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Q8WV28 (BLNK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:BLNK
Synonyms:BASH, SLP65
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length456 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.2 Ref.8 Ref.9

Subunit structure

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. Ref.1 Ref.6 Ref.9 Ref.10 Ref.11

Subcellular location

Cytoplasm. Cell membrane. Note: BCR activation results in the translocation to membrane fraction. Ref.1

Tissue specificity

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.

Post-translational modification

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. Ref.1 Ref.7

Involvement in disease

Agammaglobulinemia 4, autosomal recessive (AGM4) [MIM:613502]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2

Sequence similarities

Contains 1 SH2 domain.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8WV28-1)

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.
Isoform 2 (identifier: Q8WV28-2)

The sequence of this isoform differs from the canonical sequence as follows:
     203-225: Missing.
Isoform 3 (identifier: Q8WV28-3)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 456456B-cell linker protein
PRO_0000064940

Regions

Domain346 – 453108SH2
Compositional bias98 – 260163Pro-rich

Amino acid modifications

Modified residue721Phosphotyrosine; by SYK Ref.7
Modified residue841Phosphotyrosine; by SYK Ref.7
Modified residue961Phosphotyrosine; by SYK Ref.7
Modified residue1781Phosphotyrosine; by SYK Ref.7
Modified residue1891Phosphotyrosine; by SYK Ref.7

Natural variations

Alternative sequence203 – 22523Missing in isoform 2.
VSP_016178
Alternative sequence366 – 41752Missing in isoform 3.
VSP_045324

Experimental info

Mutagenesis721Y → F: Significant phosphorylation reduction; when associated with F-84; F-96 and F-178. Ref.1 Ref.7
Mutagenesis841Y → F: Significant phosphorylation reduction; when associated with F-72; F-96 and F-178. Ref.1 Ref.7
Mutagenesis961Y → F: Significant phosphorylation reduction; when associated with F-72; F-84 and F-178. Ref.1 Ref.7
Mutagenesis1781Y → F: Significant phosphorylation reduction; when associated with F-72; F-84 and F-96. Ref.1 Ref.7
Sequence conflict621E → Q in AAH18906. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 22, 2005. Version 2.
Checksum: 95F1D5485D03D397

FASTA45650,466
        10         20         30         40         50         60 
MDKLNKITVP ASQKLRQLQK MVHDIKNNEG GIMNKIKKLK VKAPPSVPRR DYASESPADE 

        70         80         90        100        110        120 
EEQWSDDFDS DYENPDEHSD SEMYVMPAEE NADDSYEPPP VEQETRPVHP ALPFARGEYI 

       130        140        150        160        170        180 
DNRSSQRHSP PFSKTLPSKP SWPSEKARLT STLPALTALQ KPQVPPKPKG LLEDEADYVV 

       190        200        210        220        230        240 
PVEDNDENYI HPTESSSPPP EKAPMVNRST KPNSSTPASP PGTASGRNSG AWETKSPPPA 

       250        260        270        280        290        300 
APSPLPRAGK KPTTPLKTTP VASQQNASSV CEEKPIPAER HRGSSHRQEA VQSPVFPPAQ 

       310        320        330        340        350        360 
KQIHQKPIPL PRFTEGGNPT VDGPLPSFSS NSTISEQEAG VLCKPWYAGA CDRKSAEEAL 

       370        380        390        400        410        420 
HRSNKDGSFL IRKSSGHDSK QPYTLVVFFN KRVYNIPVRF IEATKQYALG RKKNGEEYFG 

       430        440        450 
SVAEIIRNHQ HSPLVLIDSQ NNTKDSTRLK YAVKVS 

« Hide

Isoform 2 [UniParc].

Checksum: 0B36FE9FCF5DC7DC
Show »

FASTA43348,229
Isoform 3 [UniParc].

Checksum: 2288B35E399683F4
Show »

