BLNK_CHICK
ID BLNK_CHICK Reviewed; 552 AA.
AC Q9YGC1;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=B-cell linker protein;
DE AltName: Full=B-cell adapter SH2 domain-containing protein;
DE AltName: Full=Cytoplasmic adapter protein;
DE AltName: Full=Src homology 2 domain-containing leukocyte protein of 65 kDa;
DE Short=SLP-65;
GN Name=BLNK; Synonyms=BASH;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION IN BCR-MEDIATED
RP SIGNAL TRANSDUCTION, ALTERNATIVE SPLICING, AND PHOSPHORYLATION BY SYK AND
RP LYN.
RX PubMed=9834055;
RA Goitsuka R., Fujimura Y., Mamada H., Umeda A., Morimura T., Uetsuka K.,
RA Doi K., Tsuji S., Kitamura D.;
RT "BASH, a novel signaling molecule preferentially expressed in B cells of
RT the bursa of Fabricius.";
RL J. Immunol. 161:5804-5808(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION IN REGULATING THE
RP RAC1-JNK PATHWAY.
RX PubMed=10023776; DOI=10.1016/s1074-7613(00)80012-6;
RA Ishiai M., Kurosaki M., Pappu R., Okawa K., Ronko I., Fu C., Shibata M.,
RA Iwamatsu A., Chan A.C., Kurosaki T.;
RT "BLNK required for coupling Syk to PLC gamma 2 and Rac1-JNK in B cells.";
RL Immunity 10:117-125(1999).
RN [3]
RP PHOSPHORYLATION AT TYR-91; TYR-103; TYR-115; TYR-194; TYR-205 AND TYR-249
RP BY SYK, AND MUTAGENESIS OF TYR-91; TYR-103; TYR-115; TYR-194; TYR-205 AND
RP TYR-249.
RX PubMed=12456653; DOI=10.1093/emboj/cdf658;
RA Chiu C.W., Dalton M., Ishiai M., Kurosaki T., Chan A.C.;
RT "BLNK: molecular scaffolding through 'cis'-mediated organization of
RT signaling proteins.";
RL EMBO J. 21:6461-6472(2002).
RN [4]
RP FUNCTION, TYROSINE PHOSPHORYLATION, AND INTERACTION WITH GRB2; PLCG2 AND
RP VAV3.
RX PubMed=16912232; DOI=10.1182/blood-2006-02-005397;
RA Grabbe A., Wienands J.;
RT "Human SLP-65 isoforms contribute differently to activation and apoptosis
RT of B lymphocytes.";
RL Blood 108:3761-3768(2006).
RN [5]
RP FUNCTION, TYROSINE PHOSPHORYLATION, MUTAGENESIS OF ARG-468, AND SUBCELLULAR
RP LOCATION.
RX PubMed=17681949; DOI=10.1074/jbc.m704043200;
RA Abudula A., Grabbe A., Brechmann M., Polaschegg C., Herrmann N.,
RA Goldbeck I., Dittmann K., Wienands J.;
RT "SLP-65 signal transduction requires Src homology 2 domain-mediated
RT membrane anchoring and a kinase-independent adaptor function of Syk.";
RL J. Biol. Chem. 282:29059-29066(2007).
CC -!- FUNCTION: Functions as a central linker protein, downstream of the B-
CC cell receptor (BCR), bridging the SYK kinase to a multitude of
CC signaling pathways and regulating biological outcomes of B-cell
CC function and development. Plays a role in the activation of ERK/EPHB2,
CC MAP kinase p38 and JNK. Modulates AP1 activation. Important for the
CC activation of NF-kappa-B and NFAT. Plays an important role in BCR-
CC mediated PLCG1 and PLCG2 activation and Ca(2+) mobilization and is
CC required for trafficking of the BCR to late endosomes. However, does
CC not seem to be required for pre-BCR-mediated activation of MAP kinase
CC and phosphatidyl-inositol 3 (PI3) kinase signaling. May be required for
CC the RAC1-JNK pathway. Plays a critical role in orchestrating the pro-B
CC cell to pre-B cell transition (By similarity). Plays a critical role in
CC B-cell development in the bursa. Plays an important role in BCR-induced
CC apoptosis. {ECO:0000250, ECO:0000269|PubMed:10023776,
CC ECO:0000269|PubMed:16912232, ECO:0000269|PubMed:17681949,
CC ECO:0000269|PubMed:9834055}.
