FYB2_HUMAN
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 03-AUG-2022, entry version 132.
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}.
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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; Q5VWT5; -.
DR PeptideAtlas; Q5VWT5; -.
DR PRIDE; Q5VWT5; -.
DR ProteomicsDB; 65558; -. [Q5VWT5-1]
DR ProteomicsDB; 65559; -. [Q5VWT5-2]
DR Antibodypedia; 33247; 54 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 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; 343643at2759; -.
DR PhylomeDB; Q5VWT5; -.
DR TreeFam; TF337003; -.
DR PathwayCommons; Q5VWT5; -.
DR SignaLink; Q5VWT5; -.
DR BioGRID-ORCS; 199920; 7 hits in 1054 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 120 other tissues.
DR Genevisible; Q5VWT5; HS.
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 InterPro; IPR043443; FYB1/2-like.
DR InterPro; IPR029294; hSH3.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR16830; PTHR16830; 1.
DR Pfam; PF14603; hSH3; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS50002; SH3; 1.
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
