ID BLNK_HUMAN Reviewed; 456 AA. AC Q8WV28; O75498; O75499; Q2MD49; DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot. DT 22-NOV-2005, sequence version 2. DT 27-MAR-2024, entry version 171. DE RecName: Full=B-cell linker protein; DE AltName: Full=B-cell adapter containing a SH2 domain protein; DE AltName: Full=B-cell adapter containing a Src homology 2 domain 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, SLP65; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PROTEIN SEQUENCE OF 7-20; RP 140-146; 237-248; 250-257; 366-373 AND 392-405, FUNCTION, SUBCELLULAR RP LOCATION, INTERACTION WITH PLCG1; VAV1; GRB2 AND NCK1, ALTERNATIVE RP SPLICING, PHOSPHORYLATION, AND MUTAGENESIS OF TYR-72; TYR-84; TYR-96 AND RP TYR-178. RX PubMed=9697839; DOI=10.1016/s1074-7613(00)80591-9; RA Fu C., Turck C.W., Kurosaki T., Chan A.C.; RT "BLNK: a central linker protein in B cell activation."; RL Immunity 9:93-103(1998). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2), FUNCTION IN B-CELL RP DEVELOPMENT, AND INVOLVEMENT IN AGM4. RX PubMed=10583958; DOI=10.1126/science.286.5446.1954; RA Minegishi Y., Rohrer J., Coustan-Smith E., Lederman H.M., Pappu R., RA Campana D., Chan A.C., Conley M.E.; RT "An essential role for BLNK in human B cell development."; RL Science 286:1954-1957(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RX PubMed=16636677; DOI=10.1038/sj.onc.1209520; RA Sprangers M., Feldhahn N., Liedtke S., Jumaa H., Siebert R., Muschen M.; RT "SLP65 deficiency results in perpetual V(D)J recombinase activity in pre-B- RT lymphoblastic leukemia and B-cell lymphoma cells."; RL Oncogene 25:5180-5186(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=B-cell; 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 [6] RP INTERACTION WITH PLCG1; VAV1; GRB2 AND NCK1. RX PubMed=9341187; DOI=10.1074/jbc.272.43.27362; RA Fu C., Chan A.C.; RT "Identification of two tyrosine phosphoproteins, pp70 and pp68, which RT interact with phospholipase Cgamma, Grb2, and Vav after B cell antigen RT receptor activation."; RL J. Biol. Chem. 272:27362-27368(1997). RN [7] RP PHOSPHORYLATION AT TYR-72; TYR-84; TYR-96; TYR-178 AND TYR-189 BY SYK, AND RP MUTAGENESIS OF TYR-72; TYR-84 AND TYR-96. 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 [8] RP FUNCTION IN PLCG1 ACTIVATION AND CALCIUM MOBILIZATION. RX PubMed=15270728; DOI=10.1111/j.1365-2567.2004.01918.x; RA Taguchi T., Kiyokawa N., Takenouch H., Matsui J., Tang W.-R., Nakajima H., RA Suzuki K., Shiozawa Y., Saito M., Katagiri Y.U., Takahashi T., RA Karasuyama H., Matsuo Y., Okita H., Fujimoto J.; RT "Deficiency of BLNK hampers PLC-gamma2 phosphorylation and Ca2+ influx RT induced by the pre-B-cell receptor in human pre-B cells."; RL Immunology 112:575-582(2004). RN [9] RP FUNCTION, AND INTERACTION WITH GRB2. 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 [10] RP INTERACTION WITH SYK. RX PubMed=18369315; DOI=10.1038/emboj.2008.62; RA Kulathu Y., Hobeika E., Turchinovich G., Reth M.; RT "The kinase Syk as an adaptor controlling sustained calcium signalling and RT B-cell development."; RL EMBO J. 27:1333-1344(2008). RN [11] RP INTERACTION WITH SCIMP. RX PubMed=21930792; DOI=10.1128/mcb.05817-11; RA Draber P., Vonkova I., Stepanek O., Hrdinka M., Kucova M., Skopcova T., RA Otahal P., Angelisova P., Horejsi V., Yeung M., Weiss A., Brdicka T.; RT "SCIMP, a transmembrane adapter protein involved in major RT histocompatibility complex class II signaling."; RL Mol. Cell. Biol. 31:4550-4562(2011). 