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Protein

Tyrosine-protein kinase Fgr

Gene

Fgr

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 (PubMed:11672534). Required for normal ITGB1 and ITGB2 signaling, normal cell spreading and adhesion in neutrophils and macrophages (PubMed:8666673 and PubMed:9687507). Functions as positive regulator of cell migration and regulates cytoskeleton reorganization via RAC1 activation (PubMed:15561106). Phosphorylates SYK (in vitro) and promotes SYK-dependent activation of AKT1 and MAP kinase signaling (PubMed:21746961). 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. Phosphorylates HCLS1 that has already been phosphorylated by SYK, but not unphosphorylated HCLS1.8 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation1 Publication

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei279ATPPROSITE-ProRule annotation1
Active sitei370Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi257 – 265ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • Fc-gamma receptor I complex binding Source: MGI
  • immunoglobulin receptor binding Source: UniProtKB
  • non-membrane spanning protein tyrosine kinase activity Source: UniProtKB
  • phosphotyrosine binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • protein tyrosine kinase activity Source: MGI

GO - Biological processi

  • cell differentiation Source: GO_Central
  • defense response to Gram-positive bacterium Source: UniProtKB
  • innate immune response Source: UniProtKB-KW
  • integrin-mediated signaling pathway Source: UniProtKB
  • peptidyl-tyrosine autophosphorylation Source: GO_Central
  • peptidyl-tyrosine phosphorylation Source: UniProtKB
  • positive regulation of cell migration Source: UniProtKB
  • positive regulation of cytokine secretion Source: UniProtKB
  • positive regulation of mast cell degranulation Source: UniProtKB
  • positive regulation of phosphatidylinositol 3-kinase activity Source: MGI
  • positive regulation of phosphatidylinositol 3-kinase signaling Source: MGI
  • protein autophosphorylation Source: MGI
  • regulation of actin cytoskeleton organization Source: UniProtKB
  • regulation of cell proliferation Source: GO_Central
  • regulation of cell shape Source: UniProtKB
  • regulation of innate immune response Source: UniProtKB
  • regulation of phagocytosis Source: UniProtKB
  • regulation of protein kinase activity Source: UniProtKB
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Immunity, Innate immunity

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2. 3474.
ReactomeiR-MMU-432142. Platelet sensitization by LDL.
R-MMU-6798695. Neutrophil degranulation.

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:95527. Fgr.

Subcellular locationi

  • Cell membrane 1 Publication; Lipid-anchor 1 Publication; Cytoplasmic side 1 Publication
  • Cell membrane 1 Publication; Peripheral membrane protein 1 Publication; Cytoplasmic side 1 Publication
  • Cell projectionruffle membrane 1 Publication
  • Cytoplasmcytosol 1 Publication
  • Cytoplasmcytoskeleton 1 Publication
  • Mitochondrion inner membrane By similarity
  • Mitochondrion intermembrane space By similarity

  • Note: Detected in mitochondrial intermembrane space and at inner membranes (By similarity). Colocalizes with actin fibers at membrane ruffles. Detected at plasma membrane lipid rafts.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Disruption phenotypei

No visible phenotype. Mice lacking both Fgr and Hck are normal and fertile, but show increased susceptibility to infection with Listeria monocytogenes. In addition, their polymorphonuclear leukocytes show defects in cell spreading and adhesion.2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1 – 7Missing : Abolishes localization at the cell membrane. 1 Publication7
Mutagenesisi279K → R: Loss of kinase activity. 1 Publication1

Keywords - Diseasei

Proto-oncogene

Chemistry databases

ChEMBLiCHEMBL2034795.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCurated
ChainiPRO_00000880922 – 517Tyrosine-protein kinase FgrAdd BLAST516

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine1 Publication1
Lipidationi3S-palmitoyl cysteine1 Publication1
Lipidationi6S-palmitoyl cysteine1 Publication1
Modified residuei13PhosphoserineCombined sources1
Modified residuei32PhosphotyrosineBy similarity1
Modified residuei50PhosphoserineBy similarity1
Modified residuei196PhosphotyrosineCombined sources1
Modified residuei206PhosphoserineCombined sources1
Modified residuei400PhosphotyrosineCombined sources1
Modified residuei511Phosphotyrosine; by SRCBy similarity1

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. Prior phosphorylation at Tyr-511 by SRC inhibits ulterior autophosphorylation at Tyr-400 (By similarity).By similarity

Keywords - PTMi

Lipoprotein, Myristate, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP14234.
PaxDbiP14234.
PeptideAtlasiP14234.
PRIDEiP14234.

PTM databases

iPTMnetiP14234.
PhosphoSitePlusiP14234.
SwissPalmiP14234.

Expressioni

Gene expression databases

BgeeiENSMUSG00000028874.
GenevisibleiP14234. MM.

Interactioni

Subunit structurei

Interacts with ITGB1, ITGB2, MS4A2/FCER1B, FCER1G 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

Binary interactionsi

WithEntry#Exp.IntActNotes
ClnkQ9QZE23EBI-7587024,EBI-8040679

GO - Molecular functioni

  • Fc-gamma receptor I complex binding Source: MGI
  • immunoglobulin receptor binding Source: UniProtKB
  • phosphotyrosine binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi199663. 1 interactor.
IntActiP14234. 3 interactors.
MINTiMINT-85500.
STRINGi10090.ENSMUSP00000030693.

Chemistry databases

BindingDBiP14234.

Structurei

3D structure databases

ProteinModelPortaliP14234.
SMRiP14234.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini65 – 126SH3PROSITE-ProRule annotationAdd BLAST62
Domaini132 – 229SH2PROSITE-ProRule annotationAdd BLAST98
Domaini251 – 504Protein kinasePROSITE-ProRule annotationAdd BLAST254

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

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118938.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiP14234.
KOiK08891.
OMAiTWNGSTK.
OrthoDBiEOG091G0D46.
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.

