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Protein

Fibroblast growth factor receptor substrate 2

Gene

FRS2

Organism
Homo sapiens (Human)
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 NTRK1.2 Publications

GO - Molecular functioni

  • 1-phosphatidylinositol-3-kinase activity Source: Reactome
  • fibroblast growth factor receptor binding Source: MGI
  • neurotrophin TRKA receptor binding Source: UniProtKB
  • phosphatase activator activity Source: UniProtKB
  • phosphatidylinositol-4,5-bisphosphate 3-kinase activity Source: Reactome
  • Ras guanyl-nucleotide exchange factor activity Source: Reactome
  • transmembrane receptor protein tyrosine kinase adaptor activity Source: UniProtKB

GO - Biological processi

Enzyme and pathway databases

ReactomeiR-HSA-109704 PI3K Cascade
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-170968 Frs2-mediated activation
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-5654689 PI-3K cascade:FGFR1
R-HSA-5654693 FRS-mediated FGFR1 signaling
R-HSA-5654695 PI-3K cascade:FGFR2
R-HSA-5654700 FRS-mediated FGFR2 signaling
R-HSA-5654706 FRS-mediated FGFR3 signaling
R-HSA-5654710 PI-3K cascade:FGFR3
R-HSA-5654712 FRS-mediated FGFR4 signaling
R-HSA-5654720 PI-3K cascade:FGFR4
R-HSA-5654726 Negative regulation of FGFR1 signaling
R-HSA-5654727 Negative regulation of FGFR2 signaling
R-HSA-5654732 Negative regulation of FGFR3 signaling
R-HSA-5654733 Negative regulation of FGFR4 signaling
R-HSA-5655253 Signaling by FGFR2 in disease
R-HSA-5655291 Signaling by FGFR4 in disease
R-HSA-5655302 Signaling by FGFR1 in disease
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-8853334 Signaling by FGFR3 fusions in cancer
R-HSA-8853338 Signaling by FGFR3 point mutants in cancer
R-HSA-8853659 RET signaling
R-HSA-9028731 Activated NTRK2 signals through FRS2 and FRS3
SignaLinkiQ8WU20
SIGNORiQ8WU20

Names & Taxonomyi

Protein namesi
Recommended name:
Fibroblast growth factor receptor substrate 2
Short name:
FGFR substrate 2
Alternative name(s):
FGFR-signaling adaptor SNT
Suc1-associated neurotrophic factor target 1
Short name:
SNT-1
Gene namesi
Name:FRS2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000166225.8
HGNCiHGNC:16971 FRS2
MIMi607743 gene
neXtProtiNX_Q8WU20

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

Organism-specific databases

DisGeNETi10818
OpenTargetsiENSG00000166225
PharmGKBiPA134850063

Polymorphism and mutation databases

DMDMi209572769

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved
ChainiPRO_00000873442 – 508Fibroblast growth factor receptor substrate 2Add BLAST507

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine2 Publications1
Modified residuei177PhosphoserineCombined sources1
Modified residuei196Phosphotyrosine; by FGFR1By similarity1
Modified residuei211PhosphoserineCombined sources1
Modified residuei221PhosphoserineCombined sources1
Modified residuei306Phosphotyrosine; by FGFR1By similarity1
Modified residuei349Phosphotyrosine; by FGFR1By similarity1
Modified residuei365PhosphoserineCombined sources1
Modified residuei392Phosphotyrosine; by FGFR1By similarity1
Modified residuei436Phosphotyrosine; by FGFR1By similarity1
Modified residuei471Phosphotyrosine; by FGFR1By similarity1

Post-translational modificationi

Phosphorylated by ULK2 in vitro (By similarity). Phosphorylated on tyrosine residues upon stimulation by NGF or FGF2. 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.By similarity5 Publications
Ubiquitinated when tyrosine phosphorylated and in a complex with GRB2. The unphosphorylated form is not subject to ubiquitination (By similarity).By similarity

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ8WU20
MaxQBiQ8WU20
PaxDbiQ8WU20
PeptideAtlasiQ8WU20
PRIDEiQ8WU20
ProteomicsDBi74624

PTM databases

iPTMnetiQ8WU20
PhosphoSitePlusiQ8WU20

Expressioni

Tissue specificityi

Highly expressed in heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis.1 Publication

Gene expression databases

BgeeiENSG00000166225
CleanExiHS_FRS2
ExpressionAtlasiQ8WU20 baseline and differential
GenevisibleiQ8WU20 HS

Organism-specific databases

HPAiHPA038323

Interactioni

Subunit structurei

Part of a complex containing FRS2, GRB2, GAB1, PIK3R1 and SOS1. Part of a complex containing GRB2 and CBL. Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN. Binds RET (By similarity). Binds ALK, FGFR1, CKS2, 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 similarity7 Publications

