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Q6P6U0

- FGR_RAT

UniProt

Q6P6U0 - FGR_RAT

Protein

Tyrosine-protein kinase Fgr

Gene

Fgr

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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      Entry version 93 (01 Oct 2014)
      Sequence version 1 (05 Jul 2004)
      Previous versions | rss
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    Functioni

    Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors devoid of kinase activity and contributes to the regulation of immune responses, including neutrophil, monocyte, macrophage and mast cell functions, cytoskeleton remodeling in response to extracellular stimuli, phagocytosis, cell adhesion and migration. Promotes mast cell degranulation, release of inflammatory cytokines and IgE-mediated anaphylaxis. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as MS4A2/FCER1B, FCER1G and FCGR2. Acts downstream of ITGB1 and ITGB2, and regulates actin cytoskeleton reorganization, cell spreading and adhesion. Depending on the context, activates or inhibits cellular responses. Functions as negative regulator of ITGB2 signaling, phagocytosis and SYK activity in monocytes. Required for normal ITGB1 and ITGB2 signaling, normal cell spreading and adhesion in neutrophils and macrophages. Functions as positive regulator of cell migration and regulates cytoskeleton reorganization via RAC1 activation. Phosphorylates SYK (in vitro) and promotes SYK-dependent activation of AKT1 and MAP kinase signaling. Phosphorylates PLD2 in antigen-stimulated mast cells, leading to PLD2 activation and the production of the signaling molecules lysophosphatidic acid and diacylglycerol. Promotes activation of PIK3R1. Phosphorylates FASLG, and thereby regulates its ubiquitination and subsequent internalization. Phosphorylates ABL1. Promotes phosphorylation of CBL, CTTN, PIK3R1, PTK2/FAK1, PTK2B/PYK2 and VAV2 By similarity. Phosphorylates HCLS1 that has already been phosphorylated by SYK, but not unphosphorylated HCLS1.By similarity5 Publications

    Catalytic activityi

    ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.2 PublicationsPROSITE-ProRule annotation

    Enzyme regulationi

    Activated by autophosphorylation. Prior phosphorylation at Tyr-511 by SRC inhibits ulterior autophosphorylation at Tyr-400. Activated by phorbol myristate acetate, phosphatidic acid and poly-Lys. Binding (via SH2 domain) of HCLS1 that is already phosphorylated by SYK strongly increases kinase activity.2 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei279 – 2791ATPPROSITE-ProRule annotation
    Active sitei370 – 3701Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi257 – 2659ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. immunoglobulin receptor binding Source: UniProtKB
    3. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC
    4. phosphotyrosine binding Source: UniProtKB
    5. protein binding Source: RGD
    6. protein kinase binding Source: UniProtKB
    7. protein tyrosine kinase activity Source: RGD

    GO - Biological processi

    1. defense response to Gram-positive bacterium Source: UniProtKB
    2. innate immune response Source: UniProtKB-KW
    3. integrin-mediated signaling pathway Source: UniProtKB
    4. peptidyl-tyrosine phosphorylation Source: UniProtKB
    5. positive regulation of cell migration Source: UniProtKB
    6. positive regulation of cytokine secretion Source: UniProtKB
    7. positive regulation of mast cell degranulation Source: UniProtKB
    8. positive regulation of phosphatidylinositol 3-kinase activity Source: Ensembl
    9. positive regulation of phosphatidylinositol 3-kinase signaling Source: Ensembl
    10. protein autophosphorylation Source: Ensembl
    11. regulation of cell shape Source: UniProtKB
    12. regulation of innate immune response Source: UniProtKB
    13. regulation of phagocytosis Source: UniProtKB
    14. regulation of protein kinase activity Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Transferase, Tyrosine-protein kinase

    Keywords - Biological processi

    Immunity, Innate immunity

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_198646. FCGR activation.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tyrosine-protein kinase Fgr (EC:2.7.10.2)
    Alternative name(s):
    Proto-oncogene c-Fgr
    p55-Fgr
    Gene namesi
    Name:Fgr
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 5

    Organism-specific databases

    RGDi621319. Fgr.

