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Q62844

- FYN_RAT

UniProt

Q62844 - FYN_RAT

Protein

Tyrosine-protein kinase Fyn

Gene

Fyn

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 120 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      Previous versions | rss
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    Functioni

    Non-receptor tyrosine-protein kinase that plays a role in many biological processes including regulation of cell growth and survival, cell adhesion, integrin-mediated signaling, cytoskeletal remodeling, cell motility, immune response and axon guidance. Inactive FYN is phosphorylated on its C-terminal tail within the catalytic domain. Following activation by PKA, the protein subsequently associates with PTK2/FAK1, allowing PTK2/FAK1 phosphorylation, activation and targeting to focal adhesions. Involved in the regulation of cell adhesion and motility through phosphorylation of CTNNB1 (beta-catenin) and CTNND1 (delta-catenin). Regulates cytoskeletal remodeling by phosphorylating several proteins including the actin regulator WAS and the microtubule-associated proteins MAP2 and MAPT. Promotes cell survival by phosphorylating AGAP2/PIKE-A and preventing its apoptotic cleavage. Participates in signal transduction pathways that regulate the integrity of the glomerular slit diaphragm (an essential part of the glomerular filter of the kidney) by phosphorylating several slit diaphragm components including NPHS1, KIRREL and TRPC6. Plays a role in neural processes by phosphorylating DPYSL2, a multifunctional adapter protein within the central nervous system, ARHGAP32, a regulator for Rho family GTPases implicated in various neural functions, and SNCA, a small pre-synaptic protein. Participates in the downstream signaling pathways that lead to T-cell differentiation and proliferation following T-cell receptor (TCR) stimulation. Also participates in negative feedback regulation of TCR signaling through phosphorylation of PAG1, thereby promoting interaction between PAG1 and CSK and recruitment of CSK to lipid rafts. CSK maintains LCK and FYN in an inactive form. Promotes CD28-induced phosphorylation of VAV1 By similarity. Interacts with UNC119 By similarity.By similarity

    Catalytic activityi

    ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.1 PublicationPROSITE-ProRule annotation

    Cofactori

    Manganese.1 Publication

    Enzyme regulationi

    Inhibited by phosphorylation of Tyr-531 by leukocyte common antigen and activated by dephosphorylation of this site.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei299 – 2991ATP1 PublicationPROSITE-ProRule annotation
    Active sitei390 – 3901Proton acceptorBy similarityPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi277 – 2859ATPBy similarityPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. CD4 receptor binding Source: RGD
    3. CD8 receptor binding Source: RGD
    4. glycoprotein binding Source: RGD
    5. metal ion binding Source: UniProtKB-KW
    6. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC
    7. peptide hormone receptor binding Source: RGD
    8. phosphatidylinositol 3-kinase binding Source: RGD
    9. protein binding Source: RGD
    10. protein complex binding Source: RGD
    11. protein kinase activity Source: RGD
    12. protein tyrosine kinase activity Source: RGD
    13. receptor binding Source: RGD
    14. T cell receptor binding Source: RGD

    GO - Biological processi

    1. activated T cell proliferation Source: Ensembl
    2. cellular response to growth factor stimulus Source: RGD
    3. cellular response to peptide hormone stimulus Source: RGD
    4. dendrite morphogenesis Source: Ensembl
    5. detection of mechanical stimulus involved in sensory perception of pain Source: Ensembl
    6. forebrain development Source: Ensembl
    7. ionotropic glutamate receptor signaling pathway Source: RGD
    8. negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: UniProtKB
    9. negative regulation of gene expression Source: Ensembl
    10. negative regulation of neuron apoptotic process Source: UniProtKB
    11. negative regulation of protein catabolic process Source: Ensembl
    12. neuron migration Source: Ensembl
    13. peptidyl-tyrosine phosphorylation Source: RGD
    14. positive regulation of neuron projection development Source: Ensembl
    15. positive regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
    16. positive regulation of protein localization to nucleus Source: Ensembl
    17. protein autophosphorylation Source: RGD
    18. regulation of cell shape Source: Ensembl
    19. response to drug Source: RGD
    20. response to ethanol Source: Ensembl
    21. T cell receptor signaling pathway Source: Ensembl

