ID FYB1_MOUSE Reviewed; 819 AA.
AC O35601; Q9Z2H3;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 27-MAR-2024, entry version 176.
DE RecName: Full=FYN-binding protein 1;
DE AltName: Full=Adhesion and degranulation promoting adaptor protein;
DE Short=ADAP;
DE AltName: Full=FYB-120/130;
DE Short=p120/p130;
DE AltName: Full=FYN-T-binding protein;
DE AltName: Full=SLAP-130;
DE AltName: Full=SLP-76-associated phosphoprotein;
GN Name=Fyb1; Synonyms=Fyb;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM FYB-120), INTERACTION WITH FYN AND
RP LCP2, AND FUNCTION.
RC TISSUE=T-cell lymphoma;
RX PubMed=9207119; DOI=10.1073/pnas.94.14.7493;
RA da Silva A.J., Li Z., de Vera C., Canto E., Findell P., Rudd C.E.;
RT "Cloning of a novel T-cell protein FYB that binds FYN and SH2-domain-
RT containing leukocyte protein 76 and modulates interleukin 2 production.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:7493-7498(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM FYB-130), INTERACTION WITH FYN AND
RP LCP2, AND FUNCTION.
RC TISSUE=Hybridoma;
RX PubMed=10497204; DOI=10.1074/jbc.274.40.28427;
RA Veale M., Raab M., Li Z., da Silva A.J., Kraeft S.-K., Weremowicz S.,
RA Morton C.C., Rudd C.E.;
RT "Novel isoform of lymphoid adaptor FYN-T-binding protein (FYB-130)
RT interacts with SLP-76 and up-regulates interleukin 2 production.";
RL J. Biol. Chem. 274:28427-28435(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM FYB-130), FUNCTION, INTERACTION WITH
RP FYN; SKAP1 AND CLNK, AND IDENTIFICATION IN A COMPLEX WITH SKAP1 AND CLNK.
RX PubMed=12681493; DOI=10.1016/s0014-5793(03)00234-5;
RA Fujii Y., Wakahara S., Nakao T., Hara T., Ohtake H., Komurasaki T.,
RA Kitamura K., Tatsuno A., Fujiwara N., Hozumi N., Ra C., Kitamura D.,
RA Goitsuka R.;
RT "Targeting of MIST to Src-family kinases via SKAP55-SLAP-130 adaptor
RT complex in mast cells(1).";
RL FEBS Lett. 540:111-116(2003).
RN [4]
RP INTERACTION WITH SKAP2, AND IDENTIFICATION IN A COMPLEX WITH SKAP2 AND
RP PTPNS1.
RX PubMed=10469599; DOI=10.1016/s0960-9822(99)80401-1;
RA Timms J.F., Swanson K.D., Marie-Cardine A., Raab M., Rudd C.E.,
RA Schraven B., Neel B.G.;
RT "SHPS-1 is a scaffold for assembling distinct adhesion-regulated multi-
RT protein complexes in macrophages.";
RL Curr. Biol. 9:927-930(1999).
RN [5]
RP INTERACTION WITH SKAP2, IDENTIFICATION IN A COMPLEX WITH SKAP2 AND PTPNS1,
RP AND IDENTIFICATION IN A COMPLEX WITH SKAP2 AND LILRB3.
RX PubMed=11207596; DOI=10.1046/j.1462-5822.2000.00061.x;
RA Black D.S., Marie-Cardine A., Schraven B., Bliska J.B.;
RT "The Yersinia tyrosine phosphatase YopH targets a novel adhesion-regulated
RT signalling complex in macrophages.";
RL Cell. Microbiol. 2:401-414(2000).
RN [6]
RP INTERACTION WITH SKAP2, FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17003372; DOI=10.1182/blood-2006-05-022301;
RA Kasirer-Friede A., Moran B., Nagrampa-Orje J., Swanson K., Ruggeri Z.M.,
RA Schraven B., Neel B.G., Koretzky G., Shattil S.J.;
RT "ADAP is required for normal alphaIIb-beta3 activation by VWF/GP Ib-IX-V
RT and other agonists.";
RL Blood 109:1018-1025(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-559 AND SER-561, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-28, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-28; SER-46; SER-222; SER-445;
RP TYR-559; SER-561 AND SER-568, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [11]
RP INTERACTION WITH TMEM47, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=21881001; DOI=10.1152/ajpcell.00166.2011;
RA Azhibekov T.A., Wu Z., Padiyar A., Bruggeman L.A., Simske J.S.;
RT "TM4SF10 and ADAP interaction in podocytes: role in Fyn activity and
RT nephrin phosphorylation.";
RL Am. J. Physiol. 301:C1351-C1359(2011).
CC -!- FUNCTION: Acts as an adapter protein of the FYN and LCP2 signaling
CC cascades in T-cells (PubMed:9207119, PubMed:10497204). May play a role
CC in linking T-cell signaling to remodeling of the actin cytoskeleton (By
CC similarity). Modulates the expression of IL2 (PubMed:9207119,
CC PubMed:10497204). Involved in platelet activation (PubMed:17003372).
