Q8WU20 · FRS2_HUMAN
- ProteinFibroblast growth factor receptor substrate 2
- GeneFRS2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids508 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameFibroblast growth factor receptor substrate 2
- Short namesFGFR substrate 2
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ8WU20
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Cytoplasmic, membrane-bound.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_046966 | 303 | in dbSNP:rs12580717 | |||
Sequence: K → N | ||||||
Natural variant | VAR_046967 | 449 | in dbSNP:rs35232109 | |||
Sequence: N → D |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 555 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, lipidation, chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Lipidation | 2 | UniProt | N-myristoyl glycine | ||||
Sequence: G | |||||||
Chain | PRO_0000087344 | 2-508 | UniProt | Fibroblast growth factor receptor substrate 2 | |||
Sequence: GSCCSCPDKDTVPDNHRNKFKVINVDDDGNELGSGIMELTDTELILYTRKRDSVKWHYLCLRRYGYDSNLFSFESGRRCQTGQGIFAFKCARAEELFNMLQEIMQNNSINVVEEPVVERNNHQTELEVPRTPRTPTTPGFAAQNLPNGYPRYPSFGDASSHPSSRHPSVGSARLPSVGEESTHPLLVAEEQVHTYVNTTGVQEERKNRTSVHVPLEARVSNAESSTPKEEPSSIEDRDPQILLEPEGVKFVLGPTPVQKQLMEKEKLEQLGRDQVSGSGANNTEWDTGYDSDERRDAPSVNKLVYENINGLSIPSASGVRRGRLTSTSTSDTQNINNSAQRRTALLNYENLPSLPPVWEARKLSRDEDDNLGPKTPSLNGYHNNLDPMHNYVNTENVTVPASAHKIEYSRRRDCTPTVFNFDIRRPSLEHRQLNYIQVDLEGGSDSDNPQTPKTPTTPLPQTPTRRTELYAVIDIERTAAMSNLQKALPRDDGTSRKTRHNSTDLPM | |||||||
Modified residue (large scale data) | 125 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 132 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 135 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 137 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 138 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 155 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 161 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 177 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 177 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 196 | UniProt | Phosphotyrosine; by FGFR1 | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 210 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 211 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 211 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 221 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 221 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 225 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 226 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 227 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 234 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 290 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 292 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 300 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 306 | UniProt | Phosphotyrosine; by FGFR1 | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 306 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 327 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 339 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 349 | UniProt | Phosphotyrosine; by FGFR1 | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 349 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 365 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 365 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 392 | UniProt | Phosphotyrosine; by FGFR1 | ||||
Sequence: Y | |||||||
Modified residue | 436 | UniProt | Phosphotyrosine; by FGFR1 | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 457 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 463 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 471 | UniProt | Phosphotyrosine; by FGFR1 | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 503 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
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
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
Ubiquitinated when tyrosine phosphorylated and in a complex with GRB2. The unphosphorylated form is not subject to ubiquitination (By similarity).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis.
Gene expression databases
Organism-specific databases
Interaction
Subunit
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)
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)
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q8WU20 | FGFR1 P11362 | 3 | EBI-1104330, EBI-1028277 | |
BINARY | Q8WU20 | PTPN11 Q06124 | 4 | EBI-1104330, EBI-297779 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 13-115 | IRS-type PTB | ||||
Sequence: VPDNHRNKFKVINVDDDGNELGSGIMELTDTELILYTRKRDSVKWHYLCLRRYGYDSNLFSFESGRRCQTGQGIFAFKCARAEELFNMLQEIMQNNSINVVEE | ||||||
Region | 122-180 | Disordered | ||||
Sequence: NHQTELEVPRTPRTPTTPGFAAQNLPNGYPRYPSFGDASSHPSSRHPSVGSARLPSVGE | ||||||
Compositional bias | 128-144 | Polar residues | ||||
Sequence: EVPRTPRTPTTPGFAAQ | ||||||
Region | 200-243 | Disordered | ||||
Sequence: TGVQEERKNRTSVHVPLEARVSNAESSTPKEEPSSIEDRDPQIL | ||||||
Region | 270-297 | Disordered | ||||
Sequence: QLGRDQVSGSGANNTEWDTGYDSDERRD | ||||||
Region | 315-338 | Disordered | ||||
Sequence: PSASGVRRGRLTSTSTSDTQNINN | ||||||
Region | 366-385 | Disordered | ||||
Sequence: RDEDDNLGPKTPSLNGYHNN | ||||||
Region | 441-467 | Disordered | ||||
Sequence: LEGGSDSDNPQTPKTPTTPLPQTPTRR | ||||||
Region | 483-508 | Disordered | ||||
Sequence: SNLQKALPRDDGTSRKTRHNSTDLPM |
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length508
- Mass (Da)57,029
- Last updated2008-10-14 v4
- Checksum833714EE12097C75
Computationally mapped potential isoform sequences
There are 8 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 128-144 | Polar residues | ||||
Sequence: EVPRTPRTPTTPGFAAQ |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF036717 EMBL· GenBank· DDBJ | AAB92554.1 EMBL· GenBank· DDBJ | mRNA | ||
AK312477 EMBL· GenBank· DDBJ | BAG35381.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
EU332842 EMBL· GenBank· DDBJ | ABY87531.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AC018921 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471054 EMBL· GenBank· DDBJ | EAW97225.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC021562 EMBL· GenBank· DDBJ | AAH21562.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. |