FYNA_DANRE
ID FYNA_DANRE Reviewed; 537 AA.
AC Q6EWH2; F8W4M2; Q58HR4; Q6DI27; Q9I8J8;
DT 05-SEP-2012, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2012, sequence version 2.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Tyrosine-protein kinase fyna;
DE EC=2.7.10.2;
DE AltName: Full=Proto-oncogene c-Fyna;
GN Name=fyna; Synonyms=fyn;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND MUTAGENESIS OF
RP LYS-299.
RC TISSUE=Embryo;
RX PubMed=16112104; DOI=10.1016/j.ydbio.2005.07.018;
RA Sharma D., Holets L., Zhang X., Kinsey W.H.;
RT "Role of Fyn kinase in signaling associated with epiboly during zebrafish
RT development.";
RL Dev. Biol. 285:462-476(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15815683; DOI=10.1038/sj.embor.7400386;
RA Jopling C., den Hertog J.;
RT "Fyn/Yes and non-canonical Wnt signalling converge on RhoA in vertebrate
RT gastrulation cell movements.";
RL EMBO Rep. 6:426-431(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Embryo;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-153, SUBCELLULAR LOCATION, ACTIVITY
RP REGULATION, AND TISSUE SPECIFICITY.
RC TISSUE=Embryo;
RX PubMed=10993948;
RX DOI=10.1002/1097-0185(20001001)260:2<115::aid-ar10>3.0.co;2-c;
RA Rongish B.J., Kinsey W.H.;
RT "Transient nuclear localization of Fyn kinase during development in
RT zebrafish.";
RL Anat. Rec. 260:115-123(2000).
CC -!- FUNCTION: Tyrosine-protein kinase implicated in the control of cell
CC growth. Plays a role in the regulation of intracellular calcium levels.
CC Required in brain development and mature brain function with important
CC roles in the regulation of axon growth, axon guidance, and neurite
CC extension. Role in cntn1-mediated signaling (By similarity). Required
CC for convergent extension cell movements during gastrulation, acting
CC with yes via rhoa. May be required for epiboly to occur, possibly
CC through its effects in calcium signaling. {ECO:0000250,
CC ECO:0000269|PubMed:15815683, ECO:0000269|PubMed:16112104}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC -!- ACTIVITY REGULATION: Inhibited by phosphorylation of Tyr-531 by
CC leukocyte common antigen and activated by dephosphorylation of this
CC site (By similarity). Relatively inactive in the unfertilized oocyte,
CC undergoes rapid activation immediately following fertilization. Total
CC activity increases progressively during later development and remains
CC elevated during sphere and epiboly stage. {ECO:0000250,
CC ECO:0000269|PubMed:10993948}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10993948}. Nucleus
CC {ECO:0000269|PubMed:10993948}. Note=Transiently expressed in the
CC nucleus at mid-blastula stage (3.3 hpf) in a large subset of cells.
CC Nuclear localization is not observed from late blastula stage onward.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6EWH2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6EWH2-2; Sequence=VSP_044087, VSP_044088;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:10993948,
CC ECO:0000269|PubMed:15815683}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the pre-gastrula embryo (at protein
CC level).
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. SRC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAX47959.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AY948197; AAX47959.1; ALT_FRAME; mRNA.
DR EMBL; AJ620748; CAF06179.1; -; mRNA.
DR EMBL; CU306817; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC075763; AAH75763.1; -; mRNA.
DR EMBL; AF269145; AAF81748.1; -; mRNA.
DR RefSeq; NP_001315092.1; NM_001328163.1. [Q6EWH2-1]
DR AlphaFoldDB; Q6EWH2; -.
DR SMR; Q6EWH2; -.
DR STRING; 7955.ENSDARP00000123888; -.
DR PaxDb; Q6EWH2; -.
DR Ensembl; ENSDART00000150232; ENSDARP00000123888; ENSDARG00000011370. [Q6EWH2-1]
DR GeneID; 373872; -.
DR KEGG; dre:373872; -.
DR CTD; 373872; -.
DR ZFIN; ZDB-GENE-030903-5; fyna.
DR eggNOG; KOG0197; Eukaryota.
DR GeneTree; ENSGT00940000155462; -.
DR HOGENOM; CLU_000288_7_2_1; -.
DR InParanoid; Q6EWH2; -.
DR OMA; WMEKADG; -.
DR OrthoDB; 539311at2759; -.
DR PhylomeDB; Q6EWH2; -.
DR TreeFam; TF351634; -.
DR Reactome; R-DRE-1227986; Signaling by ERBB2.
DR Reactome; R-DRE-1257604; PIP3 activates AKT signaling.
DR Reactome; R-DRE-1433557; Signaling by SCF-KIT.
DR Reactome; R-DRE-1433559; Regulation of KIT signaling.
DR Reactome; R-DRE-210990; PECAM1 interactions.
DR Reactome; R-DRE-2424491; DAP12 signaling.
DR Reactome; R-DRE-373753; Nephrin family interactions.
DR Reactome; R-DRE-375165; NCAM signaling for neurite out-growth.
DR Reactome; R-DRE-389356; CD28 co-stimulation.
DR Reactome; R-DRE-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-DRE-389359; CD28 dependent Vav1 pathway.
DR Reactome; R-DRE-389513; CTLA4 inhibitory signaling.
DR Reactome; R-DRE-3928662; EPHB-mediated forward signaling.
DR Reactome; R-DRE-3928663; EPHA-mediated growth cone collapse.
DR Reactome; R-DRE-3928664; Ephrin signaling.
DR Reactome; R-DRE-3928665; EPH-ephrin mediated repulsion of cells.
DR Reactome; R-DRE-399954; Sema3A PAK dependent Axon repulsion.
DR Reactome; R-DRE-399955; SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion.
DR Reactome; R-DRE-399956; CRMPs in Sema3A signaling.
DR Reactome; R-DRE-418885; DCC mediated attractive signaling.
DR Reactome; R-DRE-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-DRE-5621480; Dectin-2 family.
DR Reactome; R-DRE-5621575; CD209 (DC-SIGN) signaling.
DR Reactome; R-DRE-5673001; RAF/MAP kinase cascade.
DR Reactome; R-DRE-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-DRE-8866376; Reelin signalling pathway.
DR Reactome; R-DRE-9032759; NTRK2 activates RAC1.
DR Reactome; R-DRE-912631; Regulation of signaling by CBL.
DR PRO; PR:Q6EWH2; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 17.
DR Bgee; ENSDARG00000011370; Expressed in mature ovarian follicle and 25 other tissues.
DR GO; GO:0005829; C:cytosol; IDA:ZFIN.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:ZFIN.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0004672; F:protein kinase activity; IDA:ZFIN.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0034334; P:adherens junction maintenance; IGI:ZFIN.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0060027; P:convergent extension involved in gastrulation; IGI:ZFIN.
DR GO; GO:0001702; P:gastrulation with mouth forming second; IMP:ZFIN.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0042552; P:myelination; IMP:ZFIN.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:ZFIN.
DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; IMP:ZFIN.
DR GO; GO:0045859; P:regulation of protein kinase activity; IGI:ZFIN.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd12006; SH3_Fyn_Yrk; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR035750; Fyn/Yrk_SH3.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF00018; SH3_1; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00452; SH3DOMAIN.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00326; SH3; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cytoplasm; Developmental protein;
KW Kinase; Lipoprotein; Manganese; Metal-binding; Myristate;
KW Nucleotide-binding; Nucleus; Palmitate; Phosphoprotein; Proto-oncogene;
KW Reference proteome; SH2 domain; SH3 domain; Transferase;
KW Tyrosine-protein kinase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250"
FT CHAIN 2..537
FT /note="Tyrosine-protein kinase fyna"
FT /id="PRO_0000418878"
FT DOMAIN 82..143
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 149..246
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 271..524
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 13..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 390
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 277..285
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 299
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 12
FT /note="Phosphothreonine; by PKC"
FT /evidence="ECO:0000250"
FT MOD_RES 420
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 531
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250"
FT LIPID 3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 6
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 293
FT /note="N -> H (in isoform 2)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_044087"
FT VAR_SEQ 294..537
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_044088"
FT MUTAGEN 299
FT /note="K->M: Loss of activity."
FT /evidence="ECO:0000269|PubMed:16112104"
FT CONFLICT 5
FT /note="Q -> R (in Ref. 4; AAH75763)"
FT /evidence="ECO:0000305"
FT CONFLICT 60..62
FT /note="GVT -> RVP (in Ref. 2; CAF06179)"
FT /evidence="ECO:0000305"
FT CONFLICT 148
FT /note="D -> E (in Ref. 1; AAX47959)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 537 AA; 60569 MW; 1C7CB34990049B96 CRC64;
MGCVQCKDKE ATKLTDERET SVSQHAGYRY GSDPTPQHYP SFGVTAIPNY NNFHAPVSQG
VTVFGGVNSS SHSGTLRSRG GTGVTLFVAL YDYEARSEDD LSFRKGEKFQ ILNSTEGDWW
EARSLTTGGT GYIPSNYVAP VDSIQAEDWY FGKLGRKDAE RQLLSNGNPR GTFLIRESET
TKGAYSLSIQ DWDETKGDHV KHYKIRKLDN GGYYITTRAQ FETLQQLVHH YSARAAGLCC
RLIVPCHKGM PRLADLSVKT KDVWEIPRES LQLIKRLGNG QFGEVWMGTW NGNTKVAVKT
LKPGTMSPES FLEEAQIMKK LRHDKLVQLY AVVSEEPIYI VTEYMSKGSL LDFLKDGEGR
GLKLPNLVDM AAQVAAGMAY IERMNYIHRD LRSANILVGD SLVCKIADFG LARLIEDNEY
TARQGAKFPI KWTAPEAALY GRFTIKSDVW SFGILLTELV TKGRVPYPGM NNREVLEQVE
RGYRMPCPQD CPSSLHELML QCWKRDPEER PTFEYLQAFL EDYFTATEPQ YQPGDNL