    Subcellular locationi

    Cell membrane Curated; Lipid-anchor Curated; Cytoplasmic side Curated. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cell projectionruffle membrane By similarity. Cytoplasmcytosol By similarity. Cytoplasmcytoskeleton By similarity. Mitochondrion inner membrane. Mitochondrion intermembrane space
    Note: Colocalizes with actin fibers at membrane ruffles By similarity. Detected at plasma membrane lipid rafts. Detected in mitochondrial intermembrane space and at inner membranes.By similarity

    GO - Cellular componenti

    1. actin cytoskeleton Source: Ensembl
    2. cytosol Source: RGD
    3. mitochondrial inner membrane Source: UniProtKB-SubCell
    4. mitochondrial intermembrane space Source: UniProtKB-SubCell
    5. plasma membrane Source: RGD
    6. ruffle membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane, Mitochondrion, Mitochondrion inner membrane

    Pathology & Biotechi

    Keywords - Diseasei

    Proto-oncogene

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 517516Tyrosine-protein kinase FgrPRO_0000413581Add
    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 residuei32 – 321PhosphotyrosineBy similarity
    Modified residuei400 – 4001Phosphotyrosine; by autocatalysis1 Publication
    Modified residuei511 – 5111Phosphotyrosine; by SRC1 Publication

    Post-translational modificationi

    Ubiquitinated. Becomes ubiquitinated in response to ITGB2 signaling; this does not lead to degradation By similarity.By similarity
    Phosphorylated. Autophosphorylated on tyrosine residues. Becomes phosphorylated in response to FCGR2 engagement, cell adhesion and signaling by ITGB2 By similarity. Prior phosphorylation at Tyr-511 by SRC inhibits ulterior autophosphorylation at Tyr-400.By similarity1 Publication

    Keywords - PTMi

    Lipoprotein, Myristate, Palmitate, Phosphoprotein, Ubl conjugation

    PTM databases

    PhosphoSiteiQ6P6U0.

    Expressioni

    Tissue specificityi

    Detected in brain cortex (at protein level).1 Publication

    Gene expression databases

    GenevestigatoriQ6P6U0.

    Interactioni

    Subunit structurei

    Interacts with ITGB1, ITGB2, MS4A2/FCER1B and FCGR2. Interacts (via SH2 domain) with SYK (tyrosine phosphorylated). Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). Interacts with PTK2/FAK1. Interacts (via SH2 domain) with HCLS1 (tyrosine phosphorylated by SYK). Interacts with SIRPA and PTPNS1. Interacts (not phosphorylated on tyrosine residues) with CBL; FGR tyrosine phosphorylation promotes dissociation By similarity.By similarity

    Protein-protein interaction databases

    BioGridi249398. 2 interactions.
    IntActiQ6P6U0. 1 interaction.
    STRINGi10116.ENSRNOP00000013779.

    Structurei

    3D structure databases

    ProteinModelPortaliQ6P6U0.
    SMRiQ6P6U0. Positions 67-515.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini65 – 12662SH3PROSITE-ProRule annotationAdd
    BLAST
    Domaini132 – 22998SH2PROSITE-ProRule annotationAdd
    BLAST
    Domaini251 – 504254Protein 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

    SH3 domain

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00620000087702.
    HOGENOMiHOG000233858.
    HOVERGENiHBG008761.
    InParanoidiQ6P6U0.
    KOiK08891.
    OMAiTWNGSTK.
    OrthoDBiEOG7GTT2V.
    PhylomeDBiQ6P6U0.
    TreeFamiTF351634.

    Family and domain databases

    Gene3Di3.30.505.10. 1 hit.
    InterProiIPR028459. FGR.
    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]
    PANTHERiPTHR24418:SF224. PTHR24418:SF224. 1 hit.
    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.

