Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Tyrosine-protein kinase Fgr

Gene

FGR

Organism
Homo sapiens (Human)
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, 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 binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • protein tyrosine kinase activity Source: UniProtKB

GO - Biological processi

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

BioCyciZFISH:HS00068-MONOMER.
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

HGNCiHGNC:3697. FGR.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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

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

WithEntry#Exp.IntActNotes
ALOX5P099172EBI-1383732,EBI-79934
ARP102753EBI-1383732,EBI-608057
EGFRP005332EBI-1383732,EBI-297353
ERBB2P046263EBI-1383732,EBI-641062
HSP90AB1P082382EBI-1383732,EBI-352572
KITP107212EBI-1383732,EBI-1379503
METP085812EBI-1383732,EBI-1039152

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108559. 23 interactors.
DIPiDIP-1049N.
IntActiP09769. 13 interactors.
MINTiMINT-1209880.
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
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.
InParanoidiP09769.
KOiK08891.
OMAiTWNGSTK.
OrthoDBiEOG091G0D46.
PhylomeDBiP09769.
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.

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 → I.1 PublicationCorresponds to variant rs34597831dbSNPEnsembl.1
Natural variantiVAR_041701130S → R.1 PublicationCorresponds to variant rs35334091dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M19722 mRNA. Translation: AAA52451.1.
AL031729 Genomic DNA. Translation: CAB62998.1.
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

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M19722 mRNA. Translation: AAA52451.1.
AL031729 Genomic DNA. Translation: CAB62998.1.
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.

3D structure databases

ProteinModelPortaliP09769.
SMRiP09769.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108559. 23 interactors.
DIPiDIP-1049N.
IntActiP09769. 13 interactors.
MINTiMINT-1209880.
STRINGi9606.ENSP00000363115.

Chemistry databases

BindingDBiP09769.
ChEMBLiCHEMBL4454.
GuidetoPHARMACOLOGYi2024.

PTM databases

iPTMnetiP09769.
PhosphoSitePlusiP09769.
SwissPalmiP09769.

Polymorphism and mutation databases

BioMutaiFGR.
DMDMi125358.

Proteomic databases

MaxQBiP09769.
PaxDbiP09769.
PeptideAtlasiP09769.
PRIDEiP09769.

Protocols and materials databases

DNASUi2268.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi2268.
DisGeNETi2268.
GeneCardsiFGR.
HGNCiHGNC:3697. FGR.
HPAiHPA002024.
MIMi164940. gene.
neXtProtiNX_P09769.
OpenTargetsiENSG00000000938.
PharmGKBiPA28135.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118938.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiP09769.
KOiK08891.
OMAiTWNGSTK.
OrthoDBiEOG091G0D46.
PhylomeDBiP09769.
TreeFamiTF351634.

Enzyme and pathway databases

BioCyciZFISH:HS00068-MONOMER.
ReactomeiR-HSA-2029481. FCGR activation.
R-HSA-432142. Platelet sensitization by LDL.
R-HSA-6798695. Neutrophil degranulation.
SignaLinkiP09769.
SIGNORiP09769.

Miscellaneous databases

ChiTaRSiFGR. human.
GeneWikiiFGR_(gene).
GenomeRNAii2268.
PROiP09769.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000000938.
CleanExiHS_FGR.
ExpressionAtlasiP09769. baseline and differential.
GenevisibleiP09769. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: P09769
Secondary accession number(s): D3DPL7, Q9UIQ3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: January 1, 1990
Last modified: November 30, 2016
This is version 187 of the entry and version 2 of the sequence. [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

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. 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.