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. {ECO:0000269|PubMed:10583958, CC ECO:0000269|PubMed:15270728, ECO:0000269|PubMed:16912232, CC ECO:0000269|PubMed:9697839}. 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-131' (PubMed:21930792). {ECO:0000269|PubMed:16912232, CC ECO:0000269|PubMed:18369315, ECO:0000269|PubMed:21930792, CC ECO:0000269|PubMed:9341187, ECO:0000269|PubMed:9697839}. CC -!- INTERACTION: CC Q8WV28; P10275: AR; NbExp=2; IntAct=EBI-2623522, EBI-608057; CC Q8WV28; Q06187: BTK; NbExp=2; IntAct=EBI-2623522, EBI-624835; CC Q8WV28; Q9Y5K6: CD2AP; NbExp=2; IntAct=EBI-2623522, EBI-298152; CC Q8WV28; P62993: GRB2; NbExp=4; IntAct=EBI-2623522, EBI-401755; CC Q8WV28; P10721: KIT; NbExp=2; IntAct=EBI-2623522, EBI-1379503; CC Q8WV28; Q5ZMQ7: RCJMB04_1g20; Xeno; NbExp=3; IntAct=EBI-2623522, EBI-7061433; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9697839}. Cell CC membrane {ECO:0000269|PubMed:9697839}. Note=BCR activation results in CC the translocation to membrane fraction. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q8WV28-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8WV28-2; Sequence=VSP_016178; CC Name=3; CC IsoId=Q8WV28-3; Sequence=VSP_045324; CC -!- TISSUE SPECIFICITY: Expressed in B-cell lineage and fibroblast cell CC lines (at protein level). Highest levels of expression in the spleen, CC with lower levels in the liver, kidney, pancreas, small intestines and CC colon. 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 CC pathways. {ECO:0000269|PubMed:12456653, ECO:0000269|PubMed:9697839}. CC -!- DISEASE: Agammaglobulinemia 4, autosomal recessive (AGM4) [MIM:613502]: CC A primary immunodeficiency characterized by profoundly low or absent CC serum antibodies and low or absent circulating B-cells due to an early CC block of B-cell development. Affected individuals develop severe CC infections in the first years of life. {ECO:0000269|PubMed:10583958}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- WEB RESOURCE: Name=BLNKbase; Note=BLNK mutation db; CC URL="http://structure.bmc.lu.se/idbase/BLNKbase/"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/804/BLNK"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF068180; AAC39936.1; -; mRNA. DR EMBL; AF068181; AAC39937.1; -; mRNA. DR EMBL; AF180756; AAF20382.1; -; Genomic_DNA. DR EMBL; AF180740; AAF20382.1; JOINED; Genomic_DNA. DR EMBL; AF180741; AAF20382.1; JOINED; Genomic_DNA. DR EMBL; AF180742; AAF20382.1; JOINED; Genomic_DNA. DR EMBL; AF180743; AAF20382.1; JOINED; Genomic_DNA. DR EMBL; AF180744; AAF20382.1; JOINED; Genomic_DNA. DR EMBL; AF180745; AAF20382.1; JOINED; Genomic_DNA. DR EMBL; AF180746; AAF20382.1; JOINED; Genomic_DNA. DR EMBL; AF180747; AAF20382.1; JOINED; Genomic_DNA. DR EMBL; AF180748; AAF20382.1; JOINED; Genomic_DNA. DR EMBL; AF180749; AAF20382.1; JOINED; Genomic_DNA. DR EMBL; AF180750; AAF20382.1; JOINED; Genomic_DNA. DR EMBL; AF180751; AAF20382.1; JOINED; Genomic_DNA. DR EMBL; AF180752; AAF20382.1; JOINED; Genomic_DNA. DR EMBL; AF180753; AAF20382.1; JOINED; Genomic_DNA. DR EMBL; AF180754; AAF20382.1; JOINED; Genomic_DNA. DR EMBL; AF180755; AAF20382.1; JOINED; Genomic_DNA. DR EMBL; AF180756; AAF20383.1; -; Genomic_DNA. DR EMBL; AF180740; AAF20383.1; JOINED; Genomic_DNA. DR EMBL; AF180741; AAF20383.1; JOINED; Genomic_DNA. DR EMBL; AF180742; AAF20383.1; JOINED; Genomic_DNA. DR EMBL; AF180743; AAF20383.1; JOINED; Genomic_DNA. DR EMBL; AF180744; AAF20383.1; JOINED; Genomic_DNA. DR EMBL; AF180745; AAF20383.1; JOINED; Genomic_DNA. DR EMBL; AF180746; AAF20383.1; JOINED; Genomic_DNA. DR