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Protein

Tyrosine-protein kinase Fgr

Gene

Fgr

Organism
Rattus norvegicus (Rat)
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. 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.By similarity5 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation2 Publications

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.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei279 – 2791ATPPROSITE-ProRule annotation
Active sitei370 – 3701Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi257 – 2659ATPPROSITE-ProRule annotation

GO - Molecular functioni

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

ReactomeiR-RNO-2029481. FCGR activation.
R-RNO-432142. Platelet sensitization by LDL.

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 5

Organism-specific databases

RGDi621319. 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

Keywords - Diseasei

Proto-oncogene

Chemistry

ChEMBLiCHEMBL4362.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved
Chaini2 – 517516Tyrosine-protein kinase FgrPRO_0000413581Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycineBy similarity
Lipidationi3 – 31S-palmitoyl cysteineBy similarity
Lipidationi6 – 61S-palmitoyl cysteineBy similarity
Modified residuei32 – 321PhosphotyrosineBy similarity
Modified residuei50 – 501PhosphoserineCombined sources
Modified residuei196 – 1961PhosphotyrosineBy similarity
Modified residuei206 – 2061PhosphoserineBy similarity
Modified residuei400 – 4001Phosphotyrosine; by autocatalysis1 Publication
Modified residuei511 – 5111Phosphotyrosine; by SRC1 Publication

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 (By similarity). Prior phosphorylation at Tyr-511 by SRC inhibits ulterior autophosphorylation at Tyr-400.By similarity1 Publication

Keywords - PTMi

Lipoprotein, Myristate, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ6P6U0.

PTM databases

iPTMnetiQ6P6U0.
PhosphoSiteiQ6P6U0.

Expressioni

Tissue specificityi

Detected in brain cortex (at protein level).1 Publication

Gene expression databases

BgeeiENSRNOG00000009912.
GenevisibleiQ6P6U0. RN.

Interactioni

Subunit structurei

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).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi249398. 2 interactions.
IntActiQ6P6U0. 1 interaction.
STRINGi10116.ENSRNOP00000013779.

Chemistry

BindingDBiQ6P6U0.

Structurei

3D structure databases

ProteinModelPortaliQ6P6U0.
SMRiQ6P6U0. Positions 67-515.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini65 – 12662SH3PROSITE-ProRule annotationAdd
BLAST
Domaini132 – 22998SH2PROSITE-ProRule annotationAdd
BLAST
Domaini251 – 504254Protein kinasePROSITE-ProRule annotationAdd
BLAST

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

SH3 domain

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118938.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiQ6P6U0.
KOiK08891.
OMAiTWNGSTK.
PhylomeDBiQ6P6U0.
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.

Q6P6U0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGCVFCKKLE PAPKEDVGLE GDFRSQGAEE RYYPDPTQGR SSSISPQPIS
60 70 80 90 100
PAFLNVGNIR SVSGTGVTIF VALYDYEART GDDLTFTKGE KFHILNNTEY
110 120 130 140 150
DWWEARSLSS GRTGYVPSNY VAPVDSIQAE EWYFGKISRK DAERQLLSDG
160 170 180 190 200
NPQGAFLIRE SETTKGAYSL SIRDWDQNRG DHIKHYKIRK LDMGGYYITT
210 220 230 240 250
RAQFESVQDL VRHYMEVNDG LCYLLTAPCM VMKPQTLGLA KDAWEIDRNS
260 270 280 290 300
IALDRRLGTG CFGDVWLGTW NCSTKVAVKT LKPGTMSPKA FLEEAQIMKL
310 320 330 340 350
LRHDKLVQLY AVVSEEPIYI VTEFMCYGSL LDFLKDRKGH NLMLPNLVDM
360 370 380 390 400
AAQVAEGMAY MERMNYIHRD LRAANILVGE HLICKIADFG LARLIVDDEY
410 420 430 440 450
NPQQGTKFPI KWTAPEAALF GRFTVKSDVW SFGILLTELI TKGRVPYPGM
460 470 480 490 500
NNREVLEQVE HGYHMPCPPG CPVSLYEVME QTWRLDPEER PTFEYLQSFL
510
EDYFTSTEPQ YQPGDQT
Length:517
Mass (Da):58,821
Last modified:July 5, 2004 - v1
Checksum:i0D960BBBCAF2911B
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti313 – 3131V → A in CAA40337 (Ref. 1) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
PIRiS24547.
RefSeqiNP_077059.2. NM_024145.2.
XP_006239141.1. XM_006239079.2.
XP_006239142.1. XM_006239080.2.
XP_006239143.1. XM_006239081.2.
XP_006239144.1. XM_006239082.2.
UniGeneiRn.11309.

Genome annotation databases

EnsembliENSRNOT00000013778; ENSRNOP00000013779; ENSRNOG00000009912.
ENSRNOT00000085674; ENSRNOP00000075272; ENSRNOG00000009912.
GeneIDi79113.
KEGGirno:79113.
UCSCiRGD:621319. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
PIRiS24547.
RefSeqiNP_077059.2. NM_024145.2.
XP_006239141.1. XM_006239079.2.
XP_006239142.1. XM_006239080.2.
XP_006239143.1. XM_006239081.2.
XP_006239144.1. XM_006239082.2.
UniGeneiRn.11309.

3D structure databases

ProteinModelPortaliQ6P6U0.
SMRiQ6P6U0. Positions 67-515.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249398. 2 interactions.
IntActiQ6P6U0. 1 interaction.
STRINGi10116.ENSRNOP00000013779.

Chemistry

BindingDBiQ6P6U0.
ChEMBLiCHEMBL4362.

PTM databases

iPTMnetiQ6P6U0.
PhosphoSiteiQ6P6U0.

Proteomic databases

PaxDbiQ6P6U0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000013778; ENSRNOP00000013779; ENSRNOG00000009912.
ENSRNOT00000085674; ENSRNOP00000075272; ENSRNOG00000009912.
GeneIDi79113.
KEGGirno:79113.
UCSCiRGD:621319. rat.

Organism-specific databases

CTDi2268.
RGDi621319. Fgr.

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118938.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiQ6P6U0.
KOiK08891.
OMAiTWNGSTK.
PhylomeDBiQ6P6U0.
TreeFamiTF351634.

Enzyme and pathway databases

ReactomeiR-RNO-2029481. FCGR activation.
R-RNO-432142. Platelet sensitization by LDL.

Miscellaneous databases

PROiQ6P6U0.

Gene expression databases

BgeeiENSRNOG00000009912.
GenevisibleiQ6P6U0. RN.

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_RAT
AccessioniPrimary (citable) accession number: Q6P6U0
Secondary accession number(s): Q63206
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 19, 2011
Last sequence update: July 5, 2004
Last modified: September 7, 2016
This is version 112 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. 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.