FASTA40444,451

References

« Hide 'large scale' references
[1]"BLNK: a central linker protein in B cell activation."
Fu C., Turck C.W., Kurosaki T., Chan A.C.
Immunity 9:93-103(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PROTEIN SEQUENCE OF 7-20; 140-146; 237-248; 250-257; 366-373 AND 392-405, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PLCG1; VAV1; GRB2 AND NCK1, ALTERNATIVE SPLICING, PHOSPHORYLATION, MUTAGENESIS OF TYR-72; TYR-84; TYR-96 AND TYR-178.
[2]"An essential role for BLNK in human B cell development."
Minegishi Y., Rohrer J., Coustan-Smith E., Lederman H.M., Pappu R., Campana D., Chan A.C., Conley M.E.
Science 286:1954-1957(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2), FUNCTION IN B-CELL DEVELOPMENT, INVOLVEMENT IN AGM4.
[3]"SLP65 deficiency results in perpetual V(D)J recombinase activity in pre-B-lymphoblastic leukemia and B-cell lymphoma cells."
Sprangers M., Feldhahn N., Liedtke S., Jumaa H., Siebert R., Muschen M.
Oncogene 25:5180-5186(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[4]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: B-cell.
[6]"Identification of two tyrosine phosphoproteins, pp70 and pp68, which interact with phospholipase Cgamma, Grb2, and Vav after B cell antigen receptor activation."
Fu C., Chan A.C.
J. Biol. Chem. 272:27362-27368(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PLCG1; VAV1; GRB2 AND NCK1.
[7]"BLNK: molecular scaffolding through 'cis'-mediated organization of signaling proteins."
Chiu C.W., Dalton M., Ishiai M., Kurosaki T., Chan A.C.
EMBO J. 21:6461-6472(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-72; TYR-84; TYR-96; TYR-178 AND TYR-189 BY SYK, MUTAGENESIS OF TYR-72; TYR-84 AND TYR-96.
[8]"Deficiency of BLNK hampers PLC-gamma2 phosphorylation and Ca2+ influx induced by the pre-B-cell receptor in human pre-B cells."
Taguchi T., Kiyokawa N., Takenouch H., Matsui J., Tang W.-R., Nakajima H., Suzuki K., Shiozawa Y., Saito M., Katagiri Y.U., Takahashi T., Karasuyama H., Matsuo Y., Okita H., Fujimoto J.
Immunology 112:575-582(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PLCG1 ACTIVATION AND CALCIUM MOBILIZATION.
[9]"Human SLP-65 isoforms contribute differently to activation and apoptosis of B lymphocytes."
Grabbe A., Wienands J.
Blood 108:3761-3768(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH GRB2.
[10]"The kinase Syk as an adaptor controlling sustained calcium signalling and B-cell development."
Kulathu Y., Hobeika E., Turchinovich G., Reth M.
EMBO J. 27:1333-1344(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SYK.
[11]"SCIMP, a transmembrane adapter protein involved in major histocompatibility complex class II signaling."
Draber P., Vonkova I., Stepanek O., Hrdinka M., Kucova M., Skopcova T., Otahal P., Angelisova P., Horejsi V., Yeung M., Weiss A., Brdicka T.
Mol. Cell. Biol. 31:4550-4562(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SCIMP.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF068180 mRNA. Translation: AAC39936.1.
AF068181 mRNA. Translation: AAC39937.1.
AF180756 expand/collapse EMBL AC list , AF180740, AF180741, AF180742, AF180743, AF180744, AF180745, AF180746, AF180747, AF180748, AF180749, AF180750, AF180751, AF180752, AF180753, AF180754, AF180755 Genomic DNA. Translation: AAF20382.1.
AF180756 expand/collapse EMBL AC list , 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.
CCDSCCDS44464.1. [Q8WV28-2]
CCDS58091.1. [Q8WV28-3]
CCDS7446.1. [Q8WV28-1]
RefSeqNP_001107566.1. NM_001114094.1. [Q8WV28-2]
NP_001245369.1. NM_001258440.1. [Q8WV28-3]
NP_037446.1. NM_013314.3. [Q8WV28-1]
UniGeneHs.665244.

3D structure databases

ProteinModelPortalQ8WV28.
SMRQ8WV28. Positions 331-456.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid118894. 33 interactions.
IntActQ8WV28. 21 interactions.
MINTMINT-110179.
STRING9606.ENSP00000224337.

PTM databases

PhosphoSiteQ8WV28.

Polymorphism databases

DMDM82592659.

Proteomic databases

MaxQBQ8WV28.
PaxDbQ8WV28.
PRIDEQ8WV28.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000224337; ENSP00000224337; ENSG00000095585. [Q8WV28-1]
ENST00000371176; ENSP00000360218; ENSG00000095585. [Q8WV28-2]
ENST00000413476; ENSP00000397487; ENSG00000095585. [Q8WV28-3]
ENST00000574329; ENSP00000461050; ENSG00000262509. [Q8WV28-1]
ENST00000574984; ENSP00000460444; ENSG00000262509. [Q8WV28-2]
GeneID29760.
KEGGhsa:29760.
UCSCuc001kls.4. human. [Q8WV28-1]
uc001klt.4. human. [Q8WV28-2]
uc001klu.4. human.

Organism-specific databases

CTD29760.
GeneCardsGC10M097941.
HGNCHGNC:14211. BLNK.
HPACAB009333.
CAB016291.
HPA038309.
HPA038310.
MIM604515. gene.
613502. phenotype.
neXtProtNX_Q8WV28.
Orphanet33110. Autosomal agammaglobulinemia.
PharmGKBPA25371.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG44661.
HOGENOMHOG000088646.
HOVERGENHBG053147.
InParanoidQ8WV28.
KOK07371.
OMAHRQENMQ.
PhylomeDBQ8WV28.
TreeFamTF326567.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
SignaLinkQ8WV28.

Gene expression databases

ArrayExpressQ8WV28.
BgeeQ8WV28.
CleanExHS_BLNK.
GenevestigatorQ8WV28.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR000980. SH2.
[Graphical view]
PfamPF00017. SH2. 1 hit.
[Graphical view]
SMARTSM00252. SH2. 1 hit.
[Graphical view]
SUPFAMSSF55550. SSF55550. 1 hit.
PROSITEPS50001. SH2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiB-cell_linker.
GenomeRNAi29760.
NextBio52250.
PROQ8WV28.
SOURCESearch...

Entry information

Entry nameBLNK_HUMAN
AccessionPrimary (citable) accession number: Q8WV28
Secondary accession number(s): O75498, O75499, Q2MD49
Entry history
Integrated into UniProtKB/Swiss-Prot: November 22, 2005
Last sequence update: November 22, 2005
Last modified: July 9, 2014
This is version 109 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM