ID FYB2_HUMAN Reviewed; 728 AA. AC Q5VWT5; Q63HM3; Q6ZUY6; DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot. DT 07-DEC-2004, sequence version 1. DT 24-JAN-2024, entry version 138. DE RecName: Full=FYN-binding protein 2 {ECO:0000312|HGNC:HGNC:27295}; DE AltName: Full=Activation-dependent, raft-recruited ADAP-like phosphoprotein {ECO:0000303|PubMed:27335501}; GN Name=FYB2 {ECO:0000312|HGNC:HGNC:27295}; GN Synonyms=ARAP {ECO:0000303|PubMed:27335501}, C1orf168; 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], FUNCTION, SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, PHOSPHORYLATION AT TYR-491 AND TYR-587, INTERACTION WITH LCP2; RP SKAP1; LCK AND FYN, AND MUTAGENESIS OF TYR-491 AND TYR-587. RX PubMed=27335501; DOI=10.4049/jimmunol.1501913; RA Jung S.H., Yoo E.H., Yu M.J., Song H.M., Kang H.Y., Cho J.Y., Lee J.R.; RT "ARAP, a novel adaptor protein, is required for TCR signaling and integrin- RT mediated adhesion."; RL J. Immunol. 197:942-952(2016). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Fetal brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Salivary gland; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). CC -!- FUNCTION: Adapter protein that plays a role in T-cell receptor (TCR)- CC mediated activation of signaling pathways. Required for T-cell CC activation and integrin-mediated T-cell adhesion in response to TCR CC stimulation (PubMed:27335501). {ECO:0000269|PubMed:27335501}. CC -!- SUBUNIT: Interacts with SKAP1, LCK and FYN. The phosphorylated form CC interacts with LCP2. {ECO:0000269|PubMed:27335501}. CC -!- SUBCELLULAR LOCATION: Membrane raft {ECO:0000269|PubMed:27335501}. CC Note=Recruited to membrane rafts and immunological synapse after TCR CC stimulation. {ECO:0000269|PubMed:27335501}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q5VWT5-1; Sequence=Displayed; CC Name=2; CC IsoId=Q5VWT5-2; Sequence=VSP_028031, VSP_028032; CC -!- TISSUE SPECIFICITY: Expressed in T-cells (at protein level). Widely CC expressed. {ECO:0000269|PubMed:27335501}. CC -!- PTM: Phosphorylation is required for its function in T-cell activation. CC {ECO:0000269|PubMed:27335501}. 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; AK125198; BAC86080.1; -; mRNA. DR EMBL; BX648439; CAH56148.1; -; mRNA. DR EMBL; AL035705; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL360295; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS30729.1; -. [Q5VWT5-1] DR RefSeq; NP_001004303.3; NM_001004303.4. [Q5VWT5-1] DR AlphaFoldDB; Q5VWT5; -. DR SMR; Q5VWT5; -. DR BioGRID; 128284; 10. DR IntAct; Q5VWT5; 1. DR STRING; 9606.ENSP00000345972; -. DR iPTMnet; Q5VWT5; -. DR PhosphoSitePlus; Q5VWT5; -. DR BioMuta; FYB2; -. DR DMDM; 74747442; -. DR EPD; Q5VWT5; -. DR MassIVE; Q5VWT5; -. DR PaxDb; 9606-ENSP00000345972; -. DR PeptideAtlas; Q5VWT5; -. DR ProteomicsDB; 65558; -. [Q5VWT5-1] DR ProteomicsDB; 65559; -. [Q5VWT5-2] DR Antibodypedia; 33247; 65 antibodies from 11 providers. DR DNASU; 199920; -. DR Ensembl; ENST00000343433.7; ENSP00000345972.6; ENSG00000187889.13. [Q5VWT5-1] DR GeneID; 199920; -. DR KEGG; hsa:199920; -. DR MANE-Select; ENST00000343433.7; ENSP00000345972.6; NM_001004303.5; NP_001004303.3. DR UCSC; uc001cym.5; human. [Q5VWT5-1] DR AGR; HGNC:27295; -. DR CTD; 199920; -. DR DisGeNET; 199920; -. DR GeneCards; FYB2; -. DR HGNC; HGNC:27295; FYB2. DR HPA; ENSG00000187889; Tissue enhanced (choroid plexus, fallopian tube, liver). DR MIM; 618478; gene. DR neXtProt; NX_Q5VWT5; -. DR OpenTargets; ENSG00000187889; -. DR PharmGKB; PA142672418; -. DR VEuPathDB; HostDB:ENSG00000187889; -. DR eggNOG; ENOG502RXZD; Eukaryota. DR GeneTree; ENSGT00530000063460; -. DR HOGENOM; CLU_023222_0_0_1; -. DR InParanoid; Q5VWT5; -. DR OMA; KPWKNFP; -. DR OrthoDB; 5323983at2759; -. DR PhylomeDB; Q5VWT5; -. DR TreeFam; TF337003; -. DR PathwayCommons; Q5VWT5; -. DR SignaLink; Q5VWT5; -. DR BioGRID-ORCS; 199920; 7 hits in 1132 CRISPR