EMBL; AF180748; AAF20383.1; JOINED; Genomic_DNA. DR EMBL; AF180749; AAF20383.1; JOINED; Genomic_DNA. DR EMBL; AF180750; AAF20383.1; JOINED; Genomic_DNA. DR EMBL; AF180751; AAF20383.1; JOINED; Genomic_DNA. DR EMBL; AF180752; AAF20383.1; JOINED; Genomic_DNA. DR EMBL; AF180753; AAF20383.1; JOINED; Genomic_DNA. DR EMBL; AF180754; AAF20383.1; JOINED; Genomic_DNA. DR EMBL; AF180755; AAF20383.1; JOINED; Genomic_DNA. DR EMBL; AM180337; CAJ55331.1; -; mRNA. DR EMBL; AC021037; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC018906; AAH18906.1; -; mRNA. DR CCDS; CCDS44464.1; -. [Q8WV28-2] DR CCDS; CCDS58091.1; -. [Q8WV28-3] DR CCDS; CCDS7446.1; -. [Q8WV28-1] DR RefSeq; NP_001107566.1; NM_001114094.1. [Q8WV28-2] DR RefSeq; NP_001245369.1; NM_001258440.1. [Q8WV28-3] DR RefSeq; NP_037446.1; NM_013314.3. [Q8WV28-1] DR PDB; 6YLU; X-ray; 1.88 A; B=147-158. DR PDBsum; 6YLU; -. DR AlphaFoldDB; Q8WV28; -. DR SMR; Q8WV28; -. DR BioGRID; 118894; 39. DR CORUM; Q8WV28; -. DR IntAct; Q8WV28; 23. DR MINT; Q8WV28; -. DR STRING; 9606.ENSP00000224337; -. DR iPTMnet; Q8WV28; -. DR PhosphoSitePlus; Q8WV28; -. DR BioMuta; BLNK; -. DR DMDM; 82592659; -. DR EPD; Q8WV28; -. DR jPOST; Q8WV28; -. DR MassIVE; Q8WV28; -. DR MaxQB; Q8WV28; -. DR PaxDb; 9606-ENSP00000224337; -. DR PeptideAtlas; Q8WV28; -. DR ProteomicsDB; 74740; -. [Q8WV28-1] DR ProteomicsDB; 74741; -. [Q8WV28-2] DR Antibodypedia; 3990; 879 antibodies from 42 providers. DR DNASU; 29760; -. DR Ensembl; ENST00000224337.10; ENSP00000224337.6; ENSG00000095585.18. [Q8WV28-1] DR Ensembl; ENST00000371176.7; ENSP00000360218.2; ENSG00000095585.18. [Q8WV28-2] DR Ensembl; ENST00000413476.6; ENSP00000397487.2; ENSG00000095585.18. [Q8WV28-3] DR GeneID; 29760; -. DR KEGG; hsa:29760; -. DR MANE-Select; ENST00000224337.10; ENSP00000224337.6; NM_013314.4; NP_037446.1. DR UCSC; uc001kls.5; human. [Q8WV28-1] DR AGR; HGNC:14211; -. DR CTD; 29760; -. DR DisGeNET; 29760; -. DR GeneCards; BLNK; -. DR HGNC; HGNC:14211; BLNK. DR HPA; ENSG00000095585; Tissue enhanced (lymphoid). DR MalaCards; BLNK; -. DR MIM; 604515; gene. DR MIM; 613502; phenotype. DR neXtProt; NX_Q8WV28; -. DR OpenTargets; ENSG00000095585; -. DR Orphanet; 33110; Autosomal agammaglobulinemia. DR PharmGKB; PA25371; -. DR VEuPathDB; HostDB:ENSG00000095585; -. DR eggNOG; ENOG502QUXR; Eukaryota. DR GeneTree; ENSGT00940000155715; -. DR HOGENOM; CLU_043673_0_0_1; -. DR InParanoid; Q8WV28; -. DR OMA; YVIPVDD; -. DR OrthoDB; 5403994at2759; -. DR PhylomeDB; Q8WV28; -. DR TreeFam; TF326567; -. DR PathwayCommons; Q8WV28; -. DR Reactome; R-HSA-912631; Regulation of signaling by CBL. DR Reactome; R-HSA-9679191; Potential therapeutics for SARS. DR Reactome; R-HSA-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers. DR SignaLink; Q8WV28; -. DR SIGNOR; Q8WV28; -. DR BioGRID-ORCS; 29760; 19 hits in 1150 CRISPR screens. DR ChiTaRS; BLNK; human. DR GeneWiki; B-cell_linker; -. DR GenomeRNAi; 29760; -. DR Pharos; Q8WV28; Tbio. DR PRO; PR:Q8WV28; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; Q8WV28; Protein. DR Bgee; ENSG00000095585; Expressed in tongue squamous epithelium and 173 other cell types or tissues. DR ExpressionAtlas; Q8WV28; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0008289; F:lipid binding; EXP:DisProt. DR GO; GO:0043274; F:phospholipase binding; IPI:ARUK-UCL. DR GO; GO:0019901; F:protein kinase binding; IPI:ARUK-UCL. DR GO; GO:1990782; F:protein tyrosine kinase binding; IPI:UniProtKB. DR GO; GO:0042169; F:SH2 domain binding; IDA:UniProtKB. DR GO; GO:0035591; F:signaling adaptor