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Protein

Tyrosine-protein kinase Fgr

Gene

Fgr

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

Activity 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

GO - Biological processi

Keywordsi

Molecular functionKinase, Transferase, Tyrosine-protein kinase
Biological processImmunity, Innate immunity
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2 3474
ReactomeiR-MMU-2029481 FCGR activation
R-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:95527 Fgr

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 Expressed in 73 organ(s), highest expression level in blood
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

Protein-protein interaction databases

BioGridi199663, 2 interactors
CORUMiP14234
IntActiP14234, 3 interactors
MINTiP14234
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

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG0197 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000118938
HOGENOMiHOG000233858
HOVERGENiHBG008761
InParanoidiP14234
KOiK08891
OMAiQTWRLDP
OrthoDBiEOG091G0D46
TreeFamiTF351634

Family and domain databases

CDDicd10367 SH2_Src_Fgr, 1 hit
Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR035693 Fgr_SH2
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 1 hit
PF00017 SH2, 1 hit
PF00018 SH3_1, 1 hit
PRINTSiPR00401 SH2DOMAIN
PR00452 SH3DOMAIN
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00252 SH2, 1 hit
SM00326 SH3, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF50044 SSF50044, 1 hit
SSF55550 SSF55550, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
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

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

Similar proteinsi

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, 2 interactors
CORUMiP14234
IntActiP14234, 3 interactors
MINTiP14234
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
OMAiQTWRLDP
OrthoDBiEOG091G0D46
TreeFamiTF351634

Enzyme and pathway databases

BRENDAi2.7.10.2 3474
ReactomeiR-MMU-2029481 FCGR activation
R-MMU-432142 Platelet sensitization by LDL
R-MMU-6798695 Neutrophil degranulation

Miscellaneous databases

PROiPR:P14234
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000028874 Expressed in 73 organ(s), highest expression level in blood
GenevisibleiP14234 MM

Family and domain databases

CDDicd10367 SH2_Src_Fgr, 1 hit
Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR035693 Fgr_SH2
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 1 hit
PF00017 SH2, 1 hit
PF00018 SH3_1, 1 hit
PRINTSiPR00401 SH2DOMAIN
PR00452 SH3DOMAIN
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00252 SH2, 1 hit
SM00326 SH3, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF50044 SSF50044, 1 hit
SSF55550 SSF55550, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
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
ProtoNetiSearch...

Entry informationi

Entry nameiFGR_MOUSE
AccessioniPrimary (citable) accession number: P14234
Secondary accession number(s): Q61404, Q8BGM0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: July 27, 2011
Last modified: September 12, 2018
This is version 179 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  2. SIMILARITY comments
    Index of protein domains and families
  3. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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