    Q6P6U0-1 [UniParc]FASTAAdd to Basket

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    MGCVFCKKLE PAPKEDVGLE GDFRSQGAEE RYYPDPTQGR SSSISPQPIS    50
    PAFLNVGNIR SVSGTGVTIF VALYDYEART GDDLTFTKGE KFHILNNTEY 100
    DWWEARSLSS GRTGYVPSNY VAPVDSIQAE EWYFGKISRK DAERQLLSDG 150
    NPQGAFLIRE SETTKGAYSL SIRDWDQNRG DHIKHYKIRK LDMGGYYITT 200
    RAQFESVQDL VRHYMEVNDG LCYLLTAPCM VMKPQTLGLA KDAWEIDRNS 250
    IALDRRLGTG CFGDVWLGTW NCSTKVAVKT LKPGTMSPKA FLEEAQIMKL 300
    LRHDKLVQLY AVVSEEPIYI VTEFMCYGSL LDFLKDRKGH NLMLPNLVDM 350
    AAQVAEGMAY MERMNYIHRD LRAANILVGE HLICKIADFG LARLIVDDEY 400
    NPQQGTKFPI KWTAPEAALF GRFTVKSDVW SFGILLTELI TKGRVPYPGM 450
    NNREVLEQVE HGYHMPCPPG CPVSLYEVME QTWRLDPEER PTFEYLQSFL 500
    EDYFTSTEPQ YQPGDQT 517
    Length:517
    Mass (Da):58,821
    Last modified:July 5, 2004 - v1
    Checksum:i0D960BBBCAF2911B
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti313 – 3131V → A in CAA40337. 1 PublicationCurated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X57018 mRNA. Translation: CAA40337.1.
    CH473968 Genomic DNA. Translation: EDL80655.1.
    CH473968 Genomic DNA. Translation: EDL80656.1.
    CH473968 Genomic DNA. Translation: EDL80657.1.
    BC062025 mRNA. Translation: AAH62025.1.
    PIRiS24547.
    RefSeqiNP_077059.2. NM_024145.2.
    XP_006239141.1. XM_006239079.1.
    XP_006239142.1. XM_006239080.1.
    XP_006239143.1. XM_006239081.1.
    XP_006239144.1. XM_006239082.1.
    UniGeneiRn.11309.

    Genome annotation databases

    EnsembliENSRNOT00000013778; ENSRNOP00000013779; ENSRNOG00000009912.
    GeneIDi79113.
    KEGGirno:79113.
    UCSCiRGD:621319. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X57018 mRNA. Translation: CAA40337.1 .
    CH473968 Genomic DNA. Translation: EDL80655.1 .
    CH473968 Genomic DNA. Translation: EDL80656.1 .
    CH473968 Genomic DNA. Translation: EDL80657.1 .
    BC062025 mRNA. Translation: AAH62025.1 .
    PIRi S24547.
    RefSeqi NP_077059.2. NM_024145.2.
    XP_006239141.1. XM_006239079.1.
    XP_006239142.1. XM_006239080.1.
    XP_006239143.1. XM_006239081.1.
    XP_006239144.1. XM_006239082.1.
    UniGenei Rn.11309.

    3D structure databases

    ProteinModelPortali Q6P6U0.
    SMRi Q6P6U0. Positions 67-515.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 249398. 2 interactions.
    IntActi Q6P6U0. 1 interaction.
    STRINGi 10116.ENSRNOP00000013779.

    Chemistry

    ChEMBLi CHEMBL4362.

    PTM databases

    PhosphoSitei Q6P6U0.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000013778 ; ENSRNOP00000013779 ; ENSRNOG00000009912 .
    GeneIDi 79113.
    KEGGi rno:79113.
    UCSCi RGD:621319. rat.

    Organism-specific databases

    CTDi 2268.
    RGDi 621319. Fgr.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00620000087702.
    HOGENOMi HOG000233858.
    HOVERGENi HBG008761.
    InParanoidi Q6P6U0.
    KOi K08891.
    OMAi TWNGSTK.
    OrthoDBi EOG7GTT2V.
    PhylomeDBi Q6P6U0.
    TreeFami TF351634.