    Keywords - Molecular functioni

    Developmental protein, Kinase, Transferase, Tyrosine-protein kinase

    Keywords - Ligandi

    ATP-binding, Manganese, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_195025. Signaling by SCF-KIT.
    REACT_196225. Regulation of signaling by CBL.
    REACT_197451. Regulation of KIT signaling.
    REACT_197531. Role of LAT2/NTAL/LAB on calcium mobilization.
    REACT_198646. FCGR activation.
    REACT_198729. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_211910. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
    REACT_212418. DAP12 signaling.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tyrosine-protein kinase Fyn (EC:2.7.10.2)
    Alternative name(s):
    Proto-oncogene c-Fyn
    p59-Fyn
    Gene namesi
    Name:FynImported
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 20

    Organism-specific databases

    RGDi2641. Fyn.

    Subcellular locationi

    Cell membrane By similarity
    Note: Present and active in lipid rafts. Palmitoylation is crucial for proper trafficking By similarity.By similarity

    GO - Cellular componenti

    1. cytosol Source: Reactome
    2. endosome Source: Ensembl
    3. intracellular membrane-bounded organelle Source: RGD
    4. membrane Source: RGD
    5. mitochondrion Source: RGD
    6. plasma membrane Source: UniProtKB-SubCell
    7. postsynaptic density Source: RGD

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi299 – 2991K → M: Loss of kinase activity and reduction in oligodendrocyte process extension and myelin membrane formation. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 537536Tyrosine-protein kinase FynPRO_0000282948Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Lipidationi2 – 21N-myristoyl glycineBy similarity
    Lipidationi3 – 31S-palmitoyl cysteineBy similarity
    Lipidationi6 – 61S-palmitoyl cysteineBy similarity
    Modified residuei15 – 151PhosphothreonineBy similarity
    Modified residuei21 – 211PhosphoserineBy similarity
    Modified residuei25 – 251PhosphoserineBy similarity
    Modified residuei185 – 1851PhosphotyrosineBy similarity
    Modified residuei213 – 2131PhosphotyrosineBy similarity
    Modified residuei214 – 2141PhosphotyrosineBy similarity
    Modified residuei257 – 2571PhosphoserineBy similarity
    Modified residuei420 – 4201Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei440 – 4401PhosphotyrosineBy similarity
    Modified residuei512 – 5121PhosphothreonineBy similarity
    Modified residuei531 – 5311Phosphotyrosine; by CSKBy similarity

    Post-translational modificationi

    Autophosphorylated at Tyr-420. Phosphorylation on the C-terminal tail at Tyr-531 by CSK maintains the enzyme in an inactive state. PTPRC/CD45 dephosphorylates Tyr-531 leading to activation. Dephosphorylation at Tyr-420 by PTPN2 negatively regulates T-cell receptor signaling By similarity.By similarity
    Palmitoylation at Cys-3 and Cys-6 regulate subcellular location.By similarity

    Keywords - PTMi

    Lipoprotein, Myristate, Palmitate, Phosphoprotein

    Proteomic databases

    PaxDbiQ62844.
    PRIDEiQ62844.

    PTM databases

    PhosphoSiteiQ62844.

    Expressioni

    Tissue specificityi

    Detected in spinal cord oligodendrocytes (at protein level).1 Publication

    Developmental stagei

    Up-regulated during oligodendrocyte differentiation.1 Publication

    Gene expression databases

    GenevestigatoriQ62844.