CC -!- SUBUNIT: Associates with PLCG1, VAV1 and NCK1 in a B-cell antigen
CC receptor-dependent fashion. Interacts through its SH2 domain with CD79A
CC (By similarity). Interacts with VAV3, PLCG2 and GRB2. {ECO:0000250,
CC ECO:0000269|PubMed:16912232}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17681949}. Cell
CC membrane {ECO:0000269|PubMed:17681949}. Note=BCR activation results in
CC the translocation to membrane fraction.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9YGC1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9YGC1-2; Sequence=VSP_016179;
CC -!- TISSUE SPECIFICITY: Highly expressed in the bursa, very low expression
CC in ovary and spleen. Expression was variable among B-cell lines. Highly
CC expressed in immature B-cell lines such as DT40 and CL18, low
CC expression was seen in relatively mature B-cell lines, such as 293B9
CC and 249L4. No expression was seen in T-cell lines.
CC -!- PTM: Following BCR activation, phosphorylated on tyrosine residues by
CC SYK and LYN. When phosphorylated, serves as a scaffold to assemble
CC downstream targets of antigen activation, including PLCG1, VAV1, GRB2
CC and NCK1. Phosphorylation is required for both Ca(2+) and MAPK
CC signaling pathways (By similarity). Phosphorylation of Tyr-103, Tyr-194
CC and Tyr-205 facilitates PLCG1 binding. Phosphorylation of Tyr-115
CC facilitates BTK binding. Phosphorylation of Tyr-91 facilitates VAV1 and
CC NCK1 binding. {ECO:0000250, ECO:0000269|PubMed:12456653,
CC ECO:0000269|PubMed:9834055}.
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DR EMBL; AB015289; BAA36275.1; -; mRNA.
DR EMBL; AF089727; AAD12783.1; -; mRNA.
DR RefSeq; NP_990239.1; NM_204908.1. [Q9YGC1-1]
DR AlphaFoldDB; Q9YGC1; -.
DR SMR; Q9YGC1; -.
DR BioGRID; 676007; 2.
DR IntAct; Q9YGC1; 1.
DR MINT; Q9YGC1; -.
DR STRING; 9031.ENSGALP00000038883; -.
DR iPTMnet; Q9YGC1; -.
DR PaxDb; Q9YGC1; -.
DR Ensembl; ENSGALT00000011296; ENSGALP00000011282; ENSGALG00000006973. [Q9YGC1-1]
DR GeneID; 395733; -.
DR KEGG; gga:395733; -.
DR CTD; 284948; -.
DR VEuPathDB; HostDB:geneid_395733; -.
DR eggNOG; ENOG502QUXR; Eukaryota.
DR GeneTree; ENSGT00940000155715; -.
DR HOGENOM; CLU_043673_0_0_1; -.
DR InParanoid; Q9YGC1; -.
DR PhylomeDB; Q9YGC1; -.
DR TreeFam; TF326567; -.
DR Reactome; R-GGA-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR PRO; PR:Q9YGC1; -.
DR Proteomes; UP000000539; Chromosome 6.
DR Bgee; ENSGALG00000006973; Expressed in spleen and 11 other tissues.
DR ExpressionAtlas; Q9YGC1; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0035473; F:lipase binding; IPI:ARUK-UCL.
DR GO; GO:0007202; P:activation of phospholipase C activity; IMP:AgBase.
DR GO; GO:0030183; P:B cell differentiation; TAS:AgBase.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0051726; P:regulation of cell cycle; TAS:AgBase.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR Pfam; PF00017; SH2; 1.
DR SMART; SM00252; SH2; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; B-cell activation; Cell membrane; Cytoplasm;
KW Membrane; Phosphoprotein; Reference proteome; SH2 domain.
