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Protein

Tyrosine-protein kinase Fgr

Gene

FGR

Organism
Homo sapiens (Human)
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, FCGR2A and/or FCGR2B. 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. Phosphorylates HCLS1 that has already been phosphorylated by SYK, but not unphosphorylated HCLS1.4 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation3 Publications

Enzyme regulationi

Activated by autophosphorylation. Prior phosphorylation at Tyr-523 by SRC inhibits ulterior autophosphorylation at Tyr-412. 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.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei291ATPPROSITE-ProRule annotation1
Active sitei382Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi269 – 277ATPPROSITE-ProRule annotation9

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-2029481 FCGR activation
R-HSA-432142 Platelet sensitization by LDL
R-HSA-6798695 Neutrophil degranulation
SignaLinkiP09769
SIGNORiP09769

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase Fgr (EC:2.7.10.2)
Alternative name(s):
Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog
Proto-oncogene c-Fgr
p55-Fgr
p58-Fgr
p58c-Fgr
Gene namesi
Name:FGR
Synonyms:SRC2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000000938.12
HGNCiHGNC:3697 FGR
MIMi164940 gene
neXtProtiNX_P09769

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

Involvement in diseasei

Mutations that cause aberrant kinase activation can confer oncogene activity and promote aberrant cell proliferation.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi523Y → F: Strongly increased catalytic activity. Functions as oncogene. 1 Publication1

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi2268
OpenTargetsiENSG00000000938
PharmGKBiPA28135

Chemistry databases

ChEMBLiCHEMBL4454
GuidetoPHARMACOLOGYi2024

Polymorphism and mutation databases

BioMutaiFGR
DMDMi125358

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved
ChainiPRO_00000880912 – 529Tyrosine-protein kinase FgrAdd BLAST528

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineBy similarity1
Lipidationi3S-palmitoyl cysteineBy similarity1
Lipidationi6S-palmitoyl cysteineBy similarity1
Modified residuei34PhosphotyrosineCombined sources1
Modified residuei208PhosphotyrosineBy similarity1
Modified residuei218PhosphoserineBy similarity1
Modified residuei412PhosphotyrosineCombined sources1
Modified residuei523Phosphotyrosine; by SRCCombined sources1

Post-translational modificationi

Ubiquitinated. Becomes ubiquitinated in response to ITGB2 signaling; this does not lead to degradation.1 Publication
Phosphorylated. Autophosphorylated on tyrosine residues. Becomes phosphorylated in response to FCGR2A and/or FCGR2B engagement, cell adhesion and signaling by ITGB2. Prior phosphorylation at Tyr-523 by SRC inhibits ulterior autophosphorylation at Tyr-412.2 Publications

Keywords - PTMi

Lipoprotein, Myristate, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP09769
MaxQBiP09769
PaxDbiP09769
PeptideAtlasiP09769
PRIDEiP09769

PTM databases

iPTMnetiP09769
PhosphoSitePlusiP09769
SwissPalmiP09769

Expressioni

Tissue specificityi

Detected in neutrophils, monocytes and natural killer cells (at protein level). Detected in monocytes and large lymphocytes.3 Publications

Gene expression databases

BgeeiENSG00000000938
CleanExiHS_FGR
ExpressionAtlasiP09769 baseline and differential
GenevisibleiP09769 HS

Organism-specific databases

HPAiHPA002024

Interactioni

Subunit structurei

Interacts with ITGB1, ITGB2, MS4A2/FCER1B, FCER1G, FCGR2A and/or FCGR2B. 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. Interacts with PIK3R1 and FASLG (By similarity).By similarity

Binary interactionsi

Show more details

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi108559, 24 interactors
DIPiDIP-1049N
ELMiP09769
IntActiP09769, 14 interactors
MINTiP09769
STRINGi9606.ENSP00000363115

Chemistry databases

BindingDBiP09769

Structurei

3D structure databases

ProteinModelPortaliP09769
SMRiP09769
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini77 – 138SH3PROSITE-ProRule annotationAdd BLAST62
Domaini144 – 241SH2PROSITE-ProRule annotationAdd BLAST98
Domaini263 – 516Protein 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
InParanoidiP09769
KOiK08891
OMAiQTWRLDP
OrthoDBiEOG091G0D46
PhylomeDBiP09769
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.

P09769-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGCVFCKKLE PVATAKEDAG LEGDFRSYGA ADHYGPDPTK ARPASSFAHI
60 70 80 90 100
PNYSNFSSQA INPGFLDSGT IRGVSGIGVT LFIALYDYEA RTEDDLTFTK
110 120 130 140 150
GEKFHILNNT EGDWWEARSL SSGKTGCIPS NYVAPVDSIQ AEEWYFGKIG
160 170 180 190 200
RKDAERQLLS PGNPQGAFLI RESETTKGAY SLSIRDWDQT RGDHVKHYKI
210 220 230 240 250
RKLDMGGYYI TTRVQFNSVQ ELVQHYMEVN DGLCNLLIAP CTIMKPQTLG
260 270 280 290 300
LAKDAWEISR SSITLERRLG TGCFGDVWLG TWNGSTKVAV KTLKPGTMSP
310 320 330 340 350
KAFLEEAQVM KLLRHDKLVQ LYAVVSEEPI YIVTEFMCHG SLLDFLKNPE
360 370 380 390 400
GQDLRLPQLV DMAAQVAEGM AYMERMNYIH RDLRAANILV GERLACKIAD
410 420 430 440 450
FGLARLIKDD EYNPCQGSKF PIKWTAPEAA LFGRFTIKSD VWSFGILLTE
460 470 480 490 500
LITKGRIPYP GMNKREVLEQ VEQGYHMPCP PGCPASLYEA MEQTWRLDPE
510 520
ERPTFEYLQS FLEDYFTSAE PQYQPGDQT
Length:529
Mass (Da):59,479
Last modified:January 1, 1990 - v2
Checksum:i6B8C1E08414E0F9C
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041700110T → I1 PublicationCorresponds to variant dbSNP:rs34597831Ensembl.1
Natural variantiVAR_041701130S → R1 PublicationCorresponds to variant dbSNP:rs35334091Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M19722 mRNA Translation: AAA52451.1
AL031729 Genomic DNA No translation available.
CH471059 Genomic DNA Translation: EAX07748.1
CH471059 Genomic DNA Translation: EAX07749.1
CH471059 Genomic DNA Translation: EAX07750.1
BC064382 mRNA Translation: AAH64382.1
X52207, X52208 Genomic DNA Translation: CAA36457.2
M12724
, M12719, M12720, M12721, M12722, M12723 Genomic DNA Translation: AAA52762.1
CCDSiCCDS305.1
PIRiA27676 TVHUFR
RefSeqiNP_001036194.1, NM_001042729.1
NP_001036212.1, NM_001042747.1
NP_005239.1, NM_005248.2
XP_006710515.1, XM_006710452.2
XP_011539312.1, XM_011541010.1
UniGeneiHs.1422

Genome annotation databases

EnsembliENST00000374003; ENSP00000363115; ENSG00000000938
ENST00000374004; ENSP00000363116; ENSG00000000938
ENST00000374005; ENSP00000363117; ENSG00000000938
ENST00000399173; ENSP00000382126; ENSG00000000938
GeneIDi2268
KEGGihsa:2268
UCSCiuc001boj.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiFGR_HUMAN
AccessioniPrimary (citable) accession number: P09769
Secondary accession number(s): D3DPL7, Q9UIQ3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: January 1, 1990
Last modified: March 28, 2018
This is version 199 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health