Q9QUN3 (BLNK_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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
Lymphocyte antigen 57
Src homology 2 domain-containing leukocyte protein of 65 kDa
Short name=Slp-65

Gene names

Name:	Blnk
Synonyms:	Bash, Ly57, Slp65

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	457 AA.
Sequence status	Complete.
Protein existence	Evidence 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.2 Ref.9 Ref.10
Subunit structure	Associates with PLCG1, VAV1 and NCK1 in a B-cell antigen receptor-dependent fashion. Interacts with VAV3, PLCG2 and GRB2 By similarity. Interacts through its SH2 domain with CD79A. Interacts (via SH2 domain) with SYK; phosphorylated and activated by SYK. Interacts with SCIMP. Ref.2 Ref.6 Ref.7 Ref.8 Ref.10 Ref.11
Subcellular location	Cytoplasm By similarity. Cell membrane By similarity. Note: BCR activation results in the translocation to membrane fraction By similarity.
Tissue specificity	Expressed in the spleen and weakly in thymus, no expression was seen in liver, testis, or brain. Expressed in B-cell lines representing different developmental stages from the pre-B to the plasma cell stage, but not in a T-cell or a fibroblast cell line. Ref.2
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-72 facilitates VAV1 and NCK1 binding. Phosphorylation is required for both Ca2+ and MAPK signaling pathways By similarity. Phosphorylation of Tyr-96 is required for the binding of BTK. Ref.2
Sequence similarities	Contains 1 SH2 domain.

Ontologies

Keywords
Biological process	B-cell activation
Cellular component	Cell membrane Cytoplasm Membrane
Domain	SH2 domain
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	B cell activation Inferred from electronic annotation. Source: UniProtKB-KW intracellular signal transduction Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 457

457

B-cell linker protein

PRO_0000064941

Regions

Domain

347 – 454

108

SH2

Compositional bias

130 – 330

201

Pro-rich

Amino acid modifications

Modified residue

72

1

Phosphotyrosine; by SYK By similarity

Modified residue

84

1

Phosphotyrosine; by SYK By similarity

Modified residue

96

1

Phosphotyrosine; by SYK By similarity

Modified residue

178

1

Phosphotyrosine; by SYK By similarity

Modified residue

189

1

Phosphotyrosine; by SYK By similarity

Experimental info

Mutagenesis

52

1

Y → F: No effect on pre-BCR down-regulation. Ref.9

Mutagenesis

96

1

Y → F: Fails to induce pre-BCR down-regulation, leading to splenomegaly and leukemia. Ref.9

Mutagenesis

373

1

R → L: Abolishes binding to CD79A and SYK. Ref.6 Ref.10

Sequence conflict

333

1

S → L in AAC40206. Ref.1

Sequence conflict

340

1

A → G in AAC40206. Ref.1

Sequence conflict

356

1

S → F in AAC40206. Ref.1

Sequence conflict

376

1

S → F in AAC40206. Ref.1

Secondary structure

1

.

.

.

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.

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.

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.

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457

Helix Strand Turn

Details...

Helix

334 – 340

7

Turn

341 – 344

4

Beta strand

346 – 351

6

Helix

354 – 364

11

Beta strand

372 – 374

3

Beta strand

383 – 390

8

Beta strand

393 – 399

7

Turn

403 – 406

4

Beta strand

410 – 412

3

Beta strand

420 – 422

3

Helix

423 – 432

10

Beta strand

440 – 442

3

Sequences

	Sequence		Length	Mass (Da)
	Q9QUN3 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 66C93D4FDDF9D260	FASTA	457	50,671
	10 20 30 40 50 60 MDKLNKITVP ASQKLRQLQK MVHDIKNNEG GIMDKIKKLK VKGPPSVPRR DYALDSPADE 70 80 90 100 110 120 EEQWSDDFDS DYENPDEHSD SEMYVMPAEE TGDDSYEPPP AEQQTRVVHP ALPFTRGEYV 130 140 150 160 170 180 DNRSSQRHSP PFSKTLPSKP SWPSAKARLA STLPAPNSLQ KPQVPPKPKD LLEDEADYVV 190 200 210 220 230 240 PVEDNDENYI HPRESSPPPA EKAPMVNRST KPNSSSKHMS PPGTVAGRNS GVWDSKSSLP 250 260 270 280 290 300 AAPSPLPRAG KKPATPLKTT PVPPLPNASN VCEEKPVPAE RHRGSSHRQD TVQSPVFPPT 310 320 330 340 350 360 QKPVHQKPVP LPRFPEAGSP AADGPFHSFP FNSTFADQEA ELLGKPWYAG ACDRKSAEEA 370 380 390 400 410 420 LHRSNKDGSF LIRKSSGHDS KQPYTLVAFF NKRVYNIPVR FIEATKQYAL GKKKNGEEYF 430 440 450 GSVVEIVNSH QHNPLVLIDS QNNTKDSTRL KYAVKVS