CC Prevents the degradation of SKAP1 and SKAP2 (By similarity). May be
CC involved in high affinity immunoglobulin epsilon receptor signaling in
CC mast cells (PubMed:12681493). {ECO:0000250|UniProtKB:O15117,
CC ECO:0000269|PubMed:10497204, ECO:0000269|PubMed:12681493,
CC ECO:0000269|PubMed:17003372, ECO:0000269|PubMed:9207119}.
CC -!- SUBUNIT: Part of a complex consisting of SKAP2, FYB1 and PTPNS1
CC (PubMed:10469599). Part of a complex consisting of SKAP2, FYB1 and
CC LILRB3 (PubMed:10469599). Part of a complex consisting of SKAP1, FYB1
CC and CLNK (PubMed:12681493). Interacts with CLNK (via its SH2 domain);
CC this interaction allows SKAP1 and FYB1 to recruit FYN to the complex,
CC thus promoting the phosphorylation of CLNK by FYN (PubMed:12681493,
CC PubMed:10497204, PubMed:9207119). Interacts with FYN (PubMed:9207119,
CC PubMed:10497204). Interacts with LCP2 (PubMed:9207119,
CC PubMed:10497204). Interacts with SKAP1 (PubMed:12681493). Interacts
CC with SKAP2 (PubMed:10469599, PubMed:11207596, PubMed:17003372).
CC Interacts with FASLG (By similarity). Interacts with EVL (By
CC similarity). Interacts with TMEM47 (PubMed:21881001). Interacts with
CC LCK (By similarity). {ECO:0000250|UniProtKB:O15117,
CC ECO:0000269|PubMed:10469599, ECO:0000269|PubMed:10497204,
CC ECO:0000269|PubMed:11207596, ECO:0000269|PubMed:12681493,
CC ECO:0000269|PubMed:17003372, ECO:0000269|PubMed:21881001,
CC ECO:0000269|PubMed:9207119}.
CC -!- INTERACTION:
CC O35601; Q60787: Lcp2; NbExp=7; IntAct=EBI-7353747, EBI-5324248;
CC O35601; Q9JJG6: Tmem47; NbExp=4; IntAct=EBI-7353747, EBI-11685657;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O15117}. Nucleus
CC {ECO:0000255|PROSITE-ProRule:PRU00768}. Cell junction
CC {ECO:0000269|PubMed:21881001}. Note=Colocalizes with TMEM47 at cell-
CC cell contacts in podocytes. {ECO:0000269|PubMed:21881001}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=FYB-130;
CC IsoId=O35601-1; Sequence=Displayed;
CC Name=FYB-120;
CC IsoId=O35601-2; Sequence=VSP_004261;
CC -!- TISSUE SPECIFICITY: Expressed in hematopoietic tissues such as myeloid
CC and T-cells, spleen and thymus. Not expressed in B-cells, nor in non-
CC lymphoid tissues. FYB-130 is preferentially expressed in mature T-cells
CC compared to FYB-120, whereas thymocytes showed a greater relative
CC amount of FYB-120. Expressed in podocytes.
CC {ECO:0000269|PubMed:21881001}.
CC -!- PTM: T-cell receptor ligation leads to increased tyrosine
CC phosphorylation.
CC -!- DISRUPTION PHENOTYPE: Slight defects in platelet function.
CC {ECO:0000269|PubMed:17003372}.
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DR EMBL; AF001863; AAB62227.1; -; mRNA.
DR EMBL; AF061744; AAD03267.1; -; mRNA.
DR CCDS; CCDS37031.1; -. [O35601-1]
DR RefSeq; NP_001265198.1; NM_001278269.1. [O35601-2]
DR RefSeq; NP_035945.1; NM_011815.5. [O35601-1]
DR AlphaFoldDB; O35601; -.
DR SMR; O35601; -.
DR BioGRID; 204772; 7.
DR CORUM; O35601; -.
DR DIP; DIP-41350N; -.
DR IntAct; O35601; 6.
DR MINT; O35601; -.
DR STRING; 10090.ENSMUSP00000087947; -.
DR iPTMnet; O35601; -.
DR PhosphoSitePlus; O35601; -.
DR EPD; O35601; -.
DR jPOST; O35601; -.
DR MaxQB; O35601; -.
DR PaxDb; 10090-ENSMUSP00000087947; -.
DR PeptideAtlas; O35601; -.
DR ProteomicsDB; 266897; -. [O35601-1]
DR ProteomicsDB; 266898; -. [O35601-2]
DR Antibodypedia; 23110; 389 antibodies from 38 providers.
DR DNASU; 23880; -.
DR Ensembl; ENSMUST00000090461.12; ENSMUSP00000087947.6; ENSMUSG00000022148.17. [O35601-1]
DR GeneID; 23880; -.
DR KEGG; mmu:23880; -.
DR UCSC; uc007vdi.2; mouse. [O35601-1]
DR UCSC; uc007vdk.2; mouse. [O35601-2]
DR AGR; MGI:1346327; -.
DR CTD; 2533; -.
DR MGI; MGI:1346327; Fyb.