    Enzyme and pathway databases

    Reactomei REACT_198646. FCGR activation.

    Miscellaneous databases

    NextBioi 614514.
    PROi Q6P6U0.

    Gene expression databases

    Genevestigatori Q6P6U0.

    Family and domain databases

    Gene3Di 3.30.505.10. 1 hit.
    InterProi IPR028459. FGR.
    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 ]
    PANTHERi PTHR24418:SF224. PTHR24418:SF224. 1 hit.
    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. "Nucleotide and deduced amino acid sequence of rat FGR."
      Yue C.C., Labash J.D., Jaye M.
      Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: Fischer 344.
      Tissue: Leukemia.
    2. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
      Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: Brown Norway.
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Prostate.
    4. "Regulation of c-Fgr protein kinase by c-Src kinase (CSK) and by polycationic effectors."
      Ruzzene M., James P., Brunati A.M., Donella-Deana A., Pinna L.A.
      J. Biol. Chem. 269:15885-15891(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: PARTIAL PROTEIN SEQUENCE, CATALYTIC ACTIVITY, PHOSPHORYLATION AT TYR-400 AND TYR-511, IDENTIFICATION BY MASS SPECTROMETRY, ENZYME REGULATION.
    5. "SH2 domains mediate the sequential phosphorylation of HS1 protein by p72syk and Src-related protein tyrosine kinases."
      Ruzzene M., Brunati A.M., Marin O., Donella-Deana A., Pinna L.A.
      Biochemistry 35:5327-5332(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF HCLS1.
    6. "Specific stimulation of c-Fgr kinase by tyrosine-phosphorylated (poly)peptides--possible implication in the sequential mode of protein phosphorylation."
      Ruzzene M., Brunati A.M., Donella-Deana A., Marin O., Pinna L.A.
      Eur. J. Biochem. 245:701-707(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF HCLS1, AUTOPHOSPHORYLATION, ENZYME REGULATION.
    7. "Molecular features underlying the sequential phosphorylation of HS1 protein and its association with c-Fgr protein-tyrosine kinase."
      Brunati A.M., Donella-Deana A., James P., Quadroni M., Contri A., Marin O., Pinna L.A.
      J. Biol. Chem. 274:7557-7564(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, FUNCTION IN PHOSPHORYLATION OF HCLS1, INTERACTION WITH HCLS1, AUTOPHOSPHORYLATION.
    8. "Activation of RBL-2H3 mast cells is dependent on tyrosine phosphorylation of phospholipase D2 by Fyn and Fgr."
      Choi W.S., Hiragun T., Lee J.H., Kim Y.M., Kim H.P., Chahdi A., Her E., Han J.W., Beaven M.A.
      Mol. Cell. Biol. 24:6980-6992(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF PLD2 AND MAST CELL ACTIVATION, INTERACTION WITH PLD2.
    9. "Src-Tyrosine kinases are major agents in mitochondrial tyrosine phosphorylation."
      Tibaldi E., Brunati A.M., Massimino M.L., Stringaro A., Colone M., Agostinelli E., Arancia G., Toninello A.
      J. Cell. Biochem. 104:840-849(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    10. "The Src family kinase Fgr is critical for activation of mast cells and IgE-mediated anaphylaxis in mice."
      Lee J.H., Kim J.W., Kim do K., Kim H.S., Park H.J., Park D.K., Kim A.R., Kim B., Beaven M.A., Park K.L., Kim Y.M., Choi W.S.
      J. Immunol. 187:1807-1815(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN MAST CELL DEGRANULATION AND PHOSPHORYLATION OF SYK, INTERACTION WITH MS4A2/FCER1B, SUBCELLULAR LOCATION ON PLASMA MEMBRANE LIPID RAFTS.

    Entry informationi

    Entry nameiFGR_RAT
    AccessioniPrimary (citable) accession number: Q6P6U0
    Secondary accession number(s): Q63206
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 19, 2011
    Last sequence update: July 5, 2004
    Last modified: October 1, 2014
    This is version 93 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, Direct protein sequencing, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3