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Protein

Fibroblast growth factor receptor substrate 2

Gene

Frs2

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

Functioni

Adapter protein that links activated FGR and NGF receptors to downstream signaling pathways. Plays an important role in the activation of MAP kinases and in the phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, in response to ligand-mediated activation of FGFR1. Modulates signaling via SHC1 by competing for a common binding site on NTRK1.5 Publications

GO - Molecular functioni

GO - Biological processi

  • activation of MAPK activity Source: MGI
  • anterior/posterior axis specification, embryo Source: MGI
  • fibroblast growth factor receptor signaling pathway Source: MGI
  • forebrain development Source: MGI
  • gastrulation with mouth forming second Source: MGI
  • lens development in camera-type eye Source: MGI
  • lens fiber cell development Source: MGI
  • negative regulation of cardiac muscle cell differentiation Source: MGI
  • neuroblast proliferation Source: MGI
  • optic placode formation involved in camera-type eye formation Source: MGI
  • organ induction Source: MGI
  • prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis Source: MGI
  • regulation of apoptotic process Source: MGI
  • regulation of epithelial cell proliferation Source: MGI
  • regulation of ERK1 and ERK2 cascade Source: MGI
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: MGI
  • ventricular septum development Source: MGI

Enzyme and pathway databases

ReactomeiR-MMU-109704 PI3K Cascade
R-MMU-1257604 PIP3 activates AKT signaling
R-MMU-170968 Frs2-mediated activation
R-MMU-5654689 PI-3K cascade:FGFR1
R-MMU-5654693 FRS-mediated FGFR1 signaling
R-MMU-5654695 PI-3K cascade:FGFR2
R-MMU-5654700 FRS-mediated FGFR2 signaling
R-MMU-5654706 FRS-mediated FGFR3 signaling
R-MMU-5654710 PI-3K cascade:FGFR3
R-MMU-5654712 FRS-mediated FGFR4 signaling
R-MMU-5654720 PI-3K cascade:FGFR4
R-MMU-5654726 Negative regulation of FGFR1 signaling
R-MMU-5654727 Negative regulation of FGFR2 signaling
R-MMU-5654732 Negative regulation of FGFR3 signaling
R-MMU-5654733 Negative regulation of FGFR4 signaling
R-MMU-5673001 RAF/MAP kinase cascade
R-MMU-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-MMU-8853659 RET signaling

Names & Taxonomyi

Protein namesi
Recommended name:
Fibroblast growth factor receptor substrate 2
Short name:
FGFR substrate 2
Alternative name(s):
FGFR-signaling adaptor SNT
FRS2-alpha
Suc1-associated neurotrophic factor target 1
Short name:
SNT-1
Gene namesi
Name:Frs2
Synonyms:Frs2a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1100860 Frs2

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

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi2G → A: Abolishes myristoylation and membrane association. 1 Publication1
Mutagenesisi196Y → F: Abolishes tyrosine phosphorylation and interactions with GRB2 and PTPN11; when associated with F-306; F-349; F-392 and F-436. 1 Publication1
Mutagenesisi306Y → F: Abolishes tyrosine phosphorylation and interactions with GRB2 and PTPN11; when associated with F-196; F-349; F-392 and F-436. 1 Publication1
Mutagenesisi349Y → F: Abolishes tyrosine phosphorylation and interactions with GRB2 and PTPN11; when associated with F-196; F-306; F-392 and F-436. 1 Publication1
Mutagenesisi392Y → F: Abolishes tyrosine phosphorylation and interactions with GRB2 and PTPN11; when associated with F-196; F-306; F-349 and F-436. 1 Publication1
Mutagenesisi436Y → F: Abolishes tyrosine phosphorylation and interactions with GRB2 and PTPN11; when associated with F-196; F-306; F-349 and F-392. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedSequence analysis
ChainiPRO_00000873452 – 508Fibroblast growth factor receptor substrate 2Add BLAST507

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine1 Publication1
Modified residuei177PhosphoserineBy similarity1
Modified residuei196Phosphotyrosine; by FGFR13 Publications1
Modified residuei211PhosphoserineCombined sources1
Modified residuei221PhosphoserineBy similarity1
Modified residuei306Phosphotyrosine; by FGFR13 Publications1
Modified residuei349Phosphotyrosine; by FGFR1Combined sources3 Publications1
Modified residuei365PhosphoserineBy similarity1
Modified residuei392Phosphotyrosine; by FGFR13 Publications1
Modified residuei436Phosphotyrosine; by FGFR12 Publications1
Modified residuei471Phosphotyrosine; by FGFR11 Publication1