DR VEuPathDB; HostDB:ENSMUSG00000022148; -.
DR eggNOG; ENOG502QTTQ; Eukaryota.
DR GeneTree; ENSGT00530000063460; -.
DR HOGENOM; CLU_339375_0_0_1; -.
DR InParanoid; O35601; -.
DR OMA; KSSTWSW; -.
DR OrthoDB; 5403214at2759; -.
DR PhylomeDB; O35601; -.
DR TreeFam; TF337003; -.
DR Reactome; R-MMU-202433; Generation of second messenger molecules.
DR Reactome; R-MMU-391160; Signal regulatory protein family interactions.
DR BioGRID-ORCS; 23880; 1 hit in 77 CRISPR screens.
DR ChiTaRS; Fyb; mouse.
DR PRO; PR:O35601; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; O35601; Protein.
DR Bgee; ENSMUSG00000022148; Expressed in granulocyte and 198 other cell types or tissues.
DR ExpressionAtlas; O35601; baseline and differential.
DR Genevisible; O35601; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0008289; F:lipid binding; IEA:InterPro.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0072659; P:protein localization to plasma membrane; IMP:MGI.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IBA:GO_Central.
DR CDD; cd11867; hSH3_ADAP; 1.
DR Gene3D; 2.30.30.40; SH3 Domains; 2.
DR InterPro; IPR043443; FYB1/2-like.
DR InterPro; IPR035540; FYB_hSH3.
DR InterPro; IPR029294; hSH3.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR16830:SF13; FYN-BINDING PROTEIN 1; 1.
DR PANTHER; PTHR16830; SH2 CONTAINING ADAPTOR PRAM-1 RELATED; 1.
DR Pfam; PF14603; hSH3; 1.
DR Pfam; PF07653; SH3_2; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50044; SH3-domain; 2.
DR PROSITE; PS50002; SH3; 2.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cell junction; Coiled coil; Cytoplasm;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; SH3 domain.
FT CHAIN 1..819
FT /note="FYN-binding protein 1"
FT /id="PRO_0000087397"
FT DOMAIN 499..560
FT /note="SH3 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 736..804
FT /note="SH3 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 1..490
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 589..635
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 649..728
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 448..495
FT /evidence="ECO:0000255"
FT MOTIF 479..493
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 584..587
FT /note="SH2-binding; to LCP2"
FT MOTIF 615..618
FT /note="SH2-binding; to FYN"
FT MOTIF 710..736
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 1..49
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 197..220
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 234..248
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 271..287
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 337..352
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 360..376
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 377..415
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 450..490
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 613..628
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 649..665
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 710..728
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 3
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O15117"
FT MOD_RES 28
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 46
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 222
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 318
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15117"
FT MOD_RES 445
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 559
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 561
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17947660,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 568
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 687
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O15117"
FT VAR_SEQ 627..672
FT /note="Missing (in isoform FYB-120)"
FT /evidence="ECO:0000303|PubMed:9207119"
FT /id="VSP_004261"
SQ SEQUENCE 819 AA; 90055 MW; 6222CC7EF1CA2BBD CRC64;
MAKFNTGSNP TEEAATSSRP FKVAGQSSPS GIQSRKNLFD NQGNASPPAG PSSMPKFGTT
KPPLAAKPTY EEKPEKEPKP PFLKPTGGSP RFGTQPNSVS RDPEVKVGFL KPVSPKPTSL
TKEDSKPVVL RPPGNKLHNL NQESDLKTPG PKPGPAPPVP ENELKPGFSK VAGAKSKFMP
AAQDTDSKPR FPRHTFGQKP SLSTEDSQEE NTSKNVPVQK GSPVQLGAKS KGAPFKPPKE
DPEDKDHGAP SSPFPGVVLK PAASRGSPGL SKNFEEKKED RKTDLAKNIF LNKLNQEEPA
RFPKAPSKLT AGTPWGQSQE KEGDKNSATP KQKALPPLSV LGPPPPKPNR PPNVDLTRFR
KADSANSATK SQTPYSTTSL PPPPPTHPAS QPPLPASHPA HPPVPSLPPR NIKPPLDLKH
PINDENQDGV MHSDGTGNLE EEQESEGETY EDIDSSKERD KKREKEEKKR LELERKEQKE
REKKEQELKK KFKLTGPIQV IHHAKACCDV KGGKNELSFK QGEDIEIIRI TDNPEGKWLG
RTARGSYGYI KTTAVEIDYD SLKRKKNSLN AVPPRLVEDD QDVYDDVAEQ DAPNSHGQSG
SGGMFPPPPT DDEIYDGIEE EDDDDGSVPQ VDEKTNAWSW GILKMLKGKD DRKKSIREKP
KVSESDNNEG SSLPSQHKQL DVGEEVYDDV DASDFPPPPA EMSQGMSVGR AKTEEKDPKK
LKKQEKEEKD LRKKFKYDGE IRVLYSTKVA SSLTSKKWGA RDLQIKPGES LEVIQSTDDT
KVLCRNEEGK YGYVLRSYLV DNDGEIYDDI ADGCIYDND
//