activity; IDA:UniProtKB. DR GO; GO:0005068; F:transmembrane receptor protein tyrosine kinase adaptor activity; TAS:ProtInc. DR GO; GO:0030183; P:B cell differentiation; NAS:UniProtKB. DR GO; GO:0050853; P:B cell receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0006959; P:humoral immune response; TAS:ProtInc. DR GO; GO:0006954; P:inflammatory response; TAS:ProtInc. DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl. DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central. DR CDD; cd09929; SH2_BLNK_SLP-76; 1. DR DisProt; DP01544; -. DR Gene3D; 3.30.505.10; SH2 domain; 1. DR InterPro; IPR000980; SH2. DR InterPro; IPR036860; SH2_dom_sf. DR PANTHER; PTHR14098:SF3; B-CELL LINKER PROTEIN; 1. DR PANTHER; PTHR14098; SH2 DOMAIN CONTAINING PROTEIN; 1. DR Pfam; PF00017; SH2; 1. DR SMART; SM00252; SH2; 1. DR SUPFAM; SSF55550; SH2 domain; 1. DR PROSITE; PS50001; SH2; 1. DR Genevisible; Q8WV28; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; B-cell activation; Cell membrane; KW Cytoplasm; Direct protein sequencing; Membrane; Phosphoprotein; KW Reference proteome; SH2 domain. FT CHAIN 1..456 FT /note="B-cell linker protein" FT /id="PRO_0000064940" FT DOMAIN 346..453 FT /note="SH2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT REGION 36..301 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..158 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 191..232 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 256..271 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 72 FT /note="Phosphotyrosine; by SYK" FT /evidence="ECO:0000269|PubMed:12456653" FT MOD_RES 84 FT /note="Phosphotyrosine; by SYK" FT /evidence="ECO:0000269|PubMed:12456653" FT MOD_RES 96 FT /note="Phosphotyrosine; by SYK" FT /evidence="ECO:0000269|PubMed:12456653" FT MOD_RES 178 FT /note="Phosphotyrosine; by SYK" FT /evidence="ECO:0000269|PubMed:12456653" FT MOD_RES 189 FT /note="Phosphotyrosine; by SYK" FT /evidence="ECO:0000269|PubMed:12456653" FT VAR_SEQ 203..225 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:9697839" FT /id="VSP_016178" FT VAR_SEQ 366..417 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:16636677" FT /id="VSP_045324" FT MUTAGEN 72 FT /note="Y->F: Significant phosphorylation reduction; when FT associated with F-84; F-96 and F-178." FT /evidence="ECO:0000269|PubMed:12456653, FT ECO:0000269|PubMed:9697839" FT MUTAGEN 84 FT /note="Y->F: Significant phosphorylation reduction; when FT associated with F-72; F-96 and F-178." FT /evidence="ECO:0000269|PubMed:12456653, FT ECO:0000269|PubMed:9697839" FT MUTAGEN 96 FT /note="Y->F: Significant phosphorylation reduction; when FT associated with F-72; F-84 and F-178." FT /evidence="ECO:0000269|PubMed:12456653, FT ECO:0000269|PubMed:9697839" FT MUTAGEN 178 FT /note="Y->F: Significant phosphorylation reduction; when FT associated with F-72; F-84 and F-96." FT /evidence="ECO:0000269|PubMed:9697839" FT CONFLICT 62 FT /note="E -> Q (in Ref. 5; AAH18906)" FT /evidence="ECO:0000305" SQ SEQUENCE 456 AA; 50466 MW; 95F1D5485D03D397 CRC64; MDKLNKITVP ASQKLRQLQK MVHDIKNNEG GIMNKIKKLK VKAPPSVPRR DYASESPADE EEQWSDDFDS DYENPDEHSD SEMYVMPAEE NADDSYEPPP VEQETRPVHP ALPFARGEYI DNRSSQRHSP PFSKTLPSKP SWPSEKARLT STLPALTALQ KPQVPPKPKG LLEDEADYVV PVEDNDENYI HPTESSSPPP EKAPMVNRST KPNSSTPASP PGTASGRNSG AWETKSPPPA APSPLPRAGK KPTTPLKTTP VASQQNASSV CEEKPIPAER HRGSSHRQEA VQSPVFPPAQ KQIHQKPIPL PRFTEGGNPT VDGPLPSFSS NSTISEQEAG VLCKPWYAGA CDRKSAEEAL HRSNKDGSFL IRKSSGHDSK QPYTLVVFFN KRVYNIPVRF IEATKQYALG RKKNGEEYFG SVAEIIRNHQ HSPLVLIDSQ NNTKDSTRLK YAVKVS //