    Interactioni

    Subunit structurei

    Interacts (via its SH3 domain) with PIK3R1 and PRMT8. Interacts with FYB, PAG1, and SH2D1A. Interacts with CD79A (tyrosine-phosphorylated form); the interaction increases FYN activity. Interacts with TOM1L1 (phosphorylated form). Interacts with SH2D1A and SLAMF1. Interacts with and phosphorylates ITCH, down-regulating its activity. Interacts with FASLG. Interacts with RUNX3. Interacts with KIT. Interacts with KDR (tyrosine phosphorylated). Interacts with EPHA8; possible downstream effector of EPHA8 in regulation of cell adhesion. Interacts with PTK2/FAK1; this interaction leads to PTK2/FAK1 phosphorylation and activation. Interacts with CAV1; this interaction couples integrins to the Ras-ERK pathway. Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated) By similarity. Interacts (via SH3 domain) with KLHL2 (via N-terminus).By similarity1 Publication

    Protein-protein interaction databases

    BioGridi247215. 2 interactions.
    IntActiQ62844. 1 interaction.
    STRINGi10116.ENSRNOP00000000733.

    Structurei

    3D structure databases

    ProteinModelPortaliQ62844.
    SMRiQ62844. Positions 81-537.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini82 – 14362SH3PROSITE-ProRule annotationAdd
    BLAST
    Domaini149 – 24698SH2PROSITE-ProRule annotationAdd
    BLAST
    Domaini271 – 524254Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation
    Contains 1 SH2 domain.PROSITE-ProRule annotation
    Contains 1 SH3 domain.PROSITE-ProRule annotation

    Keywords - Domaini

    SH2 domain, SH3 domain

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00620000087702.
    HOGENOMiHOG000233858.
    HOVERGENiHBG008761.
    InParanoidiQ62844.
    KOiK05703.
    OMAiSHNSGYR.
    OrthoDBiEOG7GTT2V.
    PhylomeDBiQ62844.
    TreeFamiTF351634.

    Family and domain databases

    Gene3Di3.30.505.10. 1 hit.
    InterProiIPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR000980. SH2.
    IPR001452. SH3_domain.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    [Graphical view]
    PfamiPF07714. Pkinase_Tyr. 1 hit.
    PF00017. SH2. 1 hit.
    PF00018. SH3_1. 1 hit.
    [Graphical view]
    PRINTSiPR00401. SH2DOMAIN.
    PR00452. SH3DOMAIN.
    PR00109. TYRKINASE.
    SMARTiSM00252. SH2. 1 hit.
    SM00326. SH3. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF50044. SSF50044. 1 hit.
    SSF55550. SSF55550. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    PS50001. SH2. 1 hit.
    PS50002. SH3. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q62844-1 [UniParc]FASTAAdd to Basket

    « Hide

    MGCVQCKDKE AAKLTEERDG SLNQSSGYRY GTDPTPQHYP SFGVTSIPNY    50
    NNFHAAGGQG LTVFGGVNSS SHTGTLRTRG GTGVTLFVAL YDYEARTEDD 100
    LSFHKGEKFQ ILNSSEGDWW EARSLTTGET GYIPSNYVAP VDSIQAEEWY 150
    FGKLGRKDAE RQLLSFGNPR GTFLIRESET TKGAYSLSIR DWDDMKGDHV 200
    KHYKIRKLDN GGYYITTRAQ FETLQQLVQH YSERAAGLCC RLVVPCHKGM 250
    PRLTDLSVKT KDVWEIPRES LQLIKRLGNG QFGEVWMGTW NGNTKVAIKT 300
    LKPGTMSPES FLEEAQIMKK LKHDKLVQLY AVVSEEPIYI VTEYMNKGSL 350
    LDFLKDGEGR ALKLPNLVDM AAQVAAGMAY IERMNYIHRD LRSANILVGN 400
    GLICKIADFG LARLIEDNEY TARQGAKFPI KWTAPEAALY GRFTIKSDVW 450
    SFGILLTELV TKGRVPYPGM NNREVLEQVE RGYRMPCPQD CPISLHELMI 500
    HCWKKDPEER PTFEYLQGFL EDYFTATEPQ YQPGENL 537
    Length:537
    Mass (Da):60,702
    Last modified:November 1, 1996 - v1
    Checksum:i11AE4420919DBF1C
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U35365 mRNA. Translation: AAA82942.1.
    PIRiPT0199.
    RefSeqiNP_036887.1. NM_012755.1.
    UniGeneiRn.19361.
    Rn.228993.