References

	« Hide 'large scale' referencesShow '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].
[2]	"SLP-65: a new signaling component in B lymphocytes which requires expression of the antigen receptor for phosphorylation." Wienands J., Schweikert J., Wollschied B., Jumaa H., Nielsen P.J., Reth M. J. Exp. Med. 188:791-795(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 7-20; 147-161; 170-186; 356-366 AND 393-412, FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION, INTERACTION WITH VAV1 AND GRB2. Strain: BALB/c. Tissue: Lymphoid tissue.
[3]	"BASH: B lymphocyte adaptor protein containing SH2 domain." Okamoto N., Hayashi K., Tsuji S., Goitsuka R., Kitamura D. Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"The murine SLP-65 gene." Nielsen P.J., Guenet J.-L. Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [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]. Strain: 129. Tissue: Mammary tumor.
[6]	"Association of SLP-65/BLNK with the B cell antigen receptor through a non-ITAM tyrosine of Ig-alpha." Engels N., Wollscheid B., Wienands J. Eur. J. Immunol. 31:2126-2134(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CD79A, MUTAGENESIS OF ARG-373.
[7]	"Receptor-facilitated antigen presentation requires the recruitment of B cell linker protein to Igalpha." Siemasko K., Skaggs B.J., Kabak S., Williamson E., Brown B.K., Song W., Clark M.R. J. Immunol. 168:2127-2138(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CD79A.
[8]	"The direct recruitment of BLNK to immunoglobulin alpha couples the B-cell antigen receptor to distal signaling pathways." Kabak S., Skaggs B.J., Gold M.R., Affolter M., West K.L., Foster M.S., Siemasko K., Chan A.C., Aebersold R., Clark M.R. Mol. Cell. Biol. 22:2524-2535(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CD79A.
[9]	"Deficiency of the adaptor SLP-65 in pre-B-cell acute lymphoblastic leukaemia." Jumaa H., Bossaller L., Portugal K., Storch B., Lotz M., Flemming A., Schrappe M., Postila V., Riikonen P., Pelkonen J., Niemeyer C.M., Reth M. Nature 423:452-456(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PRO-B CELL TO PRE-B CELL TRANSITION, MUTAGENESIS OF TYR-52 AND TYR-96.
[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: FUNCTION IN SYK ACTIVATION, INTERACTION WITH SYK, MUTAGENESIS OF ARG-373.
[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.
[12]	"Solution structure of the SH2 domain from mouse B-cell linker protein BLNK." RIKEN structural genomics initiative (RSGI) Submitted (APR-2008) to the PDB data bank Cited for: STRUCTURE BY NMR OF 328-457.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF068182 mRNA. Translation: AAC40206.1.
Y17159 mRNA. Translation: CAA76666.1.
AB015290 mRNA. Translation: BAA34944.1.
AJ298054 Genomic DNA. Translation: CAC18565.1.
BC059785 mRNA. Translation: AAH59785.1.

IPI

IPI00331479.

RefSeq

NP_032554.2. NM_008528.4.

UniGene

Mm.9749.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2EO6	NMR	-	A	330-457	[»]

ProteinModelPortal

Q9QUN3.

SMR

Q9QUN3. Positions 328-457.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9QUN3. 5 interactions.

MINT

MINT-110328.

PTM databases

PhosphoSite

Q9QUN3.

Proteomic databases

PaxDb

Q9QUN3.

PRIDE

Q9QUN3.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000054769; ENSMUSP00000057844; ENSMUSG00000061132.

GeneID

17060.

KEGG

mmu:17060.

Organism-specific databases

CTD

29760.

MGI

MGI:96878. Blnk.

Phylogenomic databases

eggNOG

NOG44661.

GeneTree

ENSGT00530000063094.

HOGENOM

HOG000088646.

HOVERGEN

HBG053147.

InParanoid

Q9QUN3.

KO

K07371.

OMA

PFARGEY.

Gene expression databases

ArrayExpress

Q9QUN3.

Bgee

Q9QUN3.

CleanEx

MM_BLNK.

Genevestigator

Q9QUN3.

GermOnline

ENSMUSG00000061132. Mus musculus.

Family and domain databases

Gene3D

3.30.505.10. 1 hit.

InterPro

IPR000980. SH2.
[Graphical view]

Pfam

PF00017. SH2. 1 hit.
[Graphical view]

SMART

SM00252. SH2. 1 hit.
[Graphical view]

PROSITE

PS50001. SH2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9QUN3.

NextBio

291162.

SOURCE

Search...

Entry information

Entry name

BLNK_MOUSE

Accession

Primary (citable) accession number: Q9QUN3
Secondary accession number(s): O88504

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 22, 2005
Last sequence update:	May 1, 2000
Last modified:	May 1, 2013
This is version 95 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program