FT CHAIN 1..552
FT /note="B-cell linker protein"
FT /id="PRO_0000064939"
FT DOMAIN 442..549
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 50..431
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 52..78
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 152..179
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 369..383
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 416..431
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 91
FT /note="Phosphotyrosine; by SYK"
FT /evidence="ECO:0000269|PubMed:12456653"
FT MOD_RES 103
FT /note="Phosphotyrosine; by SYK"
FT /evidence="ECO:0000269|PubMed:12456653"
FT MOD_RES 115
FT /note="Phosphotyrosine; by SYK"
FT /evidence="ECO:0000269|PubMed:12456653"
FT MOD_RES 194
FT /note="Phosphotyrosine; by SYK"
FT /evidence="ECO:0000269|PubMed:12456653"
FT MOD_RES 205
FT /note="Phosphotyrosine; by SYK"
FT /evidence="ECO:0000269|PubMed:12456653"
FT MOD_RES 249
FT /note="Phosphotyrosine; by SYK"
FT /evidence="ECO:0000269|PubMed:12456653"
FT VAR_SEQ 40..58
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9834055"
FT /id="VSP_016179"
FT MUTAGEN 91
FT /note="Y->F: Significant phosphorylation reduction; when
FT associated with F-103; F-115; F-194 and F-205. Loss of
FT phosphorylation; when associated with F-103; F-115; F-194;
FT F-205 and F-249."
FT /evidence="ECO:0000269|PubMed:12456653"
FT MUTAGEN 103
FT /note="Y->F: Significant reduction of Ca(2+) mobilization;
FT when associated with F-194. Loss of Ca(2+) mobilization;
FT when associated with F-194 and F-205. Significant
FT phosphorylation reduction; when associated with F-91; F-
FT 115; F-194 and F-205. Loss of phosphorylation; when
FT associated with F-91; F-115; F-194; F-205 and F-249."
FT /evidence="ECO:0000269|PubMed:12456653"
FT MUTAGEN 115
FT /note="Y->F: Significant phosphorylation reduction; when
FT associated with F-91; F-103; F-194 and F-205. Loss of
FT phosphorylation; when associated with F-91; F-103; F-194;
FT F-205 and F-249."
FT /evidence="ECO:0000269|PubMed:12456653"
FT MUTAGEN 194
FT /note="Y->F: Reduction in Ca(2+) mobilization. Significant
FT reduction of Ca(2+) mobilization; when associated with F-
FT 103. Loss of Ca(2+) mobilization; when associated with F-
FT 103 and F-205. Significant phosphorylation reduction; when
FT associated with F-91; F-103; F-115 and F-205. Loss of
FT phosphorylation; when associated with F-91; F-103; F-115;
FT F-205 and F-249."
FT /evidence="ECO:0000269|PubMed:12456653"
FT MUTAGEN 205
FT /note="Y->F: Loss of Ca(2+) mobilization; when associated
FT with F-194 and F-205. Significant phosphorylation
FT reduction; when associated with F-91; F-103; F-115 and F-
FT 194. Loss of phosphorylation; when associated with F-91; F-
FT 103; F-115; F-194 and F-249."
FT /evidence="ECO:0000269|PubMed:12456653"
FT MUTAGEN 249
FT /note="Y->F: Loss of phosphorylation; when associated with
FT F-91; F-103; F-115; F-194 and F-205."
FT /evidence="ECO:0000269|PubMed:12456653"
FT MUTAGEN 468
FT /note="R->L: Strongly reduced tyrosine phosphorylation.
FT Strongly reduced activation of NFAT."
FT /evidence="ECO:0000269|PubMed:17681949"
SQ SEQUENCE 552 AA; 61823 MW; FB232179BE38D072 CRC64;
MDKLNKLAVP AGEKFRKLQK MVHDIKKNES GIINKFKKFQ NEQVALICKT GKDTWDRLKK
KPPPSLPRRD YASEHADNEE EQWSDDFDSD YENPDGHSDS EMYVVPSEEN PDDSYEPPPS
EQEKKKIPSS FPISRGEYAD NRTSHHQLPP INKPLPSTPS SALPRPKKPS LPSPAAKPKL
PLKPRECSDD EDNYIVPVDN DDDNYIEPTE SSTPPPAKPP VNRFMKPPAK SALPTPPKPS
LASDMQEVYE VPEEEEELSP PPVTRFTKPL PATRAQNAEH SHMHSMTRES PKLDASRNIL
PLPRNRLHPK TDHEANNNDE NHSFSNTQES KFPPGAAPSP LPRALKKTSN AVNPAKPCLP
SRDTFTVNED KPTAADRRRG SSHEFPLPPL PSGTPKSSLQ KPLVLPKVPE APSRALGTSP
HSSISSISST ADQDAGVHSK AWYAATCDRK TAEDALYRSN KDGSFLIRKS SGQDSRQPYT
LVVFYNRRVY NIPIRFIEST RQYALGREKC GEERFDSVAE IVENHQHTSL VLIDSQNNTK
DSTKLKYIVR VS
