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Q6P6U0 (FGR_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 89. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tyrosine-protein kinase Fgr

EC=2.7.10.2
Alternative name(s):
Proto-oncogene c-Fgr
p55-Fgr
Gene names
Name:Fgr
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length517 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.5 Ref.6 Ref.7 Ref.8 Ref.10

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.4 Ref.7

Enzyme regulation

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. Ref.4 Ref.6

Subunit structure

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. Ref.7 Ref.8 Ref.10

Subcellular location

Cell membrane; Lipid-anchor; Cytoplasmic side Probable. 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. Ref.9 Ref.10

Tissue specificity

Detected in brain cortex (at protein level). Ref.9

Post-translational modification

Ubiquitinated. Becomes ubiquitinated in response to ITGB2 signaling; this does not lead to degradation 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. Ref.4 Ref.6 Ref.7

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.

Contains 1 protein kinase domain.

Contains 1 SH2 domain.

Contains 1 SH3 domain.

Ontologies

Keywords
   Biological processImmunity
Innate immunity
   Cellular componentCell membrane
Cell projection
Cytoplasm
Cytoskeleton
Membrane
Mitochondrion
Mitochondrion inner membrane
   DiseaseProto-oncogene
   DomainSH3 domain
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
Tyrosine-protein kinase
   PTMLipoprotein
Myristate
Palmitate
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processdefense response to Gram-positive bacterium

Inferred from sequence or structural similarity. Source: UniProtKB

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

integrin-mediated signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

peptidyl-tyrosine phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cytokine secretion

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of mast cell degranulation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of phosphatidylinositol 3-kinase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of phosphatidylinositol 3-kinase signaling

Inferred from electronic annotation. Source: Ensembl

protein autophosphorylation

Inferred from electronic annotation. Source: Ensembl

regulation of cell shape

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of innate immune response

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of phagocytosis

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of protein kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentactin cytoskeleton

Inferred from electronic annotation. Source: Ensembl

cytosol

Inferred from direct assay PubMed 9116282. Source: RGD

mitochondrial inner membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrial intermembrane space

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from direct assay PubMed 9116282. Source: RGD

ruffle membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

immunoglobulin receptor binding

Inferred from sequence or structural similarity. Source: UniProtKB

non-membrane spanning protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

phosphotyrosine binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein kinase binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein tyrosine kinase activity

Inferred from direct assay Ref.8. Source: RGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 517516Tyrosine-protein kinase Fgr
PRO_0000413581

Regions

Domain65 – 12662SH3
Domain132 – 22998SH2
Domain251 – 504254Protein kinase
Nucleotide binding257 – 2659ATP By similarity

Sites

Active site3701Proton acceptor By similarity
Binding site2791ATP By similarity

Amino acid modifications

Modified residue321Phosphotyrosine By similarity
Modified residue4001Phosphotyrosine; by autocatalysis Ref.4
Modified residue5111Phosphotyrosine; by SRC Ref.4
Lipidation21N-myristoyl glycine By similarity
Lipidation31S-palmitoyl cysteine By similarity
Lipidation61S-palmitoyl cysteine By similarity

Experimental info

Sequence conflict3131V → A in CAA40337. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q6P6U0 [UniParc].

Last modified July 5, 2004. Version 1.
Checksum: 0D960BBBCAF2911B

FASTA51758,821
        10         20         30         40         50         60 
MGCVFCKKLE PAPKEDVGLE GDFRSQGAEE RYYPDPTQGR SSSISPQPIS PAFLNVGNIR 

        70         80         90        100        110        120 
SVSGTGVTIF VALYDYEART GDDLTFTKGE KFHILNNTEY DWWEARSLSS GRTGYVPSNY 

       130        140        150        160        170        180 
VAPVDSIQAE EWYFGKISRK DAERQLLSDG NPQGAFLIRE SETTKGAYSL SIRDWDQNRG 

       190        200        210        220        230        240 
DHIKHYKIRK LDMGGYYITT RAQFESVQDL VRHYMEVNDG LCYLLTAPCM VMKPQTLGLA 

       250        260        270        280        290        300 
KDAWEIDRNS IALDRRLGTG CFGDVWLGTW NCSTKVAVKT LKPGTMSPKA FLEEAQIMKL 

       310        320        330        340        350        360 
LRHDKLVQLY AVVSEEPIYI VTEFMCYGSL LDFLKDRKGH NLMLPNLVDM AAQVAEGMAY 

       370        380        390        400        410        420 
MERMNYIHRD LRAANILVGE HLICKIADFG LARLIVDDEY NPQQGTKFPI KWTAPEAALF 

       430        440        450        460        470        480 
GRFTVKSDVW SFGILLTELI TKGRVPYPGM NNREVLEQVE HGYHMPCPPG CPVSLYEVME 

       490        500        510 
QTWRLDPEER PTFEYLQSFL EDYFTSTEPQ YQPGDQT 

« Hide

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRS24547.
RefSeqNP_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.
UniGeneRn.11309.

3D structure databases

ProteinModelPortalQ6P6U0.
SMRQ6P6U0. Positions 67-515.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid249398. 2 interactions.
IntActQ6P6U0. 1 interaction.
STRING10116.ENSRNOP00000013779.

Chemistry

ChEMBLCHEMBL4362.

PTM databases

PhosphoSiteQ6P6U0.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000013778; ENSRNOP00000013779; ENSRNOG00000009912.
GeneID79113.
KEGGrno:79113.
UCSCRGD:621319. rat.

Organism-specific databases

CTD2268.
RGD621319. Fgr.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00620000087702.
HOGENOMHOG000233858.
HOVERGENHBG008761.
InParanoidQ6P6U0.
KOK08891.
OMATWNGSTK.
OrthoDBEOG7GTT2V.
PhylomeDBQ6P6U0.
TreeFamTF351634.

Gene expression databases

GenevestigatorQ6P6U0.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR028459. 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]
PANTHERPTHR24418:SF45. PTHR24418:SF45. 1 hit.
PfamPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS00107. 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]
ProtoNetSearch...

Other

NextBio614514.
PROQ6P6U0.

Entry information

Entry nameFGR_RAT
AccessionPrimary (citable) accession number: Q6P6U0
Secondary accession number(s): Q63206
Entry history
Integrated into UniProtKB/Swiss-Prot: October 19, 2011
Last sequence update: July 5, 2004
Last modified: April 16, 2014
This is version 89 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families