screens. DR ChiTaRS; MDK; human. DR GenomeRNAi; 199920; -. DR Pharos; Q5VWT5; Tbio. DR PRO; PR:Q5VWT5; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q5VWT5; Protein. DR Bgee; ENSG00000187889; Expressed in right uterine tube and 122 other cell types or tissues. DR GO; GO:0001772; C:immunological synapse; IDA:UniProtKB. DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0033627; P:cell adhesion mediated by integrin; IMP:UniProtKB. DR GO; GO:0007229; P:integrin-mediated signaling pathway; IBA:GO_Central. DR GO; GO:0072659; P:protein localization to plasma membrane; IBA:GO_Central. DR GO; GO:0050852; P:T cell receptor signaling pathway; IMP:UniProtKB. DR Gene3D; 2.30.30.40; SH3 Domains; 1. DR InterPro; IPR043443; FYB1/2-like. DR InterPro; IPR029294; hSH3. DR InterPro; IPR036028; SH3-like_dom_sf. DR InterPro; IPR001452; SH3_domain. DR PANTHER; PTHR16830:SF1; FYN-BINDING PROTEIN 2; 1. DR PANTHER; PTHR16830; SH2 CONTAINING ADAPTOR PRAM-1 RELATED; 1. DR Pfam; PF14603; hSH3; 1. DR SUPFAM; SSF50044; SH3-domain; 1. DR PROSITE; PS50002; SH3; 1. DR Genevisible; Q5VWT5; HS. PE 1: Evidence at protein level; KW Alternative splicing; Membrane; Phosphoprotein; Reference proteome; KW SH3 domain. FT CHAIN 1..728 FT /note="FYN-binding protein 2" FT /id="PRO_0000304583" FT DOMAIN 664..724 FT /note="SH3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT REGION 17..76 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 250..287 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 367..390 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 521..524 FT /note="SH2-binding; to LCP2" FT /evidence="ECO:0000269|PubMed:27335501" FT COMPBIAS 39..76 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 253..267 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 271..286 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 375..390 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 491 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:27335501" FT MOD_RES 587 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:27335501" FT VAR_SEQ 355..358 FT /note="PTYE -> RRCL (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_028031" FT VAR_SEQ 359..728 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_028032" FT VARIANT 125 FT /note="I -> M (in dbSNP:rs17114336)" FT /id="VAR_035041" FT MUTAGEN 491 FT /note="Y->F: Decrease in phosphorylation and interaction FT with LCP2. Significant decrease in phosphorylation and loss FT of interaction with LCP2; when associated with F-587." FT /evidence="ECO:0000269|PubMed:27335501" FT MUTAGEN 587 FT /note="Y->F: Decrease in phosphorylation and interaction FT with LCP2. Significant decrease in phosphorylation and loss FT of interaction with LCP2; when associated with F-491." FT /evidence="ECO:0000269|PubMed:27335501" FT CONFLICT 103 FT /note="C -> R (in Ref. 3; CAH56148)" FT /evidence="ECO:0000305" FT CONFLICT 400 FT /note="K -> R (in Ref. 3; CAH56148)" FT /evidence="ECO:0000305" FT CONFLICT 718 FT /note="H -> R (in Ref. 3; CAH56148)" FT /evidence="ECO:0000305" SQ SEQUENCE 728 AA; 82070 MW; A98C37E6A0B7F2F9 CRC64; MEGEGVRNFK ELRAKFQNLD APPLPGPIKF PAGVSPKGDI GGTQSTQILA NGKPLSSNHK QRTPYCSSSE SQPLQPQKIK LAQKSEIPKC SNSPGPLGKS TVCSATSSQK ASLLLEVTQS NVEIITKEKV MVANSFRNKL WNWEKVSSQK SEMSSALLLA NYGSKAIHLE GQKGMGLTPE EPRKKLETKG AQTLPSQKHV VAPKILHNVS EDPSFVISQH IRKSWENPPP ERSPASSPCQ PIYECELASQ APEKQPDVRH HHLPKTKPLP SIDSLGPPPP KPSRPPIVNL QAFQRQPAAV PKTQGEVTVE EGSLSPERLF NAEFEEPHNY EATISYLRHS GNSINLCTAK EIADPTYEVG IEELQKPGKN FPYPEPSAKH EDKKMKEKQP CELKPKNTEK EPYSNHVFKV DACEGTPEKI QMTNVHTGRR NMLAGKQEAM IDIIQTNPCP EGPKLARHSQ GHCGHLEVLE STKETPDLGV SKTSSISEEI YDDVEYSRKE VPKLNYSSSL ASSSEENREL YEDVYKTKNN YPKIDLDGKE ALKRLQQFFK KEKDRFKIKK TKSKENLSAF SILLPDLELK SQEVIIYDDV DLSEKESKDE DKLKMWKPKF LTPKEKKEKN GAEESESFSP RNFFKTKKQN LEKNRMKREE KLFRERFKYD KEIIVINTAV ACSNNSRNGI FDLPISPGEE LEVIDTTEQN LVICRNSKGK YGYVLIEHLD FKHQSWSP //