P14234-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGCVFCKKLE PASKEDVGLE GDFRSQTAEE RYFPDPTQGR TSSVFPQPTS
60 70 80 90 100
PAFLNTGNMR SISGTGVTIF VALYDYEART GDDLTFTKGE KFHILNNTEY
110 120 130 140 150
DWWEARSLSS GHRGYVPSNY VAPVDSIQAE EWYFGKISRK DAERQLLSSG
160 170 180 190 200
NPQGAFLIRE SETTKGAYSL SIRDWDQNRG DHIKHYKIRK LDTGGYYITT
210 220 230 240 250
RAQFDSIQDL VRHYMEVNDG LCYLLTAPCT TTKPQTLGLA KDAWEIDRNS
260 270 280 290 300
IALERRLGTG CFGDVWLGTW NCSTKVAVKT LKPGTMSPKA FLEEAQIMKL
310 320 330 340 350
LRHDKLVQLY AVVSEEPIYI VTEFMCYGSL LDFLKDREGQ NLMLPHLVDM
360 370 380 390 400
AAQVAEGMAY MERMNYIHRD LRAANILVGE YLICKIADFG LARLIEDNEY
410 420 430 440 450
NPQQGTKFPI KWTAPEAALF GRFTVKSDVW SFGILLTELI TKGRVPYPGM
460 470 480 490 500
NNREVLEQVE HGYHMPCPPG CPASLYEVME QAWRLDPEER PTFEYLQSFL
510
EDYFTSTEPQ YQPGDQT
Length:517
Mass (Da):58,867
Last modified:July 27, 2011 - v2
Checksum:i87DF5B19BF3F4734
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti33F → Y in CAA34463 (PubMed:2674853).Curated1
Sequence conflicti33F → Y in CAA36437 (PubMed:2179817).Curated1
Sequence conflicti41T → N in CAA34463 (PubMed:2674853).Curated1
Sequence conflicti212R → Q in CAA34463 (PubMed:2674853).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X16440 mRNA. Translation: CAA34463.1.
X52191 mRNA. Translation: CAA36437.1.
AK036438 mRNA. Translation: BAC29429.1.
AK036476 mRNA. Translation: BAC29445.1.
AK038141 mRNA. Translation: BAC29939.1.
AK155902 mRNA. Translation: BAE33493.1.
AL627184 Genomic DNA. Translation: CAM14378.1.
CH466552 Genomic DNA. Translation: EDL30081.1.
CH466552 Genomic DNA. Translation: EDL30082.1.
CCDSiCCDS18739.1.
PIRiA43807.
RefSeqiNP_034338.3. NM_010208.4.
XP_006538607.1. XM_006538544.3.
XP_006538608.1. XM_006538545.3.
UniGeneiMm.271665.

Genome annotation databases

EnsembliENSMUST00000030693; ENSMUSP00000030693; ENSMUSG00000028874.
ENSMUST00000171223; ENSMUSP00000128411; ENSMUSG00000028874.
GeneIDi14191.
KEGGimmu:14191.
UCSCiuc012dmj.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X16440 mRNA. Translation: CAA34463.1.
X52191 mRNA. Translation: CAA36437.1.
AK036438 mRNA. Translation: BAC29429.1.
AK036476 mRNA. Translation: BAC29445.1.
AK038141 mRNA. Translation: BAC29939.1.
AK155902 mRNA. Translation: BAE33493.1.
AL627184 Genomic DNA. Translation: CAM14378.1.
CH466552 Genomic DNA. Translation: EDL30081.1.
CH466552 Genomic DNA. Translation: EDL30082.1.
CCDSiCCDS18739.1.
PIRiA43807.
RefSeqiNP_034338.3. NM_010208.4.
XP_006538607.1. XM_006538544.3.
XP_006538608.1. XM_006538545.3.
UniGeneiMm.271665.

3D structure databases

ProteinModelPortaliP14234.
SMRiP14234.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199663. 1 interactor.
IntActiP14234. 3 interactors.
MINTiMINT-85500.
STRINGi10090.ENSMUSP00000030693.

Chemistry databases

BindingDBiP14234.
ChEMBLiCHEMBL2034795.

PTM databases

iPTMnetiP14234.
PhosphoSitePlusiP14234.
SwissPalmiP14234.

Proteomic databases

MaxQBiP14234.
PaxDbiP14234.
PeptideAtlasiP14234.
PRIDEiP14234.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000030693; ENSMUSP00000030693; ENSMUSG00000028874.
ENSMUST00000171223; ENSMUSP00000128411; ENSMUSG00000028874.
GeneIDi14191.
KEGGimmu:14191.
UCSCiuc012dmj.1. mouse.

Organism-specific databases

CTDi2268.
MGIiMGI:95527. Fgr.

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118938.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiP14234.
KOiK08891.
OMAiTWNGSTK.
OrthoDBiEOG091G0D46.
TreeFamiTF351634.

Enzyme and pathway databases

BRENDAi2.7.10.2. 3474.
ReactomeiR-MMU-432142. Platelet sensitization by LDL.
R-MMU-6798695. Neutrophil degranulation.

Miscellaneous databases

PROiP14234.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000028874.
GenevisibleiP14234. MM.

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]
ProtoNetiSearch...

Entry informationi

Entry nameiFGR_MOUSE
AccessioniPrimary (citable) accession number: P14234
Secondary accession number(s): Q61404, Q8BGM0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: July 27, 2011
Last modified: November 30, 2016
This is version 166 of the entry and version 2 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.