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Protein

Fibroblast growth factor receptor substrate 2

Gene

Frs2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
  • 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
Complete GO annotation...

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-5654699. SHC-mediated 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-5654719. SHC-mediated cascade:FGFR4.
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.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1100860. Frs2.

Subcellular locationi

GO - Cellular componenti

  • cell-cell junction Source: MGI
  • cytoplasm Source: MGI
  • plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi2 – 21G → A: Abolishes myristoylation and membrane association. 1 Publication
Mutagenesisi196 – 1961Y → F: Abolishes tyrosine phosphorylation and interactions with GRB2 and PTPN11; when associated with F-306; F-349; F-392 and F-436. 1 Publication
Mutagenesisi306 – 3061Y → F: Abolishes tyrosine phosphorylation and interactions with GRB2 and PTPN11; when associated with F-196; F-349; F-392 and F-436. 1 Publication
Mutagenesisi349 – 3491Y → F: Abolishes tyrosine phosphorylation and interactions with GRB2 and PTPN11; when associated with F-196; F-306; F-392 and F-436. 1 Publication
Mutagenesisi392 – 3921Y → F: Abolishes tyrosine phosphorylation and interactions with GRB2 and PTPN11; when associated with F-196; F-306; F-349 and F-436. 1 Publication
Mutagenesisi436 – 4361Y → F: Abolishes tyrosine phosphorylation and interactions with GRB2 and PTPN11; when associated with F-196; F-306; F-349 and F-392. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedSequence analysis
Chaini2 – 508507Fibroblast growth factor receptor substrate 2PRO_0000087345Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycine1 Publication
Modified residuei177 – 1771PhosphoserineBy similarity
Modified residuei196 – 1961Phosphotyrosine; by FGFR13 Publications
Modified residuei211 – 2111PhosphoserineCombined sources
Modified residuei221 – 2211PhosphoserineBy similarity
Modified residuei306 – 3061Phosphotyrosine; by FGFR13 Publications
Modified residuei349 – 3491Phosphotyrosine; by FGFR1Combined sources3 Publications
Modified residuei365 – 3651PhosphoserineBy similarity
Modified residuei392 – 3921Phosphotyrosine; by FGFR13 Publications
Modified residuei436 – 4361Phosphotyrosine; by FGFR12 Publications
Modified residuei471 – 4711Phosphotyrosine; by FGFR11 Publication

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.
PhosphoSiteiQ8C180.
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

BioGridi236497. 6 interactions.
IntActiQ8C180. 2 interactions.
MINTiMINT-8013548.
STRINGi10090.ENSMUSP00000020381.

Structurei

3D structure databases

ProteinModelPortaliQ8C180.
SMRiQ8C180. Positions 11-136.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini13 – 115103IRS-type PTBPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 IRS-type PTB domain.PROSITE-ProRule annotation

Phylogenomic databases

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

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR002404. IRS_PTB.
IPR011993. PH_dom-like.
[Graphical view]
PfamiPF02174. IRS. 1 hit.
[Graphical view]
SMARTiSM00310. PTBI. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 1 hit.
PROSITEiPS51064. IRS_PTB. 1 hit.
[Graphical view]

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ8C180.
SMRiQ8C180. Positions 11-136.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi236497. 6 interactions.
IntActiQ8C180. 2 interactions.
MINTiMINT-8013548.
STRINGi10090.ENSMUSP00000020381.

PTM databases

iPTMnetiQ8C180.
PhosphoSiteiQ8C180.
SwissPalmiQ8C180.

Proteomic databases

MaxQBiQ8C180.
PaxDbiQ8C180.
PeptideAtlasiQ8C180.
PRIDEiQ8C180.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi10818.
MGIiMGI:1100860. Frs2.

Phylogenomic databases

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

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-5654699. SHC-mediated 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-5654719. SHC-mediated cascade:FGFR4.
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.

Miscellaneous databases

PROiQ8C180.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000020170.
CleanExiMM_FRS2.
GenevisibleiQ8C180. MM.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR002404. IRS_PTB.
IPR011993. PH_dom-like.
[Graphical view]
PfamiPF02174. IRS. 1 hit.
[Graphical view]
SMARTiSM00310. PTBI. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 1 hit.
PROSITEiPS51064. IRS_PTB. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFRS2_MOUSE
AccessioniPrimary (citable) accession number: Q8C180
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2005
Last sequence update: January 23, 2007
Last modified: September 7, 2016
This is version 117 of the entry and version 3 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.