GO - Molecular functioni

  • fibroblast growth factor receptor binding Source: MGI
  • neurotrophin TRKA receptor binding Source: UniProtKB
  • Ras guanyl-nucleotide exchange factor activity Source: Reactome
  • transmembrane receptor protein tyrosine kinase adaptor activity Source: UniProtKB

Protein-protein interaction databases

BioGridi116031, 29 interactors
ELMiQ8WU20
IntActiQ8WU20, 9 interactors
MINTiQ8WU20
STRINGi9606.ENSP00000299293

Structurei

Secondary structure

1508
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni15 – 18Combined sources4
Beta strandi20 – 26Combined sources7
Beta strandi32 – 34Combined sources3
Beta strandi36 – 40Combined sources5
Beta strandi45 – 49Combined sources5
Turni50 – 52Combined sources3
Beta strandi53 – 57Combined sources5
Turni59 – 61Combined sources3
Beta strandi62 – 67Combined sources6
Beta strandi69 – 76Combined sources8
Beta strandi84 – 90Combined sources7
Helixi94 – 107Combined sources14

3D structure databases

ProteinModelPortaliQ8WU20
SMRiQ8WU20
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8WU20

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
InParanoidiQ8WU20
KOiK12461
OMAiSAHKVEF
OrthoDBiEOG091G06AV
PhylomeDBiQ8WU20
TreeFamiTF324994

Family and domain databases

CDDicd01202 PTB_FRS2, 1 hit
InterProiView protein in InterPro
IPR038742 FRS2_PTB
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.

Q8WU20-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGSCCSCPDK DTVPDNHRNK FKVINVDDDG NELGSGIMEL TDTELILYTR
60 70 80 90 100
KRDSVKWHYL CLRRYGYDSN LFSFESGRRC QTGQGIFAFK CARAEELFNM
110 120 130 140 150
LQEIMQNNSI NVVEEPVVER NNHQTELEVP RTPRTPTTPG FAAQNLPNGY
160 170 180 190 200
PRYPSFGDAS SHPSSRHPSV GSARLPSVGE ESTHPLLVAE EQVHTYVNTT
210 220 230 240 250
GVQEERKNRT SVHVPLEARV SNAESSTPKE EPSSIEDRDP QILLEPEGVK
260 270 280 290 300
FVLGPTPVQK QLMEKEKLEQ LGRDQVSGSG ANNTEWDTGY DSDERRDAPS
310 320 330 340 350
VNKLVYENIN GLSIPSASGV RRGRLTSTST SDTQNINNSA QRRTALLNYE
360 370 380 390 400
NLPSLPPVWE ARKLSRDEDD NLGPKTPSLN GYHNNLDPMH NYVNTENVTV
410 420 430 440 450
PASAHKIEYS RRRDCTPTVF NFDIRRPSLE HRQLNYIQVD LEGGSDSDNP
460 470 480 490 500
QTPKTPTTPL PQTPTRRTEL YAVIDIERTA AMSNLQKALP RDDGTSRKTR

HNSTDLPM
Length:508
Mass (Da):57,029
Last modified:October 14, 2008 - v4
Checksum:i833714EE12097C75
GO

Sequence cautioni

The sequence AAH21562 differs from that shown. Reason: Erroneous termination at position 509. Translated as stop.Curated
The sequence BAG35381 differs from that shown. Reason: Erroneous termination at position 509. Translated as stop.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_046966303K → N. Corresponds to variant dbSNP:rs12580717Ensembl.1
Natural variantiVAR_046967449N → D. Corresponds to variant dbSNP:rs35232109Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF036717 mRNA Translation: AAB92554.1
AK312477 mRNA Translation: BAG35381.1 Sequence problems.
EU332842 Genomic DNA Translation: ABY87531.1
AC018921 Genomic DNA No translation available.
CH471054 Genomic DNA Translation: EAW97225.1
BC021562 mRNA Translation: AAH21562.1 Sequence problems.
CCDSiCCDS41809.1
RefSeqiNP_001036020.1, NM_001042555.2
NP_001265280.1, NM_001278351.1
NP_001265282.1, NM_001278353.1
NP_001265283.1, NM_001278354.1
NP_001265284.1, NM_001278355.1
NP_001265285.1, NM_001278356.1
NP_001265286.1, NM_001278357.1
NP_006645.3, NM_006654.4
XP_016874206.1, XM_017018717.1
XP_016874207.1, XM_017018718.1
XP_016874208.1, XM_017018719.1
UniGeneiHs.593446

Genome annotation databases

EnsembliENST00000397997; ENSP00000381083; ENSG00000166225
ENST00000549921; ENSP00000450048; ENSG00000166225
ENST00000550389; ENSP00000447241; ENSG00000166225
GeneIDi10818
KEGGihsa:10818
UCSCiuc009zrj.5 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiFRS2_HUMAN
AccessioniPrimary (citable) accession number: Q8WU20
Secondary accession number(s): B0LPF2
, B2R684, O43558, Q7LDQ6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2005
Last sequence update: October 14, 2008
Last modified: July 18, 2018
This is version 151 of the entry and version 4 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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