Post-translational modificationi

Phosphorylated on tyrosine residues upon stimulation by FGF2 or NGFB. Phosphorylated by ULK2 (in vitro). Phosphorylated on tyrosine residues by activated ALK and FGFR1. Phosphorylated on tyrosine residues upon activation of FGFR2 and FGFR3. Phosphorylated on threonine residues by MAP kinases; this inhibits tyrosine phosphorylation, and thereby down-regulates FRS2-mediated activation of MAP kinases.
Ubiquitinated when tyrosine phosphorylated and in a complex with GRB2. The unphosphorylated form is not subject to ubiquitination.1 Publication

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ8C180
PaxDbiQ8C180
PeptideAtlasiQ8C180
PRIDEiQ8C180

PTM databases

iPTMnetiQ8C180
PhosphoSitePlusiQ8C180
SwissPalmiQ8C180

Expressioni

Tissue specificityi

Ubiquitous. Expression is highest in brain, kidney, lung and testis.1 Publication

Gene expression databases

BgeeiENSMUSG00000020170
CleanExiMM_FRS2
GenevisibleiQ8C180 MM

Interactioni

Subunit structurei

Part of a complex containing FRS2, GRB2, GAB1, PIK3R1 and SOS1. Part of a complex containing GRB2 and CBL. Binds ALK, CKS2, FGFR1, RET, MAPK1/ERK2, MAPK3/ERK1 and SRC. The tyrosine-phosphorylated protein binds the SH2 domains of GRB2 and PTPN11. Interacts with NTRK1, NTRK2 and NTRK3 (phosphorylated upon ligand-binding) (By similarity). Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN.By similarity9 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Grb2Q606315EBI-6880000,EBI-1688

GO - Molecular functioni

Protein-protein interaction databases

BioGridi2364976 interactors.
CORUMiQ8C180
IntActiQ8C180 2 interactors.
MINTiQ8C180
STRINGi10090.ENSMUSP00000020381

Structurei

3D structure databases

ProteinModelPortaliQ8C180
SMRiQ8C180
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini13 – 115IRS-type PTBPROSITE-ProRule annotationAdd BLAST103

Phylogenomic databases

eggNOGiKOG4047 Eukaryota
ENOG410XS2S LUCA
GeneTreeiENSGT00510000046707
HOGENOMiHOG000290694
HOVERGENiHBG062705
InParanoidiQ8C180
KOiK12461
OMAiSAHKVEF
OrthoDBiEOG091G06AV
PhylomeDBiQ8C180
TreeFamiTF324994

Family and domain databases

InterProiView protein in InterPro
IPR002404 IRS_PTB
PfamiView protein in Pfam
PF02174 IRS, 1 hit
SMARTiView protein in SMART
SM00310 PTBI, 1 hit
PROSITEiView protein in PROSITE
PS51064 IRS_PTB, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q8C180-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGSCCSCPDK DTVPDNHRNK FKVINVDDDG NELGSGVMEL TDTELILYTR
60 70 80 90 100
KRDSVKWHYL CLRRYGYDSN LFSFESGRRC QTGQGIFAFK CARAEELFNM
110 120 130 140 150
LQEIMQNNSI NVVEEPVVER SSHQTELEVP RTPRTPTTPG LGAQNLPNGY
160 170 180 190 200
PRYPSFGDAS SHPSSRHPSV GSARLPSVGE ESTHPLLVAE EQVHTYVNTT
210 220 230 240 250
GVQEERKNRA SVHVPPEARV SNAESNTPKE EPSNPEDRDP QVLLKPEGVR
260 270 280 290 300
FVLGPTPVQK QLMEKEKLEQ LGKDPVSGSG AGNTEWDTGY DSDERRDVPP
310 320 330 340 350
VNKLVYENIN GLSIPSASGV RRGRLTSTST SDTQNINNSA QRRPALLNYE
360 370 380 390 400
NLPSLPPVWE ARKLSRDEDD NLGPKTPSLN GYHNNLDPMH NYVNTENVTV
410 420 430 440 450
PASAHKIDYS KRRDCTPTVF NFDIRRPSLE HRQLNYIQVD LEGGSDSDNP
460 470 480 490 500
QTPKTPTTPL PQTPTRRTEL YAVIDIERTA AMSNLQKALP RDDGTSRKTR

HNSTDLPM
Length:508
Mass (Da):56,794
Last modified:January 23, 2007 - v3
Checksum:iDFFE8A818BFF8631
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK028813 mRNA Translation: BAC26132.1
BC043109 mRNA Translation: AAH43109.1
BC055334 mRNA Translation: AAH55334.1
CCDSiCCDS24190.1
RefSeqiNP_808466.1, NM_177798.3
UniGeneiMm.135965

Genome annotation databases

EnsembliENSMUST00000020381; ENSMUSP00000020381; ENSMUSG00000020170
GeneIDi327826
KEGGimmu:327826
UCSCiuc007hct.1 mouse

Similar proteinsi

Entry informationi

Entry nameiFRS2_MOUSE
AccessioniPrimary (citable) accession number: Q8C180
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2005
Last sequence update: January 23, 2007
Last modified: March 28, 2018
This is version 128 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome