuc001kls.5 human [Q8WV28-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Web resourcesi

BLNKbase

BLNK mutation db

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF068180 mRNA Translation: AAC39936.1
AF068181 mRNA Translation: AAC39937.1
AF180756
, AF180740, AF180741, AF180742, AF180743, AF180744, AF180745, AF180746, AF180747, AF180748, AF180749, AF180750, AF180751, AF180752, AF180753, AF180754, AF180755 Genomic DNA Translation: AAF20382.1
AF180756
, AF180740, AF180741, AF180742, AF180743, AF180744, AF180745, AF180746, AF180748, AF180749, AF180750, AF180751, AF180752, AF180753, AF180754, AF180755 Genomic DNA Translation: AAF20383.1
AM180337 mRNA Translation: CAJ55331.1
AC021037 Genomic DNA No translation available.
BC018906 mRNA Translation: AAH18906.1
CCDSiCCDS44464.1 [Q8WV28-2]
CCDS58091.1 [Q8WV28-3]
CCDS7446.1 [Q8WV28-1]
RefSeqiNP_001107566.1, NM_001114094.1 [Q8WV28-2]
NP_001245369.1, NM_001258440.1 [Q8WV28-3]
NP_037446.1, NM_013314.3 [Q8WV28-1]
UniGeneiHs.665244

3D structure databases

ProteinModelPortaliQ8WV28
SMRiQ8WV28
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118894, 34 interactors
CORUMiQ8WV28
IntActiQ8WV28, 22 interactors
MINTiQ8WV28
STRINGi9606.ENSP00000224337

PTM databases

iPTMnetiQ8WV28
PhosphoSitePlusiQ8WV28

Polymorphism and mutation databases

BioMutaiBLNK
DMDMi82592659

Proteomic databases

MaxQBiQ8WV28
PaxDbiQ8WV28
PeptideAtlasiQ8WV28
PRIDEiQ8WV28
ProteomicsDBi74740
74741 [Q8WV28-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000224337; ENSP00000224337; ENSG00000095585 [Q8WV28-1]
ENST00000371176; ENSP00000360218; ENSG00000095585 [Q8WV28-2]
ENST00000413476; ENSP00000397487; ENSG00000095585 [Q8WV28-3]
GeneIDi29760
KEGGihsa:29760
UCSCiuc001kls.5 human [Q8WV28-1]

Organism-specific databases

CTDi29760
DisGeNETi29760
EuPathDBiHostDB:ENSG00000095585.16
GeneCardsiBLNK
HGNCiHGNC:14211 BLNK
HPAiCAB009333
CAB016291
HPA038309
HPA038310
MalaCardsiBLNK
MIMi604515 gene
613502 phenotype
neXtProtiNX_Q8WV28
OpenTargetsiENSG00000095585
Orphaneti33110 Autosomal agammaglobulinemia
PharmGKBiPA25371
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IGWN Eukaryota
ENOG410XYB6 LUCA
GeneTreeiENSGT00530000063094
HOGENOMiHOG000088646
HOVERGENiHBG053147
InParanoidiQ8WV28
KOiK07371
OMAiDSEMYVL
OrthoDBiEOG091G053I
PhylomeDBiQ8WV28
TreeFamiTF326567

Enzyme and pathway databases

ReactomeiR-HSA-912631 Regulation of signaling by CBL
R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
SignaLinkiQ8WV28
SIGNORiQ8WV28

Miscellaneous databases

ChiTaRSiBLNK human
GeneWikiiB-cell_linker
GenomeRNAii29760
PROiPR:Q8WV28
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000095585 Expressed in 193 organ(s), highest expression level in mouth mucosa
CleanExiHS_BLNK
ExpressionAtlasiQ8WV28 baseline and differential
GenevisibleiQ8WV28 HS

Family and domain databases

Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR000980 SH2
IPR036860 SH2_dom_sf
PfamiView protein in Pfam
PF00017 SH2, 1 hit
SMARTiView protein in SMART
SM00252 SH2, 1 hit
SUPFAMiSSF55550 SSF55550, 1 hit
PROSITEiView protein in PROSITE
PS50001 SH2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiBLNK_HUMAN
AccessioniPrimary (citable) accession number: Q8WV28
Secondary accession number(s): O75498, O75499, Q2MD49
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 22, 2005
Last sequence update: November 22, 2005
Last modified: November 7, 2018
This is version 142 of the entry and version 2 of the sequence. See 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, Direct protein sequencing, Reference proteome

Documents

  1. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  2. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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