    Genome annotation databases

    EnsembliENSRNOT00000000733; ENSRNOP00000000733; ENSRNOG00000000596.
    GeneIDi25150.
    KEGGirno:25150.
    UCSCiRGD:2641. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U35365 mRNA. Translation: AAA82942.1 .
    PIRi PT0199.
    RefSeqi NP_036887.1. NM_012755.1.
    UniGenei Rn.19361.
    Rn.228993.

    3D structure databases

    ProteinModelPortali Q62844.
    SMRi Q62844. Positions 81-537.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 247215. 2 interactions.
    IntActi Q62844. 1 interaction.
    STRINGi 10116.ENSRNOP00000000733.

    PTM databases

    PhosphoSitei Q62844.

    Proteomic databases

    PaxDbi Q62844.
    PRIDEi Q62844.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000000733 ; ENSRNOP00000000733 ; ENSRNOG00000000596 .
    GeneIDi 25150.
    KEGGi rno:25150.
    UCSCi RGD:2641. rat.

    Organism-specific databases

    CTDi 2534.
    RGDi 2641. Fyn.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00620000087702.
    HOGENOMi HOG000233858.
    HOVERGENi HBG008761.
    InParanoidi Q62844.
    KOi K05703.
    OMAi SHNSGYR.
    OrthoDBi EOG7GTT2V.
    PhylomeDBi Q62844.
    TreeFami TF351634.

    Enzyme and pathway databases

    Reactomei REACT_195025. Signaling by SCF-KIT.
    REACT_196225. Regulation of signaling by CBL.
    REACT_197451. Regulation of KIT signaling.
    REACT_197531. Role of LAT2/NTAL/LAB on calcium mobilization.
    REACT_198646. FCGR activation.
    REACT_198729. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_211910. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
    REACT_212418. DAP12 signaling.

    Miscellaneous databases

    NextBioi 605589.
    PROi Q62844.

    Gene expression databases

    Genevestigatori Q62844.

    Family and domain databases

    Gene3Di 3.30.505.10. 1 hit.
    InterProi IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR000980. SH2.
    IPR001452. SH3_domain.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    [Graphical view ]
    Pfami PF07714. Pkinase_Tyr. 1 hit.
    PF00017. SH2. 1 hit.
    PF00018. SH3_1. 1 hit.
    [Graphical view ]
    PRINTSi PR00401. SH2DOMAIN.
    PR00452. SH3DOMAIN.
    PR00109. TYRKINASE.
    SMARTi SM00252. SH2. 1 hit.
    SM00326. SH3. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF50044. SSF50044. 1 hit.
    SSF55550. SSF55550. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    PS50001. SH2. 1 hit.
    PS50002. SH3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Expression of three type mRNAs encoding rat FYN by alternative splicing within 5' untranslated region."
      Nemoto K., Sekimoto M., Kageyama H., Fukamachi K., Nemoto F., Ueyama T., Senba E., Tomita I.
      Submitted (SEP-1995) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: SHRSPImported.
      Tissue: BrainImported.
    2. "Novel putative protein kinase clones from a rat large granular lymphocyte tumor cell line."
      Yue C.C.
      Mol. Immunol. 28:399-408(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. "Morphological differentiation of oligodendrocytes requires activation of Fyn tyrosine kinase."
      Osterhout D.J., Wolven A., Wolf R.M., Resh M.D., Chao M.V.
      J. Cell Biol. 145:1209-1218(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, MUTAGENESIS OF LYS-299.
    4. "Process elongation of oligodendrocytes is promoted by the Kelch-related actin-binding protein Mayven."
      Jiang S., Avraham H.K., Park S.Y., Kim T.A., Bu X., Seng S., Avraham S.
      J. Neurochem. 92:1191-1203(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH KLHL2, TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiFYN_RAT
    AccessioniPrimary (citable) accession number: Q62844
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 3, 2007
    Last sequence update: November 1, 1996
    Last modified: October 1, 2014
    This is version 120 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3