BLNK_RAT
ID BLNK_RAT Reviewed; 457 AA.
AC Q4KM52;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 02-AUG-2005, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=B-cell linker protein;
DE AltName: Full=Cytoplasmic adapter protein;
GN Name=Blnk;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Spleen;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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. May play an important role in BCR-
CC induced B-cell apoptosis (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Associates with PLCG1, VAV1 and NCK1 in a B-cell antigen
CC receptor-dependent fashion. Interacts with VAV3, PLCG2 and GRB2.
CC Interacts through its SH2 domain with CD79A. Interacts (via SH2 domain)
CC with SYK; phosphorylated and activated by SYK. Interacts (via SH2
CC domain) with SCIMP; this interaction is dependent on phosphorylation of
CC SCIMP 'Tyr-120' (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q8WV28}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}. Note=BCR activation results in the translocation to
CC membrane fraction. {ECO:0000250}.
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 of Tyr-84, Tyr-178 and Tyr-189 facilitates
CC PLCG1 binding. Phosphorylation of Tyr-96 facilitates BTK binding.
CC Phosphorylation of Tyr-72 facilitates VAV1 and NCK1 binding.
CC Phosphorylation is required for both Ca(2+) and MAPK signaling pathways
CC (By similarity). {ECO:0000250}.
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DR EMBL; BC098790; AAH98790.1; -; mRNA.
DR RefSeq; NP_001020938.1; NM_001025767.1.
DR AlphaFoldDB; Q4KM52; -.
DR SMR; Q4KM52; -.
DR STRING; 10116.ENSRNOP00000019014; -.
DR iPTMnet; Q4KM52; -.
DR PhosphoSitePlus; Q4KM52; -.
DR PaxDb; Q4KM52; -.
DR PRIDE; Q4KM52; -.
DR Ensembl; ENSRNOT00000019014; ENSRNOP00000019014; ENSRNOG00000013967.
DR GeneID; 499356; -.
DR KEGG; rno:499356; -.
DR UCSC; RGD:1561933; rat.
DR CTD; 29760; -.
DR RGD; 1561933; Blnk.
DR eggNOG; ENOG502QUXR; Eukaryota.
DR GeneTree; ENSGT00940000155715; -.
DR HOGENOM; CLU_043673_0_0_1; -.
DR InParanoid; Q4KM52; -.
DR OMA; QEADLHC; -.
DR OrthoDB; 556782at2759; -.
DR PhylomeDB; Q4KM52; -.
DR TreeFam; TF326567; -.
DR Reactome; R-RNO-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR PRO; PR:Q4KM52; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000013967; Expressed in spleen and 19 other tissues.
DR Genevisible; Q4KM52; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0043274; F:phospholipase binding; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:1990782; F:protein tyrosine kinase binding; ISO:RGD.
DR GO; GO:0042169; F:SH2 domain binding; ISO:RGD.
DR GO; GO:0035591; F:signaling adaptor activity; ISO:RGD.
DR GO; GO:0042113; P:B cell activation; IEA:UniProtKB-KW.
DR GO; GO:0050853; P:B cell receptor signaling pathway; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
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 B-cell activation; Cell membrane; Cytoplasm; Membrane; Phosphoprotein;
KW Reference proteome; SH2 domain.
FT CHAIN 1..457
FT /note="B-cell linker protein"
FT /id="PRO_0000064942"
FT DOMAIN 347..454
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 38..306
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 58..76
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 124..140
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 202..223
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 257..271
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 72
FT /note="Phosphotyrosine; by SYK"
FT /evidence="ECO:0000250|UniProtKB:Q8WV28"
FT MOD_RES 84
FT /note="Phosphotyrosine; by SYK"
FT /evidence="ECO:0000250|UniProtKB:Q8WV28"
FT MOD_RES 96
FT /note="Phosphotyrosine; by SYK"
FT /evidence="ECO:0000250|UniProtKB:Q8WV28"
FT MOD_RES 178
FT /note="Phosphotyrosine; by SYK"
FT /evidence="ECO:0000250|UniProtKB:Q8WV28"
FT MOD_RES 189
FT /note="Phosphotyrosine; by SYK"
FT /evidence="ECO:0000250|UniProtKB:Q8WV28"
SQ SEQUENCE 457 AA; 50634 MW; A40DA57A13022483 CRC64;
MDKLNKITVP ASQKLRQLQK MVHDIKNNEG GIMDKIKKLK VKGPPSVPRR DYALDNPADE
EEQWSDDFDS DYENPDEHSD SEMYVMPAEE TGDDSYEPPP AEQQTRVVHP ALPFTRGEYV
DNRSSQRHSP PFSKTLPSKP SWPSAKARLA STLPAPNSLQ KPQVPPKPKD LLEDEADYVV
PVEDNDENYI HPRESSPLPA EKAPTVNRST KPNSSSKHVS PPGTVAGRNS GVWDSKSSLP
AAPSPLPRAG KKTATPLKTT PVPSLQNASN VCEEKPVPAE RHRGSSHRQD TVQSPVFPPT
QKPVLQKPVP LPRFTEGGSP AADGPVPSFP FNSTFADQEA ELHGKPWYAG ACDRKSAEEA
LHRSNKDGSF LIRKSSGHDS KQPYTLVAFF NKRVYNIPVR FIEATKQYAL GKKKNGEEYF
GSVVEIIKNH QHNPLVLIDS QNNTKDSTRL KYAVKVS
